Tumor Flashcards
What is the treatment for well-differentiated liposarcoma?
Marginal excision without radiation
What is the genetic basis of well-differentiated liposarcoma?
MDM2 amplification
t(12;16) is associated with what tumor?
Myxoid liposarcoma
Expression of PAX3-FKHR fusion gene occurs in which tumor?
rhabdomyosarcoma (alveolar)
Enchondromas are benign latent cartilaginous tumors composed of […] cartilage
hyaline
Enchondromas undergo malignant transformation in <1% to […]
chondrosarcoma
Maffucci’s syndrome is distinguished by soft-tissue […]
angiomas
Maffucci’s syndrome has increased risk of […] malignancies
visceral (astrocytoma, GI malignancy)
Overall risk of developing any malignancy with Maffucci’s syndrome is up to […] percent
100
What is the operative treatment for enchondromas?
intralesional curettage and bone grafting
What is the risk of malignant transformation to chondrosarcoma in Ollier’s disease?
25-30%
The most common location of secondary chondrosarcoma is the […]
pelvis
Secondary chondrosarcomas are most commonly a […]-grade tumor
low
In MHE, mutations affect the […] chondrocytes of the physis
prehypertrophic
What is the inheritance pattern of MHE?
autosomal dominant
In MHE, a mutation in the EXT gene decreases production of […] by chondrocytes found at the physis.
heparin sulfate
Which genetic mutation in MHE has a more severe form?
EXT-1
In osteochondromas, do sessile or pedunculated lesions have a higher risk of malignant transformation?
sessile
In adults with osteochondromas, a cartilage cap greater than […] is increased risk of chondrosarcoma
2 cm
What is the treatment for secondary chondrosarcoma?
wide surgical resection
Risk of malignant transformation is about […] percent with MHE develop secondary chondrosarcoma
5-10
Mesenchymal chondrosarcomas are characterized by […] fusion protein
HEY1-NCOA2
Mutations of […] are identified in primary and secondary conventional chondrosarcomas.
isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2)
Clear cell chondrosarcoma has a strong predilection for the […] of long bones
epiphysis
The most common locations of conventional chondrosarcoma include the […] (25% of all cases)
pelvis
What is the treatment for grade 2 or 3 chondrosarcoma?
Wide surgical resection
What is the treatment for chondrosarcoma of the pelvis, regardless of the grade?
Wide surgical resection
In chondrosarcomas, increased […] activity has been shown to directly correlate with the rate of recurrence
telomerase
Which serum labs, if elevated, can suggest a a more aggressive osteosarcoma?
LDH and ALP
What are the standard chemotherapy agents for osteosarcoma?
methotrexate, doxorubicin (adriamycin), cisplatin +/- ifosfamide
In osteosarcoma, greater than […] percent necrosis after neo-adjuvant chemotherapy is good prognostic sign
90
What is the MOA of methotrexate?
Inhibits DNA synthesis by inhibitingdihydrofolate reductase
What are the side effects of methotrexate?
mucositis, myelosuppression
What is the MOA of doxorubicin?
Blocks DNA/RNA synthesis by inhibiting topoisomerase II (pearl: fluoroquinolones inhibit prokaryotic form of topoisomerase II)
What are the side effects of doxorubicin?
cardiotoxicity
What is the MOA of cisplatin?
DNA disruption by covalent binding
What are the side effects of cisplatin?
renal failure, hearing loss, neurotoxicity
What is the MOA of ifosfamide?
DNA-alkylating agent
What are the side effects of ifosfamide?
hemorrhagic cystitis; renal failure
Osteosarcoma routinely expresses […], which is an INHIBITOR of the JNK radiation-induced apoptosis pathway and is thus a radioresistant tumor
NFkB
What are two known risk factors for infection following endoprosthesis reconstruction for osteosarcoma?
> 8 hours of surgery; >14 days of drain use
What is the most common reason for enodoprosthetic reconstruction failure for osteosarcoma?
aseptic loosening
What is the anatomic location of chondroblastomas?
epiphysis of long bones
Chondroblastomas almost exclusively arise in the […] of skeletally immature long bones
epiphysis
In chondroblastoma, chondroblasts produce areas of chondroid matrix, but […] cartilage is rarely produced
hyaline
Are chondroblastomas benign or malignant?
benign (but locally destructive)
What additional chest imaging should be obtained in chondroblastomas?
