Neoplasms of Bone and Cartilage Lecture Notes 2025 PDF

M2 Neoplasms of Bone and Cartilage Derm and Musculoskeletal Michael Ward, MD January 24, 2025 11:00-12:00  Tumor Nomenclature Three germ layers in embryo: – Ectoderm- skin, hair, glands, sensory organs, neural components – Endoderm- epithelia, liver...

M2 Neoplasms of Bone and Cartilage Derm and Musculoskeletal Michael Ward, MD January 24, 2025 11:00-12:00  Tumor Nomenclature Three germ layers in embryo: – Ectoderm- skin, hair, glands, sensory organs, neural components – Endoderm- epithelia, liver, urinary bladder – Mesoderm- gives rise to mesenchyme (embryonic connective tissue) differentiate into fibroblasts, chondroblasts, osteoblasts  Tumor Nomenclature Malignant tumors arising from epithelial origin are carcinomas Malignant tumors arising from mesenchymal origins are called sarcomas We will talk today about tumors of bone and cartilage, which arise from mesenchymal origin and are  Bone Tumors Benign more common than malignant Benign present younger than malignant 2,400 new malignancies of bone each year 1,300 death annually Specific tumors target certain bones and age groups which can aid in diagnosis – Primary (arising in otherwise normal bone) and – Secondary (arising in setting of chronic bone pathology e.g. Padget disease, chronic osteomyelitis, infarcts, metal prosthesis) Presentation is variable: asymptomatic to large, painful, deforming tumors  Bone Forming Tumors Common to all bone forming tumors is the production of bone by neoplastic cells, usually woven bone, which is variably mineralized. Lamellar bone: collagen arranged Woven bone: collagen in regularly arranged arranged sheets. In an irregular feltwork Seen in slower pattern. growth area, adult Seen in situations of rapid remodeling. bone growth including fetus, fracture repair, and  Tumors of bone Osteoma Osteoid osteoma Osteoblastoma Osteosarcoma  Osteoma Round to oval, sessile tumor arising from subperiosteal surface of facial or skull bones Usually solitary -usually middle age Gardner syndrome- – Multiple osteomas, – young age (10 – 15 yoa) associated with what? multiple GI adenomas  Osteoma Morphology: – Slow growing tumor of woven and lamellar bone in cortical pattern with haversion-like system. – Can grow outward or inward. – Little clinical significance except for obstruction of sinuses or compression of brain. Osteoma Radiopaedia.org Osteoid Osteoma and Osteoblastoma Two tumors with similar histologic features, – differ by size (by definition), – site, and – symptoms. Benign bone producing tumors. Osteoid Osteoma Osteoblastoma Size less than 2cm Greater than 2cm in Younger, 75% less than 25y Site size – Any bone but usually appendicular Site skeleton and posterior spinous processes – Spine more frequently – 50% femur and tibia Dull achy pain not – Usually cortical Nocturnal pain eased with aspirin responsive to aspirin d/t excess prostaglandins Less reactive bone secreted by osteoblasts associated with tumor Osteoid Osteoma and Osteoblastoma Morphology: – Round to oval mass of hemorrhagic tissue, well circumscribed. – Histo: Random interconnecting trabeculae of woven bone lined by osteoblasts surrounded by stroma with dilated and congested capillaries. O.O. tx with radioablation OB tx with curretage Remote malignant potential unless irradiated Osteoid Osteoma and Osteoblastoma Interconnecting trabeculae of woven bone that are rimmed by Commons.wikipedia.org Osteoblasts with stroma consisting of loose connective tissue and vascular congestion Osteoid osteoma White area surrounding Tumor nodule is reactive bone Osteoblastoma Larger, less or no reactive bone Usually spinal column  Osteosarcoma Malignant mesenchymal tumor in which cancerous cells produce a bone matrix. Most common primary malignancy of bone (20 %) – excluding myeloma and lymphoma (marrow origin). Any age, but with bimodal peaks. – 75% < 20yoa, – small peak in elderly with associated chronic conditions (Padget, osteomyelitis, etc.) M:F 1.6:1 Site – Classic is metaphyseal region of long bones of extremities. – Any bone possible, especially > 25 yoa where flat = long bones Osteosarcoma Figure 26-21 Robbins  Osteosarcoma Pathogenesis: – 70% of tumors show some sort of acquired genetic abnormality, none specific. – Frequently there is mutation of: RB (retinoblastoma gene) a cell cycle regulator P53 whose gene product regulates DNA repair. – Tumors occur in areas of bone growth where osteoblasts are more likely to acquire a mutation (ex. During teenage growth spurt).  