1、Chapter 17 Bone and joint diseases,Department of Pathology the First Affiliated Hospital, Sun Yat-sen University Wen Jianming,Non-neoplastic disorders,Osteoporosis Osteoporosis is a disease characterized by increased porosity of the skeleton resulting from reduced bone mass. Generalized osteoporosis
2、 may be primary, or secondary to a large variety of conditions.,The primary forms of osteoporosis are senile and postmenopausal osteoporosis; the former affects all aging individuals, while the latter affects only women after menopause. The secondary osteoporosis is caused by endocrine disorders, ga
3、strointestinal disorders, neoplasia, etc. and immobilization.,Mechamism of osteoporosis Menopause Aging Decreased serum estrogen Decreased replicative activity Increased IL-1, IL-6, of osteoprogenitor cells TNF levels Decreased synthetic activity Increased expression of osteoblasts of RANK, RANKL De
4、creased biological activity Increased osteoclast of matrix-bound growth factors activity Reduced physical activity,Morphology The hallmark of osteoporosis is a loss of bone, which tends to be most conspicuous in parts of the skeleton containing abundant trabecular bone. In postmenopausal osteoporosi
5、s, the bone loss is often particularly severe in the vertebral bodies, which may fracture and collapse.,The major microscopic changes are thinning of the trabeculae and widening of Haversian canals. Osteoclastic activity is present but is not dramatically increased. The mineral content of the remain
6、ing bone is normal, and thus there is no alteration in the ratio of minerals to protein matrix.,Clinical Course 1. asymptomatic or pain until fracture 2. Thoracic and lumbar vertebral fractures 3. loss of height and various deformities, including kyphoscoliosis The art for bone loss estimation invol
7、ves specialized radiographic techniques to assess density, e.g., dual-energy absorptiometry and quantitative CT.,OsteomyelitisOsteomyelitis are caused by bacteria. The offending organisms reach the bone by one of three routes: (1) hematogenous dissemination (most common); (2) extension from an infec
8、tion in adjacent joint or soft tissue; or (3) traumatic implantation after compound fractures or orthopedic procedures. Overall, Staphylococcus aureus is the most frequent causal organism.,Morphology Acute osteomyelitis induce an inflammatory reaction, and cause cell death. Entrapped bone undergoes
9、early necrosis; the dead bone in infected sites is called a sequestrum.,Bone necrosis and actinomyces,Chronic osteomyelitis: Chronic inflammatory cells become more numerous. Leukocyte cytokine release stimulates osteoclastic bone resorption, fibrous tissue ingrowth, and bone formation in the periphe
10、ry. Reactive woven or lamellar bone forms a shell of living tissue around a segment of devitalized bone it is called an involucrum.,involucrum,Infiltration of lymphocytes and plasma cells,Clinical FeaturesOsteomyelitis classically manifests as an acute systemic illness with malaise, fever, leukocyto
11、sis, and throbbing pain over the affected region. Symptoms can also be subtle with only unexplained fever, particularly in infants, or only localized pain. Chronicity may develop when there is delay in diagnosis, extensive bone necrosis, abbreviated antibiotic therapy, inadequate surgical debridemen
12、t, and/or weakened host defenses.,Rickets and osteomalacia Rickets and osteomalacia are disorders characterized by a defect in matrix mineralization, most often related to a lack of vitamin D or some disturbance in its metabolism. The term rickets refers to the disorder in children in which deranged
13、 bone growth produces distinctive skeletal deformities. In the adult the disorder is called osteomalacia, because the bone that forms during the remodeling process is inadequately mineralized.,Causes of Rickets and osteomalacia 1. Deficiency states: diet; lack of sunlight 2. Gastrointestinal causes:
14、 gastric resection; biliary and enteric causes 3. Renal tubular causes: Hypophosphatemic states Fanconi syndromes End organ defect Renal tubular acidosis 4. Unusual causes: Phosphaturic tumors Anticonvulsant therapy 5. Renal osteodystrophy: renal failure,There is insufficient ionized calcium or inor
15、ganic phosphate (or both) to mineralize the skeleton, leading to less mineralized bone per unit volume of bone. Trabeculae are surrounded by unmineralized osteoid. In rickets, pressure effects cause deformity at the epiphysis-mataphysis junction, resulting in metaphyseal flaring and a disordered phy
16、sis.,Morphology,Deformity at the epiphysis-metaphysis junction,Rachitic rosary due to accumulation of osteoid,Neoplastic disorders,Primary bone tumors exhibit great morphologic diversity and clinical behaviorsfrom benign to aggressively malignant. Most are classified according to the normal cell of
