Tumors of Bone PDF

W13 Tumors of Bone Dr. Alfred Roy, MD Associate Professor Learning Objectives 1. Classify primary bone tumors according to their origin. 2. Discuss benign bone forming tumors in terms of etiology, pathology & manifestation. 3. Discuss primary osteosarcoma according to its etiology, pathogenesi...

W13 Tumors of Bone Dr. Alfred Roy, MD Associate Professor Learning Objectives 1. Classify primary bone tumors according to their origin. 2. Discuss benign bone forming tumors in terms of etiology, pathology & manifestation. 3. Discuss primary osteosarcoma according to its etiology, pathogenesis, manifestations, radiographic & histologic findings. 4. Compare & contrast etiology, pathogenesis and features of primary & secondary osteosarcoma. 5. Discuss etiopathogenesis, gross & microscopic features and presentation of common benign cartilage forming tumors(osteochondroma & chondroma). Learning Objectives 1. Discuss etiopathogenesis, gross & microscopic features and presentation of chondrosarcoma. 2. Discuss Ewing sarcoma in terms of origin, etiology, pathology, manifestations & diagnosis. 3. Recognize pathogenesis, presentation, gross, microscopic & radiographic features of giant cell tumor of bone. 4. Identify lesions simulating primary bone neoplasm in terms of their etiopathogenesis, morphology & presentation. 5. List the primary sites of tumors that frequently metastasize to the bone & discuss their salient features. Classification Histologic Type Benign Malignant Hematopoietic Myeloma, Lymphoma Chondrogenic Osteochondroma Chondrosarcoma Chondroma Dedifferentiated chondrosarcoma Chondroblastoma Chondromyxoid Fibroma Osteogenic Osteoid Osteoma Osteosarcoma Osteoblastoma Fibrogenic Fibrous Cortical Defect (Fibroma) Fibrosarcoma Non-ossifying fibroma Fibrohistocytoma Unknown Giant cell tumor Aneurysmal bone cyst Neuroectodermal Ewing Sarcoma Notochordal Chordoma Bone Tumors Bone Forming Tumors Osteoma Introduction: - these are bosselated, round to oval sessile tumors - project from sub-periosteal surface of cortex - most seen arising from on or inside skull and facial bones Incidence: - middle-age, solitary lesions, and seen with Gardner syndrome Clinical Course: - slow growing, composite of woven and lamellar bone Osteoma: - skull Bone Forming Tumors Osteoid Osteoma and Osteoblastoma Introduction: - benign bone tumors with identical histologic features Pathogenesis: Osteoid osteoma. These are less than 2 cm in diameter, and occurs in teens, and early 20’s. More in men. - arise from appendicular skeleton, most arise from femur, and tibia - arise from cortex - severe nocturnal pain, relieved by aspirin (PGE2 released by proliferating osteoblasts) - on histology shows a ‘nidus’ surrounded by reactive bone Osteoblastoma. These are larger than 2 cm, involves spine, dull pain not relieved by aspirin Osteoid osteoma  Bone Forming Tumors Osteosarcoma Introduction: - malignant mesenchymal (sarcoma) tumor, malignant cells produce bone matrix Incidence: - bimodal age distribution. Most seen under 20 years of age. In older age group, osteosarcoma may arise from Paget disease, or prior radiation - more in males Pathogenesis: - genetic abnormalities may be noted: Rb gene (association with familial retinoblastoma), and p53 (association with Li Fraumeni syndrome) - CDKN2A inactivation - MDM2 overexpression Bone Forming Tumors Osteosarcoma Morphology: Gross: big, bulky tumor that are gritty - metaphysis, most arise around the knee (lower end of femur) - show areas of hemorrhage, necrosis, and cystic change - destroy surrounding cortex - extend through medullary cavity - usually do not penetrate epiphysis, or involve joint cavity Microscopy: - pleomorphism, abnormal mitosis, tumor giant cells may be seen - formation of bone by malignant cells is characteristic Osteosarcoma  Bone Forming Tumors Osteosarcoma Clinical course: - painful, progressively enlarging mass - radio imaging: x-ray show ‘Codman triangle’ (triangle formed by lifting of peritoneum). This finding is not specific for osteosarcoma - x-ray: ‘sunburst’ appearance - lab: increased Alkaline phosphatase, and LDH - aggressive malignancy, with high incidence of metastases (lung, brain) Cartilage forming tumors Osteochondroma Introduction: - also referred to as exostosis - benign cartilage capped tumor that is attached to underlying skeleton by a stalk Incidence: - most common benign tumor - solitary lesion (85%): late adolescence and early adulthood, more in men - multiple: ’multiple hereditary exostosis syndrome’ (mutation in EXT1 or EXT2 gene) Pathogenesis: - osteochondroma develops only in bones of enchondral origin - arise from metaphysis close to the growth plate of long bones (knee)  Cartilage forming tumors Osteochondroma Morphology: - sessile, mushroom-shaped, 1 to 20 cm - cap is composed of benign hyaline cartilage, peripherally covered by perichondrium - cortex of the stalk merges with the cortex of the host bone - this makes the medullary cavity of the osteochondroma communicate with the host bone Clinical course: - slow growing, may produce pain - incidental finding - rarely transform to chondrosarcoma Osteochondroma Cartilage forming tumors Chondromas Introduction: - benign tumors of hyaline cartilage that usually occur in enchondral bones - if these arise within medullary cavity: enchondromas - if these arise from surface: periosteal or juxtacortical chondromas Incidence: - 20 to 40 years, metaphysis, solitary lesions arising in short tubular bones (hands and feet) - multiple enchondromas: Ollier disease - multiple enchondromas with hemangiomas: Maffucci syndrome  Cartilage forming tumors Morphology: - usually smaller than 3 cm, gray-blue and transparent - histologically show benign hyaline cartilage - enchondromas associated with Ollier and Maffucci appear more cellular Clinical course: - small risk of chondrosarcoma Cartilage forming tumors Chondrosarcoma Introduction: - malignant tumor of mesenchyme (sarcoma) producing cartilage - sub-classified: by site- intramedullary, juxtacortical. By histology- conventional when containing cartilage or myxoid, - others: clear cell, and dedifferentiated Incidence: - not common, patients are older than 40 years, and affects male more - may arise from pre-existing enchondroma  Cartilage forming tumors Chondrosarcoma Morphology: - arise from central portions of skeleton- pelvis, shoulder, ribs - most originate from diaphysis - grossly they are bulky, ‘glassy’ and translucent - on histology show cartilage cells with features of malignancy Clinical course: - low-grade tumors tend to be slow growing - prognosis is generally good - when metastases appear, it most commonly involve lungs Chondrosarcoma rib Chondrosarcoma  Fibrous and fibro-osseous tumors Fibrous Dysplasia Introduction: - benign tumor, considered to be a localized developmental arrest - all the components of normal bone are seen, but they do not differentiate into mature structures (therefore you see fibro-osseous tissue) Incidence: - non-inherited developmental disorder - Localized: Monostotic Fibrous Dysplasia (70%) - Multiple bones: Polyostotic Fibrous Dysplasia without endocrine dysfunction (27%) Polyostotic Fibrous Dysplasia with endocrine dysfunction (McCune- Albright syndrome) Fibrous Dysplasia Pathogenesis: - lesions arise during skeletal growth and development - lesions arise during skeletal development, and appear in three distinctive phases: 1) Monostotic: single bone 2) Polyostotic: multiple bones 3) Mazabraud Syndrome: Fibrous Dysplasia (polyostotic) with soft tissue myxomas 4) McCune-Albright syndrome: polyostotic disease Fibrous Dysplasia Pathogenesis (cont’d): - all these result from a gain of function mutation of GNAS1 gene - inhibition of mesenchymal differentiation to osteoblasts - lesions composed of mesenchymal cells - weak imperfect bone with fibrous tissue Fibrous Dysplasia - solitary tumor, centered in the medullary cavity  Fibrous and fibro-osseous tumors Fibrous Dysplasia Morphology: - well circumscribed, intramedullary lesions - appear tan-white and gritty - on microscopy, ‘curvilinear’ trabeculae of woven bone surrounded by fibroblastic proliferation - the shapes of the curvilinear bone resemble- Chinese letters Fibrous and fibro-osseous tumors Fibrous Dysplasia Clinical course: Monostotic Fibrous Dysplasia - affects both boys and girls - early adolescence - lesions stop enlarging when the growth plate closes - femur, tibia, ribs, jaw bones, calvaria - asymptomatic Polyostotic Fibrous Dysplasia without endocrine dysfunction - earlier age, causes problem - femur, skull, tibia - tend to involve shoulder, and pelvis - shepherd-crook deformity, and risk of fractures Fibrous and fibro-osseous tumors Fibrous Dysplasia Clinical course: Polyostotic Fibrous Dysplasia with endocrine dysfunction - café-au-lait skin pigmentation, and endocrinopathies McCune-Albright syndrome - sexual precocity, hyperthyroidism, pituitary adenomas that secrete growth hormones, and