Tumor/Pathology Flashcards
Multiple hereditary exostosis has increased risk of which malignancy?
Secondary Chondrosarcoma in area of prior exostosis
Mafucci’s syndrome is associated with what?
Hemangiomas
Ollier’s disease pts have what
Multiple enchondromas
Gardner’s syndrome is associated with what?
Extra-abdominal desmoid tumors
Von Recklinghausen’s disease is associated with what?
Plexiform neurofibromas
Tumors that metastasize to lymph nodes
ESARC
- epithelioid sarcoma
- synovial sarcoma
- angiosarcoma
- rhabdomyosarcoma
- clear cell sarcoma
Multiple myeloma histology
- sheets of plasma cells w/ eccentric nuclei (small round blue cells)
- coarsely clumped nuclear chromatin
- perinuclear halo
Carcinoma metastasis histology
-nests of epithelial cells in fibrous background
Fibrous dysplasia histology
-irregular bony trabecula without rimming osteoblasts
Chondrosarcoma
- On radiograph, chondrosarcoma is a fusiform, lucent defect with scalloping of the inner cortex (endosteal scalloping) and periosteal reaction. Extension into the soft tissue may be present, as well as punctate or stippled calcification of the cartilage matrix.
- Histologically, chondrosarcoma is differentiated from benign cartilage tumors by enlarged plump nuclei, multiple cells per lacunae, binucleated cells, and hyperchromic nuclear pleomorphism.
- Treatment of most chondrosarcomas is surgery only because adjuvant treatments are not effective.
Fibrous dysplasia
Fibrous dysplasia is a common benign skeletal lesion that may involve 1 bone (monostotic) or multiple bones (polyostotic) and occurs throughout the skeleton with a predilection for the long bones. The radiographic features of fibrous dysplasia typically illustrate a grayish “ground-glass” pattern that is similar to the density of cancellous bone. The key histologic features of fibrous dysplasia are trabeculae of immature bone, with no osteoblastic rimming, contained within a bland fibrous stroma of dysplastic spindle-shaped cells without any cellular features of malignancy. The etiology of fibrous dysplasia has been linked to an activating mutation in the gene that encodes the α subunit of stimulatory G protein located at 20q13.2-13.3. This leads to a constitutive activation of adenylate cyclase and increased cyclic adenosine monophosphate formation.
FGFR3 mutation
Achondroplasia
COMP mutation
- pseudo achondroplasia
- multiple epiphyseal dysplasia
EXT-1 mutation
-multiple hereditary exostosis
Biopsy of the proximal humerus
A biopsy of the proximal humerus should be performed through the anterior third of the deltoid. A biopsy should be performed through a single compartment and be incorporated with an extensile approach because the biopsy tract will be resected with the tumor if it is a sarcoma. Performing a biopsy through the deltopectoral interval will contaminate more than 1 compartment.
Staging of sarcomas
-Staging of sarcomas is important to help predict prognosis. Not all sarcomas are reliably positive on a PET scan, so the preferred staging studies are CT scan of the chest and whole-body bone scan. Hematogenous spread of sarcomas is the most common route of metastatic disease, which speaks to the value of chest CT scans. Clear-cell sarcomas (in addition to synovial sarcoma, angiosarcoma, epithelioid sarcoma, and rhabdomyosarcoma) tend to involve lymphatic nodal metastatic disease, so sentinel node biopsy is considered when assessing these tumors. Evidence supports efficacy of sentinel node biopsy for clear-cell sarcomas in particular.
Features concerning for soft-tissue sarcoma
-For patients with rapidly enlarging painless masses, particularly those that are either large or deep, the diagnosis of a soft-tissue sarcoma should be entertained. Masses exceeding 5 cm in largest dimension that are subfascial and heterogenous on MRI are concerning. MRI with and without contrast is the preferred imaging modality for evaluation of soft-tissue sarcomas because it can delineate location of the lesion, involvement of neurovascular structures, intra-articular involvement, and underlying signal alteration in the osseous structures. Most patients can relate the onset of their symptoms to a traumatic event, and the interpretation of an MRI may include a hematoma.
Typical tx for giant cell tumor of bone?