Osteosarcoma Clinical: – Presents as a painful progressively enlarging mass, with or without pathologic fracture. – X-ray: Large lytic and blastic mass with extension beyond bony cortex “Codmans triangle” is radiographic appearance of raised periosteum above cortex at tumor – Aggressive tumor Explodes through bony cortex to adjacent tissues Hematogenous metastatic spread to lung, brain, bone – Survival Without known mets 5ys 60 – 70% With known mets 5ys 20%  Osteosarcoma Morphology: subtypes based on- – Site of origin – Degree of differentiation (histologic grade) – Primary v. secondary – Histologic features – Most common is long bone metaphysis, primary bone tumor, solitary, osteoblastic, intramedullary, poorly differentiated.  Osteosarcoma Morphology contd. Gross: – Big, bulky, gritty grey-white tumors with areas of hemorrhage and degeneration. – Disruption of bony cortex and extension into adjacent soft tissue. – Extend into medullary canal and maybe joint space. Micro: – Pleomorphic osteoblasts with large hyperchromatic nuclei, – bizarre cells and mitoses are present. – Formation of bone is in a lace like architecture or broad sheets. Other features include vascular invasion and necrosis.  Osteosarcoma Codman’s triangle Healthmark.umn.org Radiopaedia.org www.humanpath.org Osteosarcoma www.tumorsurgery.org  Osteosarcoma Osteosarcoma  Osteosarcoma Malignant osteoblasts Woven bone  Tumors of bone Osteoma Osteoid osteoma Osteoblastoma Osteosarcoma  Cartilage forming tumors Cartilage forming tumors are the most common primary bone tumor (benign and malignant). – Osteosarcoma is the most common malignant tumor. Benign > Malignant Characterized by formation of hyaline or myxoid cartilage.  Cartilagenous tumors Osteochondroma Chondroma (enchondroma) chondrosarcoma  Endochondral Bone enchondral bone formation occurs with a cartilage model -chondrocytes produce cartilage which is absorbed by osteoclasts -osteoblasts lay down bone on cartilaginous framework (bone replaces cartilage, cartilage is not converted to bone) -forms primary trabecular bone -bone deposition occurs on metaphyseal side  Osteochondroma Osteochondroma aka “exostosis” – benign cartilage capped tumor attached to underlying skeleton by bony stalk. – Most common benign tumor found in bone. – 85% solitary – Late adolescent or early adult - M>F – Develop from bones of endochondral origin and arise from metaphysis near growth plate, especially knee (occasionally pelvis, ribs, scapula)  Osteochondroma Multiple Hereditary Exostosis Syndrome – AD disorder, mutation EXT1 or EXT2 – These gene mutations result in defective endochondral ossification – Present in childhood with multiple osteochondroma – May give rise to chondrosarcoma  Osteochondroma Morphology: – Sessile to mushroom shaped lesions, 1 – 10 cm. – Tumor capped by benign hyaline cartilage covered by perichondrium. – Cartilage appears as a disorganized growth plate with enchondral ossification. – Cortex of tumor merges and blends with bony cortex as does the tumor medulla.  Osteochondroma Clinical: – slow growing mass that is often incidentally found on x-ray or palpation. – Hereditary exostosis may have deformity of involved bone. – Tend to stop growing at time of growth plate closure. – Malignant transformation rare in solitary tumors, increased in Multiple Hereditary Exostoses Syn.  Osteochondroma Mypacs.net Radiopaedia.org  Osteochondroma Webpathology.com Normal enchondral bone formation  Chondroma (enchondroma) Benign tumor of hyaline cartilage of enchondral bone. Preferred site is metaphyseal portion of tubular bones of hands and feet. Enchondromatosis is multiple enchondromas – Ollier disease = Enchondromatosis – Maffucci syndrome = enchondromatosis with hemangiomas  Chondroma (enchondroma) Morphology: – 40 years – M>F 2:1 – 15% of chondrosarcomas arise as transformation from multiple enchondroma syndromes (Ollier and Maffucci)  Chondrosarcoma Morphology: – Conventional- malignant hyaline and myxoid cartilage – Large bulky tumors with nodules of gray white translucent tissue – The more myxoid, the more gelatinous  Chondrosarcoma Tumor grade 1-3 (low to high) – Low grade (1): minimal hypercellularity, more bland, few mitoses. May have endochondral ossification. – High grade (3): marked hypercellularity, pleomorphism, bizarre tumor cells, frequent mitoses.  