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Description

Save time identifying and diagnosing pathology specimens with High Yield Bone and Soft Tissue Pathology, edited by Drs. Andrew Horvai and Thomas Link. Part of the High-Yield Pathology Series, this title is designed to help you review the key pathologic features of bone and soft-tissue malformations, recognize the classic look of each disease, and quickly confirm your diagnosis. Its templated format, excellent color photographs, concise bulleted text, and authoritative content will help you accurately identify more than 160 discrete disease entities.

  • Find information quickly and easily with a templated, easy-to-reference format.
  • Confirm your diagnoses with excellent color photographs that demonstrate the classic appearance of each disease.
  • Find the answers you need fast with concise, bulleted text.
  • Depend on authoritative information from leading experts in the field.

Sujets

Ebooks
Savoirs
Medecine
Médecine
Osteonecrosis
Osteogénesis imperfecta
Embryonal rhabdomyosarcoma
Nuchal fibroma
Palisaded encapsulated neuroma
Inflammatory myofibroblastic tumor
Lipoblastoma
Fibroma of tendon sheath
Reticulohistiocytoma
Mesenchymal chondrosarcoma
Chondromyxoid fibroma
Cutaneous myxoma
Spindle cell lipoma
Chondroid lipoma
Neurothekeoma
Solitary neurofibroma
Plexiform fibrohistiocytic tumor
Collagenous fibroma
Intravascular papillary endothelial hyperplasia
Angiolymphoid hyperplasia with eosinophilia
Metastatic carcinoma
Epithelioid hemangioendothelioma
Fibrous hamartoma of infancy
Fibromatosis colli
Aponeurotic fibroma
Hibernoma
Kaposi's sarcoma
Angiomyxoma
Angiofibroma
Osteoid osteoma
Angiolipoma
Enchondromatosis
Alveolar rhabdomyosarcoma
Juvenile xanthogranuloma
Osteoblastoma
Chondroblastoma
Traumatic neuroma
Schwannoma
Aneurysmal bone cyst
Synovial chondromatosis
Acute myeloid leukemia
Subungual exostosis
Ganglioneuroma
Ossifying fibroma
Pyogenic granuloma
Pleomorphism
Myositis
Osteitis fibrosa cystica
Giant cell
Large cell
Hemosiderin
Neurofibroma
Periostitis
Desmoplastic fibroma
Ochronosis
Hamartoma
Massive
Inclusion body
Dysplasia
Malignant peripheral nerve sheath tumor
Leiomyosarcoma
Ameloblastoma
Osteolysis
Langerhans cell histiocytosis
Chondroma
Fibrosarcoma
Neuroblastoma
Fibrous dysplasia of bone
Paraganglioma
Liposarcoma
Fibromatosis
Benign fibrous histiocytoma
Chondrosarcoma
Dermatofibrosarcoma protuberans
Fibroma
Proliferation
Hereditary multiple exostoses
Myxoma
Hemangioma
Hyperparathyroidism
Paget's disease of bone
Osteomalacia
Osteopetrosis
Ewing's sarcoma
Osteoarthritis
Xanthoma
Granuloma
Hemangiosarcoma
Squamous cell carcinoma
Sclerosis
Osteosarcoma
Multiple myeloma
Soft tissue
Soft tissue sarcoma
Lipoma
Necrotizing fasciitis
Keloid
Mastocytosis
Aggression
Acrochordon
Tumor
Rickets
Rheumatoid arthritis
Osteoporosis
Magnetic resonance imaging
Collagen
Fractures
Human
Gout

Informations

Publié par
Date de parution 29 novembre 2011
Nombre de lectures 3
EAN13 9781455737901
Langue English
Poids de l'ouvrage 27 Mo

Informations légales : prix de location à la page 0,0527€. Cette information est donnée uniquement à titre indicatif conformément à la législation en vigueur.

Exrait

High-Yield Pathology
Bone and Soft Tissue Pathology

Andrew E. Horvai, MD, PhD
Associate Clinical Professor, Department of Pathology, University of California, San Francisco, San Francisco, California

Thomas Link, MD
Professor in Residence, Department of Radiology, University of California, San Francisco, San Francisco, California
Saunders
Front Matter

High-Yield Pathology Bone and Soft Tissue Pathology
Andrew E. Horvai, MD, PhD
Associate Clinical Professor, Department of Pathology, University of California, San Francisco, San Francisco, California
Radiology Editor
Thomas Link, MD
Professor in Residence, Department of Radiology, University of California, San Francisco, San Francisco, California
Copyright

1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
BONE AND SOFT TISSUE PATHOLOGY ISBN: 978-1-4377-2520-9
Copyright © 2012 by Saunders, an imprint of Elsevier Inc.
No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies, and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions .
This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notice
Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.
Library of Congress Cataloging-in-Publication Data
Bone and soft tissue pathology / [editor], Andrew E. Horvai; radiology editor,
Thomas Link. — 1st ed.
p. ; cm. — (High-yield pathology)
Includes index.
ISBN 978-1-4377-2520-9 (hardcover : alk. paper)
I. Horvai, Andrew E. II. Link, Thomas M. III. Series: High-yield pathology.
[DNLM: 1. Bone Diseases—pathology. 2. Soft Tissue Neoplasms—pathology. WE 225]
616.71071—dc23 2011040031
Executive Content Strategist: William R. Schmitt
Senior Content Development Specialist: Kathryn DeFrancesco
Publishing Services Manager: Anne Altepeter
Associate Project Manager: Jessica L. Becher
Design Direction: Steve Stave
Printed in the United States of America
Last digit is the print number: 9 8 7 6 5 4 3 2 1
Dedication
To Terrie, Brooke, my dear mother, Gizella, and my late father George

Andrew E. Horvai, MD, PhD
To my wife, Heike, and my parents, Sieglinde and Bruno Link

Thomas Link, MD
Contributors

Michael Barnes, MD, Neuropathology Fellow, Department of Pathology, University of California, San Francisco, San Francisco, California

Michael Bonham, MD, PhD, Clinical Instructor, Anatomic Pathology, Department of Pathology, University of California, San Francisco, San Francisco, California

Nancy Ciau, MD, Clinical Instructor, Department of Pathology, University of California, San Francisco, San Francisco, California

Vijay George, MD, Clinical Pathology Resident, Department of Pathology, University of California, San Francisco, San Francisco, California

Ryan Gill, MD, PhD, Assistant Clinical Professor, Department of Pathology, University of California, San Francisco, San Francisco, California

Anne Hiniker, MD, PhD, Neuropathology Fellow, Department of Pathology, University of California, San Francisco, San Francisco, California

Andrew E. Horvai, MD, PhD, Associate Clinical Professor, Department of Pathology, University of California, San Francisco, San Francisco, California

Abel Jarell, MD, Dermatopathology Fellow, Department of Pathology, University of California, San Francisco, San Francisco, California

Cindy Jimenez, MD, Surgical Pathology Fellow, Department of Pathology, University of California, San Francisco, San Francisco, California

Ellen Krasik, MD, Clinical Pathology Resident, Department of Pathology, University of California, San Francisco, San Francisco, California

Thomas Link, MD, Professor in Residence, Department of Radiology, University of California, San Francisco, San Francisco, California

Judy Pang, MD, Assistant Professor, Department of Pathology, University of Michigan, Ann Arbor, Michigan

Raga Ramachandran, MD, PhD, Assistant Professor of Clinical Pathology, Department of Pathology, University of California, San Francisco, San Francisco, California

Anatoly Urisman, MD, PhD, Anatomic Pathology Resident, Department of Pathology, University of California, San Francisco, San Francisco, California

Maria Vergara, MD, Surgical Pathology Fellow, Department of Pathology, University of California, Los Angeles, Los Angeles, California
Preface
Specimens from the musculoskeletal system are infrequently encountered by the practicing pathologist. Many of the most common diagnoses, such as traumatic fractures, usually do not require tissue diagnosis. Furthermore, the rarity of bone and soft tissue neoplasms and the disfiguring surgery endorsed by a malignant diagnosis present unique challenges for the pathologist. The difficulty is compounded by the myriad diagnostic entities and the absence of universal classification systems. For the pathologist-in-training, learning the material has been equally demanding. The purpose of this textbook is to present the pathology of bone and soft tissue in a practical, focused, and easily accessible format. The text emphasizes the diagnostic hallmarks of each entity, to allow straightforward, rapid comparison of diagnoses within a single differential. More than 1000 illustrations are provided to supplement the critical details of the text. To achieve this format, discussion of minutiae and controversies is reduced.
In most organ systems, non-neoplastic diseases constitute a significant proportion of diagnoses. Although this is also true of the skeletal system, the pathology of somatic soft tissue is dominated by neoplasms. The resulting disparity between the bone and soft tissue sections of this book, thus, reveals the reality of routine pathology practice rather than omission.
Finally, although this book is intended for pathologists, diseases of bone cannot be diagnosed accurately without evaluation of corresponding radiographic studies. The fundamental radiographic findings for each diagnosis are described and illustrated with high-quality images so that the pathologist can effectively contribute to the multidisciplinary care of the patient.
This volume would not have been possible without the hard work and dedication of the contributors. Thanks especially to Dr. Andrew Folpe and Dr. Carrie Inwards for their assistance and guidance.

Andrew E. Horvai, MD, PhD

Thomas Link, MD
Table of Contents
Front Matter
Copyright
Dedication
Contributors
Preface
I: Bone and Joint
A: Metabolic Conditions
Chapter 1: Paget Disease
Chapter 2: Osteoporosis
Chapter 3: Osteomalacia
Chapter 4: Rickets
Chapter 5: Osteogenesis Imperfecta
Chapter 6: Hyperparathyroidism
Chapter 7: Serous Fat Atrophy
Chapter 8: Xanthomatosis
Chapter 9: Osteopetrosis
Chapter 10: Ochronosis
Chapter 11: Melorheostosis
Chapter 12: Gaucher Disease
B: Infectious and Inflammatory Conditions
Chapter 13: Osteoarthritis
Chapter 14: Rheumatoid Arthritis
Chapter 15: Septic Arthritis
Chapter 16: Gout
Chapter 17: Other Crystal-Induced Synovitis and Calcium Deposition
Chapter 18: Acute Osteomyelitis
Chapter 19: Chronic Osteomyelitis
Chapter 20: Osteonecrosis
Chapter 21: Bone Fracture and Fracture Callus
C: Cystic Lesions
Chapter 22: Aneurysmal Bone Cyst
Chapter 23: Unicameral Bone Cyst
Chapter 24: Intraosseous Ganglion
D: Giant Cell–Rich Lesions
Chapter 25: Giant Cell Tumor
Chapter 26: Giant Cell–Reparative Granuloma
Chapter 27: Brown Tumor
Chapter 28: Tenosynovial Giant Cell Tumor, Localized Type
Chapter 29: Tenosynovial Giant Cell Tumor, Diffuse Type
E: Mixed Periosteal Lesions
Chapter 30: Bizarre Parosteal Osteochondromatous Proliferation
Chapter 31: Subungual Exostosis
Chapter 32: Florid Reactive Periostitis
F: Cartilage-Forming Lesions
Chapter 33: Solitary Osteochondroma
Chapter 34: Multiple Hereditary Exostoses
Chapter 35: Enchondroma
Chapter 36: Multiple Chondroma Syndromes (Ollier Disease, Maffucci Syndrome)
Chapter 37: Periosteal Chondroma
Chapter 38: Synovial Chondromatosis
Chapter 39: Chondro-Osseous Loose Body
Chapter 40: Chondromyxoid Fibroma
Chapter 41: Chondroblastoma
Chapter 42: Conventional Intramedullary Chondrosarcoma
Chapter 43: Chondrosarcoma of the Small Bones of the Hands and Feet
Chapter 44: Periosteal Chondrosarcoma
Chapter 45: Secondary Chondrosarcoma
Chapter 46: Clear Cell Chondrosarcoma
Chapter 47: Dedifferentiated Chondrosarcoma
Chapter 48: Mesenchymal Chondrosarcoma
G: Bone-Forming Lesions
Chapter 49: Bone Island
Chapter 50: Osteoid Osteoma
Chapter 51: Osteoblastoma
Chapter 52: Conventional Osteosarcoma
Chapter 53: Small Cell Osteosarcoma
Chapter 54: Telangiectatic Osteosarcoma
Chapter 55: High-Grade Surface Osteosarcoma
Chapter 56: Post-Treatment Osteosarcoma
Chapter 57: Parosteal Osteosarcoma
Chapter 58: Periosteal Osteosarcoma
Chapter 59: Low-Grade Central Osteosarcoma
Chapter 60: Chondroblastoma-Like Osteosarcoma
H: Notochordal Tumors
Chapter 61: Benign Notochordal Cell Tumor
Chapter 62: Chordoma
I: Fibrous Lesions
Chapter 63: Fibrous Dysplasia
Chapter 64: Osteofibrous Dysplasia
Chapter 65: Desmoplastic Fibroma
Chapter 66: Nonossifying Fibroma
Chapter 67: Ossifying Fibroma
J: Vascular Lesions
Chapter 68: Hemangioma
Chapter 69: Synovial Hemangioma
Chapter 70: Epithelioid Hemangioma
Chapter 71: Epithelioid Hemangioendothelioma
Chapter 72: Angiosarcoma of Bone
Chapter 73: Massive Osteolysis
Chapter 74: K. Ewing Sarcoma
L: Hematopoietic Lesions
Chapter 75: Primary Osseous Lymphoma
Chapter 76: Acute Myeloid Leukemia
Chapter 77: Plasmacytoma
Chapter 78: Langerhans Cell Histiocytosis
Chapter 79: Mastocytosis
Chapter 80: M. Undifferentiated Pleomorphic Sarcoma of Bone
Chapter 81: N. Adamantinoma
O: Lipomatous Tumors
Chapter 82: Intraosseous Lipoma
Chapter 83: Synovial Lipomatosis
P: Carcinoma
Chapter 84: Metastatic Carcinoma
Chapter 85: Squamous Cell Carcinoma Arising in a Draining Sinus of Chronic Osteomyelitis
II: Soft Tissue
A: Inflammatory and Pseudosarcomatous Myofibroblastic Proliferations
Chapter 86: Nodular Fasciitis
Chapter 87: Proliferative Myositis and Proliferative Fasciitis
Chapter 88: Ischemic Fasciitis
Chapter 89: Postoperative Spindle Cell Nodule
Chapter 90: Necrotizing Fasciitis
B: Fibrosing Lesions and Fibromatoses
Chapter 91: Elastofibroma
Chapter 92: Desmosplastic Fibroblastoma
Chapter 93: Hypertrophic Scar
Chapter 94: Keloid
Chapter 95: Fibrous Hamartoma Of Infancy
Chapter 96: Gardner Fibroma
Chapter 97: Nuchal Fibroma
Chapter 98: Fibromatosis Colli
Chapter 99: Calcifying Aponeurotic Fibroma
Chapter 100: Fibroma Of Tendon Sheath
Chapter 101: Superficial Fibromatosis
Chapter 102: Deep Fibromatosis
Chapter 103: Inclusion-Body Fibroma
Chapter 104: IgG4-Related Sclerosing Disease
C: Myofibroblastic Tumors
Chapter 105: Myofibroblastoma (Mammary Type)
Chapter 106: Inflammatory Myofibroblastic Tumor
Chapter 107: Myofibroma and Myofibromatosis
Chapter 108: Intranodal Myofibroblastoma
Chapter 109: Myofibroblastic Sarcoma
D: Perivascular Tumors
Chapter 110: Glomus Tumor
Chapter 111: Glomuvenous Malformation
Chapter 112: Myopericytoma
E: Fibroblastic and Fibrohistiocytic Tumors
Chapter 113: Reticulohistiocytoma
Chapter 114: Juvenile Xanthogranuloma
Chapter 115: Benign Fibrous Histiocytoma
Chapter 116: Angiomatoid Fibrous Histiocytoma
Chapter 117: Plexiform Fibrohistiocytic Tumor
Chapter 118: Superficial Acral Fibromyxoma
Chapter 119: Superficial Angiomyxoma
Chapter 120: Dermatofibrosarcoma Protuberans
Chapter 121: Giant Cell Fibroblastoma
Chapter 122: Fibrosarcoma Arising in Dermatofibrosarcoma Protuberans
Chapter 123: Adult Fibrosarcoma
Chapter 124: Infantile Fibrosarcoma
Chapter 125: Sclerosing Epithelioid Fibrosarcoma
Chapter 126: Low-Grade Fibromyxoid Sarcoma
Chapter 127: Atypical Fibroxanthoma
Chapter 128: Intramuscular Myxoma
Chapter 129: Myxofibrosarcoma
F: Adipose Tumors
Chapter 130: Lipoblastoma
Chapter 131: Lipoma and Lipomatosis
Chapter 132: Angiolipoma
Chapter 133: Neural Fibrolipoma
Chapter 134: Hibernoma
Chapter 135: Chondroid Lipoma
Chapter 136: Spindle Cell and Pleomorphic Lipoma
Chapter 137: Well-Differentiated Liposarcoma and Atypical Lipomatous Tumor
Chapter 138: Dedifferentiated Liposarcoma
Chapter 139: Myxoid and Round Cell Liposarcoma
Chapter 140: Pleomorphic Liposarcoma
G: Smooth Muscle Tumors
Chapter 141: Angioleiomyoma
Chapter 142: Pilar Leiomyoma
Chapter 143: Leiomyoma of Deep Soft Tissue
Chapter 144: Leiomyosarcoma of Soft Tissue
Chapter 145: Vascular Leiomyosarcoma
Chapter 146: Epstein-Barr Virus–Associated Smooth Muscle Tumor
H: Genital Stromal Tumors
Chapter 147: FibroepithelIal Polyp
Chapter 148: Angiomyofibroblastoma
Chapter 149: Cellular Angiofibroma
Chapter 150: Aggressive Angiomyxoma
I: Skeletal Muscle Tumors
Chapter 151: Adult Rhabdomyoma
Chapter 152: Fetal Rhabdomyoma
Chapter 153: Genital Rhabdomyoma
Chapter 154: Alveolar Rhabdomyosarcoma
Chapter 155: Embryonal Rhabdomyosarcoma
Chapter 156: Pleomorphic Rhabdomyosarcoma
J: Nerve and Nerve Sheath Tumors
Chapter 157: Traumatic Neuroma
Chapter 158: Schwannoma
Chapter 159: Ancient Schwannoma
Chapter 160: Ganglioneuroma
Chapter 161: Neurothekeoma
Chapter 162: Cellular Schwannoma
Chapter 163: Neurofibroma
Chapter 164: Plexiform Neurofibroma
Chapter 165: Palisaded Encapsulated Neuroma
Chapter 166: Perineurioma
Chapter 167: Malignant Peripheral Nerve Sheath Tumor
Chapter 168: Malignant Triton Tumor
Chapter 169: Granular Cell Tumor
Chapter 170: Malignant Granular Cell Tumor
Chapter 171: Neuroglial Heterotopia
Chapter 172: Neuroblastoma
Chapter 173: Esthesioneuroblastoma
Chapter 174: Paraganglioma
Chapter 175: Melanotic Neuroectodermal Tumor of Infancy
K: Vascular Tumors
Chapter 176: Papillary Endothelial Hyperplasia
Chapter 177: Pyogenic Granuloma
Chapter 178: Arteriovenous Malformation
Chapter 179: Capillary Hemangioma
Chapter 180: Cavernous Hemangioma
Chapter 181: Lymphangioma
Chapter 182: Epithelioid Hemangioma
Chapter 183: Kimura Disease
Chapter 184: Spindle Cell Hemangioma
Chapter 185: Sinusoidal Hemangioma
Chapter 186: Epithelioid Hemangioendothelioma
Chapter 187: Hobnail Hemangioendothelioma
Chapter 188: Angiosarcoma
Chapter 189: Intimal Sarcoma
Chapter 190: Kaposi Sarcoma
Chapter 191: Kaposiform Hemangioendothelioma
L: Bone and Cartilage Tumors of Soft Tissue
Chapter 192: Soft Tissue Chondroma
Chapter 193: Extraskeletal Myxoid Chondrosarcoma
Chapter 194: Nuchal Fibrocartilaginous Pseudotumor
Chapter 195: Myositis Ossificans
Chapter 196: Ossifying Fibromyxoid Tumor
Chapter 197: Soft Tissue Osteosarcoma
Chapter 198: M. Perivascular Epithelioid Cell Neoplasms
N: Tumors of Uncertain Lineage
Chapter 199: Pleomorphic Hyalinizing Angiectatic Tumor of Soft Parts
Chapter 200: Soft Tissue Myoepithelioma
Chapter 201: Alveolar Soft Part Sarcoma
Chapter 202: Clear Cell Sarcoma
Chapter 203: Synovial Sarcoma
Chapter 204: Extrarenal Rhabdoid Tumor
Chapter 205: Epithelioid Sarcoma (Proximal and Distal)
Chapter 206: Desmoplastic Small Round Cell Tumor
Chapter 207: Primitive Neuroectodermal Tumor (Ewing Sarcoma)
Chapter 208: Giant Cell Tumor of Soft Tissue
Chapter 209: Undifferentiated Pleomorphic Sarcoma
Chapter 210: Phosphaturic Mesenchymal Tumor
Chapter 211: Myxoinflammatory Fibroblastic Sarcoma
Chapter 212: Ectopic Hamartomatous Thymoma
Chapter 213: Solitary Fibrous Tumor and Hemangiopericytoma
Index
I
Bone and Joint
A
Metabolic Conditions
Paget Disease