Chest XR; Chest CT only if CXR shows mets
“coffee bean” nuclei are classic finding in what bony tumor?
Chondroblastoma
Which bony tumors are positive for vimentin, neuron-specific enolase,S100+, and Sox9
Chondroblastomas
Chondroblastomas are positive for what four cellular markers?
Vimentin, neuron specific enolase, S100, and Sox9
Bony tumor that is: diaphyseal, rarely epiphyseal; nocturnal pain relieved by NSAIDs; nidus on CT
Osteoid osteoma
Bony tumor that is: multicystic bone lesion with fluid-fluid levels on MRI
Aneurysmal bone cyst
Is a giant cell tumor typically in skeletally mature or immature patients?
mature
Is chondroblastoma typically in skeletally mature or immature patients?
Immature
What is the standard of care for most chondroblastomas?
Intralesional curettage, bone grafting, local adjuvant (phenol, cryotherapy, HPO, etc)
In chondroblastoma, surveillance radiographs should be performed for […] years to monitor for local recurrence
5
What lab is a marker of prognosis/disease severity in Multiple Myeloma?
beta-2 microglobulin
Tumor with histology showing: round plasma cells with an eccentric nucleus, prominent nucleolus, and clock face organization of chromatin
Multiple myeloma
Greater than […] percent plasma cells on bone marrow biopsy is needed for diagnosis of multiple myeloma
10
What is the treatment for solitary plasmacytoma?
external beam irradiation (45-50 Gy)
What is the treatment for chondrosarcoma?
wide surgical resection
NOF most commonly occur in the […] of long bones
metaphysis
What congenital syndrome has multiple NOFs, cafe au lait pigmentation, and mental retardation?
Jaffe-Campanacci syndrome
Bony tumor with histology of: fibroblastic spindle cells in whirled or storiform pattern and positive for hemosiderin
NOF
What is the treatment for NOF?
Observation
What is the classification of unicameral bone cysts?
active or latent
In a latent unicameral bone cysts, […] separates cyst from physis
normal bone
An active unicameral bone cyst is […] to the physis
adjacent (~1cm)
A “fallen leaf” sign is pathognomic for what bony tumor?
Unicameral bone cyst
Aneurysm bone cysts typically have a transverse diameter […] than the epiphysis
wider
Unicameral bone cysts have a transverse diameter is […] than the epiphysis
smaller
What is the most commonly described translocation of an aneurysmal bone cyst?
TRE17-USP6
What is the treatment for an aneurysmal bone cyst without fracture?
Curettage, bone grafting, +/- local adjuvant (phenol, argon beam, liquid nitrogen)
What is the treatment for aneurysmal bone cyst with fracture?
non-operative, allow to heal, then treat with curettage + bone grafting
Fibrous dysplasia is a developmental abnormality caused by a […] protein mutation
Gs alpha
Patients with fibrous dysplasia and subsequent malignant transformation have […] overall survival rate compared with primary sarcomas
lower
Medical management with […] is indicated in symptomatic patients with Paget’s disease.
bisphosphonates
Increased […] is the primary cellular abnormality in Paget’s disease.
osteoclastic bone resorption
What is the primary cellular abnormality in Paget’s Disease
Increased osteoclastic bone resorption
What viruses are associated with Paget’s disease?
Paramyxovirus; RSV
In Paget’s disease, serum calcium levels are […]
normal
Paget’s osteoclasts are […] with […] nuclei than typical osteoclasts
larger; more
Which medication is contraindicated in Paget’s disease due to risk of secondary osteosarcoma?
Teriperatide
What is the most common complication of a TKA in a patient with Paget’s disease?
Malignment (pagetoid bone increases risk)
What is the most common complication of a THA in a patient with Paget’s disease?
Bleeding (treat preoperatively with meds)
Heterotopic ossification occurs between what two structures?
muscle and capsule
What start point has a higher risk of heterotopic ossification in antegrade femoral nailing?
piriformis
Which approach to the acetabulum has the highest rate of HO?
