bone tumer clasification pethology .pptx

Bone Tumor Pathology - bone tumer clasification pethology .pptx

1. BONE TUMORS

2. Bone forming tumors, Benign – Osteoid osteoma , osteoblastoma , malignant--osteosarcoma

3. Cartilage forming Benign- osteochondroma , chondroma , chondroblastoma ,, chondromyxoid fibroma, malignant-- chondrosarcoma

4. Unknown origin benign—giant cell tumor Aneurysmal bone cyst, malignant—Ewing sarcoma Adamantinoma ,

5. Notochordal malignant--- chordoma Haematopoietic malignant—myeloma lymphoma

6. Bone forming tumors produce unmineralised osteoid and mineralized woven bone, Osteoid osteoma and osteoblastoma - have identical histologic features, - differ in size, sites of origin, symptoms, - less than 2 cm, metaphysis of long bones, typically arise in cortex, severe nocturnal pain that is relived by aspirin and NSAIDS, -PGE2 produced by the proliferating osteoblasts cause pain,

7. MORPHOLOGY Round to oval masses of hemorrhagic gritty tan tissue, interconnecting trabeculae of woven bone rimmed by single layer of osteoblasts, stroma consists of loose connective tissue with dialated &congested capillaries, osteoid osteomas elicit the formation of a tremendous amount reactive bone, which encircles the lesion, known as nidus , manifests radiologicaly small round lucency ,

8. OSTEOSARCOMA malignant tumor, produce osteoid matrix or mineralized bone, MC primary malignant tumor of bone, exclusive of myeloma & lymphoma, bimodal age distribution, 75% --younger than 20 years of age, second peak– older adults, predisposing – paget disease, bone infarcts and prior radiation,

9. Men more commonly affected than women, Metaphyseal region of long bones of extremities, 50% --distal femur & proximal tibia, Painful, progressively enlarging masses, sudden fracture of bone, Breaks through the cortex & lifts the periosteum , reactive periosteal bone formation,

10. CODMAN TRIANGLE,--Triangular shadow between the cortex & raised periosteum , indicative of aggressive tumor, PATHOGENESIS Genetic abnormalities, complex structural & numerical chromosomal aberrations, Germline mutations in RB --negative regulator of the cell cycle, TP53 mutations—promoting DNA repair & apoptosis of damaged cells ,

11. INK4a– encodes two tumor suppressors p16 & p14, MDM2 & CD4 inhibit p53 &RB function,

12. MORPHOLOGY Several subtypes, grouped according to, Site of origin—intramedullary, intracortical , Histologic grade—low, high Primary ( underlying bone is unremarkable ) & secondary to pagets , bone infarcts , previous radiation, Histological features– osteoblastic , chondroblastic , fibroblastic, telangiectatic , small cell, giant cell

13. MC subtype arise in metaphysis of long bones & is primary, intramedullary, osteoblastic , high grade, gross—bulky tumors, gritty, gray white, contain areas of heg &cyst --- destroy the surrounding cortices & produce soft tissue masses, ----Spread in medullary canal, replacing haematopoietic marrow, ----penetrate the epiphyseal plate or enter the joint,

14. Microscopy—vary in size & shape, hyperchromatic nuclei, bizarre tumor giant cell, mitoses, The formation of bone by the tumor cells is diagnostic, Bone has a fine lace like architecture ,deposited in broad sheets or as primitive trabeculae , May produce cartilage or fibrous tissue, Malignant cartilage is abundant– chondroblastic osteosarcoma,

15. --treated with multimodality approach, neoadjuvant chemotherapy,& surgery, 5 yrs survival rates reaching 60- 70%, spread hematogenously to lungs, Outcome for patients with metastases is poor , less than 20%- 5yrs survival rate,

16. CARTILAGE FORMING TUMORS Characterized by formation of hyaline or myxoid cartilage, benign cartilage tumors are much more common than malignant ones, OSTEOCHONDROMA Known as an exostosis , the most common benign bone tumor, 85% solitary, remainder, multiple hereditary exostosis syndrome,