Intralesional curettage w/ adjuvants
Adjuvant therapy for recurrent giant cell tumor of bone?
-Denosumab
Aggressive fibromatosis/Desmoid tumor has been associated with Gardner syndrome and familial adenomatous polyposis. This patient is at high risk for colon cancer. Gardner syndrome is associated with osteomas, epidermal cysts, periampullary carcinomas, lipomas, and dental abnormalities in addition to desmoid tumors.
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extra-abdominal fibromatosis/desmoid tumor
Aggressive fibromatosis has been associated with Gardner syndrome and familial adenomatous polyposis. This patient is at high risk for colon cancer. Gardner syndrome is associated with osteomas, epidermal cysts, periampullary carcinomas, lipomas, and dental abnormalities in addition to desmoid tumors.
Ringed chromosomes and expression of MDM2, but do NOT have 12;16 translocation are typical of what?
Atypical lipomatous tumor (well-differentiated Liposarcoma)
12;16 translocation in lipomatous mass is consistent w/ what diagnosis?
Myxoid Liposarcoma
Achondroplasia
Achondroplasia is caused by the arginine-to-glycine amino acid substitution in the FGF-3 receptor gene and is characterized by rhizomelic limb shortening with normal trunk length attributable to inhibition of chondrocyte proliferation in the physis. Associated findings include macrocephaly, midface hypoplasia, trident hands, genu varum, and early gross motor delays that usually normalize with time. People with achondroplasia also can have foramen magnum stenosis with cervicomedullary spinal cord compression and diminished respiratory drive; the incidence of sudden infant death in this population is 2% to 5% and is thought to be attributable to the combination of central sleep apnea, tonsillar hypertrophy, and midface hypoplasia. Other signs of foramen magnum stenosis include swallowing difficulties and hyperreflexia. The American Academy of Pediatrics recommends neuroimaging of the craniocervical junction and polysomnography for infants with achondroplasia and suspected foramen magnum stenosis. Achondroplasia is not directly associated with neonatal cardiac abnormalities.
Translocation associated w/ Ewing’s sarcoma
T(11;22)
Synovial sarcoma associated gene
SYT
Multiple hereditary exostosis associated gene
EXT1
Ewing sarcoma associated gene
EWS
Osteogenesis imperfecta associated gene
COL1A
tenosynovial giant cell tumor
aka PVNS
- characterized by an overexpression of CSF1. CSF1R activation leads to recruitment of CSF1R-expressing cells of the mononuclear phagocyte lineage.
The characteristic histologic finding in synovial chondromatosis is what?
SYNOVIAL METAPLASIA (the cartilaginous change of the synovial membrane)
chondrocyte cloning is found in what?
chondrosarcoma
Cords of eosinophilic cell in myxoid stroma are characteristic for what?
extraskeletal chondrosarcoma
Atraumatic vertebra plana in a young child is most commonly the result of a pathologic compression fracture through a lesion of what?
Langerhans cell histiocytosis (LCH).
Ewing’s sarcoma is treated by what?
Radiotherapy, Chemotherapy, and wide resection
how is adamantinoma treated?
surgery alone
Paget’s disease of bone
osteoclastic abnormality marked by focally increased skeletal remodeling within the axial or appendicular skeleton. There is an initial wave of osteoclast-mediated bone resorption, followed by the second phase of disorganized skeletal repair. This process leads to excessively disorganized woven bone and lamellar bone, characterized by osteosclerosis and hyperostosis, respectively, and results in the characteristic findings of cement lines seen histologically. The disorganized bone is weaker and prone to fractures. The final phase of the disease is the quiescent phase in which there is little bone turnover. Because of the increased bone remodeling, there is usually an associated increased vascularity which should be taken in account when surgery is performed. There is no bony replacement of the bone marrow.