primary adrenal hyperplasia - café-au-lait tend to be on the side of the bone lesions (if the bone lesions are unilateral) - café-au-lait pigmentation tend to be large forming: “coastline of Maine” Fibrous Dysplasia Unknown Giant Cell Tumor (GCT) Introduction: - benign tumor contains mononuclear cells along with multi-nucleated cells - locally aggressive, even though benign - called erroneously as ‘osteoclastoma’ Incidence: - mostly adults (20 to 40 yrs), more in females Pathogenesis: - the mononuclear cells are the neoplastic component - these cells express RANKL - and the multi-nucleate (osteoclast-like) giant cells are likely to complete the - RANK-RANKL pathway - tumor involves epiphysis and metaphysis in adults (adolescent: metaphysis) Unknown Giant Cell Tumor (GCT) Morphology: - large, red-brown tumors, cystic degeneration - on histology: uniform, oval mononuclear cells form the proliferating component - within this tumor cell population, scattered multi-nucleated giant cells - these osteoclast-like giant cells have more than 100 nuclei - secondary changes within tumor: necrosis, hemorrhage, reactive bone formation, hemosiderin Clinical course: - most tumors arise around the knee (distal femur, proximal tibia), but any bone can be involved - GCT erodes subchondral bone plate, and destroy the overlying cortex - this produces a bulging soft tissue mass delineated by a thin shell of reactive bone  Unknown Giant Cell Tumor (GCT) Clinical course (cont’d): - GCT is difficult to predict - though benign, it shows local aggressiveness - conservative management include tumor curettage - however, recurrence rate is between 40% to 60% - some of the GCT may produce metastases to lungs (4%) Giant cell tumor (GCT) Unknown Aneurysmal Bone Cyst (ABC) Introduction: - tumor characterized by multiloculated blood-filled cystic spaces Incidence: - mostly during the first 2 decades of life - no sex predilection - sometimes occurs as secondary reaction to other bone tumors Unknown: Aneurysmal Bone Cyst Pathogenesis: - tumor arises from spindle cells which shows chromosomal rearrangement (chromosome 17) - this results in fusion genes which promote NFkB - NFkB activity may upregulate matrix metalloproteases (MMP’s) that lead to cystic resorption of bone Morphology: - multiple blood-filled cystic spaces separated by thin septa - septa are composed of plump uniform fibroblasts, multinucleated osteoclast-like giant cells, and reactive woven bone Aneurysmal bone Cyst Unknown: Aneurysmal Bone Cyst Clinical Features: - treatment of aneurysmal bone cyst is surgical, - usually curettage or, in certain situations, en-bloc resection - recurrence rate is low, and spontaneous regression may occur following incomplete removal Neuroectodermal Ewing Sarcoma (Primitive Neuroectodermal Tumor: PNET) Introduction: - Ewing sarcoma family of tumors are a part of PNET - these are malignant small round-cell tumors of bone and soft tissue - tumors which exhibit neuronal differentiation are considered as PNET - those tumors which appear undifferentiated are considered as Ewing sarcoma - therefore, these tumors put together form a spectrum Incidence: - age group: 10- to 15-year-old - boys more than girls - mostly Caucasians Neuroectodermal: Ewing Sarcoma Pathogenesis: - most tumors show translocation involving the EWSR1 gene located in chromosome 22 - and EWSR1/FLI1 fusion gene in the remaining - malignant tumor arises from diaphysis Morphology: - arise from medullary cavity, invade the cortex, periosteum and then into soft tissue - on histology: small round-cells which are larger than lymphocytes, little cytoplasm which contains glycogen  Neuroectodermal: Ewing Sarcoma Morphology (cont’d): - Homer-Wright rosettes: tumor cells arranged in a circle about a central fibrillary circle - necrosis within tumor is prominent Ewing sarcoma Metastatic Bone Disease Introduction: - most common form of skeletal malignancy Pathogenesis: - seen in the later part of malignancy - reach bone through: direct extension, lymphatic, most importantly through hematogenous route. Another type of bone involvement is intra-spinal through Batson plexus Clinical correlation: - most common malignancies: prostate, breast, kidney, and lung. In children: neuroblastoma, Wilms tumor, rhabdomyosarcoma Osteoblastic: Prostate carcinoma (tumor cells secrete WNT proteins which stimulate osteoblasts) Osteolytic: Renal cell carcinoma, lung (tumor cells secrete cytokines) Metastatic Bone Disease Thank you