17. Solitary type-late adolescence, early adulthood , Multiple -childhood , hereditary, autosomal dominant, Men affected more often, Attached to underlying skeleton by stalk, Arise from metaphysis, near the growth plate, around the knee Pelvis, scapula & ribs,---sessile Slow growing masses, painful Bowed, shortened bone--hereditary

18. Pathogenesis germline loss of function mutations in EXT1 &EXT2 gene, -encode enzymes that synthesize heparin sulfate glycosaminoglycans , -may prevent normal diffusion of the factor INDIAN HEDGEHOG,a local regulator of cartilage growth, Distruping normal chondrocyte differentiation

19. Morphology sessile or pedunculated , size from 1 to20cm, the cap composed of benign hyaline cartilage, covered by perichondrium, disorganized growth plate undergoes enchondral ossification, With the newly made bone forming the inner portion of head and stalk, cortex of the stalk merges with cortex of the host bone, medullary cavity of trs and bone from which it arises are in continuity,

20. Stop growing at the time of growth plate closure, cured by simple exision ,

21. CHONDROMAS benign tumors of hyaline cartilage, Arise within the medullary cavity,--- enchondromas , On the surface of bone— juxtacortical chondromas , 20-50yrs of age, Solitary metaphyseal lesions of tubular bones of hands and feet, X-ray shows circumscribed lucencies with central irregular calcification, a sclerotic rim & an intact cortex, Ollier disease & maffucci syndrome---multiple enchondromas , Spindle cell hemangiomas ,

22. Asymptomatic, detected incidentally, Painful & cause pathological fracture, Enchondromatosis – numerous, large, producing severe deformities,

23. Morphology smaller than 3cm, gray blue translucent, well circumscribed nodule of hyaline cartilage, containing benign chondrocytes, peripheral portion undergo enchondral ossification, Treatment depends on the clinical situation, Usually observation or curettage,

24. CHONDROSARCOMA malignant tumors that produce cartilage, histologically classified as conventional , clear cell, dedifferentiated & mesenchymal variants, conventional subdivided by central( intramedullary) & peripheral( juxtacortical ), conventional central constitute about 90%, 40yrs or older, men , pelvis, shoulder, ribs,

25. Slow growing, low grade trs reactive thickening of the cortex, More aggressive, high grade trs destroy the cortex forms soft tissue mass, Clear cell variant originates in epiphyses of long tubular bones, 15% of trs are secondary, arising from preexisting enchondroma or osteochandroma ,

26. Morphology large bulky trs made up of nodules of glistening grey white translucent cartilage with gelatinous or myxoid matrix, Myxoid matrix ooze from the cut surface, Spotty calcifications, central necrosis are present, Trs spreads through the cortex into surrounding muscle or fat, Histologically cartilage infiltrates the marrow space, & surrounds pre existing bony trabeculae , Trs vary in cellularity, cytologic atypia ,& mitotic activity,

27. Dedifferentiated chondrosarcoma ---high grade component does not produce cartilage, Clear cell chondrosarcoma —sheets of large malignant chondrocytes that have abundant clear cytoplasm, numerous osteoclast type giant cell & intralesional reactive bone formation, Mesenchymal cs --- islands of well differentiated hyaline cartilage surrounded by sheets of small round cells,

28. painful, progressively enlarging masses, Most conventional cs grade 1 tumors with 5yr survival rates of 80-90% Grade1 cs rarely metastasize , grade3 spread haematogenously to lungs,

29. TUMORS OF UNKNOWN ORIGIN EWING SARCOMA FAMILY TUMORS Malignant bone tumor characterized by primitive round cells without differentiation, ESFT &PNET have been unified into single category, Second most common tr in children, 80%--younger than 20yrs, boys, Diaphysis of long tubular bones, femur, Painful enlarging masses, affected site is tender, warm, &swollen, Systemic finding that mimic infection, including fever, ESR, anemia ,leukocytosis,