Myxoid liposarcoma
- translocation t(12;16)
- In addition to posing risk for pulmonary metastases, myxoid liposarcomas have an unusual predilection for extrapulmonary metastases. Most notable are bone metastases, particularly involving the spine. Sarcoma metastases to the brain or liver are relatively uncommon and typically are late findings. Lymph node metastases have been reported in about 2.6% of soft-tissue sarcomas, but they are more common in histologic subtypes including angiosarcoma, rhabdomyosarcoma, clear-cell sarcoma, epithelioid sarcoma, and synovial sarcoma. However, for myxoid liposarcoma, nodal metastases remain uncommon.
osteoblastoma
The combination of immature woven bone with osteoblastic rimming surrounded by a vascular fibrous bland stroma seen in Figure 9 and scattered giant cells within the lesion seen in Figure 8 should arouse suspicion for osteoblastoma. Osteoblastoma most often is diagnosed in adolescents and young adults, with 75% of patients younger than 25 years of age at diagnosis. Within tubular bones, osteoblastoma most often arises in the metadiaphyseal region, but it is more commonly seen in the spine within the posterior elements and flat bones. The lesion is well defined on radiographs, with lucent to mixed-lucent and blastic areas. MR imaging findings reveal low to intermediate–signal intensity on T1-weighted images and intermediate to high–signal intensity on T2-weighted images.
characteristic translocation of synovial sarcoma?
t(X;18)
Clear cell chondrosarcoma
Clear-cell chondrosarcoma is a rare, slow-growing, low-grade malignancy that typically involves the epiphysis of long bones. The tumor is lytic, and the proximal femur is the most common location. Chemotherapy and radiation are not used because the tumor is low grade. Placement of a nail would result in an intralesional resection and pose risk for both local recurrence and metastatic disease. When treated appropriately with a wide resection, surgery alone usually is curative.
Tx of lipomatous tumors
- Intramuscular lipomas and atypical lipomatous tumors are treated with marginal resection alone.
- Surgical treatment of a high-grade sarcoma involves wide surgical resection. Radiation decreases local recurrence but does not clearly influence overall survival. The role of chemotherapy in high-grade soft-tissue sarcomas remains investigational; there is a modest (8%-15%) associated improvement in overall survival.
- Radiation therapy for soft-tissue sarcomas may be given before or after surgery. When administered before surgery, patients have a higher wound complication rate but better long-term function attributable to lower rates of lymphedema, fibrosis, and contractures (lower dose given compared to post-op radiation).
Synovial sarcoma associated translocation and staining?
T(X;18)
Keratin +
Hemangioma
A phlebolith is identified on the radiograph. MR imaging demonstrates a heterogeneous mass with signal dropout of the phlebolith and evidence of fat within the tumor. The history of a chronic mass that changes in size helps confirm the diagnosis. A biopsy is not necessary considering the clinical and radiographic findings. Marginal resection is likely to result in recurrence. Chest CT findings likely will be normal, and a CT would be considered only in a scenario involving a soft-tissue sarcoma diagnosis
High grade undifferentiated pleomorphic sarcoma
Histologically, UPS is characterized by high cellularity, marked nuclear pleomorphism, abundant mitotic activity (including atypical mitoses), and a spindle cell morphology. Necrosis is common and characteristic of high-grade lesions. Treatment consists of wide surgical excision and, in almost all cases, radiation. Radiation eliminates the need for limb amputation, and there is level I evidence to show that it leads to equivalent rates of survival. Radiation may be delivered either before or after surgery depending on the surgeon’s and multidisciplinary tumor board’s recommendations. There may be a role for presurgical embolization in some cases of high-grade soft-tissue sarcoma, but this is not appropriate as a standalone treatment. Chemotherapy provides limited survival improvement in adults with high-grade soft-tissue sarcomas.
translocation associated w/ myxoid liposarcoma
t(12;16)
translocation associated w/ alveolar soft tissue sarcoma
t(x;17)
translocation associated w/ Ewing sarcoma
t(11;22)
translocation associated w/ alveolar rhabdomyosarcoma
t(2;13)
t(9;22) translocation is associated w/ what?
The t(9;22) translocation occurs in extraskeletal myxoid chondrosarcoma
Low-grade cartilage lesions are among the few diagnoses for which proceeding to definitive surgical treatment without a definitive histologic diagnosis is appropriate. Extended curettage with adjuvants is an acceptable treatment option for both enchondroma and low-grade chondrosarcoma of the extremities; as such, it is appropriate to proceed to definitive treatment when these are the only diagnoses in the differential. There is no consensus regarding the number and type of adjuvants used in intralesional curettage. There is also lack of consensus regarding how to reconstruct the resultant defect, with some favoring cement and others favoring bone grafting. A wide resection with intercalary resection is not indicated. Most commonly, serial radiologic studies are recommended to ensure no change occurs over time when the lesion is found incidentally, as in this patient.
