Pathology of Bones Dr Mohanad Mahdi Normal anatomy

Pathology of Bones Dr. Mohanad Mahdi

Normal anatomy of bone

Normal histology of bone

Bone Pathology Main categories of bone diseases are 1. Congenital bone diseases. 2. Metabolic bone diseases. 3. Inflammatory diseases 4. Tumors of the bone.

Congenital bone diseases Achondroplasia. impaired maturation of cartilage in developing growth plate. Ø Ø Ø It is the major cause of dwarfism. caused by a mutation in the FGF receptor 3 (FGFR 3) Osteogenesis Imperfecta. Ø Ø Also called brittle bone diseases Characterized by collagen type I abnormality which result in generalized bone fragility.

Osteogenesis imperfecta / spine deformity

I. n Metabolic bone diseases. Osteoporosis. Characterized by n Low bone mass. Microarchitectural deterioration (failure of formation of bone trabeculae that render the bone fragile, increase in bone fragility & susceptibility to fractures). n Types of Osteoporosis. n 1. Localized Osteoporosis. Like disuse osteoporosis. 2. Generalized Osteoporosis. either primary or secondary. Causes of primary osteoporosis. 1. Postmenapausal osteoporosis. (Commonest) 2. Senile osteoporosis. 3. Idiopathic osteoporosis.

Causes of secondary osteoporosis. 1. Endocrine disorders (hyper & hypothyroidism, Cushing syndrome). 2. Neoplasia (Multiple Myeloma) 3. GIT causes like malabsorption, hepatic insufficiency. 4. Drugs like anticoagulants, steroid. 5. Rheumatologic diseases like rheumatoid arthritis. 6. Others like pulmonary diseases, and anemias.

Pathogenesis of Osteoporosis. Normally there is equilibrium between bone formation (osteoblastic activity) & bone resorption (osteoclastic activity). v In osteoporosis there is loss of this equilibrium with more bone resorption (increase osteoclastic activity). Causes of increase osteoclastic activity. 1. Age related decrease in bone density. n Occur in all individuals & in both sexes (after thirty). n Site: spine & femoral neck (commonest sites of fractures). n Cause: increase osteoclastic activity. v

2. Hormonal factors. (Evidence of hormonal causes of Osteoporosis) n Postmenapausal females (decrease estrogen) n Treatment with estrogen decrease bone loss & fractures. 3. Genetic factors. (Unclear mechanisms). 4. Mechanical factors. Like weight bearing & reduced physical activity (immobilized limbs). 5. Dietary factors. Dietary calcium intake in adolescent female appear to be less than in males (more liable to develop osteoporosis)

Morphology of osteoporosis. Gross. Loss of bone mass ( mainly trabecular bone, become thinner & more widely separated than usual, that result in increase susceptibility to fractures). Important sites: are (vertebral bodies & femoral neck) specially in postmenapausal females. Mic. Thinning of trabeculae. Prominent osteoclasts. Mineral contents of the remaining bone are normal.

Osteoporosis / Gross

Osteoporosis / Mic

II. Osteomalasia (adult rickets). It is qualitative disorder of bones, characterized by defective mineralization of bone (unlike osteoporosis). Inflammatory disorders of bones. (Osteomyelitis). v v v Inflammation of bone & marrow cavity. May be acute or chronic. Most common organisms are pyogenic bacteria, & tuberculosis. Pyogenic Osteomyelitis. Either acute or chronic

Acute pyogenic osteomyelitis. n n n Causative organism : Staphylococcus aureus(most common organisms). Routes of infection are hematogenous dissemination, (most common route) Direct extension from a focus of acute infection in the adjacent joint or soft tissue. Traumatic implantation after compound fractures or orthopedics surgery. In 50% of cases of pyogenic osteomyelitis, the causative organisms cannot be isolated because of previous antibiotic treatment, inadequate sampling for culture, or suboptimal methods of culture.

Sites of bone infection are varied according to age 1. In children are the metaphysis of long bones like tibia, which is thought to be due to sluggish blood flow at those areas allow the bacteria to be settled. 2. In adult the site of infection is mainly at the vertebral bodies that remain quite vascular which is also aid bacteria to settle those sites. Mic. neutrophils (may persist for weeks), lymphocytes and plasma cells with bone necrosis, reactive new bone formation, capillary proliferation and fibrosis. Sequele of acute Osteomyelitis. 1. 2. 3. Necrosis of involved bones within days, due to compression of blood vessels by increase pressure inside the bone marrow & releasing of hydrolytic enzymes of inflammation (sequestrum). Subperiosteal abscess (mainly in children). Formation of sinuses within the adjacent soft tissues(may complicate into squamous cell carcinoma within this sinuses)

4. Extension of infection to the adjacent joints (more in children because of less attached periosteum to articular surfaces). Chronic osteomyelitis. This is usually occurring as a sequel of acute infection, or due to inappropriate antibiotic treatment of acute osteomyelitis. Mic. there is influx of chronic inflammatory cells into the focus of osteomyelitis that initiate a repair reaction which include. A. osteoclasts activation. B. fibroblasts proliferation. C. resorption of sequestrum. D. reactive bone formation (involucrum). E. formation of Brodie abscess (sclerotic rim surrounding the residual abscess within the cortex).

