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156 Cards in this Set

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Which anatomical structure is abnormal in achondroplasia?
growth plate
What is the mode of inheritance and the pathogenesis in achondroplasia?
autosomal dominant; Point mutation in gene that encodes FGFR3 leading to inhibition of cartilage formation
Describe the histological features of achondroplasia at the level of the growth plate?
disorganized and narrowed zone of proliferation in growth plate with clusters of chondrocytes instead of columns; premature ; bone formation seals the plate; intramembranous bone formation is normal
What is the life expectancy and intelligence in achondroplasia:?
Describe clinical and pathogenetic difference between achondroplasia and thanatophoric dwarfism?
Thanatophric dwarfism: mutation of FGFR3 that is different from achondroplasia; lethal with death from respiratory insufficiency; limb shortening and small chest
Why is the bone brittle in osteogenesis imperfecta?
Deficiencies in synthesis of type 1 collagen leads to cortical thinning, attenuated trabeculae, and hypercellular woven bone
What is the clinical difference between type 1 and 2 OI?
Type II is lethal in utero with multiple intrauterine fractures; Type I has a normal life span, increased number of fractures, blue sclerae, hearing loss, misshapen teeth; often acquired. Less normal collagen synthesized result in mild skeletal abnormalities. More severe or lethal forms result from abnormal polypeptide chains that cannot form the triple helix of collagen
Describe the pathological features of OI?
Cortical thinning, attenuated trabeculae, hypercellular woven bone – too little bone
Why is osteoporosis a major health care problem?
Complications of fracture of femoral neck, pelvis, spine with pulmonary embolism or pneumonia secondary to fractures
List the 3 main types of osteoporosis?
Age-related bone loss (senile osteoporosis), post-menopausal osteoporosis, disuse osteoporosis
What is the difference between low- and high-turnover variant of OP?
Low turnover variant: osteoblasts from older individuals have reduced reproductive and biosynthetic potential – senile OP; High turnover variant: activation of osteoclasts – post-menopausal OP
Describe the the gross and microscopic features of OP?
Gross: bones lack medullary canal, and the ends of long bones are bulbous and misshapen Histology: thinned trabeculae, microfractures, vertebral collapse (post-menopausal); Cortex thinned, Haversian system widened (senile)
How sensitive is a plain X-ray to detect OP?
Plain x-rays only detect greater than 30% bone loss
Are serum calcium and phosphate abnormal in OP?
Define Paget disease and name 3 stages?
Increased osteoclastic and osteoblastic activity with disordered and architecturally abnormal bone formation resulting in a gain in bone mass; Osteolytic → mixed osteoclastic-osteoblastic (predominant ostoblastic) → burn-out quiescent osteoclerotic stage
How common is Paget disease?
Very common (5 to 11% of adults are affected)
Describe the histological features of Paget’s in term of stages?
Increased osteoclastic activity with numberous absorption pit, then prominent osteoblasts lining bone surfaces. Adjacent marrow hypervascular. Woven bone formation followed by lamellar bone with mosaic pattern (“jigsaw puzzle”). Prominent cement line annealing haphazardly oriented units of lamellar bone
How many bones and which bones are typically involved in Paget’s?
Monostotic (15%), polyostotic (85%). Axial skeleton and proximal femur
Is there a laboratory abnormality in Paget’s?
Serum alkaline phosphatase increased
Describe the clinical features of Paget’s and long term risk(s)?
Pain (microfractures, compression of nerve roots). Deformities (bowing of femur). Increased blood flow may lead to high output cardiac failure (AV shunting) . Malignant transformation (high-grade bone sarcoma) in 5-10% of pts with severe polyostotic disease
Define “pathological” and “stress” fracture?
Pathological fracture: bone was already altered by disease process. Stress fracture: slowly developing incomplete fracture after increased physical activity
Describe the histological changes over time in fracture healing?
Soft callus (procallus): hematoma → influx of imflammatory cells → fibroblasts → new capillary vessels → activation of osteoprogenitor cells → osteoclastic and osteoblastic activity Bony callus:; Subperiosteal formation of woven bone. ; Trabecualae perpendicular to cortical axis. ; Chondroblasts may form cartilage with subsequent enchondral ossification. ; Then remodeling; bone may return to completely normal shape
List factors that predispose to avascular necrosis (list 6)?
mechanical vascular interruption (fracture).; corticosteroids.; thrombosis and embolism (sickle cell anemia).; vasculitis, radiation injury.; increased intraosseous pressure.; venous hypertension.