30. Xray shows lytic trs with permeative margins that extends into tissues, Characteristic periosteal reaction produces layers of reactive bone deposited in an onion-skin fashion, Pathogenesis Chromosomal translocations t(11;22)(q24; q12) in 90% of cases, EWS gene is present on long arm of chromosome22 band12----(22q12), FLT1 gene is present on long arm of chromosome 11 band24—11q24

31. The FLT gene &EWS gene now form a ,fusion gene, This produces a chimeric protein , acts as a transcription factor causing uncontrolled proliferation of marrow elements, MORPHOLOGY Soft, tan white mass contain areas of hge & necrosis, sheets of uniform small round cells, clear scant cytoplasm, rich in glycogen, Homer- wright rosettes indicates neuroectodermal differentiation, having little stroma ,

32. Aggressive malignancies treated with neoadjuvant chemotherapy, surgery with or without irradiation,

33. GIANT CELL TUMOR OSTEOCLASTOMA, histology is dominated by multinucleated osteoclast –type giant cells, uncommon benign but locally aggressive neoplasm, age groups 20-40 yrs , neoplastic cells express high levels of RANKL, which promotes the proliferation of osteoclast precursors & their differentiation into mature osteoclast,

34. Morphology Gross club shaped tumors generally well circumscribed, C/S—soft, red to brown cystic and hgeic areas Microscopic 2types of cells - plump to oval mononuclear stromal cells; - multinucleated giant cells— osteoclastic type, -stromal cells arranged in sheets, shows mitosis, -numerous large osteoclastic giant cells, have more than100 nuclei,

35. ANEURYSMAL BONE CYST (ABC) Multiloculated blood filled cystic spaces, primary and secondary ABC Affect all age groups but generally during first 2 decades of life, has no sex predilection, metaphysis of long bones, posterior elements of vertebral bodies, pain & swelling, compress nerves, produce neurologic symptom,

36. Secondary ABC present in the setting of primary neoplasms, GCT & CB X ray- eccentric, expansile lesion with well defined margins, -completely lytic & contain thin shell of reactive bone at the periphery, -CT &MRI shows internal septa & characteristic fluid- fluid levels, rearrangements of chromosome 17p13, leading to USP6 overexpression, regulate the activity of the transcription factor NFkB , That upregulate genes such as matrix metalloproteases lead to cystic resorption of bone,

37. Morphology consists of multiple blood filled cystic spaces separated by thin, tan white septa Septa composed of plump,uniform fibroblasts, multinucleated osteoclast like giant cells,& reactive woven bone, Bone lined by osteoblasts,follow the contours of the fibrous septa, One third of cases contain an unusual densely calcified matrix—BLUE BONE,

38. METASTATIC TUMORS the most common form of skeletal malignancy, Pathways of spread include, 1) direct extension, 2) lymphatic or haematogenous dissemination, 3)intra spinal seeding(via the B atson plexus of veins)

39. In adults- more than 70% of trs originate from CA of prostate, breast ,kidney & lung, In children metastases to bone originate from neuroblastoma , wilms tumor, osteosarcoma, E wing sarcoma ,& Rhabdomyosarcoma . typically multifocal, CA of Kidney ,thyroid present with solitary lesions Involves the axial skeleton(vertebral column, pelvis,ribs,skull,sternum ) Red marrow with its rich capillary network & slow blood flow,

40. Small bones of the hands and feet are uncommon, originate from CA of lung, kidney, or colon. Xray shows purely lytic (bone destroying), purely blastic (bone forming), or mixed lytic, blastic , Prostatic adeno CA, is blastic CA of the kidney, lung, GIT, & malignant melanoma are lytic lesions, Trs secrete subs such as PG, cytokines and PTHrP that upregulate RANKL on osteoblasts and stromal cells thereby stimulating osteoclast activity,

41. Tumor cell growth is supported by release of matrix- bound growth factors(TGF-B,IGF-1,FGF) as bone is resorbed, Sclerotic Trs produced by tumor cells secreting WNT proteins that stimulate osteoblastic bone formation, Bone metastases carries a poor prognosis since it indicates wide dissemination of the cancer, Treatment strategies aim at managing symptoms and limiting further spread,

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