17、origin and apparent pattern of differentiation.,Clinically, benign lesions are frequently asymptomatic. Others produce pain or a slowly growing mass. Occasionally, a sudden pathologic fracture is the first manifestation. Radiologic imaging is critical in the evaluation of bone tumors; however, biops
18、y and histologic study are necessary for the final diagnosis.,WHO classification1. Cartilage tumors2. Osteogenic tumors3. Fibrogenic tumors4. Fibrohistiocytic tumors5. Ewing sarcoma/PNET6. Haematopoietic tumors7. Giant-cell tumors8. Tumors of undefined neoplastic nature,Osteogenic tumors,Osteoma Ost
19、eomas are benign lesions of bone that in many cases represent developmental aberrations or reactive growths rather than true neoplasms. They are most commonly encountered in the head and neck, including the paranasal sinuses.,Morphology Osteomas are usually solitary and present as localized, slowly
20、growing, hard, exophytic masses on the bone surface. Histologically, osteomas are a bland mixture of woven and lamellar bone.,Lamellar bone,Woven bone,Osteomas on the bone surface,Osteosarcoma,Osteosarcoma is a bone-producing malignant mesenchymal tumor. The most common type of osteosarcoma is prima
21、ry, solitary, intramedullary, and poorly differentiated, producing a predominantly bony matrix, and spread hematogenously; at the time of diagnosis, approximately 10% to 20% of patients have demonstrable pulmonary metastases.,75% of osteosarcoma patients are younger than age 20. Men are more commonl
22、y affected than women (1.6:1). Most tumors arise in the metaphyseal region of the long bones of the extremities, with almost 60% occurring about the knee, 15% around the hip, 10% at the shoulder, and 8% in the jaw.,MorphologyGrossly, osteosarcomas are gritty, gray-white tumors, often destroy the sur
23、rounding cortices, lifted the periosteum, and formed soft tissue masses on the bone.,Histologically, the tumor cells vary in size and shape, and frequently have large hyperchromatic nuclei; bizarre tumor giant cells are common, as are mitoses. The production of mineralized or unmineralized bone (ost
24、eoid) by malignant cells is essential for diagnosis of osteosarcoma.,The tumor cells produce high grade hyaline cartilage,Note the anaplastic tumor cells, neoplastic bone, mitotic figures.,Fibroblastic osteosarcoma,Small cell osteosarcoma,An osteosarcoma composed of small cells with variable degree
25、of osteoid production. Prognosis of this type of osteosarcoma is worse than conventional ones.,Telangictatic osteosarcoma,A malignant bone-forming tumour characterized by large spaces filled with blood with or without septa. Highly malignant tumor cells produce minimal amounts of fine, lace-like ost
26、eoid. Prognosis is similar to conventional osteosarcoma.,Parosteal osteosarcoma,Parosteal osteosarcoma is a low grade osteosarcoma which arises on the surface of bone. It consists of well formed bony trabeculae in a hypocellular stroma.,Parosteal osteosarcoma,Periosteal osteosarcoma,Periosteal osteo
27、sarcoma is an intermediate grade chondroblastic osteosarcoma arising on the surface of bone. There are lobules of malignant-appearing cartilage with bone formation in the center of the lobules.,Periosteal osteosarcoma,Cartilage tumors,Osteochondroma Osteochondroma is a cartilagecapped bony projectio
28、n arising on the external surface of bone containing a marrow cavity that is continuous with that of the underlying bone.Most cases appear in the first 3 decades. It is the most common bone tumor.,Morphology,The most common site of involvement is the metaphyseal region of long bone. The tumor may be
29、 sessile or pedunculated and has three layers - outer perichondrium, cartilage cap and underlying bone.,Chondromas Chondromas are benign hyaline cartilage neoplasm. They differ with respect to location and clinical features. Enchondroma and periosteal chondroma are sporadic whil enchondromatosis usu
30、ally manifests as a congenital tumor syndrom.,Chondroma affects mostly the small tubular bones. The long tubular bones, especially proximal humerus and proximal and distal femur, are next in frequency. Chondroma tissue is whit-grey and opalescent, and hypocellular, avascular tumor with abundant hyal
31、ine cartilage matrix. The chondrocytes are situated within lacunar spaces, have uniform small round nuclei.,Morphology,Chondrosarcoma Chondrosarcoma is a malignant tumor with pure hyaline cartilage differentiation. The majority of patients are older than 50 years. The most common skeletal sites are
32、the bones of the pelvis, femur and humerus.,The cut surfaces of the tumor tend to have blue-grey or white color corresponding to the presence of hyaline cartilage. A lobular growth pattern is a consistent finding. The chondrocytes are atypical varying in size and shape and contain enlarged, hyperchr
33、omatic nuclei. Binucleation is frequently seen.,Morphology,Mesenchymal chondrosarcoma is a rare malignant tumor characterized by a bimorphic pattern that is comosed of highly undifferentiated small round cells and islands of well differentiated hyaline cartilage.,Giant cell tumor It is a locally agg