Describe the gross and microscopic features of bone infarct (medullary vs. subcortical)?
Medullary infarcts: cancellous bone and marrow (cortex not affected due to collateral blood flow). ; Subcortical infarct: wedge-shaped, overlying cartilage is viable. Dead bone: empty lacunae, necrotic adipocytes
Define creeping substitution?
fatty acids bind calcium with formation of insoluble calcium soaps; resorption of dead bone with new bone formation (“creeping substitution”)
Describe the clinical symptoms and possible complications of bone infarct (list 2 complcations)?
Subchondral infarct: chronic pain (collapse of dead bone leads to severe osteoarthritis). Medullary infarct: often silent Complications: osteoarthritis and malignant transformation to sarcoma
Which are the routes of infection in pyogenic osteomyelitis?
Hematogenous (most common). Extension from contiguous site. Direct implantation
Which organisms are typically found in acute osteomyelitis and which is the most common?
Staph. Aureus (most common); E. coli, Pseudomonas, Klebsiella, Group B strep (neonates), salmonella in sickle cell anemia
Describe the histological features of osteomyelitis?
Acute inflammation → bone necrosis → bacteria within shafts and along Haverisian system to reach periosteum (sub-periosteal abscesses)
Define the following terms:?
Sequestrum – dead piece of bone. Draining abscess – rupture of periosteum, thru soft tissue to the skin. Involucrum – sleeve of reactive bone around sequestrum. Brodie’s abscess – small intracortical abscess
Describe the radiographic appearance of osteomyelitis?
Lytic focus surrounded by sclerosis
List 4 complications of osteomyelitis?
Fracture, endocarditis, sepsis, squamous cell carcinoma (long-standing draining sinuses)
Which sites are typically involved in tuberculous osteomyelitis?
spine (“Pott disease”), knees, hips
Define Pott’s disease?
Tuberculous osteomyelitis involving the spine
Define osteoarthritis?
a degenerative joint disease that involves progressive erosion of articular cartilage
List conditions that predispose to osteoarthritis?
developmental deformity, diabetes, marked obesity, repeated trauma (athletes)
Describe the histological features of osteoarthritis and progression of changes?
Chondrocyte proliferation → formation of clones → fibrillatin and cracking of chondroid matrix → softening, then sloughing of cartilage → “eburnation” (subchondral bone appears like polished ivory) Sclerosis and remodeling of underlying bone; Small fractures lead to dislodgement of small pieces of bone and cartilage (loose bodies or joint mice); Subchondral cysts; Osteophytes (bony outgrowths) at margins of joints
Which joints are most frequently involved in osteoarthritis?
Hips, knees, lumbar and cervical spine, interphalangeal and 1st carpometacarpal and tarsometatarsal joints
Describe the histological features of rheumatoid arthritis?
Thick, hyperplastic synovium with villous fronds; Prominent lymphoplasmacytic infiltrate; “rice bodies” and pannus
Fibrocellular mass of synovium and stroma containing inflammatory cells and fibroblasts, causing erosion of cartilage leading to fibrous and bony ankylosis
How common are rheumatoid nodules in the setting of RA?
25% of patients
Describe the typical location and histological appearance of rheumatoid nodules?
Areas subject to pressure (less commonly in viscera – lungs, myocardium) Central fibrinoid necrosis, rim of epithelioid palisaded histocytes and mononuclear cells
Explain why gangrene of the fingers is a possible complication of RA?
Describe the histological features of acute and chronic gout?
Acute gout: dense neutrophilic infiltrate; urate crystals in neutrophils in synovium and fluid; Chronic gout: urate deposits encrust articular surfaces → hyperplastic synovium → pannus → bony erosions → ankylosis
Describe the crystals in gout and how they are distinguished from the crystals in pseudogout?
yellow and parallel, negatively birefringenent, needle-shaped in gout; Pseudogout: white friable deposits, weakly positively birefringent
Define tophus?
large aggregations of urate crystals surrounded by inflammatory cells and multinucleated foreign body giant cells
How does the histology of osteoid osteoma differ from the histology of osteoblastoma?
both histologically identical
Describe the typical age, size, location and symptoms in osteoid osteoma?