Chondrosarcoma Clinical: – Arise in central portion of skeleton (pelvis, shoulders, ribs). – Chondrosarcomas rarely involve distal extremeties. – Painful progressively enlarging mass. – X-ray with cartilaginous nodules demonstrating endosteal scalloping, with flocculent densities (focal calcification of matrix) – Slow growing low grade tumors stimulate reactive bone. – Fast growing high grade tumors have soft tissue invasion.  Chondrosarcoma Direct correlation between grade and biologic behavior. – Most conventional chondrosarcomas are indolent, low grade tumors. Grade 1 90% 5ys no mets Grade 2 81% 5ys Grade 3 43% 5ys 70% mets – Larger tumors more aggressive than small (>10cm) – Mets usually to lung and skeleton – Tx with wide surgical excision Chondrosarcoma webpathology Chondrosarcoma Grade 1 Grade 2 Grade 3  Cartilagenous tumors Osteochondroma Chondroma (enchondroma) chondrosarcoma  Fibrous and Fibro-osseous tumors These are tumors and tumor like lesions composed solely or predominantly by fibrous elements Diverse Very common – Fibrous cortical defect – Non-ossifying fibroma – Fibrous dysplasia of bone – Fibrosarcoma  Fibrous Cortical Defect Very common 30 – 50% of children >2 years Developmental defect, not neoplasm Vast majority arise at the metaphysis of distal femur/proximal tibia ½ are multiple or bilateral Usually less than 0.5cm  Fibrous Cortical Defect Morph: Elongated, sharply demarcated radio-lucency surrounded by sclerotic bone. Gross: gray to yellow brown tumor. Histo: – proliferation of fibroblasts in a “storiform” or pinwheel pattern – with scattered histiocytes as multinucleated giant cells and macrophage clusters.  Fibrous cortical defect/Non-ossifying fibroma A fibrous cortical defect greater than 5 – 6cm is called a Non-ossifying fibroma. Clinical – FCD: asymptomatic, usually incidental finding on x-ray with limited growth potential and will usually resolve. – NOF: progressive enlargement, may present with pathologic fracture. Biopsy and curettage to diagnose and treat. Distinguish from other tumor types. Fibrous Cortical Defect/Non-Ossifying Fibroma Webpathology.com  Fibrous Dysplasia Benign tumor – likened to developmental arrest – where components of normal bone are present but without differentiation into mature bone. Arise in utero during growth and development. 3 flavors: – Monostotic – Polyostotic – Polyostotic with café-au-lait spots and endocrine abnormalities  Fibrous Dysplasia Monostotic: Single bone – Most common type – Early adolescence usually stops enlarging with closure of growth plate. – Femur, tibia, jaw, ribs, calvarium, humerus – Usually asymptomatic, incidentally found. Pain, path fracture, alteration of limb length. – Can be disfiguring – Monostotic does not progress to polyostotic  Fibrous Dysplasia Polyostotic: multiple bones – Next most common – Slightly younger age, may progress into adulthood. – Can occur virtually any bone – Cranio-facial involvement common. 100% when disease is extensive. – May cause crippling deformities.  Fibrous Dysplasia Polyostotic with café-au-lait + endocrine: – Least common AKA McCune-Albright Syndrome. – Endocrine: sexual precocity, hyperthyroidism, pituitary adenoma (GH), primary adrenal hyperplasia. – Skin: usually hyperpigmented serpigenous lesions, “coast of Maine”, limited to same side of body (neck, chest, back and shoulders). – Bone same as polystotic.  Fibrous Dysplasia All types have same genetic mutation, – phenotype depends on stage of fetal development when mutation occurs. – Early is worse. Genetics: – somatic gain of function mutation of GNAS gene during embryogenesis.  Fibrous Dysplasia Clinical: Monostotic: minimal sx unless critical location (femoral neck). Tx is conservative surgery. polyostotic: often progressive disease. Rarely transform to sarcoma. X-ray with ground glass appearance with well defined margins.  Fibrous Dysplasia Morphology: – well circumscribed, intramedullary, and variably sized, larger lesions distort bone. – Gross: tan-white and gritty textured. – Histo: curvilinear trabeculae of woven bone surrounded by a moderately cellular fibroblastic proliferation. Trabecular shapes resemble Chinese characters.  