Definition and synonyms

• A chronic skeletal bone disorder due to overactivation of osteoblasts and osteoclasts with resultant abnormal remodeling of bone (osteitis deformans)

Clinical features

Epidemiology and presentation

• Bone pain, warmth, tenderness, and arthritis
• Localized skeletal deformity and spinal stenosis
• Stress fractures with minimal trauma
• Headaches, deafness, and increased hat size with skull involvement
• Markedly elevated serum alkaline phosphatase with normal calcium and phosphorus

Prognosis and treatment

• Usually asymptomatic; may be focal, multifocal, and progressive
• Severe forms show marked deformity, intractable pain, neurologic symptoms, and cardiac failure
• One to 3% of cases complicated by sarcoma (osteosarcoma, undifferentiated sarcoma)
• Asymptomatic patients require no treatment except in extensive skull involvement
• Symptomatic treatment with analgesics
• Bisphosphonates and calcitonin medical therapy

Radiology

• Osteolytic change in the early phase
• Initial lesions may be destructive and radiolucent, especially in the skull (osteoporosis circumscripta)
• Later bone deformity, thick cortical bone, coarsening of bone trabeculae, and loss of demarcation between cortical and trabecular bone
• Window frame appearance of vertebral bodies: increased density of the vertebral body periphery and accentuation of the trabeculae in the body
• Hot on bone scans unless it is in the inactive phase
• Stress fractures with multiple fissures in long bones at later stages
• Focal bone proliferation with malignant transformation

Pathology

Gross

• Bone is hyperemic with distortion of the normal contour and structure

Histology

• Osteolytic phase shows primarily osteoclastic activity with increased multinucleated osteoclasts mimicking hyperparathyroidism
• Active or mixed phase shows increased osteoclastic and osteoblastic activity with remodeling, fibrosis, and osteoid formation
• Thick and thin bone trabeculae are often present
• Sclerotic phase shows prominent irregular, wavy cement lines that reflect abnormal remodeling and may be the only feature in inactive disease
• Reticulin stain highlights disorganization of lamellar bone

Main differential diagnosis

• Hyperphosphatasia
• Polyostotic fibrous dysplasia
• Chronic osteomyelitis

Fig 1 Lateral radiograph of the skull in a patient with Paget disease showing thickening of the cortex with increased sclerosis mixed with lytic areas, also referred to as a cotton-wool appearance.


Fig 2 Lateral radiograph of the right tibia and fibula ( A ) and anteroposterior radiographs of the ankle ( B ) and knee ( C ). Note transverse fractures in the tibia and fibula, which are common because bone is inherently weak. There is marked cortical thickening of the tibia extending from the articular surface of the knee to the articular surface of the ankle. Deformity of the right tibia with anterior and lateral bowing is also shown.

Fig 3 Polarized light histopathology of normal bone ( A ) and bone from a patient with Paget disease ( B ). In Paget disease, the laminar sheetlike orientation is disrupted, leading to less refractile, interrupted collagen.

Fig 4 Scanning magnification in a patient with Paget disease showing thick and thin irregular trabecular bone, extensive fibrosis, and increased vascularity of bone marrow and irregular cement lines.

Fig 5 Higher magnification in a patient with Paget disease showing thick and prominent trabecular bone with large multinucleated osteoclasts.

Fig 6 In the sclerotic phase of Paget disease bone is formed with thickened, irregular trabeculae with osteoid seams creating a mosaic pattern of cement lines. This reflects prior incidences of bone resorption and formation.
Osteoporosis

Definition and synonyms

• Decrease in bone density of normally mineralized bone; the World Health Organization defines it as a bone mineral density that is 2.5 standard deviations (SD) below the mean peak value in young adults (porous bone)

Clinical features

Epidemiology

• Most common metabolic bone disease
• Most common in patients older than 50 years
• Postmenopausal women are affected because of estrogen deficiency
• Secondary causes include endocrine disorders, gastrointestinal disturbances, drugs, and immobilization
• Risk factors include smoking, caffeine, and alcohol consumption
• 1.5 million fractures per year leading to 37,500 deaths per year in the United States

Presentation

• Back pain, loss of height, thoracic kyphosis, fractures with minimal trauma
• Vertebral crush fractures and spontaneous fractures in severe form
• Cancellous compartment of vertebral bone, pelvis, and wrist most commonly affected
• Normal serum parathyroid hormone, calcium, phosphorus, and alkaline phosphatase

Prognosis and treatment

• Increased mortality rate due to complications of fractures; better prognosis with early maintained treatment
• Vitamin D and calcium supplementation
• Bisphosphonates increase bone thickness and lower the risk for fractures and are used for prevention and treatment
• Selective estrogen receptor modulators (raloxifene) act on bone to slow resorption by osteoclasts

Radiology

• Substantial bone loss (approximately 30% to 40%) must occur before routine radiographs are sensitive enough to detect
• Techniques to measure bone mineral density include dual energy X-ray absorptiometry and quantitative CT
• A bone mineral density 2.5 SD below the mean of a young adult is considered osteoporosis (T score of −2.5); between 1 and 2.5 SD below the mean is osteopenia
• Conventional radiographs show cortical thinning, increased radiolucency, vertebral compression, widening and swelling of intervertebral disks
• Three types of spinal fractures are identified in advanced disease: wedge fractures, biconcave fractures, and crush fractures
• The most severe complication is proximal femur fracture, typically femoral neck and intertrochanteric

Pathology

Gross

• Loss of trabecular bone
• Kyphosis of the thoracic spine due to osteoporosis involving more than one vertebral body (dowager sign)

Histology

• Cortical and trabecular bone is decreased with trabecular bone more severely affected
• Bone cortices are thin with widened haversian canals
• Osteoid seams are of normal width
• Trabeculae are thin, discontinuous, and separated

Main differential diagnosis

• Osteogenesis imperfecta
• Malabsorption
• Cushing’s syndrome
• Osteomalacia

Fig 1 Anteroposterior plain radiograph of the pelvis in a female patient with an osteoporotic intertrochanteric left proximal femur fracture with avulsion of the lesser trochanter ( arrow ). The large calcification in the pelvic soft tissues is a uterine fibroid.

Fig 2 Osteoporotic bone initially affects the trabeculae in the medulla, but this more advanced example shows involvement of the cortex ( bottom ) that is markedly thinned.

Fig 3 Scanning magnification of normal bone with broad, anastomosing trabeculae ( A ) and bone from a patient with osteoporosis ( B ) showing thin, separated, and discontinuous trabeculae.

Fig 4 Sequelae of osteoporosis in the lumbar spine. Anteroposterior ( A ) and lateral ( B ) radiographs of the lumbar spine with an osteoporotic fracture of the L3 vertebra ( arrow ) associated with a concave end plate and height loss of the vertebral body.
Osteomalacia

Definition

• General term for a defect in skeletal mineralization that results in the accumulation of unmineralized bone (osteoid); rickets represents defective endochondral ossification at the growth plate resulting in dwarfism (see Osteogenisis Imperfecta, later)

Clinical features

Epidemiology

• Commonly seen in deficiencies or disorders of calcium, vitamin D, or phosphorus metabolism
• Aluminum and iron metal poisoning
• Associated with certain bone and soft tissue tumors (oncogenic osteomalacia), specifically phosphaturic mesenchymal tumor (see Section IIM, Phosphaturic Mesenchymal Tumor)

Presentation

• Generalized musculoskeletal weakness and bone pain
• Fractures with minimal trauma, particularly in vertebral bodies and femoral necks
• Low vitamin D with or without low calcium or low phosphorus levels with high levels of alkaline phosphatase

Prognosis and treatment

• May be a contributing factor to hip fractures in elderly patients
• Treatment is aimed at correcting vitamin deficiencies or underlying medical conditions
• Adequate sunlight exposure and supplemental oral calcium and vitamin D

Radiology

• Symmetrical pseudofractures: unmineralized areas caused by rapid bone resorption and slow mineralization (Looser zones)
• Generalized osteopenia with coarse bone structure
• Multiple bilateral and symmetrical linear insufficiency fractures
• Technetium-99 bone scanning reveals multiple hot spots corresponding to pseudofractures and insufficiency fractures

Pathology

Gross

• Bone particularly from the vertebral column is soft, weak, and prone to fracture easily

Histology

• Bone must be processed without decalcification, and usually embedded in plastic for sectioning
• Increased amount of unmineralized bone or osteoid, surface osteoid greater than 25% (normal is ~2%)
• Increase in osteoid seam thickness, presence of greater than five birefringent lamellar lines in the osteoid seam
• Decreased mineralization or calcification rate
• Tongues of uncalcified cartilage extending into metaphysis

Ancillary studies

• Tetracycline taken before bone biopsy labels sites of new bone formation; a diminished number of osteoid seams taking up tetracycline reflects an absence of mineralization
• Osteoid evaluation can be performed using von Kossa, Goldner, modified trichrome, or Villanueva stain

Main differential diagnosis

• Osteopenia, osteoporosis

Fig 1 Plain anteroposterior radiographs of bilateral feet in a patient with oncogenic osteomalacia. The bones are severely osteopenic, and a diaphyseal insufficiency fracture is visualized at the left third metatarsal ( arrow ).


Fig 2 Bone biopsy using von Kossa stain in an undecalcified section with osteomalacia. Osteoid is the eosinophilic unmineralized portion of bone at the surface of trabeculae. The mineralized front is stained dark gray to black ( A and B ). Note that a significant fraction of the bone (~50%) is unmineralized.
(Courtesy of Roberto Garcia, MD.)