10-30 y/o (male), <2 cm, appendicular skeletal (cortex of femur and tibia), intense nigh pain relieved by aspirin
Why is aspirin effective in relieving pain in osteoid osteoma?
Inhibits prostaglandin synthesis
Describe the difference between osteoid osteoma and osteoblastoma (size of lesion, patient age, location, symptoms)?
Osteoblastoma: larger lesions; similar but wider age range; spine; dull pain unresponsive to aspirin
Describe the histological features of osteoid osteoma and osteoblastoma?
Randomly interconnecting trabeculae of woven (immature) bone; prominent osteoblastic rimming; increased vascularity (congested capillaries)
Actual tumor in osteoid osteoma, surrounded by prominent bone sclerosis
Is a nidus seen in osteoblastoma?
Define osteosarcoma?
a malignant mesenchymal tumor in which cancerous cells producing bone matrix (malignant bone formation); The formation of bone by the tumor cells is most characteristic of osteosarcoma
Describe frequency and typical age for conventional type osteosarcoma?
20% of primary non-hematopoietic bone malignancies; Bimodal: 75% younger than 20yrs, older patients secondary to pre-existing conditions (Paget disease, bone infarct/radiation)
Which conditions predispose to osteosarcoma?
Paget disease, bone infarct, bone radiation
Describe the typical location of conventional type osteosarcoma?
Metaphysic of long bones (around knee, hip, proximal humerus, craniofacial bones)
Describe the histological features of high grade osteosarcoma (is the growth plate involved, is cartilaginous differentiation seen…?
) ; Hemorrhagic, variably gritty; infiltrates the medullary canal (not growth plate); destroys overlying cortex and produce a soft tissue mass; Large hyperchromatic nuclei; bizarre tumor giant cells; mitoses; The noeplastic bone has a course, lacelike architecture; When malignant cartilage is abundant, the tumor is called chondroblastic osteosarcoma
List metastatic sites of osteosarcoma?
lungs, bones, brain
Describe the typical X-ray appearance of conventional osteosarcoma?
lytic/blastic, permeative margins, reactive periosteal bone formation, Codman triangle (raised periosteum/cortex)
Define Codman’s triangle?
triangular shadow b/w cortex and raised ends of periosteum
What is the treatment for conventional type osteosarcoma?
Chemotherapy and complete wide resection
Define osteochondroma and explain its histogenesis?
A benign cartilage-capped outgrowth that is attached to the underlying skeleton by a bony stalk
Describe the shape, site and direction of growth of osteochondroma?
Grows diagonal to long axis away from joint ; Arise from metaphysic near the growth plate of long tubular bones, esp. about the knee
Describe the histological features of osteochondroma (what relationship exists between the medullary canal of the underlying bone and the lesion?
).; Enchondral ossification of inner aspect of cartilage and bone similar to growth plate; Medullary cavity of underlying bone and osteochondroma are continuous.; Outer layer of head of osteochondroma: benign hyaline cartilage delineated peripherally by perichondrium; cartilage has the appearance of disorganized growth pate and undergoes endochondrial ossification with the underlying bone
Define enchondroma?
benign bumors of hyaline cartilage arising within medullary cavity (enchondroma) or on the surface (sub)periosteal
What is the typical patient’s age and site involved in enchondroma?
20-50 y/o; metaphysic of tubular bones (hands and feet)
Define Ollier’s disease and Mafucci’s disease?
Ollier disease: multiple enchondromatosis.; Mafucci disease: multiple enchondromatosis + soft tissue hemangiomas
Describe the typical gross, radiographic, and histologic features of enchondroma?
Gross: gray/blue translucent (like hyaline cartilage); Micro: well-circumscribed nodules with a hyaline matrix surrounded by metaplastic bone. Slow growth with endosteal scalloping but no cortical destruction
“O-ring sign:”?
Thin rim of radio-dense bone around lobules of cartilage present in x-rays of osteochondroma
How common is malignant transformation in enchondroma?
more common than solitary chondromas. Maffucci syndrome is at risk for developing other types of malignancies
What is the typical age and site of involvement in chondroblastoma (note that the lesion is usually in the epiphysis)?
