PathologyBoneTumors2024F.pptx

Musculoskeletal Tumor I Tumors of bone Robbins and Cotran Pathologic Basis of Disease, 10th edition Pages 1187-1197, 1207-1208 https://www.uptodate.com/contents/benign-bone- tumors-in-children-and-adolescents http://drjunwangpathologynotes.blogspo...

Musculoskeletal Tumor I Tumors of bone Robbins and Cotran Pathologic Basis of Disease, 10th edition Pages 1187-1197, 1207-1208 https://www.uptodate.com/contents/benign-bone- tumors-in-children-and-adolescents http://drjunwangpathologynotes.blogspot.com/ 2018/07/neoplasms-of-bone.html 1  Objectives Compare and contrast pathogenesis, clinical presentation, radiologic findings, histologic features of benign bone and cartilage forming tumors and tumor like lesions Compare and contrast pathogenesis, clinical presentation, radiologic findings, histologic features, treatment and prognosis of osteosarcoma, chondrosarcoma, Ewing sarcoma, giant cell tumor of bone Describe common features of metastatic tumors to bone Describe commonly seen tumor and tumor-like lesions of joints 2  Structure Epiphysis: Between the growth plate or growth plate scar and the extended end of bone Metaphysis: Between the growth plate and diaphysis Diaphysis or shaft: Between metaphyses, composed mainly of compact cortical bone https://en.wikipedia.org/wiki/Metaphysis 3 http://bioserv.fiu.edu/~walterm/B/musculoskeletal/ skeleton_lecture.htm  Histology Low power (Left): network of regularly distributed, irregularly-shaped sheets and spikes of bone (trabeculae); the trabeculae are only a few cell layers thick High power (Right): Osteoblasts, Osteoclasts http://eugraph.com/histology/crtbone/spongbo.html 4 https://www.histologyguide.com/slideview/MH-046-bone-development/05-slide-3.html?  Bone tumors Most common type: Metastatic malignancies Most primary bone tumors are benign Pay attention to patient age, bone involved, area of bone involved and radiologic appearance before making pathologic diagnosis Radiologic studies important to define the tumor’s location and aggressiveness Clinical symptoms usually NOT helpful in making a diagnosis 5  Classification of bone tumors Hematopoietic: Myeloma, lymphoma Bone forming: Osteoid osteoma, osteoblastoma, osteosarcoma Cartilage forming: Osteochondroma, chondroma, chondroblastoma, chondromyxoid fibroma, chondrosarcoma Unknown origin: Giant cell tumor, aneurysmal bone cyst, Ewing sarcoma, adamantinoma Notochordal: Chordoma 6 Bone forming Osteoid osteoma Benign, bone-forming tumor, < 1.5 cm More common in male, 5-24 years old Most common sites: Long bones, especially femur and tibia Associated with pain, worse at night, relieved by NSAIDs, associated with prostaglandin E2 or nerves in reactive zone Radiolucent lesion with surrounding bony sclerosis and central sclerotic dot Treatment: Excision, https://radiopaedia.org/articles/osteoid-osteoma 7 Bone forming Osteoblastoma Also called giant osteoid osteoma Usually > 2 cm Slightly more common in female, mean age 20 years old Most common sites: Spine and sacrum Associated with progress pain, NOT respond to NSAIDs Spinal tumors may cause neurological findings and scoliosis Identical histological features with osteoid osteoma Treatments: Curettage, en bloc resection 8 Osteoblastoma Radiologic findings Cortical expansion of the spinous process and ossified matrix 9 https://emedicine.medscape.com/article/392248- overview  Osteoblastoma Pathologic findings Intracortical osteoblastoma: Well demarcated, gritty tumor Anastomosing trabeculae of osteoblastoma connecting to surrounding bone Rimmed by single layer of benign activated osteoblasts Numerous osteoclasts Normal bone with evenly arranged trabeculi http://eugraph.com/histology/crtbone/spongbo.html http://www.pathologyoutlines.com/topic/ 10 boneosteoblastoma.html Bone forming Osteosarcoma Malignant bone tumor that produces osteoid directly from tumor cells and unconnected with cartilage Most common primary bone tumor after myeloma Slightly more common in men, usually 10-25 years If > 40 years old, usually associated with Paget disease, post-radiation exposure, Thorotrast administration, chemotherapy in children, fibrous dysplasia, osteochondromatosis, chondromatosis, etc Most common presentation: Localized pain 11 Osteosarcoma Clinical features Sites: Most commonly metaphysis, especially around the knee Usually arises within medullary cavity and extends to cortex Multicentric: Usually children, densely sclerotic by Xray, extremely aggressive, associated with p53 mutations Post-radiation: 10-15 years after exposure; usually high grade, poor prognosis unless excised with wide margin Metastasis: Lung (most common), other bones, pleura, heart; rarely to lymph nodes, GI tract, liver, brain 12 Osteosarcoma Pathogenesis Etiology unclear, but most likely associated with rapid bone growth No specific translocations or other molecular abnormalities RB, p53, INK4a, MDM2 and CDK4 abnormalities Combined inactivation of RB and p53 common 13 Osteosarcoma Radiologic findings Large, destructive, lytic or blastic mass Permeative margins May break through cortex and elevate periosteum Sunburst pattern due to new bone formation in soft tissue Codman's triangle: Shadow between cortex and raised ends of periosteum (due to reactive bone formation), non-specific 14 Osteosarcoma Blastic type Distal femur: Codman's triangle 15 http://www.pathologyoutlines.com/topic/ Osteosarcoma Pathological findings Bulky, gritty, hemorrhagic tumor, commonly at metaphysis http://pathologyoutlines.com/wick/osteosarcoma%20femur%20gross 16 %20photo2.jpg Osteosarcoma Pathological findings Osteoid matrix producing tumor unconnected by cartilage (Left) High grade tumor cells with irregular bone formation (Right) Normal bone in small image http://eugraph.com/histology/crtbone/spongbo.html http://www.webpathology.com/case.asp?case=335 17 http://www.pathologyatlas.ro/osteosarcoma-osteogenic- Osteosarcoma Classification Site of origin (intramedullary, intracortical, or surface) Primary (underlying bone is unremarkable) or secondary to preexisting disorders (benign tumors, Paget disease, bone infarcts, previous radiation) Histologic features (osteoblastic, chondroblastic, fibroblastic, telangiectatic, small cell, and giant cell) 18 Osteosarcoma Treatment and prognosis Treatment: Surgery, preoperative chemotherapy for limb preserving, radiation therapy if unresectable Poor prognostic factors:  Paget disease  Telangiectatic histology  Elevated serum alkaline phosphatase  Minimal postchemotherapy tumor necrosis  Involvement of craniofacial bones (not jaw) or vertebrae  Multifocal tumor  Loss of heterozygosity of RB gene 19 Cartilage forming Osteochondroma Exostosis Most common benign bone tumor 50-75% males, usually age 20 years or less Solitary or multiple Sites: Metaphysis, not medullary cavity; commonly distal femur, proximal tibia; NOT in intramembranous bones Slow growing, painful if impinges on nerve or stalk is broken Usually stops growing and ossifies at puberty May transform into chondrosarcoma Treated by simple excision 20 Osteochondroma Multiple hereditary exostoses syndrome Osteochondromatosis Autosomal dominant hereditary disease Abnormalities of 8q24.1, 11p11-12, 19 Associated with germline loss-of-function mutations in either the EXT1 or the EXT2 gene (chain elongation of heparan sulfate) Diagnosed during childhood May be associated with bowing of underlying bones, retarded growth and wide metaphysis 0.5 to 5% of patients have evolution to chondrosarcoma 21 Osteochondroma Radiologic findings Pedunculated osteochondromas often point away from the nearest joint Cortex and medulla are continuous with underlying bone 22 http://www.webpathology.com/case.asp?case=328 Osteochondroma Pathologic findings Cartilaginous cap with disorganized growth plate and ossification towards base Relatively normal bone trabeculae and marrow Normal growth plate in small image http://www.mhhe.com/biosci/ap/histology_mh/ 23 endochbl.jpg  Chondromas Benign cartilaginous tumor Either enchondroma (arise from diaphyseal medullary cavity), subperiosteal/juxtacortical chondroma or soft tissue chondroma More common in long bones of hands and feet, followed by femur, proximal humerus Rare in flat bones (UNLIKE chondrosarcoma) Commonly with 12q13-15 (HMGA2 / HMGI-C) rearrangements 24  Enchondromas Benign, intramedullary neoplasms of hyaline cartilage Usually asymptomatic or pain due to pathologic fracture Age 20-49 years, no gender preference May be due to displaced growth plate IDH1 and IDH2 mutations may present Sites: Small bones of hands and feet (rare in thumb or ribs) Treatment: Usually do NOT need treatment Curettage and histopathologic evaluation: If the diagnosis uncertain, predominantly lytic, symptomatic and borderline in size, or in any 25 Enchondroma Radiologic findings Lytic