Fig 3 Undecalcified normal bone stained with hematoxylin-eosin ( A and B ). Compared with Figure 2 , the mineralization front ( purple ) extends essentially up to the surface of the trabeculae, with very little unmineralized osteoid ( pink ).
Rickets

Definition

• A metabolic bone disorder due to vitamin D, calcium, or phosphate depletion that impairs mineralization of bones in children before growth plate closure, resulting in growth retardation and delayed skeletal development

Clinical features

Epidemiology

• Occurs only in children whose growth plates have not closed, before age 17 years in females and 19 years in males
• Boys and girls are equally affected
• Commonly due to vitamin D deficiency, also from abnormal metabolism of phosphate or gastrointestinal tract disorders
• Hypophosphatasia is a rare X-linked disease characterized by extremely low levels of alkaline phosphatase
• Rare autosomal recessive type I and II vitamin D–dependent rickets (VDDR) due to impaired renal synthesis of 1,25(OH)-D or organ hyporesponsiveness to vitamin D

Presentation

• Clinical findings depend on age of onset and severity of defective mineralization
• Bone pain, tenderness, muscle weakness, fractures, and skeletal deformity are common
• Toddlers present with bowing of the legs; older children present with knock-knees
• Type II VDDR presents in childhood with bone deformity and total-body alopecia

Prognosis and treatment

• No increase in morbidity with adequate treatment
• Prevention of vitamin D deficiency is achieved with adequate sunlight exposure and vitamin D supplementation
• Vitamin D deficiency is treated with ergocalciferol
• Patients with X-linked or idiopathic hypophosphatemia are treated with oral phosphate supplements and calcitriol
• Human recombinant growth hormone reduces phosphaturia
• Type I VDDR is treated with high-dose vitamin D

Radiology

• Plain radiographs show widening and cupping of the metaphyseal region, widening of the growth plate, and fraying of the metaphysis
• Bowing of long bones
• Knock-knees (genu valgum)
• Beading of the ribs at the costochondral junctions (“rachitic rosary”)
• Symmetrical and linear pseudofractures (Looser zones)
• Early disease is radiographically difficult to diagnose with nonspecific findings (e.g., osteopenia)

Pathology

Gross

• Frontal bossing of skull, chest deformation, anterior protrusion of the sternum (pigeon breast deformity), kyphosis, scoliosis, and narrowing of the pelvis

Histology

• Wide osteoid seams due to excess osteoid
• Failure of mineralization of the epiphyseal growth plate
• Disordered endochondral ossification with persistence of cartilage growth plate penetrating into medullary cavity

Fig 1 A, In this term infant with rickets, disorganized growth plate with cartilage penetrating into the medulla is seen at scanning magnification. B, By comparison, a normal growth plate has a sharp line of ossification replacing the cartilage of the growth plate.

Fig 2 Higher magnification demonstrates marked disorganization of the growth plate with haphazard mixture of hypertrophic zone of chondrocytes and bone in this infant with rickets.

Fig 3 Lateral radiograph of the tibia and fibula in a patient with rickets demonstrating bowing of the tibia and fibula as well as a pseudofracture at the tibia (Looser zone). Coarse trabecular bone structure in the proximal tibia, which is typical of osteomalacia and rickets, is shown.
Osteogenesis Imperfecta

Definition and synonyms

• A family of genetic bone disorders primarily due to defective synthesis and secretion of collagen type I, characterized by fragile bones that break easily (brittle bone disease, Lobstein disease).

Clinical features

Epidemiology

• Rare heritable connective tissue disorder with most cases caused by a dominant mutation of type 1 collagen ( COL1A1 or COL1A2 ) genes
• Approximately 35% of patients with OI have no family history
• Type V through type VIII do not involve deficits in type I collagen genes
• Fibrogenesis imperfecta ossium is an extremely rare acquired disorder in which normal bone is replaced by a collagen-deficient tissue that is excessively fragile

Presentation

• Flattened skull, scoliosis, and kyphotic collapsing deformities
• Discoloration of sclera
• Conductive and sensorineural hearing loss
• Small, misshapen, translucent gray-yellow teeth, with enamel that fractures easily (dentinogenesis imperfecta)
• Presentation varies depending on the type of OI inherited
• Type I: mild bone fragility, rib deformities, blue sclerae
• Type II: perinatal lethal
• Type III: progressive severe deformities, fractures, short stature
• Types IV to VII: moderate growth retardation, deformities
• Type VIII: severe growth deficiency, normal sclerae

Fig 1 Anteroposterior ( A ) and lateral ( B ) radiographs of a fetus at 32 weeks’ gestation with osteogenesis imperfecta type II. Bones show diffuse demineralization and limited calvarial mineralization. Limbs are severely malformed with very short, broad femurs and marked bowing of the tibiae and fibulae.

Prognosis and treatment

• No cure currently; treatment directed toward preventing and controlling symptoms and maximizing independence
• Bisphosphonates improve bone strength
• Percutaneous surgical pinning of fractures and surgical insertion of metal rods through long bones
• Type II usually perinatal lethal

Radiology

• Marked osteoporosis with severe thinning of cortical bone, multiple fractures, and nonunion of healed fractures
• Severe bony deformities
• Diaphysis is thin and wavy; metaphysis is expanded
• Calcified cartilaginous nodules at the growth plates look like popcorn on conventional radiographs

Pathology

Gross

• Biopsy rarely done on lesions
• Fetal cases may be seen at autopsy
• Widened and irregular growth plates
• Cartilaginous nodules at growth plates

Histology

• Severe forms have increased osteocytes, absence of an organized trabecular pattern, and large areas of woven bone
• Bone trabeculae are thin, delicate, and widely separated
• Less severe forms have increased osteocytes with thin lamellar bone

Main differential diagnosis

• Child abuse
• Vitamin D deficiency

Fig 2 The bone is hypercellular with increased osteocytes in osteogenesis imperfecta.


Fig 3 Osteogenesis imperfecta type II in a fetus at 16 weeks’ gestation. A, Fracture callus ( left ) and abnormal growth plate with very scant ossification of cartilage matrix ( right ) are shown. B, Higher magnification of calcifying cartilage at growth plate.

Fig 4 Osteogenesis imperfecta type II in a fetus at 32 weeks’ gestation. Increased osteocytes in a disorganized trabecular pattern ( A ) and hypercellular cortical bone ( B ) are shown.

Fig 5 Fracture callus from a patient with osteogenesis imperfecta type V. At low ( A ) and intermediate ( B ) magnification, the callus has exuberant cartilage with very scant new bone formation, despite osteoblast activity.
Hyperparathyroidism

Definition

• Hyperparathyroidism, primary or secondary, leads to the overproduction or excessive secretion of parathyroid hormone, which plays a role in calcium metabolism and contributes to the regulation of osteoblast and osteoclast activity

Clinical features

Epidemiology

• Peak incidence in 50s
• Female predilection
• Associated with other endocrine disorders, including multiple endocrine neoplasia types I and IIA
• Secondary hyperparathyroidism is commonly associated with renal failure or malabsorption

Presentation

• Marked hypercalcemia and hypophosphatemia
• Bone pain and pathologic fractures
• Brown tumors are the result of the accumulation of fibrovascular tissue and giant cell reactions (see Section ID, Giant Cell–Rich Lesions)
• Later in the course, may present with multiple large cystic lesions (osteitis fibrosa cystica)
• Nephrolithiasis, polyuria, and polydipsia
• Constipation, nausea, peptic ulcers, pancreatitis, and gallstones
• Weakness, fatigue, lethargy, depression, and seizures

Prognosis and treatment

• Parathyroidectomy of adenomas generally results in a permanent cure
• Patients with multiple endocrine neoplasia undergoing subtotal parathyroidectomy will have a long remission, but hyperparathyroidism usually recurs
• Bone deformity, fractures, and severe cyst formation will heal if a parathyroid tumor is successfully removed
• Treatment of primary or secondary hyperparathyroidism will cause brown tumors to regress

Radiology

• Severe chronic disease shows osteopenia, subperiosteal bone resorption typically at the second and third phalanges on the radial side as well as the tufts of the distal phalanges
• Occasionally, osteosclerosis may be observed
• Brown tumors are well-circumscribed lytic lesions that frequently are in multiple locations and may resemble cysts on plain radiographs

Pathology

Gross

• Brown tumors are highly vascular lesions, red to brown in color as a result of hemorrhage and hemosiderin deposition

Histology

• Increased osteoclasts, intratrabecular osteoclastic tunneling, and resorption holes
• Secondary hyperparathyroidism is associated with abundant fibrosis and bone sclerosis
• Acellular holes may be present after treatment in areas of previous osteoclast tunneling
• Brown tumors consist of aggregates of osteoclasts, numerous reactive giant cell aggregates around hemorrhage, and hemosiderin (see Part D, Giant Cell–Rich Lesions)

Main differential diagnosis

• Myelofibrosis
• Acute-phase Paget disease
• Giant cell tumor of bone
• Giant cell reparative granuloma (histologically indistinguishable from brown tumor)

Fig 1 Anteroposterior radiograph of the second and third digit of the right hand showing subperiosteal bone resorption at the radial aspect of the middle and proximal second and third phalanges as well as the tufts consistent with hyperparathyroidism.


Fig 2 Coronal computed tomographic reconstruction of the lumbar spine demonstrating multiple lytic lesions throughout the vertebral bodies consistent with multiple small brown tumors.

Fig 3 Histologically, bone in a patient with hyperparathyroidism shows marrow space replaced by fibrous tissue with multiple osteoclasts located on the surface of resorbing bone.

Fig 4 At higher magnification, the trabeculae of bone show central replacement by fibrous stroma and numerous osteoclasts (a process known as tunneling resorption ).

Fig 5 Marked, continuous resorption results in thin delicate trabeculae surrounded by a loose fibrous matrix.

Fig 6 A and B, Brown tumor is characterized by a proliferation of scattered osteoclasts and fibroblasts in a vascular fibrous background with hemorrhage and hemosiderin deposition and entrapped lamellar bone (see also Part D, Giant Cell–Rich Lesions).
Serous Fat Atrophy

Definition

• Changes of bone marrow characterized by atrophy of fat cells and hematopoietic cells and accumulation of extracellular gelatinous substance (serous degeneration, gelatinous bone marrow transformation, mucoid atrophy of fat)

Clinical features

Epidemiology

• A rare disorder of unknown pathogenesis associated with extreme malnourishment
• Condition is seen in adults and elderly people; rare in children
• Male predominance
• In young individuals, it is most commonly associated with anorexia nervosa, AIDS, or acute febrile illnesses
• In middle-aged adults, it is associated with alcoholism and lymphoma
• In older individuals, it is associated with congestive heart failure

Presentation

• Weight loss, anemia, or pancytopenia

Prognosis and treatment

• The condition is reversible with resolution of the nutritional deficit

Radiology

• Findings are nonspecific
• MRI is characterized by a low signal intensity on T1-weighted images and a high signal intensity on T2-weighted images, reflecting the presence of serous marrow and myxoid degeneration

Pathology

Histology

• Bone marrow changes include fat cell atrophy, focal loss of hematopoietic cells, and deposition of extracellular gelatinous material (gelatinous transformation)
• The gelatinous material is mucopolysaccharides rich in hyaluronic acid that stains with Alcian blue at pH 2.5
• Eosinophilic serous fluid accumulation in the interstitium with a fine granular appearance on routine hematoxylin and eosin staining and pale pink on periodic acid–Schiff and Giemsa stain

Main differential diagnosis

• Amyloidosis
• Aplastic anemia
• Liposarcoma

Fig 1 Scanning magnification of hypocellular bone marrow with marrow fat surrounded by amorphous eosinophilic material ( A ) and fat cell atrophy ( B ). The eosinophilic “gelatinous” material is thought to represent an increase in the normal acid mucopolysaccharide ground substance of the bone marrow.

Fig 2 High magnification of bone marrow with atrophic medullary fat and extensive eosinophilic material with a fine fibrillary appearance. Atrophic fat cells may contain multiple vacuoles but should not be mistaken for liposarcoma, which is an exceedingly rare primary bone tumor.
Xanthomatosis

Definition

• Proliferation of foamy histiocytes, which may be solitary (xanthoma) or multifocal (xanthomatosis); Erdheim-Chester disease is a rare histiocytic disorder of unknown etiology that involves bone and lung preferentially (lipid granulomatosis)

Clinical features

Epidemiology

• Rare disease in mid to late adulthood
• No gender or race preference

Presentation

• Some cases associated with hyperlipidemia
• Pathologic fractures have been reported
• Clinically can mimic osteomyelitis
• Tissue destruction and bone distortion lead to orthopedic complications

Prognosis and treatment

• Prognosis depends on extent of extraosseous disease; extensive disease can potentially be fatal
• Xanthomatosis of the Achilles tendon treated with local excision has a 50% recurrence rate

Radiology

• Poor cortical medullary distinction with zones of radiolucency and radiodensity
• Most often, sclerotic bone lesions
• Pathologic fractures at the site of osseous, lytic lesions

Pathology

Gross

• Yellow replacement of normal tissue
• Progressive infiltration of bone marrow

Histology

• Diffuse infiltration of large, foamy histiocytes with conspicuous nuclei, lymphoid aggregates, fibrosis, and giant cell proliferations
• Clefts of cholesterol deposition in tissue

Ancillary studies

• Histiocytes are CD68 positive
• Histiocytes are S-100 and CD1a negative

Main differential diagnosis

• Gaucher disease
• Langerhans cell histiocytosis
• Chronic osteomyelitis
• Fibrous dysplasia (foam cells and cholesterol clefts)

Fig 1 Localized xanthomatosis involving the distal radius presents as a predominantly lytic, well-circumscribed lesion. This patient had hypercholesterolemia, tendinous xanthomas, and xanthelasmas.

Fig 2 Bilateral and nearly symmetrical increased sclerosis of the distal tibias are shown in this patient with Erdheim-Chester disease.


Fig 3 Scanning magnification of xanthomatosis. Bone has thick trabeculae and is distorted and partially destroyed by a histiocytic infiltrate.

Fig 4 Extracellular cholesterol produces slitlike clefts associated with a foreign body reaction. This is a nonspecific finding, however, and may be seen as a degenerative feature in a number of bone lesions.

Fig 5 A and B, At higher magnification, the lesion consists of sheets of round, polygonal, and spindle cells with foamy cytoplasm of variable sizes.
Osteopetrosis

Definition and synonyms

• A group of rare genetic disorders of skeletal development due to a defect in bone remodeling caused by osteoclast dysfunction (marble bone disease, Albers-Schönberg disease)

Clinical features

Epidemiology

• Autosomal dominant or adult forms, type I and type II
• Autosomal recessive forms related to carbonic anhydrase-2 deficiency
• All bones are affected, but those most severely affected include the long bones of the extremities, vertebrae, pelvic bones, and base of the skull

Presentation

• Infantile form is characterized by profound anemia, leukopenia, thrombocytopenia, extramedullary hematopoiesis, fractures, failure to thrive, and increased infections
• Adult form is characterized by bone pain and increased fractures with the absence of severe hematopoietic abnormalities
• Cranial nerve abnormalities include optic atrophy, deafness, and facial paralysis
• Failure to acidify urine

Prognosis and treatment

• Infantile form is fatal in utero or infancy
• Adult form has a near-normal life expectancy
• Bone marrow transplantation

Radiology

• Bones are diffusely dense, and the cortex is thick
• Skull base shows increased density and thickening

Fig 1 Whole-mount transverse section of the humerus in a patient with osteopetrosis showing increased density of the cortex and absence of the medullary canal with no evidence of hematopoietic marrow.
• Bone-in-bone appearance, particularly at the lumbar spine and pelvis
• Long bones are bulbous and misshapen with flaring of the distal femoral metaphysis (Erlenmeyer flask deformity), but this finding is not specific and may also be seen with bone marrow replacing processes such as Gaucher disease and hemoglobinopathies
• Increased fracture occurrence, in particular in type II
• Adult type I is characterized by marked sclerosis of the cranial vault
• Adult type II is characterized by skull sclerosis at the base and by bone-in-bone appearance at the spine and the pelvis

Pathology

Gross

• Lack of cortical-medullary demarcation
• Infantile form lacks development of bone marrow cavity

Histology

• Increased density and thickness of the cortex, in extreme examples with complete absence of medulla
• Increase in the number and size of bony trabeculae
• Central core of cartilage with dense and irregular bony trabeculae
• Persistence of spicules of calcified cartilage in medullary and cortical bone in adults
• No consistent reported change in osteoclast number

Main differential diagnosis

• Osteoblastic metastases
• Myelosclerosis
• Paget disease
• Melorheostosis

Fig 2 Anteroposterior radiograph of bilateral knees showing diffuse sclerosis of the bones with mild lucency in the epiphyseal and metaphyseal portions of the femur, tibia, and fibula.


Fig 3 A, Marked reduction in both the marrow space and haversian system. B, Note the absence of osteoclasts and cortical-appearing bone.

Fig 4 Osteopetrotic bone from an adult with calcifying cartilaginous tissue not remodeling into mature bone.