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Chromosome translocation for Ewing sarcoma
11;22
Chromosome translocation for synovial cell sarcoma
X;18
Chromosome translocation for myxoid Liposarcoma
12;16
Chromosome translocation for extra-skeletal myxoid chondrosarcoma
9;22
biopsy principles
Biopsy principles dictate that a biopsy should be performed in line with an extensile approach through one compartment and that contamination should be minimized. Performing the biopsy through the knee joint has caused the entire joint to be considered contaminated. It will have to be resected by an extra-articular resection or amputation at the time of definitive surgery. This substantially increases the morbidity of the procedure, in which a standard distal femoral replacement or distal femoral osteoarticular allograft could have been used for reconstruction.
Treatment of chondrosarcoma
Surgical resection and reconstruction
-There is no known benefit of radiation or chemotherapy in the treatment of high-grade chondrosarcoma.
treatment of low-grade chondrosarcomas
curettage
Myxoid liposarcoma chromosomal translocation
12;16
Synovial cell sarcoma chromosomal translocation
X;18
Alveolar soft-part sarcoma chromosomal translocation
X;17
Ewing sarcoma chromosomal translocation
11;22
Alveolar rhabdomyosarcoma chromosomal translocation
2;13
Synovial hemangioma
Histologically, vascular lakes within fine capillaries with a synovium on the surface of the lesion are characteristic of this condition. Many patients with synovial hemangioma have pain, swelling, stiffness, or mechanical symptoms.
- As with PVNS, the disease can be localized or diffuse. Surgical excision, either open or arthroscopic, is the recommended treatment. PVNS is the most common intra-articular tumor, but hypointensity in either the diffuse or localized type is characteristic in both T1- and T2-weighted images.
MRI appearance of PVNS?
PVNS is the most common intra-articular tumor, but hypointensity in either the diffuse or localized type is characteristic in both T1- and T2-weighted images.
Langerhans cell histiocytosis
Also called eosinophilic granuloma, histiocytosis X, Langerhans cell granulomatosis
Rare disorder of Langerhans cells
Variable clinical picture with single or multiple lesions or disseminated disease
Nodal involvement may be sole manifestation of disease or associated with systemic disease
May also have nodal involvement by lymphoma
Rarely have frankly malignant cells (Langerhans cell sarcoma) associated with more aggressive clinical behavior
-Partial effacement of lymph node with preservation of follicular centers but distension of nodal sinuses by Langerhans cells, which are 12 - 15 microns in diameter with abundant, pale eosinophilic cytoplasm, irregular and elongated nuclei with prominent nuclear grooves and folds, fine chromatin and indistinct nucleoli
Occasionally multinucleated
Sinuses commonly have foci of necrosis, often surrounded by rim of eosinophils
Rarely eosinophilic abscess incite a granulomatous response (J Clin Pathol 2006;59:548)
Variable mitotic activity
hematological conditions associated with multiple bone infarcts
Polycythemia, sickle-cell disease, hemophilia, aplastic anemia, thalassemia, and acute lymphoblastic leukemia
bisphosphonate-induced stress fracture
- typically lateral cortical beaking (tension side of femur)
- Tx is immediate IMN without further work-up
Biopsy principles around the knee
The biopsy should cross only 1 compartment if possible and proceed as directly as possible to the tumor. The lateral parapatellar and medial parapatellar approaches cross the knee joint, potentially visualizing tumor into the knee. A direct anterior approach will contaminate an extensive portion of the quadriceps muscle and potentially complicate limb salvage. Biopsy should be performed at the institution at which definitive resection is planned.
Although postsurgical radiation is associated with lower rates of wound complication, radiation that is administered after surgery necessitates higher radiation doses and a larger tissue field than radiation administered before surgery. Risk for radiation-associated fracture increases with larger fields and higher doses. Retrospective studies have demonstrated increased fracture risk with postsurgical radiation doses of at least 60 Gy compared with presurgical radiation doses of 50 Gy.