expansile lesion 26 http://emedicine.medscape.com/article/389224-overview Enchondroma Pathologic findings Well circumscribed, pale- blue, solid, resembles cartilage Benign tumor of mature hyaline cartilage; calcification, endochondral ossification may present 27 http://www.webpathology.com/case.asp?case=329  Maffucci syndrome Very rare Non inherited condition due to somatic IDH1 mutations Multiple enchondromas, hemangiomas (subcutaneous), and soft tissue lymphangiomas Short stature, underdeveloped muscles and bone deformities Symptoms and signs usually detectable around age of 5 Higher risk for ovarian and liver carcinomas, brain gliomas 28  Ollier disease Nonhereditary disease of multiple enchondromas of long bones and flat bones Associated with IDH2 and PTHR1 mutations Associated skeletal deformities NO angiomas Most lesions regress when skeleton matures Higher risk for ovarian sex-cord tumors 29  Chondrosarcoma Malignant tumors that the tumoral matrix is entirely cartilage May arise from osteochondroma Third most common primary bone malignancy after myeloma and osteosarcoma Most common in axial skeleton, especially pelvis and ribs Overall slightly more common in male, > 40 years of age Deep dull achy pain, pain at night Classification: Conventional (central, peripheral, juxtacortical/periosteal) and variants (clear cell, dedifferentiation, mesenchymal, myxoid) Conventional type: Most common, usually >50 30 Chondrosarcoma Radiologic findings Destructive, expansile lesion with or without calcification http://emedicine.medscape.com/article/388869- 31 overview#a2 Chondrosarcoma Pathological findings Destructive tumor with bluish- Chondrosarcoma permeating white areas of cartilaginous and entrapping the bony differentiation (right half) were trabeculae admixed with firm, gray-white Normal bone in small image areas of high-grade tumor http://eugraph.com/histology/crtbone/spongbo.html http://www.webpathology.com/case.asp?case=332 32 Chondrosarcoma Pathological findings Normal chondrocytes with small Atypical chondrocytes with regular nuclei large irregular nuclei in a chondroid stroma http://medcell.med.yale.edu/histology/connective_tissue_lab/hyaline_cartilage.php http://www.pathologyoutlines.com/wick/chondrosarcoma%20hyaline%20type%20grade 33 %201%20micro.jpg Chondrosarcoma Classification Dedifferentiated chondrosarcoma: Coexistence of well differentiated (low grade) cartilaginous component and high grade anaplastic component, high grade, poor prognosis Clear cell chondrosarcoma: More common in young men, tumor cells with clear or ground- glass cytoplasm with vacuoles Mesenchymal chondrosarcoma: Usually teenagers, dimorphic pattern of well differentiated cartilage with abrupt boundary from undifferentiated stroma composed of small round/oval cells resembling lymphoma, hemangiopericytoma or Ewing’s sarcoma/PNET, unpredictable prognosis 34 wing sarcoma/primitive neuroectodermal tumor (PNE A member of Ewing sarcoma family tumors (EFT) Other EFT members include Askin tumor, peripheral primitive neuroectodermal turmor, etc #2 bone sarcoma in children, after osteosarcoma May occur in soft tissue Commonly harbor t(11,22)(q24;q12)/EWSR1-FLI1 and other abnormalities involving EWSR1 Sites: Medullary cavity of long bones or flat bones; may permeate cortex and invade soft tissue Treatments: Chemotherapy, surgery and/or radiation 5 year survival: 75%; 50% are cured; metastases to lung, skull, pleura, CNS; 10-25% have multiple lesions at presentation 35 Ewing's sarcoma Radiologic findings Mottled, osteolytic lesion (blue circle) with sunburst periosteal reaction (red circle) and lamellated periosteal reaction (white arrows) http://www.learningradiology.com/archives2007/COW%20279-Ewing%20Sarcoma/ 36 ewingscorrect.html Ewing's sarcoma Pathologic findings Sheets of small, uniform cells with scant cytoplasm, round nuclei, small punctate nucleoli, and CD99 expression Normal bone http://eugraph.com/histology/crtbone/spongbo.html http://www.webpathology.com/case.asp?case=340 in small image 37  Giant cell tumor of bone Also called osteoclastoma Benign but locally aggressive Numerous multinucleated giant cells in a background of uniform mononuclear cells More common: 20-40 years, women, oriental countries Associated with Paget disease of bone Most common presentations: Pain, swelling and limitation of joint movements Sites: Knee is common site (distal femur, proximal