Fig 5 Anteroposterior radiograph of the pelvis ( A ) and frog-leg lateral view of the right hip ( B ) in a patient with osteopetrosis showing diffuse sclerosis of the proximal femur and the pelvis with femoral bowing. The bone-in-bone appearance of the pelvic bones is well visualized. Deformity of the right femoral head suggests remote fracture.
Ochronosis

Definition and synonyms

• Deposition of dark pigment in cartilage and connective tissue due to a metabolic disorder of homogentisic acid oxidase (alkaptonuria) or from exposure to various toxic substances (ochronotic arthropathy)

Clinical features

Epidemiology

• Alkaptonuria is a rare autosomal recessive disease with equal sex distribution
• Large peripheral joints are most commonly affected, including knees, shoulders, and hips

Presentation

• Early degenerative arthritis and tendon insufficiency
• Narrowing of the joint spaces and disk calcifications
• Spine is affected through degenerative changes of the intervertebral disks
• Dark urine and skin pigmentation, particularly the axilla
• Gray to brown patch of pigmentation in the sclera, between the margin of the cornea and the outer or inner canthus
• Accumulation of pigment in cardiac tissue leads to heart valve dysfunction

Prognosis and treatment

• No cure is available for alkaptonuria
• Diets low in tyrosine and phenylalanine and high in vitamin C may reduce the toxic byproduct homogentisic acid
• Ochronotic arthropathy is treated with physiotherapy, analgesia, rest, and prosthetic joint replacement when necessary

Radiology

• Accelerated degenerative changes, particularly at the spine and hip
• Joint and disk space narrowing with minimal osteophytosis
• Calcification of disk spaces
• Fusion of disk spaces

Pathology

Gross

• Cartilage, tendons, and ligaments have a black pigmentation
• Cartilage is brittle and easily fragmented

Histology

• Deposits of brown pigmentation in cartilage and elastic tissue
• Skin sections have yellowish brown pigment deposits seen in the dermis, macrophages, endothelial cells, apocrine glands, and the epidermal basement membranes

Main differential diagnosis

• Argyria pseudo-ochronosis
• Minocycline-induced hyperpigmentation

Fig 1 Lateral radiograph of the lumbar spine showing severe multilevel disk space narrowing and calcification as well as minimal osteophytosis. In addition, anterior fusion of the T12-L2 disk spaces with osteopenia is present.

Fig 2 Dark pigmented fragments of cartilage engulfed by synovium at low power. Because cartilage is easily fragmented in patients with ochronosis, the particles of destroyed cartilage embed in the synovium. These small shards of cartilage may lead to synovitis or hypertrophic synovium.


Fig 3 Grossly, the articular cartilage of the tibial plateau and femoral condyles are darkly pigmented in this specimen from a total knee replacement in a patient with ochronosis.
(Courtesy Kenneth Leipper, MD.)

Fig 4 A and B, Articular cartilage has a darkly pigmented appearance histologically that tends to be greatest around chondrocytes.
Melorheostosis

Definition and synonyms

• Sporadic abnormality involving hyperostosis of cortical bone, predominantly affecting the cortex of affected limb long bones with a characteristic radiographic finding resembling flowing candle wax (flowing hyperostosis). Osteopoikilosis is an autosomal dominant disorder with multiple, asymptomatic bone islands (see Section IG, Bone Island) in the medullary cavity

Clinical features

Epidemiology

• Wide age range, may present in children or adults
• No gender predilection

Presentation

• Most cases affect a single limb or single bone
• Long bones of limbs most commonly involved
• Axial skeleton spared
• Children usually asymptomatic; rarely limb deformity
• Adults present with pain, deformity or decreased range of motion
• Distribution may be related to a spinal root (sclerotome)

Prognosis and treatment

• Pain usually self-limited, so management in adults consists of observation
• Surgery to correct deformities in children or severe adult cases
• Rare reported cases of sarcoma arising in affected bone

Radiology

• Characteristic hyperostosis of the cortical surface in a characteristic flowing or candle wax appearance
• Nearby soft tissue mineralization may be present

Pathology

Gross

• Increased and irregular endosteal and periosteal cortical surfaces

Histology

• Small biopsies are usually nonspecific
• If sufficient tissue present: irregular contour of cortical surface
• Increased woven or lamellar bone expanding cortex
• Cellularity of abnormal areas higher than surrounding normal cortex
• Fibrosis and calcification in surrounding soft tissue may be present

Main differential diagnosis

• Parosteal osteosarcoma
• Florid reactive periostitis

Fig 1 Anteroposterior radiograph of the proximal femur demonstrating candle wax–like ossifications along the femur diaphysis.

Fig 2 Irregular cortical periosteal surface ( left ) characterizes melorheostosis.


Fig 3 Increased amounts of woven and lamellar bone expand the cortex with uneven endosteal surface ( A, top ) and irregular haversian canals ( B ). However, these findings are relatively nonspecific, and the diagnosis of melorheostosis requires radiographic correlation.

Fig 4 The periosteal surface is markedly irregular with fibrous tissue and new bone formation covering the surface, as seen at low ( A ) and high ( B ) magnification.
Gaucher Disease

Definition

• A lysosomal storage disease caused by a hereditary deficiency of the enzyme glucocerebrosidase leading to the accumulation of glucocerebroside primarily in cells of the reticuloendothelial system

Clinical features

Epidemiology

• The most common lysosomal storage disease
• 1 in 100 individuals in the U.S. population is a carrier for type I Gaucher disease, with a prevalence of 1 in 40,000
• Most common among people of Ashkenazi Jewish descent
• Affects men and woman equally

Presentation

• Three common clinical subtypes; presentation is related to the subtype inherited
• Type I: weakness, bone disease, anemia
• Type II: rapidly progressive central nervous system damage, hepatosplenomegaly, bone disease
• Type III: chronic neuropathy, bone disease, hepatosplenomegaly
• Bone involvement includes osteoporosis, bone pain, aseptic necrosis of the femur
• Yellow-brown skin pigmentation

Prognosis and treatment

• Prognosis and treatment are related to the subtype
• Type I: slight decrease in life expectancy
• Type II: rapid progression, fatal by age 2 years
• Type III: chronically progressive, death often by age 30 years
• Treatment with intravenous enzyme replacement therapy improves outcome, especially in type I
• Bone symptoms and deformities can regress after enzyme replacement therapy

Radiology

• Plain radiographic abnormalities include diffuse osteopenia, osteonecrosis, periosteal reactions, bone erosions, and infarcts
• Pathologic fractures commonly affect the distal femur, proximal tibia, and thoracic and lumbar regions of the spine
• Erlenmeyer flask deformity (widening of the distal femoral metaphysis) due to defective remodeling and bone marrow expansion
• Erlenmeyer flask deformity and epiphyseal osteonecrosis on the same radiograph is suggestive of Gaucher disease
• MRI can be useful in demonstrating bone marrow infiltration and to calculate bone marrow burden; it also allows differentiation of bone marrow infiltration versus bone marrow infarct

Pathology

Histology

• Accumulation of glucocerebroside (glycosphingolipid) in macrophages (Gaucher cells) replacing bone marrow space
• Gaucher cells are large, vacuolated cells with abundant crumpled cytoplasm and small nucleus pushed to one side
• Gaucher cells are primarily identified in the spleen, liver, lymph nodes, and bone marrow
• Gaucher cells stain positive for periodic acid–Schiff and iron

Main differential diagnosis

• Storage diseases and macrophage proliferation disorders
• Von Gierke disease
• Niemann-Pick disease

Fig 1 Anteroposterior radiograph of the left knee showing osteopenia and Erlenmeyer flask deformity.


Fig 2 T1-weighted coronal ( A ) and fat-saturated T2-weighted coronal ( B ) magnetic resonance images of bilateral knees. Bilateral diffuse bone marrow infiltration is shown with Erlenmeyer flask deformity. The substantial bone marrow edema pattern at the left distal femur in the fat-saturated T2-weighted image ( B ) suggests additional bone marrow infarction. Typically, Gaucher cell infiltration is low in signal in T1- and T2-weighted images.

Fig 3 Scanning magnification of bone involved by Gaucher disease shows infiltration of the marrow space by a uniform population of eosinophilic cells.

Fig 4 At higher magnification, Gaucher cells have abundant cytoplasm and small nuclei ( A ). The cells are filled with abundant crumpled cytoplasm and a single, eccentrically placed nucleus ( B and C ). The lipids within Gaucher cells are glucocerebroside, a lipid molecule with a single sugar residue that accumulates as a result of the absence of the enzyme.
B
Infectious and Inflammatory Conditions
Osteoarthritis

Definition and synonyms

• Non-neoplastic joint disorder characterized by progressive erosion of articular cartilage associated with aging, trauma, occupational injury, or genetic predisposition manifested by cycles of degradation and repair of cartilage, bone, and synovium (degenerative joint disease)

Clinical features

Epidemiology

• Common condition, may be present in up to 80% of people older than 65 years
• Onset usually after age 40 years
• Commonly affected joints: cervical and lumbar spine, first carpometacarpal, proximal interphalangeal, distal interphalangeal (Heberden nodes), hip, knee, subtalar, first metatarsophalangeal
• Uncommonly affected joints: shoulder, wrist, elbow, metacarpophalangeal
• Most cases limited to one or same joint bilaterally, at least initially

Presentation

• Symptoms: pain (worse in joints), stiffness, gelling
• Physical examination: crepitus, bony enlargement, decreased range of motion, misalignment, tenderness to palpation
• Synovial fluid: usually clear, normal viscosity, white blood cell count (WBC) less than 2000 cells/mm 3
• Patterns of presentation
• Monoarticular in young adults
• Pauciarticular, large joint in middle age
• Polyarticular generalized; rarely rapidly progressive
• Classified as idiopathic (localized or generalized) or secondary (due to trauma, congenital abnormality, or systemic disease)
• Charcot joint: severe secondary osteoarthritis due to diabetes or other neuropathic condition, such as tabes dorsalis or pernicious anemia; knee or ankle most commonly affected

Prognosis and treatment

• Variable clinical course, generally slowly progressive
• Treatment: analgesics, anti-inflammatory agents, weight loss, alternative medicine

Radiology

• Conventional radiographs
• Joint space narrowing
• Subchondral sclerosis
• Marginal osteophytes
• Subchondral cysts
• MRI
• Extensive cartilage loss and meniscal damage (degenerative tears)
• Subchondral bone marrow edema pattern
• Synovitis

Pathology

Gross

• Degeneration of cartilage at articular surface characterized by granularity or grooving, fragmentation, thinning, and overgrowth of apposing joint surfaces
• Eburnation (exposure of underlying bone with smooth polished appearance resembling ivory)
• Alteration of joint shape due to bone loss
• Sclerosis of bone underlying eroded articular cartilage
• Fibrous walled cysts filled with mucoid fluid immediately below articular surface
• Osteophytes (bony outgrowths) at joint periphery
• Chondro-osseous loose bodies (see Section IF, Chondro-Osseous Loose Body)

Histology

• Thinning, surface cracking, deep clefting, and loss of articular cartilage
• Necrotic chondrocytes
• Irregular, thickened, granular, or reduplicated tidemark (interface between articular cartilage and bone; see Fig. 4 B)
• Foci of cartilage regeneration
• Intrinsic: hypercellular nests of dividing chondrocytes within cartilage matrix
• Extrinsic: new fibrocartilage extending over the surface from periphery of the joint
• Depletion of proteoglycan in cartilage matrix
• Sclerosis of underlying and exposed bone
• Subchondral cysts, often containing acellular or hypocellular myxoid matrix
• Focal synovial hypertrophy and hyperplasia
• Usually no significant inflammatory component, although synovial lymphocytic inflammation, rarely with lymphoid follicles, may be seen

Ancillary Tests

• No specific tests available
• Proteoglycan stains (e.g., Alcian blue or safranin O) highlight depletion of proteoglycan

Main differential diagnosis

• Rheumatoid arthritis
• Crystal-induced arthritis
• Septic arthritis

Fig 1 Lateral radiograph of the cervical spine ( A ) and sagittal CT reconstruction ( B ) showing multilevel disk space narrowing ( A, arrow ), osteophytes ( A, arrowhead ), and subchondral cystic changes ( B, arrows ).

Fig 2 Anteroposterior radiograph of the pelvis demonstrating severe left hip osteoarthritis with superolateral joint space narrowing, osteophytes, subchondral sclerosis, and a subchondral cyst in the femur. Mild to moderate right hip osteoarthritis with osteophytes at the femoral head and os acetabuli is visible.

Fig 3 Photograph of proximal femur with cartilage fragmentation and cracking.


Fig 4 Microscopic changes of osteoarthritis. A, Cartilage necrosis with scattered ghost chondrocytes ( arrows ) and loss of proteoglycan matrix density. B, Reduplication and irregularity of tidemark ( arrows ). C, Cartilage cracking and clefting. D, Exposure and sclerosis of bone at a site of eburnation. E, Subchondral cysts.
Rheumatoid Arthritis

Definition and synonyms

• Chronic systemic nonsuppurative inflammatory disorder primarily affecting synovial lining of joints, bursae, and tendon sheaths, not uncommonly associated with systemic nonarticular manifestations in the skin, blood vessels, muscles, heart, lungs, kidneys, and eyes

Clinical features

Epidemiology

• Common disease, annual U.S. incidence about 30/100,000, prevalence 0.1% to 5% (~1% of whites)
• Women affected two to three times more than men, about 5% of women older than 65 years affected
• Peak onset between 30 and 55 years of age
• Risk factors: female gender, nulliparity, smoking, HLA-DR β gene variant (“shared epitope”), gene polymorphisms in TNF-α, STAT4, PTPN, TCR
• Affected joints: typically symmetrical peripheral polyarthritis; classically metacarpophalangeal, metatarsophalangeal, and proximal interphalangeal joints of hands and feet; also wrist, elbow, knee; less commonly axial joints or monoarthritis

Presentation

• Symptoms: morning stiffness; swelling of joints with redness, pain, deformities, limited range of motion, subcutaneous nodules, fatigue, muscle weakness
• Extra-articular manifestations: anemia, subcutaneous rheumatoid nodules, myositis, vasculitis, neutrophilic dermatitis, pericarditis or myocarditis, interstitial lung disease
• Laboratory findings: 50% to 70% have rheumatoid factor (immunoglobulin M [IgM] autoantibodies to Fc portion of IgG), which has low specificity; autoantibodies to cyclic citrullinated peptides (CCPs) both sensitive and more than 90% specific
• Synovial fluid: leukocytosis with neutrophil predominance (particularly in acute stage) but WBC lower than in septic arthritis (<75,000 cells/µL), protein approaching plasma concentration, low glucose, low C3 and C4

Prognosis and treatment

• Variable clinical course—most patients have periodic flares, some have unabating activity, remissions are possible; structural damage is cumulative and irreversible over years; if untreated may progress to destruction of articular cartilage and joint ankylosis
• Treatment: nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressive drugs, surgery (joint replacement, synovectomy)

Radiology

• Joint effusions and soft tissue swelling
• Juxta-articular osteopenia
• Bone and cartilage erosions, typically at marginal joint regions
• Narrowing of joint space
• Joint deformities: radial wrist deviation, ulnar deviation of digits, swan-neck finger deformities
• Affects typically metacarpophalangeal joints and carpal region at the hand and metatarsophalangeal joints at the foot

Pathology

Gross

• Joint destruction and joint deformities
• Little or no reparative tissue, proliferative cartilage, bone sclerosis, or osteophytes (unlike osteoarthritis)
• Joints have edematous, thick, hyperplastic synovium covered by delicate and bulbous fronds

Histology

• Hypertrophic and hyperplastic synovium
• Chronic inflammation, uncommonly with lymphoid follicles and germinal centers cuffed by a dense population of plasma cells
• Hyperplasia of synovial cells may result in multinucleation (Grimley-Sokoloff giant cells)
• Focal fibrinoid exudate and neutrophils at the synovial surface
• Organizing fibrin may float into joint space as rice bodies
• Reactive synovium extends from periphery to cover entire articular surface forming a pannus with destructions of underlying cartilage characterized by enlarged and often empty chondrocyte lacunae (Weichselbaum lacunae)
• Wall thickening and onion-skin appearance of synovial arteries
• Chronic inflammation also often involves subchondral bone
• Synovitis typically less pronounced in advanced disease with little remaining cartilage or following joint replacement but typically recurs following synovectomy
• Rheumatoid nodules in about 25% of cases
• Usually in subcutaneous tissue along extensor surfaces of forearm, elbow, and shin
• Less commonly in visceral organs (heart, lungs, intestinal tract) or in joint synovium
• Characterized by central fibrinoid necrosis rimmed by palisaded histiocytes and giant cells and a cuff of lymphocytes and plasma cells

Cytology

• Joint aspirate may have inflammatory exudate with neutrophils, which may suggest septic arthritis

Ancillary tests

• Serology (rheumatoid factor, CCPs) used as one of the diagnostic criteria

Main differential diagnosis

• Osteoarthritis
• Crystal-induced arthritis
• Septic arthritis, particularly if monoarticular disease
• Rheumatoid nodule: infection, epithelioid sarcoma

Fig 1 Radiographic findings of Rheumatoid arthritis. Lateral ( A ), oblique ( B ), and anteroposterior ( C ) radiographs of the left wrist show typical erosions at the carpal bones, in particular the scaphoid, capitate, and lunate (cystic erosions). Erosions are also seen at the styloid process of the ulna. Adjacent soft tissue swelling is present. Findings at the first carpometacarpal joint are related to coincidental osteoarthritis and not Rheumatoid arthritis.

