Musculoskeletal P athology Part I Bones

1. Musculoskeletal Pathology Part I Bones

2. Bone diseases Metabolic bone diseases Osteoporosis Osteomalacia and rickets Fibrous osteodystrophy Paget’s disease Fractures Inflammations Osteomyelitis Tuberculous osteomyelitis Tumours Primary Secondary (metastatic)

3. Osteoporosis absolute decline in the bone mass (bone atrophy) Pathogenesis excessive amount of osteoclastic resorption or impairment of osteoblast-mediated bone formation, or both Primary osteoporosis: type I osteoporosis (postmenopausal):↓oestrogen →↑bone resorption (↑number and activity of osteoclasts) type II osteoporosis (senile): individuals older than 70 years impairment of bone formation (failure to replace resorbed bone)

4. Secondary osteoporosis Cushing’s syndrome hyperthyreoidism hypogonadism (early oophorectomy) malnutrition subtotal gastrectomy immobilisation, hemiplegia, paraplegia treatment with glucocorticoids or certain anticonvulsants Clinical features: fractures as a result of minimal trauma hip fractures compressive fractures of the vertebral bodies – kyphosis (“dowager’s hump“) fractures of the distal radius (Colles’ fracture) Morphology: thinning of individual trabecula loss of normal trabecular network mineralisation is normal

5. Osteomalacia and Rickets (rachitis) defective mineralisation of osteoid matrix Lack of vitamin D: low dietary intake lack of sunlight small gut malapsorption chronic liver and/or renal diseases (impaired hydroxylation of vitamin D precursors) Hypophosphataemia (much less common, resistance to treatment with vitamin D): hereditary (abnormality of phosphate transport by the renal tubular epithelium) tumour-associated (effect of certain mesenchymal neoplasms)

6. Osteomalacia adults with closed epiphyses normal bone mass, but increase in amount of osteoid (more than 20% of the trabecular surface) deformities (kyphoscoliosis, contracted pelvis, limb curvature), fractures Rickets children(epiphyses still open and active) failure of matrix mineralisation disturbance of endochondral ossification: very poor formation of zone of provisional calcification, marked enlargement of zone of hypertrophic cartilage deformities: craniotabes rhachitica, caput quadratum (frontal and parietal bossing), bulging of the costochondral junctions („rickety rosary“)

7. Fibrous osteodystrophy severe hyperparathyreoidism (especially primary) excessive osteoclastic resorption of bone outline of bony trabeculae shows deep indentations filled with numerous osteoclasts and connective tissue In severe cases occur so-called brown tumors (a misnomer): areas in which trabecular bone has been completely eroded away and replaced by vascular fibrous tissue with many osteoclasts and hemosiderin depositions (brown color) – should not to be confused with true giant cell tumor uf bone Clinical features: bone pain, pathological fractures occasionally, hypercalcaemia

8. Paget’s disease of bone (osteitis deformans) chronic condition, enlargement and deformities of affected bones individuals over the age of 45 years, frequency increases with advancing age only one bone or many bones (polyostotic form) Sites: skull, pelvis, spine Aetiologyunknown, some osteoclasts contain intranuclear inclusions resembling the nucleocapsid structure of paramyxoviruses→ viral infection suggested, but attempts to isolate virus failed Macroscopic features: bones enlarged and thickened (thick calvarium) and softer (deformities – bowing of lower limbs), narrowing of the foramina of cranial nerves (neuropathies, deafness) Microscopic features: repeated episodes of intense bone resorption and subsequent reparation Osteolytic phase Mixed or osteoblastic phase Osteosclerotic or burned-out phase(mosaic-like appearance due to numerous cement lines) Greater risk of developing osteosarcoma

9. Fractures breaks in the continuity of bone Infraction = incomplete fracture Pathological fracture: bone altered by some previous lesion (osteoporosis, cysts, tumours), only minor trauma or spontaneously Fracture healing: haematoma between severed ends of bone + necrosis of bone marrow organization of haematoma with granulation tissue connection of bone ends by fibrous tissue (fibrous callus) woven bone and cartilage in fibrous tissue (provisional callus) gradual remodelling to mature lamellar bone (definite callus) Impaired fracture healing (infection, poor immobilization, metabolic bone diseases): exuberant callus with excessive cartilage formation, sometimes non-union of bone ends (pseudo-arthrosis)

10. Osteomyelitis infection-mediated inflammation of bone pus-forming organisms (staphylococci, streptococci...) infection may penetrate bone: directly (compound fractures, operations) via the bloodstream from distant primary focus (haematogeneous osteomyelitis) Morphology acute pyogenic inflammation of bone marrow – rise in interstitial pressure compromises the local blood supply – ischaemic necrosis of cancellous bone spread of inflammation to the subperiosteal space (subperiosteal abscess) – periosteal blood vessels shear off - ischaemic necrosis of cortical bone perforation of the periosteum – spread through soft tissues and skin forming a sinus track, portions of dead bone can be discharged onto the skin Complications sepsis, amyloidosis, pyogenic arthritis, squamous carcinoma of the skin (after many years)

11. Tuberculous osteomyelitis children, blood-borne infection long bones, vertebrae bone destruction associated with granulomatous lesion with caseation Tuberculosis of the spine (Pott’s disease): sharp anterior angulation of the spine (kyphosis), caseation may spread to the paravertebral soft tissues and track down along the psoas muscle to form an inguinal subcutaneous mass