Extended iliofemoral
Which approach to the femoral head has the highest rate of HO?
Anterior
Do cemented or cementless components have a higher risk of HO in THA?
Cementless
Which approach in a THA has the lowest risk for HO?
Posterior
What dose of indomethacin is used to prevent HO?
75 mg/day x 10days-6 weeks
What genetic defect is seen in fibrous dysplasia?
G protein; affects the cAMP
In Achondroplasia, a mutation in the FGFR3 gene leads to abnormal […] production by chondroblasts
chondroid
Osteopetrosis is an inherited metabolic bone disease caused by defective […] resorption of immature bone
osteoclastic
Prior to excision of HO, which lab should be normalized?
ALP (CRP could also be a marker)
Giant Cell Tumors are benign, aggressive tumors typically found in the […] of long bones
epiphysis
What is the most common location of giant cell tumor?
Distal femur
In giant cell tumor, which locations have the higher risk of metastasis?
hand and wrist
In giant cell tumors, overexpression of […] by mononuclear stromal cells considered the instrumental pathogenicpathway
RANK-Ligand
What two medications can be used in the treatment of giant cell tumor?
denosumab; bisphosphonate
What is the treatment for giant cell tumor?
curettage, bone grafting, local adjuvant (phenol, cryo, argon beam, etc)
What is the MOA of denosumab?
monoclonal antibody against RANK-Ligand
Giant cell tumor can undergo malignant transformation to what tumor?
high grade sarcoma
What is the translocation of Ewing Saroma?
11:22
What is the fusion protein of Ewing sarcoma?
EWS-FLI1
Positive CD99 is seen in what tumor?
Ewing Sarcoma
What is the treatment for Ewing sarcoma?
neoadjuvant chemo + wide surgical resection + adjuvant chemo +/- radiation
Patients with Ewing sarcoma and lung mets should undergo what additional adjuvant therapy?
Radiation
What chemotherapy agents are used in Ewing sarcoma?
vincristine, doxorubicin, cyclophosphamide
What is the most important prognostic indicator in Ewing sarcoma?
mets
Are lung mets or bone mets a better prognostic indicator for Ewing sarcoma?
lung mets
Ewing sarcoma tumors greater than […] in size are a poor prognostic indicator
8 cm
Age greater than […] is a poor prognostic indicator in Ewing sarcoma.
14
A […] mutation in addition to t(11:22) translocation is a worse prognostic indicator
p53
What are the four most common bony sites for metastatic cancer?
spine >pelvis >proximal femur > humerus
acral (distal extremities) lesions are rare, but when present are most commonly from […] carcinoma
lung
What cell adhesion molecule (CAM) on tumor cells modulates release from primary tumor focus into bloodstream?
E cadherin
It metastatic cancer, tumor cells secrete […] which stimulates the release of RANKL from osteoblasts
PTHrP (parathyroid related protein)
Which two metastatic cancers cause osteoblastic lesions?
prostate and breast
Tumor secretion of […] leads to metastatic osteoblastic lesions
endothelin-1
What is the valveless venous plexus of the spine that provides a route of metastasis?
Batson’s vertebral plexus
A Mirel’s score greater than […] indicates prophylactic fixation
8
What is the best predictor for fracture healing due to a metastatic pathologic fracture?
life expectancy >6 months
Radiation therapy for metastatic pathologic fracture should begin […] weeks post surgery
2-3
Which bony mets should undergo preoperative embolization?
renal and thyroid cancer
What translocation is associated with clear cell sarcoma?
t12:22
What translocation is associated with synovial sarcoma?
t(X;18)
What translocation is associated with chondrosarcoma?
t(9;22)
What translocation is associated with myxoid liposarcoma?
t(12;16)
What is the most common site for mets in giant cell tumor of the bone?
lungs
What medication has been found to be most effective at reducing skeletal morbidity in giant cell tumor of the bone?
Denosumab (more effective the bisphosphonates)
What fusion protein is seen in synovial sarcoma?