Fig 2 Subcutaneous rheumatoid nodule. A, At low magnification, the nodule is composed of zones of fibrinoid necrosis surrounded by a rim of inflammatory cells embedded in dense collagenous stroma. B, The necrosis is rimmed by palisading histiocytes and a rim of plasma cells and lymphocytes.


Fig 3 Microscopic findings of rheumatoid arthritis. A, At low magnification, inflamed, hypertrophic, and hyperplastic synovium is present. B, The inflammation commonly forms lymphoid follicles with germinal centers. C, The synovial membrane is covered by a fibrinous exudate ( at left ). D, High magnification of the inflamed synovium shows numerous plasma cells, admixed lymphocytes, and macrophages, without significant neutrophilic component. E, Russell bodies ( arrows ) may be present.
Septic Arthritis

Definition and synonyms

• Joint inflammatory condition due to intra-articular infection by a microbial pathogen resulting from hematogenous seeding, extension from neighboring bone or soft tissue site, or direct implantation from trauma or surgery (infectious arthritis)

Clinical features

Epidemiology

• Bacterial (suppurative) arthritis (most common)
• More common in children than adults, male-to-female ratio of 1.5:1
• Large weight-bearing joints most commonly affected (usually by hematogenous spread)
• Small joints of hands and feet (usually due to penetrating trauma)
• Usually monoarticular (85%), polyarticular often associated with immunocompromise
• Risk factors: preexisting joint disease (particularly rheumatoid arthritis), chronic skin ulcers, intravenous drug use, alcoholism, chronic steroid use, or immunosuppressed state (e.g., AIDS, diabetes)
• Prosthetic joint: may be responsible for loosening of prosthesis
• Most common pathogens: Staphylococcus aureus (40% to 50%), Streptococcus pyogenes , Streptococcus pneumoniae , gram-negative bacilli (10%, often associated with intravenous drug use)
• Gonococcal arthritis ( Neisseria gonorrhoeae ): most common arthritis due to sexually transmitted bacterial infection
• Lyme arthritis ( Borrelia burgdorferi )
• Acute Lyme arthritis seen in 50% to 60% of cases
• Associated with erythema migrans (90% of Lyme cases)
• Mycobacterial arthritis ( Mycobacterium tuberculosis )
• Usually follows infection of the spine and affects hip or knee most commonly
• Fungal arthritis
• Rare, usually in immunocompromised hosts
• Candida species most common

Presentation

• Symptoms: fever; swollen, warm, erythematous and painful joint
• Synovial fluid: gray-green, WBC 20,000 to 200,000 cells/μL, more than 75% neutrophils

Prognosis and treatment

• Adjacent tendon sheath or bursa may be involved; secondary osteomyelitis in about 8%
• May result in severe destruction of musculoskeletal structures, permanent disability (30%), and, very rarely, death
• Diagnosis relies on compatible history, physical examination, and synovial fluid Gram stain, microbiology culture, and cell count
• Treatment: prompt appropriate antibiotic therapy, joint tap with drainage, debridement in some cases
• Loosening of prosthetic joint: intraoperative frozen section and Gram stain to assess for acute inflammation and organisms; if evidence of infection is present, prosthetic replacement delayed until after antibiotic therapy

Radiology

• Plain films and CT
• May be normal in early-stage disease
• Joint effusion
• Joint space narrowing
• Bony erosion and later destruction
• Periosteal bone formation
• MRI
• Synovial thickening and enhancement
• Joint effusion, surrounding edema
• Bone marrow edema pattern and bony erosions

Pathology

Gross

• Swollen periarticular soft tissue
• Thickened or nodular synovial tissue with or without exudate
• Cloudy, milky, or thick green joint aspirate
• Scarring and erosion of articular cartilage

Histology

• Suppurative inflammation (pyogenic bacteria, gonococcal arthritis, Lyme arthritis, Candida species)
• Synovial edema and dense neutrophilic infiltrate
• If not treated promptly, necrosis and destruction of articular cartilage
• Eventually, lymphocytes, plasma cells, and histiocytes predominate with development of chronic papillary synovitis, fibrin deposits and thickening of arterial walls (similar to that seen in other inflammatory arthritides)
• Organisms can be demonstrated with special histochemical stains (see later)
• Granulomatous inflammation (mycobacteria, most fungi)
• Acute and chronic synovitis with necrotizing or non-necrotizing granulomas and giant cells
• Septic loosening of prosthesis
• Neutrophil count on intraoperative frozen section of synovium or prosthetic capsule:
• Five neutrophils per high-power field in more than 5 high-power fields (Feldman criteria)
• Ten neutrophils per 10 high-power fields (Athanasou criteria)
• Neutrophils in fibrinous exudate or blood are not counted

Ancillary tests

• Gold standard of diagnosis is positive microbiologic culture
• Tissue stains
• Molecular tests (polymerase chain reaction and reverse-transcriptase polymerase chain reaction techniques) can detect a wide range of microorganisms
• Serology (Lyme arthritis, viral arthritides)

Main differential diagnosis

• Rheumatoid arthritis
• Gout
• Other crystal-induced arthritides
• Osteoarthritis

Fig 1 Septic arthritis, radiographic findings. A, Axial CT section of the pelvis shows erosive changes at the right hip joint (in particular the femoral head). B, Fluid-sensitive coronal magnetic resonance image of the pelvis demonstrates large joint effusion at the right hip ( arrows ) with erosive changes at the femoral head and bone marrow edema pattern at the proximal femur. In addition, extensive soft tissue edema is present around the right hip, as are abscesses of the iliopsoas and adductor ( arrowheads ).

Fig 2 A, Early changes of septic arthritis from Staphylococcus aureus with dense neutrophilic infiltrate, synovial edema, and fibrin. B, Later changes of articular cartilage destruction and necrosis. Bacterial colonies are rarely evident in routine histologic evaluation.

Fig 3 In the intraoperative evaluation of septic loosening, the quantity of neutrophils in synovium, implant capsule ( A ), or granulation tissue should be scored. Neutrophils associated with fibrin ( B ) do not correlate with septic loosening.
Gout

Definition and synonyms

• Inflammatory joint condition resulting from deposition of monosodium urate in and around affected joints due to hyperuricemia (monosodium urate crystal deposition disease)

Clinical features

Epidemiology

• Common condition, affects 3 to 5 million people in the United States, accounts for 2% to 5% of chronic joint disease
• Age of onset usually between 40 and 50 years
• Risk factors
• Men older than 40 years with hypertension, obesity, alcohol-use
• Women older than 70 years with chronic kidney disease, on diuretics, with osteoarthritis
• Transplant recipients on calcineurin inhibitors (cyclosporine) with or without diuretics
• Patients with leukemia or other malignancy
• High uric acid levels (>8 mg/dL) are required, but only about 10% of people with elevated uric acid will have clinically evident gout

Classification

• Primary gout (~90% of cases): hyperuricemia due to a primary error in synthesis or excretion of purine (~58% idiopathic); known defects include hypoxanthine-guanine phosphoribosyl transferase deficiency (including Lesch-Nyan syndrome), other defects in purine biosynthesis, and renal excretion
• Secondary (~10% of cases): hyperuricemia due to increased cell breakdown (leukemia or other malignancy), chronic renal disease, or use of diuretics (e.g., thiazides)

Presentation

• Episodic acute attacks of inflammatory arthritis, usually monoarticular
• Predilection for the first metatarsophalangeal joint (most common initial presentation), but also affects ankles, heels, knees, wrists, fingers, elbows
• Development of sodium urate deposits (tophi) around affected joints
• Uric acid nephrolithiasis, chronic nephropathy, or both

Prognosis and treatment

• Chronic relapsing condition with variable rate of progression and frequency of acute flares
• Treatment: uric acid–lowering agents, discontinuation of diuretics, fluid administration, and alkalinization of urine during chemotherapy

Radiology

• Swelling of periarticular soft tissues, typically at the first metatarsophalangeal joint
• Subsequent erosion of periarticular bone leading to classic punched-out appearance with overhanging edges
• Tophi are radiolucent but may also calcify
• Little reactive sclerosis
• Usually no regional osteopenia (in contrast to rheumatoid arthritis)
• Occasionally soft tissue deposits, which mimic soft tissue tumors

Pathology

Gross

• Tophaceous deposits in the joints and periarticular soft tissue have chalky-white appearance
• Destruction of articular cartilage and adjacent bone

Histology

• Synovial fluid cytology in acute gouty synovitis
• Inflammatory exudate (neutrophils and lymphocytes) can be mistaken for septic arthritis
• Sodium urate crystals: needle shaped, with strong negative birefringence (appear bright yellow under polarized light)
• Sections of tophi show variably sized deposits of fluffy eosinophilic material rimmed by macrophages, giant cells, and fibrous tissue
• Crystals are usually dissolved by conventional aqueous processing; for better preservation, ethanol fixation with or without examination of fresh tissue is recommended

Ancillary tests

• Demonstration of sodium urate crystals in synovial fluid
• Blood uric acid level may be elevated but is neither diagnostic nor specific

Main differential diagnosis

• Septic arthritis
• Other crystal-induced synovitis
• Rheumatoid arthritis
• Osteoarthritis

Fig 1 Radiographic changes of gout. This plain dorsoplantar radiograph of the right foot shows extensive periarticular, bony erosions at the metatarsophalangeal 1, 2, 3, and 5 joints with surrounding soft tissue swelling. Joint space narrowing is consistent with secondary degenerative changes. A small punched-out lytic lesion in the distal lateral portion of the second middle phalanx ( arrow ) also represents an intraosseous tophus.

Fig 2 Tophaceous deposits; ethanol-fixed tissue. A, Large crystalline deposits of monosodium urate are preserved and easily visualized as yellow-brown aggregates. B, The crystals are needle shaped and are negatively birefringent under polarized light ( bright yellow ).

Fig 3 Microscopic findings of gout; formalin-fixed tissue. A, Low magnification shows amorphous eosinophilic deposits rimmed by inflammatory cells and embedded in dense collagenous stroma; urate crystals have been dissolved by conventional formalin fixation and processing. B, Intermediate magnification shows epithelioid histiocytes, scattered lymphocytes, and giant cells at the periphery of the tophaceous deposits. C, High magnification of smaller deposits surrounded by foreign body–type giant cell reaction.
Other Crystal-Induced Synovitis and Calcium Deposition

Definition

• Several unrelated conditions characterized by different forms of calcium deposits involving articular and periarticular synovial tissue as well as nonsynovial soft tissue
• Calcium pyrophosphate deposition disease (CPPD), including pseudogout and chondrocalcinosis
• Calcium hydroxyapatite deposition
• Metastatic calcification
• Dystrophic calcification
• Tumoral calcinosis

Clinical features

• CPPD
• Primary (most cases): familial or sporadic
• Secondary: associated with hyperparathyroidism, hypothyroidism, gout, or hemochromatosis
• Chondrocalcinosis: term used in the past by radiologists to describe calcium deposits in the knee menisci of elderly patients (most cases are due to CPPD)
• Pseudogout: term used to describe clinically CPPD cases presenting with an acutely swollen joint mimicking gout (<25% of CPPD cases)
• Most common presentation is similar to osteoarthritis; about 50% have progressive arthritis, usually affecting multiple joints; onset is usually in the fourth decade
• Most commonly affected joints are knees, ankles, wrists, elbows, hips, and shoulders; involvement of metacarpals and metatarsals is rare
• Other forms include rapidly degenerating arthritis similar to Charcot joint, a tumor-like mass (very rare), or involvement of the spine with stiffening (usually familial)
• Treatment: joint aspiration, corticosteroid injection, NSAIDs
• Hydroxyapatite deposition
• Deposits are in nonsynovial soft tissues (calcific tendonitis)
• May be associated with trauma, renal failure, scleroderma, hyperparathyroidism, sarcoidosis, metastatic malignancy, myeloma, or hypermetabolic state
• Metastatic calcification
• Occurs in patients with disturbed calcium homeostasis and hypermetabolic states (e.g., hyperparathyroidism or Paget disease of bone), particularly if prolonged bed rest
• Frequent sites of involvement include kidneys, lungs, cornea, conjunctiva, stomach mucosa, media, and intima of blood vessels
• Dystrophic calcification
• Not related to disturbances in calcium homeostasis
• Common at sites of coagulative necrosis and fat necrosis
• May be secondary to trauma
• Tumoral calcinosis
• Most cases sporadic, some familial cases reported
• Usual onset in second decade of life
• Characterized by deposition of painless calcific masses around hips, elbows, shoulders, and gluteal areas
• Lesions are usually bilateral, affect multiple sites and can be massive
• Rarely, intra-articular or intraosseous deposits are present
• Serum phosphate is usually elevated
• Treatment: excision, low phosphate diet, phosphate binders, diuretics

Radiology

• CPPD
• Radiodense deposits (unlike radiolucent deposits in gout) are characteristically in fibrocartilage in particular menisci (punctate or linear) but may also be in hyaline cartilage (usually parallel subchondral bone end plate)
• Punctate deposits may also be seen in synovium
• Accelerated degenerative changes, including joint space narrowing and bony sclerosis
• Hydroxyapatite deposition, metastatic calcification, dystrophic calcification, tumoral calcinosis
• Radiodense soft tissue deposits (calcifications)

Pathology

Gross

• CPPD
• Small chalky-white deposits in the affected tissues
• Hydroxyapatite deposition
• Small calcified soft tissue deposits
• Metastatic calcification
• Small calcified deposits may not be apparent grossly
• Dystrophic calcification
• Small calcified deposits may not be apparent grossly
• If large enough, may form irregular calcified nodules or masses
• Tumoral calcinosis
• Irregular calcified soft tissue deposits, masses

Histology

• CPPD
• Crystalline or amorphous deposits composed of small rhomboidal crystals with weak positive birefringence (appear dim blue)
• For optimal crystal preservation, ethanol fixation or examination of fresh tissue (smears), or both, may be needed (particularly if gout is in the differential)
• In nonvascularized tissue, inflammatory changes are typically not present
• Deposits in vascularized tissue may be surrounded by chronic inflammatory and giant cell reaction, often mimicking findings of gout
• Hydroxyapatite deposition, metastatic calcification, dystrophic calcification, tumoral calcinosis
• Calcified deposits of varying size surrounded by varying, usually mild degree of chronic inflammation with macrophages and frequently giant cells
• No birefringent crystals

Ancillary tests

• CPPD
• Demonstration of sodium pyrophosphate crystals in synovial fluid (see earlier)
• Hydroxyapatite deposition, metastatic calcification
• Specific testing for associated conditions
• Tumoral calcinosis
• Serum phosphate is usually elevated

Fig 1 A and B, Tumoral calcinosis appears as amorphous basophilic deposits associated with a fibrotic stroma and limited inflammation. Polarizable crystals are absent.