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How do you treat renal cell carcinoma mets to proximal femur?
Proximal femur resection would be a reasonable choice in isolated renal cell carcinoma metastasis, which tends to be radioresistant and for which resection has been shown to have an oncologic benefit.
Renal cell carcinoma
Renal cell carcinoma typically is radioresistant. With improvements in chemotherapy treatments, survival is increasing and fixation failure is more likely to occur. A curettage resection is likely to leave disease behind and puts patients at risk for progression of disease and hardware failure. Wide resection can improve implant survival, and complete resection of metastatic disease in renal cell carcinoma results in improved overall survival. Embolization should be performed with renal cell carcinoma prior to any surgical intervention because substantial blood loss can occur with placement of an intramedullary nail.
Role of chemotherapy in high-grade soft tissue sarcomas?
Surgical treatment of a high-grade sarcoma involves wide surgical resection. Radiation decreases local recurrence but does not clearly influence overall survival. The role of chemotherapy in high-grade soft-tissue sarcomas remains investigational; there is a modest (8%-15%) associated improvement in overall survival.
Tx for intramuscular lipomas and atypical lipomatous tumors?
marginal resection alone
Enchondroma
well-mineralized lesion within the intramedullary canal with punctate calcifications. This by itself suggests an enchondroma or low-grade chondrosarcoma. It is important to note that enchondromas in the long bones rarely cause pathologic fractures. This is not the case when they are present in the hands and feet, where enchondromas frequently have a more aggressive radiologic appearance and pose higher risk. Radiographic findings concerning for malignant dedifferentiation of an enchondroma include cortical thinning or breach, a soft-tissue mass, or periosteal elevation.
Is renal cell carcinoma typically radioopaque or radiolucent?
radiolucent
Dedifferentiated chondrosarcoma
highly aggressive malignancy, with average 5-year survivals of less than 50%. As with most sarcomas, the most likely site of metastatic dissemination of chondrosarcoma is pulmonary. As with other bone sarcomas, staging entails a CT scan of the chest and a bone scan
staging study for multiple myeloma
skeletal survey (NOT bone scan)
Treatment of chondrosarcoma?
Wide surgical resection (NOT chemo or radiotherapy)
Telangiectatic osteosarcoma
variant of high-grade osteosarcoma. The second decade of life is usually the most common age for this condition. The most common sites of metastasis are the lungs and other bones. Typical radiographic characteristics include an expansile destructive metaphyseal lesion with very little to no new bone formation. It is similar in appearance to an aneurysmal bone cyst. MR imaging demonstrates a low-signal intensity lesion on T1-weighted images, and fluid-fluid levels and high signal intensity may be present on T2-weighted images. Low-power histology resembles an aneurysmal bone cyst with cavernous blood-filled spaces. However, on high power, the septa have pleomorphic cells. Histology usually shows blood-filled cystic cavities with areas of hemorrhagic necrosis, giant cells, pleomorphic cells, and minimal osteoid. Typical treatment includes neoadjuvant chemotherapy followed by wide resection and postsurgical chemotherapy
what should pelvic incidence/lumbar lordosis mismatch be to be within normal range?
within 10 degrees
If an open biopsy of a musculoskeletal neoplasm is to be performed, the incision should be placed?
If an open biopsy is to be performed, the incision should fall along any line of future tumor resection. This line is NOT longitudinal about the shoulder or pelvic girdles, nor is it often in the place of a “standard” orthopaedic approach, which may contaminate surrounding structures.
renal cell carcinoma histology
malignant cells with cytoplasmic inclusions
chondrosarcoma
speckled calcifications on plain film and chondroid matrix on histology
Multiple hereditary exostoses (MHE) has what genetic abnormality?