Complications of chronic osteomyelitis. 1. 2. 3. 4. 5. Chronic sinuses of the skin. Pathological fractures. Bactermia & endocarditis. squamous cell carcinoma within a longstanding sinus tract. osteosarcoma & secondary amyloidosis. Clinical features. v v Systemic symptoms (fever, malaise, & leukocytosis) Local signs & symptoms (local pain, swelling, hotness & redness) these symptoms are more seen in adult than children.

Tuberculous osteomyelitis. n More in immunocompromised patients like AIDS. Usually as a complication of pulmonary T. B. Typical site of infection is the synovium (because of high concentration of O 2 at this area). Route of infection is mainly by blood stream. Sites either vertebrae (pott disease) or long bones. Complications are Vertebral deformity. Cold abscess in psoas muscle. n Mic. granulomatous inflammatory reaction, with caseous necrosis. n n n n

Osteomyelitis / PERIOSTEAL REACTION

Acute osteomyelitis / Mic

Complications of Osteomyelitis (skin sinus)

Tuberculous osteomyelitis

Tuberculous osteomyelitis / Granuloma formation with giant cells

Paget disease (Osteitis Deformans). It is a disorder characterized by episodes of localized, increased osteoclastic activity & bone resorption, followed by exuberant bone formation. The end result of these intermittent processes is skeletal deformity. n Uncommon under 40 years, male < female. n Usually sporadic but some cases are familial with abnormality on chromosome 18. Pathogenesis of Paget disease. n Paget disease is inflammatory in origin (unfavoured explanation). n Current evidence suggests that Paget disease is of infectious etiology, depend on following facts. I. Paramyxovirus like particles & antigens have been identified within osteoclasts obtained from patients with Paget disease. II. More recently other virus agents are isolated from the lesion of Paget disease which is Measles virus. n These viral agents are thought to be play a role in pathogenesis of Paget disease by activating osteoclastic activity. n

Morphology of Paget disease. Gross. Either solitary or mutifocal lesions. Mic. Usually pass in phases. 1. Primay (osteolytic) phase. There is bone resorption by osteoclasts. 2. Osteoclasts & Osteoblasts proliferation. (Mixed phase). 3. Osteosclerotic bone formation phase. Which characterized by cessation of osteoclastic activity & continuing osteoblastic activity, that result in formation of WOVEN BONE (weak bone & is subject to fracture & deformity).

Complications of paget disease. 1. 2. 3. 4. 5. Bone deformity (enlargement of head, kyphosis, scoliosis…). Backache is due to involvement of vertebrae (vertebral fractures & nerve root compression). Chalkstick fracture of long bones. Osteosarcoma in les than 1% of cases(usually multicentric & poor prognosis malignancy). High cardiac output failure in extensive cases.

Paget disease / Gross

Paget disease / Mic

Paget disease complicate into Osteosarcoma

Tumors of bones. Either benign or malignant tumors. n Malignant tumors are either primary or secondary (metastatic tumors). n Metastatic tumors are much more common than primary malignancy of the bone. n The most common originating sites for bone metastases are (prostate, breast, lung, kidney, GIT (colon), & thyroid). n Most metastases are present as osteolytic lesions; sometimes both osteolytic & osteoblastic lesions are seen in same metastases, other like metastases from prostate are mainly osteoblastic lesions. Classification of bone tumors. 1. Bone forming tumors (like osteoma, osteosarcoma…). 2. Cartilaginous tumors. (chondromas, chondrosarcoma…). 3. Miscellaneous (Ewing sarcoma…. . ). n

Osteomas. n Benign, sometime regard as developmental abnormality rather than tumors. n More on the head & neck. n Grossly present as localized, solitary, hard, exophytic growths (can multiple lesions that are associated with Gardner syndrome). n Mic. mixture of woven & lamellar bone. n Osteomas are not invasive & do not undergo malignant transformation. Osteosarcomas(osteogenic sarcomas). Most common primary malignant bone tumor after multiple myeloma. Definition: malignant bone tumor that produces osteoid directly from tumor cells and unconnected with cartilage, regardless of the amount of neoplastic cartilage or fibrous tissue present elsewhere