Main differential diagnosis

• CPPD
• Gout
• Osteoarthritis
• Rheumatoid arthritis
• Septic arthritis

Fig 2 A and B, The crystals of calcium pyrophosphate deposition disease are dense and basophilic on hematoxylin and eosin staining, often with little to no inflammation. C, Under polarized light, the crystals are small and rhomboid.


Fig 3 Anteroposterior ( A ) and lateral ( B ) radiographs of the knees show bilateral meniscal and periarticular calcifications consistent with calcium pyrophosphate deposition disease (CPPD). In addition, severe degenerative disease of the patellofemoral joint is more advanced compared with the other joint compartments, which is a typical finding for CPPD.

Fig 4 A and B, Hydroxyapatite (HA) deposition disease, seen here within a tendon (calcific tendonitis), demonstrates dense, basophilic matrix similar to bone. The distinction between HA deposition disease and tumoral calcinosis rests on the clinical setting and the absence of other underlying metabolic disease (e.g., hypervitaminosis D, renal failure, milk-alkali syndrome) in tumoral calcinosis.
Acute Osteomyelitis

Definition and synonyms

• Acute inflammation of the bone resulting from infection by a microbial pathogen (acute bacterial osteomyelitis, acute suppurative osteomyelitis)

Clinical features

Epidemiology

• Most cases are caused by bacteria, less commonly fungi
• Three modes of pathogen entry: hematogenous, contiguous spread, and direct inoculation
• Osteomyelitis from hematogenous spread (~20% of cases)
• Most common in children (1 to 16 years old), male-to-female ratio of 2:1
• Risk factors: indwelling catheters, chronic infections, debilitating conditions, immunocompromised states, nonpenetrating trauma, intravenous drug use
• Most common sites:
• Children: long bones, usually limited to metaphysis
• Adults: spine more than pelvis more than long bones
• Usually solitary and primary and associated with a single pathogen
• Most frequent pathogens: S. aureus , S. pyogenes, enteric gram-negative rods; Salmonella frequently complicates sickle cell disease
• Neonatal osteomyelitis (<1 year old)
• Risk factors: prematurity, immunocompromised states
• Up to 40% of cases are polyostotic
• Most common pathogens: group A and B streptococci
• Osteomyelitis from contiguous spread
• Bacteria gain entry through periosteum or articular cartilage
• Periodontal disease, decubitus ulcers, often polymicrobial
• Osteomyelitis from direct inoculation
• Post-traumatic (3% to 30% of open fractures become infected)
• Implant related
• Most common pathogens: Staphylococcus and Streptococcus species

Presentation

• Pain
• Fever
• Leukocytosis; elevated C-reactive protein and erythrocyte sedimentation rate
• Blood cultures are frequently negative; biopsy with culture needed to establish pathogen

Prognosis and treatment

• Inadequate or delayed treatment may lead to chronic infection
• Treatment: antibiotics, typically several weeks of intravenous administration, with or without curettage of necrotic bone

Radiology

• Soft tissue swelling and gas within lesion may be present in the early phase of disease
• Plain films may not show any changes until sufficient bone destruction is present
• Focus of infection appears as radiolucency with destructive or erosive changes in radiographs; however, depending on how aggressive the infectious organism is, this may take 10 to 14 days
• In addition to erosive changes, bony proliferations are demonstrated, typically as periosteal bone formation
• Later, reactive bone deposition (involucrum) is seen at the lesion periphery and beneath the raised periosteum
• MRI is the most sensitive technique to diagnose osteomyelitis in the early phase

Pathology

Gross

• Most specimens are from curettage and may have subtle findings
• May contain green-tan pus, can be putrid
• Resection specimens are usually from long-standing chronic disease (see separate section on chronic osteomyelitis)

Histology

• Initially neutrophilic inflammation with edema, fibrin, and hemorrhage
• Within days, bone necrosis with empty lacunae (sequestrum)
• Colonies of bacteria or fungal elements
• Periosteal new bone deposition (involucrum)
• May evolve to chronic osteomyelitis: reactive fibrovascular tissue with lymphocytes, plasma cells, and macrophages

Ancillary tests

• Microbiologic culture of the curetted tissue is the gold standard in diagnosis
• Bacterial histochemical stains on formalin-fixed sections
• Systemic markers of inflammation (C-reactive protein, erythrocyte sedimentation rate) are nonspecific

Main differential diagnosis

• Acute subchondral inflammation in severe arthritis
• Acute stages of fracture
• Langerhans cell histiocytosis (eosinophilic granuloma)
• Radiographically: osteosarcoma, Ewing sarcoma, lymphoma

Fig 1 Osteomyelitis involving the base of the first metacarpal. Lateral radiograph of the wrist shows erosive lesion ( arrowheads ) with periosteal bone formation ( arrow ) at the base of the metacarpal. The carpometacarpal joint is also involved, and marked swelling of the surrounding soft tissue is present.

Fig 2 Necrotic bone (sequestrum) is characterized by the presence of empty lacunae. The surfaces of the bony trabeculae are undergoing destruction, imparting a “chewed” or scalloped configuration.

Fig 3 At low magnification, acute osteomyelitis consists of necrotic bone (sequestrum) and a fibrinopurulent exudate.

Fig 4 An infiltrate of neutrophils replaces the marrow space.

Fig 5 Involucrum, new periosteal bone formation associated with osteomyelitis, develops several days to weeks after infection in a pattern similar to fracture callus.
Chronic Osteomyelitis

Definition

• Established (>6 weeks), nonsuppurative bone inflammation arising as a complication of untreated or treatment-refractory acute osteomyelitis or as a result of infection by an indolent pathogen (includes granulomatous osteomyelitis)

Clinical features

Epidemiology

• Fifteen to 30% of acute osteomyelitis (see separate section) go on to chronic disease
• Other causes: nonpyogenic bacteria, fungi, and very rarely parasites or viruses
• Mycobacterial osteomyelitis
• Tuberculous osteomyelitis ( Mycobacterium tuberculosis )
• One to 3 percent of cases of pulmonary and 10% of extrapulmonary tuberculosis
• Usually a solitary bone lesion, frequently multifocal in patients with AIDS
• Most frequent sites: spine (Pott disease) usually involves anterior column, T6-L3; hips; knees
• Nontuberculous mycobacterial osteomyelitis (atypical mycobacteria)
• Five to 10 percent of infections have bone involvement
• Risk factors: immunocompromised state, trauma, surgery
• Lepromatous osteomyelitis
• Most common sites: facial bones, hands and feet
• Treponemal osteomyelitis
• Skeletal syphilis ( Treponema pallidum )
• Congenital
• Usually bilateral symmetrical bone involvement with variable severity
• Most common in diaphysis of long bones and costochondral junction
• Acquired
• Usually not before early tertiary stage (2 to 5 years after initial infection)
• Most common sites: facial and skull bones, clavicle, tibia
• Fungal osteomyelitis
• Candida species (most common)
• Bone involvement in 1% to 2% of bloodstream Candida species infections
• Risk factors: immunosuppression; chronic illness, particularly diabetes; invasive catheters; and parenteral drug use
• Most common sites: lumbar spine and long bones, usually single focus
• Other fungi: Aspergillus , Cryptococcus , Coccidioides , Paracoccidioides , Histoplasma , Blastomyces species (rare, usually in patients with a primary lung infection); Sporothrix (usually due to penetrating trauma)
• Chronic, recurrent multifocal osteomyelitis
• Multifocal inflammatory disorder involving skeletal system of children and adolescents
• Female preponderance (5:1 female-to-male ratio)
• Protracted relapsing course
• Cultures typically negative for organisms
• Definition evolving, may represent an autoimmune syndrome rather than true infection

Presentation

• Low-grade fever
• Weight loss
• Pain over affected area
• Swelling, local warmth, erythema

Prognosis and treatment

• May result in severe disability, pathologic fracture, or extensive soft tissue involvement
• Treatment: usually a combination of intravenous antibiotics and surgical debridement

Radiology

• Compared with acute osteomyelitis, osteopenia and soft tissue swelling are less frequently observed and relatively atypical
• Lytic destructive bone lesions with surrounding sclerosis; sclerosis is characteristic and can be abundant
• Periosteal reaction is typically solid but can be atypical, including complex, irregular, and layered appearance
• Involvement of surrounding soft tissue or sinus tract formation, or both
• Bone tumors can have a similar appearance, and differential diagnosis can be difficult
• Spine: cortical bone collapse, disk destruction, intervertebral body fusion
• Gibbus deformity: kyphosis caused by collapse of vertebral bodies in tuberculous osteomyelitis (Pott disease)

Pathology

Gross

• In curettings, infected bone is discolored white-yellow-gray
• In larger specimens, areas of bone destruction are poorly circumscribed and appear as firm white-yellow-gray fibroinflammatory tissue
• Larger granulomas can sometimes be seen grossly as nodules, often with caseation
• Extension through cortex into soft tissue may be present

Histology

• Variable histology depending on the causal agent and host immune factors
• Necrotizing or non-necrotizing granulomatous inflammation (mycobacteria, fungi), or both
• Lymphoplasmacytic or histiocytic inflammation ( Treponema species, Mycobacterium leprae ), or both
• May see a component of suppurative inflammation (fungi)
• Areas of bone necrosis with osteoclastic activity and bone resorption
• Marrow replacement with fibrosis
• Reactive bone formation and periosteal reaction at the lesion periphery
• Microorganisms are visualized by histochemical stains or routine hematoxylin and eosin staining
• Diagnosis relies on presence of diagnostic fungal forms or positive culture, or both

Ancillary tests

• Culture, Gram, and acid-fast stains from biopsy material
• Tissue stains
• Acid fast stain ( Mycobacteria species)
• Warthin-Starry or similar silver stains ( Treponema species)
• Gomori methenamine silver (fungi)
• Immunohistochemical stains
• Molecular tests (polymerase chain reaction)
• Serology

Fig 1 Chronic osteomyelitis radiographic findings. A, Anteroposterior radiograph of a femur showing a large lytic lesion with surrounding sclerosis and exuberant periosteal reaction with a sunburst pattern mimicking osteosarcoma. B, Anteroposterior radiograph of the knee joint demonstrating mixed osteolytic-osteosclerotic lesion in the proximal tibia ( small arrows ) and periosteal reaction at the lateral aspect of the tibia ( large arrow ).

Main differential diagnosis

• Subchondral inflammation in severe arthritis
• Hematopoietic malignancies (myeloma, lymphoma)
• Sarcoidosis (1% to 13% of cases have bone involvement)
• Langerhans cell histiocytosis (eosinophilic granuloma)
• Plasmacytoma/myeloma

Fig 2 Granulomatous osteomyelitis due to Coccidioides immitis A, Low magnification showing granulomatous inflammation. B, Diagnostic spherules of Coccidioides are seen within giant cells at higher magnification.


Fig 3 Chronic osteomyelitis microscopic findings. A, Intermediate magnification showing osteonecrosis and marrow replacement by fibrosis. B, Higher magnification of the fibrosis with sparse patchy lymphoplasmacytic inflammation. C, A plasma cell infiltrate is most common in chronic osteomyelitis and raises the differential diagnosis of a plasma cell neoplasm.
Osteonecrosis

Definition and synonyms

• Noninfectious bone destructive lesion characterized by necrosis and secondary degenerative changes due to infarct or chronic vascular insufficiency (avascular bone necrosis, aseptic bone necrosis)

Clinical features

Epidemiology

• Common condition in middle-aged and older patients, also occurs in children
• Most common in the hip and knee but may affect other bones
• More than 50% bilateral or multifocal
• Accounts for about 10% of joint replacements
• Classification by etiology
• Circulatory or vascular compromise (necrosis best categorized as infarct)
• Thrombotic conditions (e.g., sickle cell disease, Gaucher disease, decompression sickness)
• Vasculitis
• Venous flow obstruction: secondary to trauma and other types of injury
• Subcapital femoral neck fracture
• Arthritis
• Idiopathic (primary)
• Risk factors
• Corticosteroids, alcoholism, family history
• Pediatric syndromes
• Usually in preteen-aged or teen-aged athletes with rapidly growing bones, boys more than girls
• Thought to be secondary to trauma in genetically susceptible individuals
• Legg-Calvé-Perthes (proximal femoral epiphysis)
• Osgood-Schlatter disease (tibial tuberosity)

Presentation

• Variable presentation depending on etiology
• Usually joint pain, limited function, may present with a pathologic fracture

Prognosis and treatment

• May result in fractures through articular surface following collapse of infarcted, necrotic bone or replacement by granulation tissue
• Also may result in detachment of cartilage and secondary degenerative joint disease
• Eventually leads to severe arthritis in most cases
• Treatment is usually surgical (joint replacement, bone curettage, and stabilization with hardware)
• Rarely, a sarcoma may arise in the area of avascular necrosis

Radiology

• Little if any changes in early stage on radiographs; however, early changes are well visualized on MRI with central fatty necrosis with a margin of granulation tissue (bright on T2-weighted images, low signal on T1-weighted images) and adjacent bone marrow edema pattern
• At later stages, radiographs are positive with the following:
• Moderately thick calcified serpentine border outlining a central area of radiolucency or wedge-shaped increased sclerosis without deformity
• Subchondral collapse (crescent sign)
• Flattening of articular surface
• Joint narrowing
• Advanced degenerative changes

Pathology

Gross

• Early changes
• Intact articular cartilage except at edge of necrosis where cartilage may be folded and cracked
• Cross section of necrotic subchondral bone is yellow, opaque, and chalky with hyperemic fibrous tissue at margin
• Adjacent bone with thickened trabeculae
• Late changes
• Flattening of joint surface
• Detachment and destruction of overlying articular cartilage
• Loss of bone and secondary changes of degenerative joint disease

Histology

• Early changes
• Necrosis of bone marrow fat and hematopoietic tissue (easiest to recognize)
• Osteocyte lacunae may be enlarged and empty or normal size with pyknotic nuclei
• Later changes
• Ingrowth of granulation tissue from the lesion periphery with layering of new bone over dead trabeculae (“creeping substitution”), which results in formation of a highly collagenized and, later, calcified rim

Main differential diagnosis

• Subchondral insufficiency fracture
• Osteoarthritis
• Calcified enchondroma

Fig 1 Plain radiograph ( A ) and magnetic resonance image ( B ) of the pelvis showing two different patients with avascular necrosis (AVN) of the femoral heads. A, The anteroposterior radiograph of the pelvis demonstrates bilateral subchondral fractures with femoral head deformity and increased sclerosis in a patient with sickle cell disease. B, On the coronal T1-weighted magnetic resonance image, bilateral AVN is shown with a subchondral area of fatty necrosis (bright in signal), surrounded by a rim of granulation tissue (low in signal) and adjacent bone marrow edema pattern (intermediate-low in signal).