In addition to chondroblastoma, name another 2 benign cartilage tumors and the respective typical patient’s age?
No answer
Describe the typical age, gender and site of involvement for chondrosarcoma?
> 40 y/o (male); Central skeleton (pelvis, shoulder, ribs) and proximal extremities
Describe the radiographic features of chondrosarcoma. Note that stippled calcifications (irregular opacities) can be seen in benign and low grade malignant cartilage tumors?
prominent endosteal scalloping, cortical destruction, soft tissue extensions
Describe gross and histological features of chondrosarcoma in relation to tumor grade?
Gross: large bulky tumors are nodules of gray-white translucent, glistening tissue. Grade 1: hyaline matrix, mild atypia; Grade 2: more myxoid matrix, increased cellularity, mitoses. Viscous and gelatinous and ooze from the cut surface; Grade 3: little matrix, increased pleomorphism
What is the prognosis for chondrosarcoma in relation to histological grade?
Grades 1 and 2 are usually indolent with a good prognosis; Grade 3 tend to disseminate; Think "C" is 3rd letter, so 3 grades.
What therapy is effective for chondrosarcoma?
Complete surgical exscision (chemo/radiotherapy not effective)
Define dedifferentiated chondrosarcoma and its frequency?
Transformation to high-grade sarcoma lacking chondroid differentiation – 10%
Define fibrous cortical defect, its frequency and most likely pathogenesis?
Very common (30-50%) of children.; Most likely developmental defect.; Eccentric metaphyseal lesion.
Describe the typical location and radiographic appearance of fibrous cortical defect?
Distal femur and proximal tibia; Eccentric lobulated raiolucency surrounded by a thin zone of sclerosis
What is the difference between fibrous cortical defect and non-ossifying fibroma?
Non-ossifying fibroma is a large fibrous cortical defect extending into the medullary canal
Describe the histological features of fibrous cortical defect/non-ossifying fibroma?
Spindled fibroblasts in a “storiform” (pin-wheel) pattern, admixture of osteoclast-like giant cells and foamy histiocytes
What is the clinical evolution of fibrous cortical defect?
Spontaneously resolve, unless complicated by fracture
Define fibrous dysplasia?
Tumor-like lesion characterized by localized developmental arrest of bone formation
Describe the typical patient’s age, site, X-ray appearance, clinical evolution of fibrous dysplasia?
Monostotic variant: Early adolescence; variable sites; asymptomatic. ; Polystotic variant: earlier age than monostotic; multiple bones with frequent craniofacial involvement; deformities common (“shepherd crook), fractures; rare malignant transformation
Describe the histological features of fibrous dysplasia?
Curvilinear trabeculae of woven bone surrounded by fibroblastic proliferation without osteoblastic rimming of trabeculae. ; Shapes of trabeculae resemble “Chinese leters” or “alphabet soup”.
How common is the monostotic vs. polyostotic variant of FD respectively?
Monostotic (70%), polyostotic (27%)
Define McCune Albright syndrome?
Polyostotic fibrous dysplasia with endocrine abnormalties (precocious puberty, etc)
Define Ewing’s sarcoma?
A primary malignant small round cell tumor of bone
What is the difference between Ewing’s sarcoma and PNET and does this distinction have clinical relevance?
The most undifferentiated tumors – Ewing’s; those with evidence of neural differentiation – PNET
What is the typical patient’s age and site involved in Ewing’s sarcoma?
10-15 y/o (young age at presentation of all bone sarcomas); Diaphysis of long bones and pelvis
Describe the radiographic features of Ewing’s sarcoma?
Destructive permeative lesion, often extensive soft tissue component, periosteal reaction (“onion skin”)
Describe the histological features of Ewing’s sarcoma (is this histological appearance specific for this tumor?
) ; Sheets of uniform small round cells with scant cytoplasm; few mitoses. Evidence of neural differentiation in minority – Homer Wright rosettes
How could you confirm the suspected pathology diagnosis of Ewing?
Translocation t(11:22)
What is the prognosis and treatment for Ewing’s sarcoma?