Fibrous Dysplasia Ground glass lesion Mskcases.com monostotic polyostotic Radiopaedia.org Fibrous Dysplasia  Fibrosarcoma – Sarcoma with a fibroblastic phenotype. – Any age but usually older. – M=F – Usually arise de novo – May be associated with benign tumors of bone, bone infarcts, chronic bone lesions.  Fibrosarcoma Morphology: – Gross- large hemorrhagic tumors which destroy bone and extend into soft tissue. – Histo- Malignant fibroblast arranged in a herringbone pattern. Fibrosarcoma Orthopaedicsone.com  Fibrosarcoma Clinical: – enlarging painful mass that usually arises in the metaphysis of long bones and pelvis. – X-ray shows large lytic mass extending into soft tissue. – Prognosis depends on size, location, stage, and grade. – Large high grade tumors that are difficult to resect have poor prognosis.  Miscellaneous Tumors of Bone Ewing Sarcoma/Primitive Neuroectoderemal Tumor Giant Cell Tumor of Bone Aneurysmal Bone Cyst  Ewing Sarcoma/Primitive Neuroectodermal Tumor (EWS/PNET) EWS/PNET are two variants of the same tumor (referred in 9th ed. of Robbins as Ewing Sarcoma Family Tumor) – Identical chromosomal translocation – Neural differentiation = PNET – Undifferentiated = EWS – 6 – 10% of primary bone tumors – Second most common malignant tumor of bone in children (osteosarcoma #1) Ewing Sarcoma/Primitive Neuroectodermal Tumor (EWS/PNET) EWS/PNET – has youngest average age at presentation of malignant bone tumors 10 – 15 years. – B>G slightly. Whites >>>Blacks – 11;22 gene translocation involving the EWS gene  Ewing Sarcoma/Primitive Neuroectodermal Tumor (EWS/PNET) Morph: – EWS/PNET arise in medullary cavity, invade the cortex, periosteum, and soft tissue. – Gross: soft tan-white with focal areas of hemorrhage. – Histo: Sheets of small round blue cells, uniform in appearance, scant cytoplasm. Homer-Wright rosettes (cells arranged in circle about a central space) are indicative of neural differentiation.  Ewing Sarcoma/Primitive Neuroectodermal Tumor (EWS/PNET) Clinical: – diaphysis of long tubular bones (femur) and flat bones of pelvis. – Painful mass that is warm and tender. – Systemic signs (fever, increased sedimentation rate, anemia, leukocytosis) – X-ray- lytic lesion extending into soft tissue. Periosteal bone reaction with onion-skin appearance.  EWS/PNET Translocation of 11;22 with involvement of EWS gene. 11 + 22 = 33 Patrick Ewing Birjournal.org  EWS/PNET webpathology Sheets of round blue cells with minimal cytoplasm Pathologypics.com Homer Wright Rosette  Giant Cell Tumor of Bone – Benign, – uncommon, – locally aggressive tumor – named for the mixture of mononuclear cells and multinucleated osteoclast-type giant cells. – Adults 20 – 40s  Giant Cell Tumor of Bone Clinical: – Adult at epiphysis or metaphysis May involve joint space – Adolescent at metaphysis – Usually located at knee, solitary – Arthritic like symptoms at involved joint – X-ray with tumor eroding into subchondral bone plate, destroying overlying cortex with thin shell of reactive bone.  Giant Cell Tumor of Bone Morph: – large red brown tumor with cystic degeneration. – Histo: Uniform oval mononuclear cells (proliferating component) with scattered multi-nucleate osteoclast-type giant cells (reactive component). Necrosis, hemorrhage, and reactive bone commonly found.  Giant Cell Tumor of Bone Clinical: – Biologically unpredictable. – Conservative treatment with curettage has up to 60% recurrence rate – and 4% mets to lung (tumor pushed into vascular spaces during procedure) Giant Cell Tumor of BoneOval uniform mononuclear cells (proliferatin Multi-nucleate giant cells (reactive) epiphyseal webpathology  Aneurysmal Bone Cyst – Benign tumor of bone with multiloculated blood filled cystic spaces. – May present as a rapidly growing tumor. – Behaves in benign fashion. – 17p13 translocation with up-regulation of USP6 (deubiquitinating enzyme).  Aneurysmal Bone Cyst Morph: Gross with multiple blood filled cystic spaces separated by thin gray septae. Histo: – septal walls have plump uniform fibroblasts with mitoses, – multinucleated osteoclast giant cells, – and woven bone lined by osteoblasts. Aneurysmal Bone Cyst  Metastatic Disease Most common skeletal malignancy Occur late in tumor progression Spread – Direct extension, hematogenous/lymphatic, intraspinal seeding Any tumor but – adults (prostate, breast, kidney, lung) – and kids (neuroblastoma, Wilms tumor) Usually axial skeleton Lytic, blastic, or mixed on x-ray