EXT1 or EXT2 genes
Treatment for Ewing sarcoma
Chemotherapy plus wide surgical resection
Imaging study of choice to diagnose osteoid osteoma?
thin cut CT scan
when an osteoid osteoma occurs in the spine
located in posterior elements, and paraspinal pain and scoliosis often are present
adductor insertion avulsion syndrome, also known as thigh splints
This is a painful condition that worsens with resisted hip adduction. Treatment consists of activity cessation with use of crutches and nonsteroidal anti-inflammatory drugs. Repeat imaging and monitoring for resolution of the symptoms should be performed to confirm the diagnosis.
Staging of osteosarcoma of bone
includes local imaging of the affected extremity with radiographs,MR imaging, chest imaging with a CT scan, and a whole-body bone scan. Because the treatment of osteosarcoma begins with neoadjuvant chemotherapy, immediate referral to a pediatric oncologist is critical.A CT scan of the abdomen and pelvis is not indicated in primary bone sarcomas, but it may have a role in the staging of some soft-tissue sarcomas. Bone marrow biopsy is not a component of osteosarcoma staging but is used in the staging of Ewing sarcoma of bone. Radiation is not used in the standard treatment of osteosarcoma of bone.
Nests of polyhedral cells
Squamous cell carcinoma
fat embolism syndrome (FES)
- Classic findings of FES are mental status changes, hypoxemia, and petechial rash developing after intramedullary instrumentation procedures. FES is more common after closed femoral nailing for cancer treatment than after traumatic fractures. Patients with preexisting cardiopulmonary dysfunction are at increased risk. FES remains a clinical diagnosis, although a high-resolution CT scan may distinguish fat emboli from thrombi, and diffusion-weighted brain MRI may demonstrate fat emboli. Aggressive supportive care including as-needed mechanical ventilation and fluid resuscitation remains the primary treatment.
- FES prophylaxis generally consists of intraoperative hydration and oxygenation. Some authors suggest that distal femoral venting is beneficial to decrease intramedullary pressure and subsequent fat embolism. Broad-spectrum antibiotics would be an appropriate treatment for aspiration pneumonia. This patient has diffuse bilateral infiltrates as opposed to a focal infiltrate. Furthermore, the mental status changes are more consistent with FES than pneumonia. Anticoagulation would be the treatment of choice for pulmonary embolism. The timing after surgery is more consistent with FES, as are the changes in mental status.
treatment for giant cell tumors of tendon sheath
marginal excision
treatment of parosteal osteosarcoma
wide resection alone (same with chondrosarcoma)
Denosumab, the human monoclonal antibody that specifically binds and inactivates receptor activator of nuclear factor-kB ligand (RANKL), is commonly used in the setting of metastatic disease. Its cell surface receptor is expressed by
Both osteoclast precursors and mature osteoclasts
Osteoblasts produce osteoprotegerin, which stimulates osteoclasts to induce apoptosis by acting as a decoy for RANKL, preventing the binding of RANKL to RANK.
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When evaluating postmenopausal women who are taking osteoporosis medication, history should include use of
antiepileptics
Treatment for Ewing sarcoma
Radiotherapy and chemotherapy and surgery
treatment of adamantinoma
surgery alone
Chromosomal translocation associated with Synovial Sarcoma?
t(x;18)
Synovial sarcoma
- soft-tissue sarcoma that usually occurs in young adults.
- often causes pain, unlike most soft-tissue sarcomas, which generally do not cause pain
- Imaging characteristics include soft-tissue calcifications on plain radiographs and a heterogeneous mass that is generally isointense to muscle on T1-weighted images and hyperintense to muscle on T2-weighted images
- There are biphasic and monophasic types of synovial sarcoma. The biphasic type has both spindle cell and epithelial components and will stain for both vimentin and cytokeratin
- More than 90% of patients with synovial sarcoma have a characteristic genetic translocation of t(X;18), which results in the fusion protein SS18-SSX
t(11;12)
Ewing sarcoma
t(9;22)
Extraskeletal myxoid chondrosarcoma
t(12;16)
Myxoid Liposarcoma
MSTS staging system
-assigns progressively higher degrees of risk to neoplasms based on their surgical grade, anatomic location, and presence or absence of metastases. Lesions that are low grade are assigned a score of I, while high-grade lesions are assigned a score of II. Lesions contained in the bone or those that are intracompartmental are designated as A, and extracompartmental lesions are designated as B. Metastases elevates the score to III