Highly lethal without adjuvant therapy. With chemo/surgery (and maybe radiation) survival >50%
Define giant cell tumor?
Contains a profusion of multinucleated osteoclast type giant cells
Describe the typical age and sites for GCT?
Young to middle aged adults, after growth plate closure; Epiphyseal or epiphyseal/metaphyseal; around knee, but many sites may be involved
What is the clinical behavior of GCT?
Location of tumors in ends of bones near joints causes complaints of arthritic symptoms; pathologic fractures
Describe the radiographic appearance of GCT (can you see soft tissue involvement?
Lytic, often eccentric; may erode thru articular cartilage and cortex or extend into soft tissue
Describe the histological features of GCT (what significance would you attribute to mitotic figures?
Mononuclear cell component: proliferating component of the tumor, plump oval cells with frequent mitoses; Osteoclast-like giant cell component: numerous large giant cells interspersed with mononuclear cells
Would the presence of lung metastases exclude a diagnosis of GCT?
NO. ; There is a 4% chance of lung metastases in GCT
What is more common: a primary or a metastatic bone tumor?
How does this ratio relate to patient’s age?
How do bone metastases reach the bone?
direct extension; lymphatic or vascular dissemination; intraspinal seeding
Which tumors metastasize to bone frequently?
Adults: prostate, breast, kidney, lung; Children: neuroblastoma, Wilms tumor, osteosarcoma, Ewing’s rhabdomyosarcoma
What are the most common sites for bone metastases?
Axial skeleton, proximal femur, humerus
Define blastic vs. lytic bone metastases and which type is more common?
Lytic: metastatic cells secrete substances such as prostaglandins, ILs, and PTH-related proteins that stimulate osteoclastic bone resorption (tumor cells themselves do not directly resorb the bone); Blastic: elicit a sclerotic response by stimulating osteoblastic bone formation; Most metastases: mixed lytic/blastic
Which tumors tend to form blastic metastases?
Prostate and breast
Describe the typical age, location and histology of lipoma?
Most common soft tissue tumor ; Mid-adulthood; Resembles mature fat, but more variation in cell size
Name 3 histological variants of lipoma?
Angiolipoma, spindle cell lipoma, pleomorphic lipoma
Define liposarcoma?
Arise in deep soft tissues of proximal extremities and retroperitoneum
How common is liposarcoma (relatively speaking)?
Most common adult sarcoma;
List the main histological subtypes of liposarcoma and their respective grade?
Well-differentiated; Myxoid: intermediate grade; Round cell, pleomorphic: high grade; Dedifferentiated: high grade sarcoma arising in a well differentiated liposarcoma What is the histological hallmark of lliposarcoma?
Define nodular fasciitis?
Reactive pseudo-sarcomatous proliferation
Why is nodular fasciitis referred to as a “pseudosarcomatous” proliferation (pay attention to both clinical and histological features)?
It is clinically alarming because of rapid growth and histological appearance (increased cellularity and mitoses)
Describe the typical age and site of involvement for nodular fasciitis?
Adults. Subcutaneous or intramuscular nodule on forearm, chest, or back
How common is a history of trauma in nodular fasciitis?
History of trauma <15%
Describe the histological features of nodular fasciitis?
Richly cellular, plump immature fibroblasts; spindle to stellate cells, prominent nucleoli, high mitotic activity, admixed inflammatory cells and extravasated red blood cells
Define myositis ossificans?
Ossifying benign fibrous lesion, intramuscular or subcutaneous, with metaplastic bone
How common is a history of trauma in myositis ossificans?
Describe the histological features and their evolution over time in myositis ossificans?
Initially fibrous proliferation → then bone formation in the periphery → zonation
Define zonation?
Center soft with fibroblasts; immediate zone of osteoblastic deposition of trabeculae of woven bone; peripheral zone of mature bone; eventually, the entire lesion ossifies
Define fibromatosis?
Nodular or poorly defined fascicles of mature-appearing fibroblasts surrounded by abundant dense collagen
List 3 types of superficial fibromatoses?
Palmar (Dupuytren’s contracture), plantar, penile (Peyronie’s disease)
Describe the histology of fibromatosis?
Nodular proliferation of mature appearing fibroblasts
Define desmoid fibromatosis?