34、ressive neoplasm of undefined neoplastic nature. The tumor is composed of sheets of neoplastic ovoid mononuclear cells interspersed with uniformly distributed large, osteoclast-like giant cells. The peak incidence is between the ages of 20 and 45.,GCT typically affect the ends of long bones, especia
35、lly the distal femur, proximal tibia, distal radius and proximal humerus.,distal femur,The appearance of an intact specimen is eccentric location and fairly well defined area of bone destruction. The tissue is usually soft and reddish brown. Blood filled cystic spaces are sometimes seen.,Morphology,
36、Large haemorrhagic tumor of the distal femur with extensive cortical destruction and soft tissue extension.,The characteristic histopathological appearance is of round to oval polygonal or elongated mononuclear cells evenly mixed with numerous osteoclast-like giant cells which contain 50 to 100 nucl
37、ei. Malignancy in GCT is a high grade sarcoma arising in a giant cell tumor or at the site of previously documented GCT.,Grade I,Grade II,Grade III,Ewing sarcoma/Primitive neuroectodermal tumor (PNET) Ewing sarcoma and PNET are defined as round cell sarcomas that lack evidence of neuroectodermal dif
38、ferentiation (Ewing sarcoma) and demontrate neuroectodermal features (PNET). Ewing sarcoma/PNET shows a predilection for male younger than 20 yrs.,Ewing sarcoma/PNET tends to arise in the diaphysis or metaphyseal- diaphyseal portion of long bones. The tumor in bone and soft tissue is tan-grey and of
39、ten necrotic and haemorrhagic.,The tumor is composed of uniform small round cells with round nuclei containing fine chromatin, scanty clear or eosinophilic cytoplasm, and indistinct cytoplasmic membranes. In PNET, Rosette-like structures are occasionally found. Immunohistochemical expression of CD99
40、 shows characteristic reactivity on the cell membranes.,Morphology,Fibrous dysplasia Fibrous dysplasia is a benign medullary fibro-osseous lesion which may involve one or more bones. The most common site of involvement in the gnathic (jaw) bones, femur and tibia or other bones. Fibrous dysplasia may
41、 present in a monostotic or polyostotic form, and in the latter case, can be confined to one extremity or one side of the body or be diffuse.,The lesions of fibrous dysplasia are well circumscribed, intramedullary, and vary greatly in size. The lesional tissue is tan-white and gritty and is composed
42、 of curvilinear trabeculae of woven bone surrounded by a moderately cellular fibroblastic proliferation. The trabecular bone sometimes lacks prominent osteoblastic rimming. Cystic degeneration, hemorrhage, and foamy macrophages are other common findings.,Morphology,Aneurysmal bone cyst Aneurysmal bo
43、ne cyst is a benign tumor of bone characterized by multiloculated blood-filled cystic spaces that may present as a rapidly growing expansile tumor.,Grossly, aneurysmal bone cyst consists of multiple blood-filled cystic spaces separated by thin, tan-white septa. The walls are composed of plump unifor
44、m fibroblasts, multinucleated osteoclast-like giant cells, and reactive woven bone. Deposition of the bone typically follows the contours of the fibrous septa.,Morphology,Osteoarthritis Osteoarthritis, or degenerative joint disease, is the most common joint disorder. It is an important cause of phys
45、ical disability in individuals over the age of 65. The fundamental feature of osteoarthritis is degeneration of the articular cartilage. In most cases, osteoarthritis appears insidiously with age and without apparent initiating cause (primary osteoarthritis).,When osteoarthritis strikes in youth, th
46、ere is typically some predisposing condition, such as previous traumatic injury, developmental deformity, or underlying systemic disease such as diabetes or marked obesity. In these settings the disease is called secondary osteoarthritis and often involves one or several predisposed joints.,The earl
47、iest structural changes in osteoarthritis include enlargement, proliferation, and disorganization of the chondrocytes in the superficial part of the articular cartilage. Subsequently, vertical and horizontal fibrillation and cracking of the matrix occur as the superficial layers of the cartilage are
48、 degraded. Gross examination at this stage reveals a soft granular articular cartilage surface. Small fractures can dislodge pieces of cartilage and subchondral bone into the joint, forming loose bodies (joint mice).,Morphology,GoutGout is a disorder caused by the tissue accumulation of excessive am
49、ounts of uric acid, an end product of purine metabolism. It is marked by recurrent episodes of acute arthritis, sometimes accompanied by the formation of large crystalline aggregates called tophi, and chronic joint deformity. All of these result from precipitation of monosodium urate crystals from supersaturated body fluids.,Classification of Gout,HGPRT, hypoxanthine guanine phosphoribosyl transferase,