12. Bone metastases much more common than the primary bone tumours usually multiple Osteolytic (bone destruction) Osteoblastic (reactive bone formation) Tumors commonly producing bone metastases: prostatic carcinoma, breast carcinoma, renal cell carcinoma, carcinoma of stomach, thyroid carcinoma

13. Primary bone tumours Less common, usually solitary Features of considerable diagnostic value: age of the patient, site of the lesion Classification (simplified): Bone-forming tumours Osteoma Osteoid osteoma Osteoblastoma Osteosarcoma Cartilage-forming tumours Osteochondroma Chondroma Chondrosarcoma Other tumours Giant cell tumor of bone Ewing’s sarcoma Tumour-like lesions Fibrous dysplasia Bone cysts

14. Osteoma benign lesion dense mature lamellar bone skull, facial bones, paranasal sinuses, orbit Macro usually small bony outgrowth Micro mature lamellar bone may be a component of Gardner’s colonic polyposis syndrome

15. Osteoid osteoma benign osteoblastic lesion young people (5-24 years), male predominance Clinical features: quite severe pain long bones (femur, tibia), ends of the shafts Morphology sharply outlined osteolytic defect (nidus) less than 1 cm in diameter, surrounded by rim of sclerotic bone nidus composed of haphazardly oriented trabeculae of woven bone and highly vacularized fibrous stroma trabeculae lined by plump osteoblasts and rare osteoklasts

16. Osteoblastoma rare, closely related to osteoid osteoma, but larger than 1cm (“giant osteoid osteoma“), and generally lacking the reactive rim of dense sclerotic bone age similar to that of osteoid osteoma spine, small bones of the hands and feet Microscopical appearance very similar to osteoid osteoma (trabeculae of woven bone lined by plump osteoblasts and osteoclasts, vascularized fibrous stroma) benign, but examples showing atypical osteoblast and a poorly demarcated edge tend to recur, although not metastasise (aggressive osteoblastoma)

17. Osteosarcoma most common primary malignant neoplasm of bone peak incidence between 10-25 years, in middle-aged and elderly people associated with Paget’s disease, predominance of males metaphyseal region of the long bones (lower end of femur, upper end of tibia, upper end of humerus) arises from within medullary cavity and invades the cortical bone, elevates the periosteum (Codman’s triangle) and penetrates into soft tissues Microscopic features: bone or osteoid formation by the tumour cells (irregular „lace-like“ osteoid trabeculae surrounded by atypical malignant osteoblasts), areas of malignant cartilage and sarcomatous spindle cell stroma highly malignant neoplasm with poor prognosis, metastases to lungs

18. Parosteal osteosarcoma variant of osteosarcoma in slightly older people juxtacortical position of metaphyseal region large lobulated mass tending to encircle the shaft very slow growth well-formed bone and osteoid set in spindle cell stroma with only scanty cytological signs of malignancy very good prognosis with adequate resection

19. Osteochondroma (exostosis) very common, hamartomas rather than true neoplasms young people, male predominance long bones (femur, tibia, humerus), metaphyses pedunculated or sessile lesions consisting of bone covered by a cap of cartilage ordered columnar arrangement of chondrocytes and zone of endochondral ossification Osteochondromatosis: multiple osteochondromas, some risk of malignant transformation (secondary chondrosarcoma)

20. Chondroma benign tumour consisting of mature hyaline cartilage children, adolescents and young adults, incidence equal in both sexes medullary cavity of the small bones of the hands and feet (enchondroma) radiolucent lesion expanding and thinning cortical bone lobules of mature hyaline cartilage, some irregularity and atypia of chondrocytes without any adverse prognostic significance Ollier’s disease (multiple chondromas)

21. Chondrosarcoma malignant cartilaginous tumour, primary (arising de novo) or secondary (malignant transformation of benign cartilaginous tumours) middle aged and elderly (primary chondrosarcoma), younger age group (secondary chondrosarcoma), M/F ratio 3:2 central skeleton (ribs, pelvis, proximal end of femur and humerus) aggressive growth (destruction of cortical bone, extension into the soft tissues) high cellularity, cytologic atypia of chondrocytes, binucleated cells, mitotic activity, necrosis

22. Giant cell tumor of bone third decade long bone epiphyses lytic and radiolucent lesion brown with grey and red areas (fibrosis and haemorrhage) mononuclear cells (the only neoplastic element) and multinuclear giant cells resembling osteoclasts (reactive) locally aggressive, may recur metastases to the lungs in about 4% of cases

23. Ewing’s sarcoma primitive neuroectodermal tumour (PNET) 5-20 years, male preponderance almost any bone, most often long bones and pelvis lytic destruction of the bone, widening of the medullary cavity, cortical infiltration and elevation of the periosteum – “onion-skin“ or “sun-ray“ periosteal reaction grayish white, focal necrosis and haemorrhage sheets of small uniform round cells, droplets of glycogen in the cytoplasm of the tumor cells (PAS positive material) very aggressive tumour with poor prognosis, metastatic spread to lungs and other bones

24. Fibrous dysplasia non-neoplastic condition children and adolescents ribs, femur, tibia, maxilla, mandibula, humerus monostotic and polyostotic form well-demarcated localized area of bone replaced by the fibrous tissue containing spicules of woven bone with peculiar sickle or fish-hook shape McCune-Albright syndrome: polyostotic FD + patchy skin pigmentation + precocious puberty

25. Bone cysts Solitary bone cyst unicameral cavity lined by smooth fibrous membrane Aneurysmal bone cyst multiple spaces filled with red blood cells separated by thin fibrous septa with numerous osteoclasts