Fig 2 Microscopic changes of osteonecrosis. A, Low magnification showing the periphery of the lesion with ingrowth of granulation tissue ( center ) and necrosis ( right ). B, Intermediate magnification showing bone marrow fat necrosis and necrotic bone with empty lacunae. C, High magnification of granulation tissue adjacent to necrotic bone with empty lacunae. D, Irregular calcifications and granulation tissue at the edge of a well-established lesion.
Bone Fracture and Fracture Callus

Definition

• Fracture: loss of bone integrity due to mechanical injury, failure of neuromuscular coordination, or diminished bone strength
• Fracture callus: reparative tissue forming at the fracture site resulting in immobilization and regeneration of the bone

Clinical

Epidemiology

• Trauma is the most common etiology, particularly in children
• Young males more than females, elderly females more than males (osteoporosis)
• Pathologic fractures are due to weakening of the bone (e.g., neoplasm, infection, osteoporosis, metabolic bone disease)
• Stress fractures: result from repetitive injury (e.g., dancers, gymnasts)
• Osgood-Schlatter disease: avulsion injury or fracture at the tibial tuberosity in physically active teenagers

Presentation

• Symptoms depend on location and etiology, involvement of vessels, nerves, and adjacent soft tissue
• Classified according to location (bone name, bone part, aspect), orientation (transverse, oblique, or spiral), open versus closed, complete versus incomplete, with or without displacement, angulation, impaction, fragmentation (comminution)

Prognosis and treatment

• Prognosis depends on extent of trauma, involvement of vital organs, and presence of hemorrhage
• Treatment varies depending on location and type of fracture; may include immobilization, closed or open reduction, external or internal fixation, repair of adjacent neurovascular structures

Radiology

• Location and orientation are useful to establish mechanism
• In pathologic fractures, associated features (e.g., neoplasm, osteomyelitis, osteoporosis) help establish the etiology
• Loss of bone integrity; may be subtle if no displacement or in incomplete fractures
• Fracture fragments appear increasingly indistinct over time, and calcified callus formation is demonstrated
• As callus evolves, eventually bony bridging develops

Pathology

Gross

• Acutely: loss of bone integrity, hemorrhage, damage to surrounding soft tissue
• In delayed resections: formation of yellow-pink callus; necrotic bone may appear yellow or gray

Histology

• Acute changes (days): hemorrhage, necrosis of bone marrow, osteoblasts, osteoclasts
• Early callus (about 2 weeks)
• Proliferation of mesenchymal fibroblast-like cells and small vessels, irregular islands of immature (woven) bone, and variable amounts of cartilage
• Starts along disrupted periosteum and extends around both ends of broken bone
• Larger callus size and greater proportion of cartilage are seen in poorly immobilized fractures
• Definitive repair (once immobilization is achieved)
• Deposition of lamellar bone with restoration of union between cortical and medullary components
• Remodeling and resorption of the callus
• Restoration of bone marrow

Ancillary tests

• Usually not required

Main differential diagnosis

• Osteosarcoma
• Chondrosarcoma
• Chronic osteomyelitis

Fig 1 Imaging findings of fracture and callus. A, A plain radiograph of traumatic femoral fracture shows displacement and angulation of the distal femur with normal-appearing cortical and medullary bone. B, By comparison, a pathologic fracture of the proximal humerus shows similar displacement but with a preexisting ill-defined mixed lytic and sclerotic lesion of the humeral diaphysis. C, A plain radiograph of the wrist illustrates a distal radius fracture with internal fixation and callus formation ( arrows ) at the fracture site.

Fig 2 Fracture callus. A, At low magnification, a well-established callus with mesenchymal granulation-like tissue filling trabecular spaces of native bone ( lower part of image ) and buttressing islands of new bone deposition along the fracture line ( upper right ); foci of cartilage formation are also present. B, Higher magnification of the callus demonstrates spindled fibroblast-like cells and numerous small vessels. C, An island of immature woven bone formation is surrounded by numerous active osteoblasts. D, Frequently, new bone ( arrow ) is formed that is attached or “buttressed” on a scaffold of necrotic bone ( arrowheads ).
C
Cystic Lesions
Aneurysmal Bone Cyst

Definition and synonyms

• A benign, often rapidly expansile, locally destructive multicystic bone lesion of unknown etiology; both reactive and likely neoplastic forms have been described

Clinical features

Epidemiology

• Account for 2% of primary bone tumors undergoing biopsy
• Slight female predominance
• Can occur in any age group, but most often in the first two decades of life
• Most common in the distal femur and proximal tibia as well as the cervical vertebra body
• May occur as a secondary finding in other neoplasms, especially chondroblastoma

Presentation

• Joint pain varies in duration from weeks to years
• Joint swelling, often rapid increase in size
• Can have symptoms of cord compression if spine is involved
• Rarely, visible pulsations are seen

Prognosis and treatment

• Good prognosis, 90% of patients have a cosmetically and functionally acceptable resolution
• Surgical excision with curettage and cement or bone graft is treatment of choice but can cause functional derangement
• Recurrence is rare
• Cryotherapy also associated with low recurrence
• Radiation helpful for vertebral lesions with cord compression, but postirradiation sarcoma is rare complication

Radiology

• Area of lucency usually eccentrically located in the medullary cavity of metaphysis of long bone
• Can also be located centrally, in the cortex, or on the bone surface
• Margins usually well defined
• Rapid growth can cause cortical destruction, and if lesion expands into soft tissue, a rim of calcification can be seen
• Usually lytic, but traces of mineral can be seen within lesion
• On CT peripheral bone shell and fluid-fluid lesions visible
• On MRI internal septations produce a honeycomb appearance as well as fluid-fluid levels, contrast enhancement of cyst walls, and septations

Pathology

Gross

• Usually received as red-brown curettage fragments
• Fragments usually smaller than dimensions recorded radiographically
• If lesion resected, cystic spaces containing blood separated by fibrous septa of varying thickness

Histology

• Cavernous spaces filled with blood, but no endothelial lining vascular smooth muscle
• Fibrous septa containing collagen, osteoid, giant cells, capillaries, hemosiderin, spindled fibroblast-like cells
• Spindled cells in septa have plump nuclei without hyperchromasia; mitotic figures can be abundant
• Solid variant has predominantly components of septae rather than cavernous blood-filled spaces
• Bone formation is often densely calcified (referred to as blue bone )

Ancillary tests

• Approximately two thirds of cases demonstrate a translocation involving 17p13.2, detectable by fluorescence in situ hybridization

Main differential diagnosis

• Giant cell tumor
• Telangiectatic osteosarcoma
• Ossifying hematoma; pseudotumor of hemophilia

Fig 1 Anteroposterior plain radiographs of the distal tibia ( A ) and mid-humerus ( B ). Both demonstrate the typical radiographic features of an aneurysmal bone cyst. In both examples, the lesion is lytic and radiolucent with well-defined margins ( arrows ). In the distal tibia ( A ), traces of mineral are visible within the lesion.

Fig 2 Grossly, this aneurysmal bone cyst of the cervical spine is a cystic space filled with blood. Septae are visible within the cyst wall.

Fig 3 Sagittal fluid-sensitive ( A ) and axial contrast-enhanced ( B ) fat-saturated magnetic resonance images demonstrating fluid-fluid levels ( A ) and contrast-enhancing cyst walls and septations ( B ).

Fig 4 This scanning magnification image of an aneurysmal bone cyst demonstrates the cavernous spaces, fibrous septae, and focal osteoid formation at the periphery of the lesion.


Fig 5 A, The fibrous septae of an aneurysmal bone cyst are characterized by loose collagen, spindled cells, and osteoclast-like giant cells. B, The septae lack an endothelial lining or smooth muscle.

Fig 6 A, Aneurysmal bone cyst can demonstrate osteoid peripherally and within the fibrous septae. B, The bone is often densely calcified, so-called blue bone.
Unicameral Bone Cyst

Definition and synonyms

• A benign, intramedullary, usually unilocular cyst located within bone and containing clear or sanguineous fluid (simple cyst, solitary bone cyst, benign bone cyst)

Clinical features

Epidemiology

• Accounts for 3% of primary bone tumors undergoing biopsy
• Male predominance (up to 3:1 male-to-female ratio)
• Most often presents in first two decades of life, but rare examples in older adults have been reported
• Most commonly found in the proximal humerus and proximal femur of children and the calcaneus and ilium of adults

Presentation

• Pain, swelling, or stiffness of nearest joint
• Two thirds of patients have a sudden onset of pain due to a pathologic fracture

Prognosis and treatment

• Traditionally treated with curettage and packing of cavity with allograft or cement
• More recently treated with aspiration and steroid injection
• Recurrence rate is 15% to 20% for either procedure and requires curettage

Radiology

• Cystic space within the metaphysis of long bones
• Overlying cortex is thin and slightly expanded
• Cyst may appear trabeculated or multiloculated as a result of osseous ridges along wall
• Often the cyst arises in contact with the epiphyseal plate, but in skeletally mature individuals, it is “pushed” away from the plate as the bone lengthens; in other words, the lesion moves toward the diaphysis as patient ages

Pathology

Gross

• Usually received as sparse curettage fragments in background of serous fluid or serosanguineous fluid
• Cyst wall is shiny and usually thin
• Fibrous septa can be present

Histology

• Hypocellular
• Thin membrane lined with collagen, or a thicker membrane lined with fibroblasts and vessels
• Degenerating fibrin can be present in the cyst wall, which can become calcified and resemble cementum
• Osteoclast-like giant cells may be present, especially if steroids have been injected into cyst cavity
• Osteoid can be rarely seen
• Hemosiderin, granulation tissue, chronic inflammation can be present
• Calcified spherules within a loose fibrous stroma are seen in 9% of cases

Main differential diagnosis

• Aneurysmal bone cyst

Fig 1 Amorphous masses of fibrin tend to fill the cyst cavities. A, When calcified, this material can resemble cementum. B, A phosphotungstic acid–hematoxylin stain highlights the fibrin.


Fig 2 The septae contain scant, wispy collagen and bland spindle cells.

Fig 3 A, In this plain film of unicameral bone cyst of the midshaft of the femur ( arrow ), the lesion is radiolucent and multiloculated, whereas the overlying cortex is expanded and thin. Note the benign appearance with well-defined sclerotic margins. B, A coronal T1-weighted magnetic resonance image of a proximal femoral cyst ( arrow ) shows a hypointense, well-circumscribed lesion.

Fig 4 At scanning magnification, unicameral bone cyst is paucicellular with thin fibrous septae and amorphous eosinophilic deposits (fibrin).

Fig 5 Although the cyst usually contains serous fluid, secondary hemorrhage ( bottom ) can be seen focally creating morphologic overlap with aneurysmal bone cyst in some cases.
Intraosseous Ganglion

Definition and synonyms

• A benign, intramedullary, non-neoplastic cyst containing viscous mucinous fluid (juxta-articular bone cyst)

Clinical features

Epidemiology

• Slight male predominance
• Occur in first decade of life and on, with most patients between 30 and 60 years
• Most common sites of occurrence: proximal femur, distal tibia, distal fibula, proximal tibia, and carpal and metacarpal bones

Presentation

• Patients complain of pain and tenderness; occasionally, a mass is present
• Pathologic fracture is rare
• Occasionally, patients are asymptomatic, and lesion is an incidental radiologic finding

Prognosis and treatment

• Surgical excision with curettage is curative
• Recurrence is rare

Radiology

• Cystic space within the epiphysis or originating from a joint (as shown in Figure 1 )
• Eccentric, lytic defect with sharply defined margins and slight perilesional sclerosis
• Adjacent articular surface usually normal
• Size ranges from several millimeters up to 6 cm in greatest dimension, most are 2 to 4 cm

Pathology

Gross

• Strands of fibrous tissue intermixed with gelatinous or mucoid material

Histology

• Usually scant tissue received in pathology
• Dominant feature is acellular mucinous material
• Cyst lining may contain a loosely arranged spindled cell proliferation in a myxoid background
• Surrounding cyst is an outer fibrous capsule that is heavily collagenized and contains few capillaries
• Reactive new bone formation can be found on the outer portion of the capsule

Main differential diagnosis

• Extragnathic fibromyxoma
• Chondromyxoid fibroma
• Subchondral cyst associated with degenerative joint disease

Fig 1 The defining feature of this lesion is mucinous material within the cyst ( A ), which contains a few chronic inflammatory cells ( B ) or is acellular.


Fig 2 This anteroposterior plain radiograph of an intraosseous ganglion at the knee shows a lytic lesion with well-defined margins located in the proximal tibia and is associated with tibiofibular joint compartment.

Fig 3 Uncommonly, woven bone can be seen in the cyst wall ( arrow ). This, coupled with occasional giant cells, may lead to misinterpretation as an aneurysmal bone cyst.

Fig 4 A curettage specimen of intraosseous ganglion consists of acellular mucinous material, lamellar bone, and fibrous tissue.
D
Giant Cell–Rich Lesions
Giant Cell Tumor

Definition and synonyms

• A benign but locally aggressive neoplasm composed of uniformly distributed osteoclast-like giant cells (osteoclastoma)

Clinical features

Epidemiology

• Accounts for 5% of resected primary bone tumors and 20% of benign bone tumors
• Slight female predominance
• Almost always affects a mature skeleton, most often in third and fourth decades of life
• Usually occurs at the epiphyses of long bones
• Most commonly occurs in the distal femur, proximal tibia, distal radius, and sacrum

Presentation

• Swelling and pain
• Pathologic fracture is rare
• Neurologic symptoms possible if tumor involves vertebrae or sacrum

Prognosis and treatment

• Standard treatment is curettage to preserve joint function followed by cement
• Larger lesions can require resection of involved bone
• Recurrence rate 25% to 50%; recurrence related to thoroughness of removal, slightly higher if soft tissue extension
• Rare metastasis to lung (“benign metastases”) that may spontaneously regress but sometimes requires surgical excision
• Sarcomatous transformation rare

Radiology

• Lytic neoplasm with trabeculations and discrete, well-defined borders but without sclerotic rim; occasionally border may be more indistinct with a wider zone of transition
• Matrix calcifications are absent
• Almost always involves epiphysis, often with metaphyseal extension
• Most abut the articular cartilage
• If there is extension into the surrounding soft tissue, there is usually a thin layer of periosteal new bone that may not be visible radiographically

Pathology

Gross

• Curetted specimens usually received in laboratory; resection specimens uncommon
• Highly variable gross appearance, can range from predominantly hemorrhagic (resembling an aneurysmal bone cyst) to soft and fleshy
• Typically, there is a sharp margin between the tumor and surrounding bone
• Surrounding bone is typically expanded with a thinned cortex

Histology

• Classic examples consist of sheets of multinucleated osteoclast-like giant cells in a background of mononuclear cells
• Both the multinucleated and mononuclear cells have round or oval nuclei with smooth chromatin and small nucleoli
• Mitotic figures abundant in mononuclear cells but no atypical mitoses
• Cellular pleomorphism and nuclear hyperchromasia absent
• The tumor is usually devoid of stroma (osteoid, cartilage, collagen), but a thin rim of woven bone may be present if there is cortical destruction and soft tissue spread
• Features that may be present in some cases but do not correlate with a prognosis
• Intravascular tumor
• Infarct-type necrosis
• Storiform or fascicular spindle cell–rich areas

Main differential diagnosis

• Giant cell–reparative granuloma
• Brown tumor of hyperparathyroidism
• Aneurysmal bone cyst, especially solid variant
• Osteosarcoma with giant cells
• Metaphyseal fibrous defect

Fig 1 Radiographically, giant cell tumor presents as an expansile, epiphyseal, lytic tumor. A, The example from the distal radius shows a thin shell of bone at the interface with the soft tissue. B, These same characteristics are present in the proximal fibula. The tumors are lytic and involve the epiphysis and metaphysis. Trabeculations are visible, and the borders are relatively well defined. A fracture is present at the interface between tumor and fibula diaphysis ( B ).

Fig 2 A, In this resection specimen of a giant cell tumor of the distal femur, the tumor extends to the articular cartilage. A sharp margin is present between the tumor and the surrounding bone. The cortex is expanded and thin. B, Most giant cell tumor specimens are curetted tissue fragments of blood clot and fleshy soft tissue.

Fig 3 Giant cell tumor is characterized by a diffuse population of multinucleated giant cells and abundant mononuclear cells visible at low power ( A ) and at higher magnification ( B ). Note the relative absence of stroma and the similar nuclear features between mononuclear and multinucleated giant cells.

Fig 4 Although giant cell tumor is usually devoid of stroma, a thin shell of woven bone may be present if the tumor has extended through the cortex into soft tissue.


Fig 5 Rare cases of giant cell tumor may demonstrate features that might suggest malignant behavior but have no prognostic significance. These include intravascular invasion ( A ), necrosis ( B ), and spindle cell–rich areas ( C ).

Fig 6 Abundant mitotic figures are often present in giant cell tumor, but atypical mitotic forms, cellular pleomorphism, and nuclear hyperchromasia are absent.