(deep-seated fibromatosis) lie in interface between exuberant fibrous proliferations and low-grade librosarcomas
Why is desmoid fibromatosis often difficult to treat?
Locally invasive with high recurrence rate when incompletely removed
What is the risk of malignant transformation in desmoid fibromatosis?
Does not metastasize
List typical sites of involvement in desmoid fibromatosis?
Extra-abdominal (trunk and proximal extremities); Abdominal (anterior abdominal wall following pregnancy); Intra-abdominal (mesentery or pelvis
Define Gardner’s syndrome?
Familial adenomatous polyposis and desmoids
List one characteristic histological feature of fibrosarcoma?
Herringbone pattern of intersecting fascicles ; Think FI_S...FISH
Define fibrous histiocytoma vs. dermatofibroma?
The dermal variant of fibrous histiocytoma is called dermatofibroma
Describe the histological features of fibrous histiocytoma/dermatofibroma ;
Define malignant fibrous histiocytoma?
Aggressive adult sarcoma characterized by marked cytologic atypia (“very ugly tumor”)
How common is MFH in comparison to other soft tissue sarcomas?
Once considered the most common sarcoma of adults
What is the cell of origin of MFH?
Unknown, but clearly not histiocytic (maybe fibrous)
Is the histological appearance of MFH specific for this diagnosis?
No Describe gross and histological features of MFH?
What is the clinical behavior of MFH?
Most variants are aggressive with mestatses Define rhabdomyosarcoma?
What is the histological hallmark of RMS?
Rhabdomyoblast (eosinophilic cytoplasm, round or elongated shape (tadpole or strap cells)
List 4 histological types, their respective patient’s age and site of involvement?
Embryonal: <10 y/o; nasal cavity, orbit, prostate, parotid, testicular region; Sarcoma botryoides: <10 yr; polypoid grape-like protruding into hollow viscera (bladder, vagina, bile duct, nasopharynx); Alveolar: adolescents; deep muscles of extremities; Pleomorphic: adults
Define sarcoma botryoides (what does that name mean and which anatomical sites are typically involved?
); Grape-like appearance (botryoid); subtype of embryonal rhabdomyosarcoma
Describe the main histological features of the main histological types of RMS?
Embryonal: round and spindle cells with myxoid stroma; cambium layer seen in sarcoma botryoides (submucosal hypercellular zone of tumor cells). Alveolar: tumor cells more round and divided by delicate fibrous septa to tumor cells discohesive imparting a “pseudoalveolar” pattern (resemblance to lung alveoli). Pleomorphic: histology resembles malignant fibrous histiocytoma
What is the prognosis for the respective types of RMS?
Best fro embryonal (especially botryoid), poor for alveolar and pleomorphic
Define leiomyosarcoma?
Malignant tumor of smooth muscle
How common is soft tissue leiomyosarcoma?
10-20% of soft tissue sarcomas
What are the typical sites of involvement for leiomyosarcoma?
Skin or deep soft tissue of extremities and retroperitoneum
Describe the histological features of leiomyosarcoma?
Malignant spindle cells in interweaving fascicles with cigar-shaped nuclei; Histochemical and ultrastructural evidence of smooth muscle differentiation
What is the prognosis of leiomyosarcoma?
Depend on size, location, and histological grade
Describe the histological difference between leiomyoma and leiomyosarcoma?
Leiomyoma: spindle cells with blunt elongated nuclei; no pleomorphism or significant mitotic activity
Define synovial sarcoma?
Malignant tumor occurring near joints of extremities (mostly knees)
What is the cell of origin of synovial sarcoma?
Unknown, but not synovial cell origin
What is the typical patient’s age and site of involvement in synovial sarcoma?
Describe the histological types of synovial sarcoma and their relative frequency?
Monophasic spindle cell variant (most common). ; Biphasic variant (areas of epithelial differentiation with gland-like structures surrounded by spindle cells). ; Pure epithelial variant (least common)
List a single feature that sets synovial sarcoma apart from other sarcomas?
Has epithelial features by morphology and immunohistochemistry
How would you confirm the pathology diagnosis if in doubt?
Translocation t(X:18)
What is the prognosis and treatment for synovial sarcoma?
Aggressive sarcoma treated with surgery/chemo or radiation. ;