tibia), usually epiphysis Tumor cells express RANKL Treatment: Surgery, and radiation if excision impossible 38 Giant cell tumor of bone RANKL and bone destruction RANKL: Receptor activator of nuclear factor kappa-B ligand 39 IBMS BoneKEy (2009) 6, 116–126 Giant cell tumor of bone Radiologic findings Expanding lytic lesion with NO surrounding sclerosis or periosteal reaction 40 May have “soap bubble” appearance http://www.webpathology.com/case.asp?case=339 Giant cell tumor of bone Pathologic findings Expansile lytic lesion with total Numerous RANKL+ giant cells in a destruction of the cortical bone background of uniform mononuclear cells http://www.anatomybox.com/tag/bone-remodeling/ http://www.webpathology.com/case.asp?case=339 Normal bone in small image 41  Aneurysmal bone cyst Uncommon Osteolytic lesion, blood-filled spaces separated by connective tissue septa Usually ages 1-20 years, no gender preference May be secondary to trauma or other bone lesions Benign but grows rapidly Clinical presentation: Localized pain and swelling, pathologic fracture Sites: Metaphysis of long bones and posterior vertebrae USP6 overexpression upregulate transcription factor NFκB Treatment: Aggressive curettage or en bloc 42 resection  Aneurysmal bone cyst Expansile, lytic metaphyseal Large cystic spaces separated by lesions with an "eggshell" septa containing giant cells and sclerotic rim spindle cells Cysts may be filled with blood http://www.webpathology.com/case.asp?case=344 No endothelial lining cysts 43 Fibrous cortical defect/Nonossifying fibroma AKA metaphyseal fibrous defect Called nonossifying fibroma if loose, > 5 cm and associated with intramedullary component Affects teenagers, probably a developmental defect Benign; asymptomatic except for possibly pain Usually incidental finding Usually resolves in a few years, replaced by cortical bone Sites: usually metaphysis of distal femur, tibia; 50% are multiple; often < 1 cm Management: Usually do not need follow up unless pain developed, curettage/bone grafting if pain or larger than 50% of diameter of 44  Fibrous Cortical Defect/Nonossifying fibroma Sharply demarcated Loose storiform pattern spindle radiolucency with zone of cell proliferation with scattered sclerosis, NO periosteal reaction giant cells Normal bone in small image http://eugraph.com/histology/crtbone/spongbo.html 45 http://www.webpathology.com/case.asp?case=345  Fibrous Dysplasia Developmental lesion with bone-forming stroma Bone maturation arrest at the woven bone stage May be associated with activating point mutation (possibly a submit of GNAS1), resulting elevated intracellular cAMP Usually begins before puberty, grows slowly Can occur in any age Slightly more common in men Medulla of diaphysis or metaphysis of craniofacial bones, femur, ribs most common Curettage, bone grafting, and stabilization may be warranted for patients with symptoms (pain, deformity) or fracture Malignant transformation: Rare, probably dedifferentiation of low-grade osteosarcoma; may46  Fibrous Dysplasia Skull deformities caused by fibrous dysplasia http://maayafoundation.org/?page_id=317 47  Fibrous Dysplasia Cyst like radiolucent lesion Curvilinear trabeculae of with “ground glass” metaplastic woven bone appearance (never matures) in hypocellular, fibroblastic tp://eugraph.com/histology/crtbone/spongbo.html stroma tp://www.webpathology.com/image.asp?n=7&Case=346 48 tp://pocketdentistry.com/23-other-bone-diseases/  Metastatic tumors of bone Most common malignant bone tumor Adults, 80% from prostate, breast, kidney, lung or thyroid Children, from neuroblastoma, Wilm tumor, osteosarcoma, Ewing/PNET or rhabdomyosarcoma Common sites: Axial skeleton, proximal femur, proximal humerus; usually marrow Radiologic features: Blastic or lytic Blastic lesions: Prostate, carcinoid tumor, neuroendocrine tumors Lytic lesions: Kidney, lung, gastrointestinal tract and malignant melanoma 49  Tumors or tumor-like lesions of joints Ganglion cysts:  Small cyst-like mass (no epithelial lining)  Caused by mucoid degeneration of joint capsule, tendon or tendon sheath  May cause pain, weakness, partial disability of joint  Treated by surgery Tenosynovial giant cell tumor:  Diffuse (pigmented villonodular synovitis) or localized (giant cell tumor of tendon sheath)  Benign neoplasm characterized by proliferating histiocytes intermingled with multinuclear giant cells  Treated by surgery 50