Fig 7 Lung metastases are rare in giant cell tumor and are considered “benign metastases” because they may spontaneously regress.
Giant Cell–Reparative Granuloma

Definition and synonyms

• A benign, reactive, intraosseous proliferation characterized by aggregates of giant cells in a fibrovascular stroma (giant cell reaction of bone, giant cell granuloma)

Clinical features

Epidemiology

• Can occur in any age group, but 75% of cases occur in the first three decades of life (unlike giant cell tumor)
• No male or female predominance
• Most common sites: hands and feet (phalanges, metatarsals, metacarpals), jaw bones

Presentation

• Nonspecific pain and swelling of varying duration, from days to years
• Rarely, there is a history of trauma
• Pathologic fractures can occur
• By definition, laboratory parathyroid studies are normal

Prognosis and treatment

• Curettage with or without bone grafting is usually adequate
• Recurrence is uncommon, and typically treatment with curettage is sufficient
• No documented occurrences of “benign metastases” or sarcomatous differentiation

Radiology

• Unifocal
• Radiolucent, fusiform expansion centered in the diaphysis or metaphysis
• Most cases show fine to coarse trabeculation
• Cortex expanded and thin but characteristically intact
• No sclerosis of surrounding bone

Pathology

Gross

• Tissue usually received as curetted fragments
• Nondescript pink-tan to gray-brown friable material

Histology

• Prominent collagenous stroma containing giant cells centered around zones of hemorrhage
• Giant cells tend to be smaller and have fewer nuclei than those seen in giant cell tumor
• Stromal mitotic figures common, but less than those seen in giant cell tumor
• Trabeculae of reactive woven bone and osteoid are common
• Foci of secondary aneurysmal bone cyst can be seen

Main differential diagnosis

• Brown tumor of hyperparathyroidism (may be histologically indistinguishable)
• Giant cell tumor
• Aneurysmal bone cyst (solid variant may be indistinguishable from giant cell–reparative granuloma)
• Nonossifying fibroma

Fig 1 Plain radiograph of giant cell–reparative granuloma of the third metatarsal. The arrow highlights a radiolucent expansile lesion in the distal portion of the metaphysis. The surrounding cortex is thin but intact.

Fig 2 Giant cell–reparative granuloma consists of a heterogeneous mix of fibrous stroma, spindle cells, osteoclast-like giant cells and osteoid at scanning ( A ) and higher magnification ( B ).


Fig 3 The giant cells tend to be widely scattered and smaller in giant cell–reparative granuloma than giant cell tumor, but significant morphologic overlap exists.

Fig 4 Trabeculae of reactive woven bone and hemorrhage are common in giant cell–reparative granuloma.
Brown Tumor

Definition and synonyms

• A benign intraosseous tumor due to osteoclast hyperactivity, usually in the setting of hyperparathyroidism

Clinical features

Epidemiology

• Occurs in 1% of the adult population
• Female predominance
• Increased incidence with age
• Can involve any portion of the skeleton

Presentation

• Clinical presentation is variable, but some patients have nonspecific pain and swelling
• Laboratory testing shows hyperparathyroidism

Prognosis and treatment

• Surgical removal of hyperfunctioning parathyroid gland is curative

Radiology

• Radiolucent lytic lesions without matrix pattern, usually well circumscribed, (may be multiple) background of diffuse subperiosteal bone resorption

Pathology

Gross

• Typically not treated with surgery, but if patient goes to surgery, tissue is received as friable curetted fragments

Histology

• Proliferation of osteoclast-like giant cells in a background of spindled cells and fibrosis
• The giant cells are usually arrayed in clusters
• Bony trabeculae tend to be shrunken and show increased osteoblastic and osteoclastic activity
• Similar histology to giant cell reparative granuloma

Main differential diagnosis

• Giant cell tumor of bone
• Giant cell–reparative granuloma (may be indistinguishable histologically)

Fig 1 Reactive woven bone is often present in brown tumor. Note the prominent osteoclast activity.

Fig 2 Anteroposterior radiograph of the left hand in a child with chronic renal failure, secondary hyperparathyroidism, and brown tumor. Note the well-circumscribed osteolytic lesion without matrix pattern in the distal radius metaphysis. Also note widening of the distal radius and ulna growth plates consistent with abnormal skeletal maturation related to renal osteodystrophy.

Fig 3 Brown tumor usually contains aggregates of osteoclast-like giant cells ( A ) and hemosiderin-laden macrophages ( B ). No pleomorphism or nuclear hyperchromasia is present.
Tenosynovial Giant Cell Tumor, Localized Type

Definition and synonyms

• A discrete intra-articular mass that does not involve the entire synovium, with varying proportions of histiocytes, foam cells, giant cells, inflammatory cells, and fibrous tissue; recent evidence suggests that localized and diffuse types (see next section) of tenosynovial giant cell tumor may be molecularly related entities because both demonstrate fusion of the COL6A3 to CSF1R genes by a t(2q35;1p11-13) translocation (giant cell tumor of tendon sheath, benign synovioma, localized nodular synovitis)

Clinical features

Epidemiology

• Male predominance (2:1 male-to-female ratio)
• Occurs in the second to seventh decades of life, slight peak in the fourth decade
• Most commonly occurs in the knee
• Localized type more common in flexor tendons of hands and feet than diffuse type

Presentation

• Patients invariably complain of pain: abrupt onset or mild and intermittent of up to several years’ duration
• Half of patients report symptoms consistent with internal mechanical joint derangement (locking or clicking)
• A history of trauma is present in a subset of patients

Prognosis and treatment

• Simple excision is often curative
• Recurrences very rare

Radiology

• Typically a well-circumscribed soft tissue mass
• Erosion or perforation of adjacent cortex can rarely occur

Pathology

Gross

• Mass may be sessile but often attached to synovium by a variably sized pedicle
• Rarely, mass is a loose body in the joint space
• Size reported to range from 0.9 to 8.2 cm
• Irregularly shaped and color ranges from white to dark brown
• Shallow grooves may be present on the deep surface of the tumor due to underlying tendons

Histology

• Broad, patternless sheets of histiocytes with bland nuclei and variable cytoplasm
• Multinucleated giant cells can be numerous or absent
• Stroma may be heavily collagenized or hyalinized and sparsely cellular
• Foam cells often present
• Large areas of nodule may be necrotic

Ancillary tests

• Mononuclear cells show positive immunohistochemical staining for CD68
• Desmin staining may be seen in up to 40% of cases; myogenin is negative

Main differential diagnosis

• Giant cell tumor of soft tissue
• Necrobiotic granuloma
• Fibroma of tendon sheath
• Desmin immunopositivity, out of context, may lead to an incorrect diagnosis of a myogenic neoplasm, especially alveolar rhabdomyosarcoma

Fig 1 Localized-type tenosynovial giant cell tumor. Axial T2-weighted MRI (MRI) of the fingers shows focal soft tissue mass at the flexor tendon of the second digit with intermediate signal and without bony erosion.

Fig 2 The gross appearance of this tumor is variable, but typically it is solid and reasonably well circumscribed.


Fig 3 At low magnification, localized-type tenosynovial giant cell tumor is unencapsulated but circumscribed. Fibrous or hyalinized areas may be peripherally located ( A ) or more haphazardly arranged within the lesion ( B ).

Fig 4 Foamy macrophages are commonly present and are likely a degenerative feature.

Fig 5 Some examples may be extensively hyalinized with cracking of the collagen and scant entrapped macrophages and spindle cells.

Fig 6 A, In localized-type tenosynovial giant cell tumor, multinucleated giant cells may be numerous. B, A cellular example that is entirely devoid of giant cells, despite the name.
Tenosynovial Giant Cell Tumor, Diffuse Type

Definition and synonyms

• A locally destructive fibrohistiocytic proliferation that involves the entire synovium and produces villous and nodular synovial protrusions; large quantities of hemosiderin give the lesion a grossly pigmented appearance (pigmented villonodular synovitis)

Clinical features

Epidemiology

• Occurs most often in the third and fourth decades of life
• Female predominance (2:1 female-to-male ratio)
• Most common sites are the knee (80%) and the hip (15%)
• Rarely multiple joint involvement is present

Presentation

• Patients complain of pain, intermittent or steadily progressive swelling, and range of motion limitations
• Symptom duration recorded from 6 months to 25 years; average duration is 6 years
• Bloody joint effusions occur in 67% of patients

Prognosis and treatment

• Difficult to excise completely due to diffuse synovial involvement
• Local surgical excision results in recurrence in 21% to 46% of cases
• Spontaneous regression is rare
• Extensive, destructive local growth may, in extreme cases, require amputation
• Symptomatic relief can be obtained with external beam radiation or intra-articular radiocolloid injection

Radiology

• In standard radiographs, soft tissue swelling within the joint is demonstrated with or without joint space narrowing
• MRI is very typical and shows an intra-articular soft tissue mass, which is not very destructive; low signal intensity areas in T1- and T2-weighted images are characteristic and indicate hemosiderin deposits.
• Twenty-five percent of patients have multiple cysts in the bones around the involved joint

Pathology

Gross

• Synovium diffusely involved; only small patches of normal synovium may be present
• Soft, spongy tissue that is brown to yellow in color
• Villous projections are variable in size and shape and can number to the thousands
• Villous projections can be plump, filamentous, or beaded and often are broad nodules
• Articular cartilage can be eroded by lesional tissue; lesion can also extend into local muscle

Histology

• Villi covered with reactive-appearing synovial cells containing abundant hemosiderin
• The synovial layer merges imperceptibly into the underlying inflammatory cellular infiltrate occupying the villi
• Fibroblasts, chronic inflammatory cells, foamy histiocytes, and multinucleated giant cells are commonly seen
• Broad areas of fibrosis can be present

Main differential diagnosis

• Reactive traumatized synovium
• Rheumatoid arthritis
• Detritic synovitis (seen in prosthetic joints)
• Intra-articular hemorrhage in hemophiliacs

Fig 1 Radiographic findings in diffuse-type tenosynovial giant cell tumor. Anteroposterior radiograph of the pelvis ( A ) shows cystic destructions at the left femoral neck ( arrow ), and axial T2-weighted fat-saturated MRI ( B ) shows multiple tumor deposits at the right hip joint, including anterior femoral head and acetabular cystic destructions and a soft tissue mass posterior to the femoral head. Note intermediate signal of these lesions indicating hemosiderin content.


Fig 2 A and B, Grossly, diffuse-type tenosynovial cell tumor often has a brown appearance due to large amounts of hemosiderin. Villous projections can range from short and plump ( A ) to long and thin ( B ).

Fig 3 At low magnification, a villous projection of the synovial layer merges with a cellular infiltrate with abundant hemosiderin.

Fig 4 At higher magnification, the infiltrate is a heterogeneous population of capillaries, chronic inflammatory cells, hemosiderin-laden macrophages, and multinucleated giant cells amid a vascular stroma.

Fig 5 Degenerative features, including foamy macrophages ( A ) and cholesterol clefts ( B ), are common in tenosynovial cell tumor.
E
Mixed Periosteal Lesions
Bizarre Parosteal Osteochondromatous Proliferation

Definition and synonyms

• A reactive process composed of bone, cartilage, and fibrous tissue attached to the surface of bone. The term bizarre is used to describe the cartilage, which can be proliferative (Nora lesion)

Clinical features

Epidemiology

• Occurs most frequently in the second and third decades of life
• No male-female predominance
• Most common sites are the tubular bones of the hands and feet, usually the proximal phalanges of the hand
• The humerus or radius is rarely involved

Presentation

• Patients complain of swelling and tenderness
• Rapid growth is often present
• No association with trauma or prior radiation

Prognosis and treatment

• Simple excision is treatment of choice
• Recurrences are common but can be managed with re-excision
• No documented cases of metastases

Radiology

• A calcified rounded mass arises directly from the surface of the bone
• This mass is heavily and uniformly mineralized and well circumscribed
• There is no continuity between the cortex and medulla of the involved bone and the tumor (unlike in osteochondroma)

Pathology

Gross

• A mass with a cartilaginous cap and a stalk composed of bony trabeculae that grossly resembles an osteochondroma
• Cartilage can be abundant and haphazardly arranged

Histology

• Resembles an osteochondroma at low power
• The cartilaginous cap is very cellular with enlarged nuclei; binucleated cells are common
• The interface with underlying bone is irregular with variably sized aggregates of bone intermixed with cartilage
• Under the cartilage, endochondral ossification can be seen and is blue because of dense calcification (referred to as blue bone )
• Fibrous tissue may be intermixed, especially at the periphery of the lesion

Main differential diagnosis

• Osteochondroma (although these seldom occur in the small bones)
• Florid reactive periostitis
• Soft tissue chondroma

Fig 1 Plain anteroposterior radiograph of the third digit with bizarre osteochondromatous proliferation shows a uniformly mineralized, well-circumscribed, rounded mass that appears to arise directly from the base of the middle phalanx.


Fig 2 At low magnification, the cartilaginous component of bizarre osteochondromatous proliferation caps the periphery of the lesion with an irregular interface between the cartilage and the underlying bone.

Fig 3 The cartilage ( top of Figure ) can be seen here maturing into bone. The cartilage is cellular, and in other circumstances, the nuclear enlargement might be concerning for malignancy.

Fig 4 A and B, Fibrous tissue consisting of loose collagen and bland spindle cells is often intermixed between the islands of ossification. Note that the bone is often densely mineralized resulting in a very basophilic appearance (blue bone).
Subungual Exostosis

Definition and synonyms

• A proliferative process involving the nail bed and consisting of bone and cartilage in a subungual or periungual location.

Clinical features

Epidemiology

• Occurs most frequently in the second and third decades of life but affects a wide age range
• Pronounced male predominance
• Most commonly occurs in the distal phalanx of the great toe (75%)

Presentation

• History of significant trauma present in 25% of cases
• Patients present with a painful mass lesion that elevates the nail
• Occasionally, ulceration is present
• Growth can be rapid, but symptoms can last from months to years

Prognosis and treatment

• Simple excision is treatment of choice
• Recurrences are rare but can be managed with re-excision
• No documented cases of metastases

Radiology

• Early lesions arise as a soft tissue density with no apparent attachment to bone
• There is progressive calcification and the formation of a trabecular pattern of bone over time
• In later lesions, the trabecular bone at the base of the lesion connects to the underlying phalanx
• There is no periosteal reaction or bone destruction

Pathology

Gross

• A well-circumscribed mass with a cartilaginous cap and a bony stalk
• The cartilaginous cap is smooth and shiny unless ulceration is present (when it is covered with a fibrous layer of granulation tissue)

Histology

• Generally a zonal arrangement of three components that merge (from superficial to deep):
• A proliferating fibrous stroma that can extend into dermis
• Abundant cartilage in a platelike arrangement
• Trabecular-appearing bone
• The cartilage is cellular and the nuclei enlarged
• There is prominent osteoblastic rimming along the newly formed bone
• The intertrabecular spaces contain loosely arranged spindled cells

Main differential diagnosis

• Bizarre parosteal osteochondromatous proliferation
• Osteochondroma (very rare in digits)
• Subungual melanoma

Fig 1 A and B, Plain radiographs of subungual exostoses ( arrows ) show a small calcified mass overlying the distal phalanx of the first toe. The lesions are best demonstrated on lateral views.


Fig 2 At low power, subungual exostosis shows zonation of a fibrous proliferation beneath the dermis ( top ), a platelike layer of cartilage ( middle ) with endochondral ossification ( bottom ).

Fig 3 The cartilaginous portion of subungual exostosis shows high cellularity and some nuclear pleomorphism.

Fig 4 Prominent osteoblastic rimming can be seen adjacent to newly formed bone.

Fig 5 A spindled cell population can be seen in the intertrabecular spaces.
Florid Reactive Periostitis

Definition and synonyms

• A reactive fibrous, osteoblastic, and focally cartilaginous proliferation that occurs on the surface of the bones (parosteal fasciitis, fibro-osseous pseudotumor, periostitis ossificans)

Clinical features

Epidemiology

• Age varies from children to elderly people; mean age, 25 to 30 years
• Slight female predominance (female-to-male ratio of 1.5:1)
• Most commonly occurs in the proximal phalanx, middle and distal phalanx, metacarpal and metatarsal bones
• Can involve any bone

Presentation

• Patients complain of a painful swelling of the affected bone
• The pain is exacerbated by weight bearing and relieved by rest, corticosteroids, and anti-inflammatory medications
• A history of trauma exists in 40% of cases

Prognosis and treatment

• Local excision is usually curative
• Recurrences are rare (10% of patients) but can be managed with re-excision

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