SYT-SSX1
Which drug is a human monoclonal antibody which targets receptor activator of nuclear factor kappa-Β ligand (RANKL)?
Denosumab
Is renal cell carcinoma radiosensitive?
no
Is renal cell carcinoma chemosensitive?
no
Who’s soft tissue sarcomas metastasize to the lymph nodes?
Rhabdomyosarcoma, angiosarcoma, clear cell sarcoma, epithelia sarcoma, synovial sarcoma
A poor prognostic indicator for soft tissue sarcoma is a mass greater than […] cm
5
What additional CT imaging is needed for myxoid liposarcoma?
CT chest, abdomen, pelvis
What is the standard treatment for soft tissue sarcoma?
Wide surgical resection + radiation
What is the treatment for synovial sarcoma?
Wide surgical resection + radiotherapy + chemotherapy
What is the first line treatment for lung Mets in soft tissue sarcoma?
Surgical resection
In soft tissue sarcoma, resection of greater than […] cm of periosteum increases the risk of fracture and prophylactic fixation should be considered
10
What is the standard preop dose of radiation therapy for soft tissue sarcomas?
50 Gy
What is the standard post dose of radiation therapy for soft tissue sarcomas?
66 Gy
Pre-operative radiotherapy for soft tissue sarcoma is associated with a […] percent risk of wound complications.
20-30
Following resection of soft tissue sarcoma, the most common location for recurrence of low grade STS is […]
Locally
What is the most common mistake in treatment of soft tissue sarcomas?
Unplanned excision
What is the most common location for PVNS?
Anterior knee (patellofemoral compartment)
PVNS is caused by over expression of […] gene
CSF-1
What is the gold standard for diagnosis of PVNS?
Diagnostic arthroscopy
What is the MOA pexidartinib?
CSF-1 receptor antagonist
What medication can be used for PVNS?
Pexidartinib
Translocation t(X;18) is seen in what tumor?
Synovial sarcoma
What is the translocation mutation fusion protein seen in synovial sarcoma?
SS18;SSX
What is the most common sarcoma of the foot?
Synovial sarcoma
What chromosomal translocation is observed in synovial sarcoma?
t(X;18)
Which fusion protein observed in synovial sarcoma has a better survival prognosis?
SYT-SSX2
What type of biopsy should be performed for synovial sarcoma?
Core need or incision (not FNA)
What is the treatment for synovial sarcoma?
Wide resection + radiotherapy
What is the most important prognostic factor for synovial sarcoma?
SYT-SSX fusion protein type
Extra-abdominal desmoid tumors are 100% positive for what genetic receptor?
Estrogen receptor beta
What is the most common type of liposarcoma?
Myxoid liposarcoma
Is myxoid liposarcoma low, intermediate, or high grade?
Intermediate
What additional CT imaging is used for staging in myxoid liposarcoma?
CT CAP with contrast
Immature lipoblasts (signet ring type cells) are seen in what type of tumor?
Liposarcoma
What is the treatment for atypical lipomatous tumors?
Marginal resection without radiotherapy
Myxoid chondrosarcoma is associated with what translocation?
t(9;22)
Clear cell sarcoma is associated with which translocation?
12;22
Bone cells are derived from undifferentiated […] cells
Mesenchymal
Osteoclasts originate from […] cells
Myeloid hematopoietic cells
[…] are site of bone resorption where ruffled borer meets bone surface.
Howship’s lacunae
Which osseous cell secretes tartrate-resistant acid phosphatase?
Osteoclast
What is the major proteolytic enzyme that digests organic matrix at the ruffled border?
Cathepsin K
Which sequence of extracellular bone proteins directly allows binding to integrins?
Arg-Gly-Asp (RGD)
Does calcitonin activate or inhibit osteoclasts?
Inhibit
Which somite layer becomes the vertebral bodies and annulus fibrosus?
Sclerotome
Which embryonic structure forms the spinal cord?
Neural tube
Which embryonic structure forms the anterior vertebral bodies and nucleus pulposus?
Notochord
The nucleus pulposus is formed by what embryonic structure?
Notochord
The annulus fibrosus is formed by what embryonic structure?
Sclerotome