60% of cases are male; usually ages 10 -25 years, & rare below 5 years. Etiology: 1. Paget disease (such osteosarcoma occur after the age of 40 years). 2. Post-radiation exposure (after 10 -15 years from exposure to radiation). 3. Chronic osteomyelitis. 4. Thorotrast administration. 5. Chemotherapy in children. 6. Chondromatosis, rarely with hip implants. v Not associated with trauma, although trauma may lead to discovery of tumor. v Sites: metaphysis of long bones (distal femur, proximal tibia, & proximal humerus).

Sites of metastasis: lung (98%), other bones, rarely to lymph nodes, GI tract, liver, & brain. Sometimes osteosarcomas are divided into primary (arise de novo) & secondary which follow paget disease, chronic osteomyelitis…. . Morphology of osteosarcoma. Gross. n Large, ill-defined lesion at the metaphysis of involved bones, destroy the cortex, marrow & extend outward into adjacent soft tissues. The tumor often elevates the periosteum to produce the so called Codman triangle on X-ray. Mic. The hallmark of osteosarcoma is the formation of osteoid by malignant cells, & this malignant osteoid is characterized by:

Unconnected by cartilage. 2. Basophilic thin trabeculae of neoplastic bone resembling fungal hyphae. 3. Osteoblastic rimming; destroys or grows around trabeculae. 4. Osteoid may be variable in amount; with bizarre giant cells in stroma or acellular stroma. Tumor cells may be spindly, oval or round of variable size; 25% have osteoclast-like multinucleated giant cells. 1. Clinical features. 1. Painful masses of bone, or may be as pathological fractures.

Osteosarcoma / Gross

Osteosarcoma / Mic

Chondromas (Enchondroma). n n n n Benign lesions composed of mature hyaline cartilage. Site: small bones of the hands, & feet. Age: Most common in the third to fifth decades of life. Several cases are associated with congenital syndromes like Ollier syndrome(multiple chondromas involve one side of the body). Gross: usually within the medullary cavity of the bone, less commonly; they may occur on the surface of the bone. Mic. Sheets of mature hyaline cartilage. Solitary chondromas are almost always innocuous. In contrast, chondrosarcomas develop in about one third of patients with multiple chondroma syndromes.

Chondrosarcomas. n n n Malignant cartilage forming tumors, does not produce osteoid. Third most common bone malignancy after myeloma and osteosarcoma. As compared with osteosarcomas, chondrosarcomas occur in older patients, with a peak incidence in the sixth decade, & 75% are male. Sites: large bones - pelvis, ribs, femur, humerus, vertebrae; unusual in hands, feet, jaw, skull. Clinical features: are progressive enlarging painful masses & metastasize via blood to the lungs. n Mophology of chondrosarcomas. Gross. Masses within the medullary cavity that frequently erodes the cortex, Occasional lesions arise on the surface of the bone.

Mophology of chondrosarcomas. Mic. In well differentiated chonrosarcomas(low grade chondrosarcomas), difficult to distinguish from non neoplastic cartilage. In dedifferentiated chonrosarcomas(high grade chondrosarcomas), 1. Composed of highly pleomorphic cells with frequent mitotic figures. 2. Multinucleated cells are present. 3. Lacunae containing two or more chondrocytes.

Ewing's sarcoma. n n n n It is a member of a family of tumors which are called PNET (primitive neuroectodermal tumors). Account for 6% to 10% of all primary bone tumors, & the second most common bone tumors in children following the osteosarcoma. All members of PNET TUMORS FAMILY are characterized by chromosomal abnormality in form of (t (11; 22), this abnormality occur in 95% 0 f Ewing's sarcoma. Age: predominantly in children & adolescents, with peak incidence in the second decade of life. Clinical features: pain, fever, weight loss, leukocytosis and increased erythrocyte sedimentation rate mimicking osteomyelitis. Sites: marrow of femur, tibia, humerus, fibula, pelvis, ribs, vertebra, mandible. Xray: destructive, lytic tumor with reactive periosteal bone resembling onion skin. Metastases: to lung, skull, pleura, CNS.

Gross: n ill-defined tumor with extensive involvement of medulla and cortex with periosteal elevation. Micro: sheets of small, round, uniform cells (larger than lymphocytes) with scant clear cytoplasm. Formation of Rosettes (central fibrillary space) or Pseudorosettes (cells arrange themselves around vessels).