CAP CHECK SAMPLE

Question 1

Mutation in pediatric cystic nephroma (PCN)

Answer 1

DICER1 mutations are identified in
more than 90% of PCN, and up to two-thirds of these are associated with a germline
mutation. DICER1 mutations are not present in MEST or adult cystic nephroma.

Question 2

most common congenital viral infection

Answer 2

CMV

Question 3

What gene is altered in sclerosing stromal tumor?

Answer 3

GLI2. Sclerosing stromal tumors show recurrent
FHL2::GLI2 fusions in approximately 65% of cases, and other GLI2 rearrangements in an additional 15%. Germline mutational inactivation of either the SUFU or PTCH1 gene is seen in Gorlin syndrome, and patients often have bilateral calcified fibromas presenting at a young age. FOXL2 mutation is characteristic of adult granulosa cell tumor. TP53 mutations are seen in many high-grade tumors, including high-grade serous ovarian carcinoma.

Question 4

Alteration of which gene is most frequently identified in chordoid gliomas?

Answer 4

PRKCA. Chordoid gliomas have a hallmark
missense mutation on PRKCA, specifically a p.D463H mutation.

Question 5

Chordoid gliomas

Answer 5

well-circumscribed, solid glial neoplasms that occur in or around the third ventricle. The tumor cells have abundant eosinophilic cytoplasm with round to oval nuclei and vesicular chromatin. No significant mitotic activity is noted, though focal necrosis is present. Rare intranuclear pseudoinclusions are identified. They are thought to arise from tanycytic ependymal cells in that region. They most frequently occur in adults with a median age of 45 years and bear a slight female predominance. On T1-weighted MRI, they are isointense to background brain and show avid homogenous contrast enhancement. Patients most often present with symptoms of obstructive hydrocephalus such as headache, nausea, vomiting, and/or ataxia.

Question 6

Mutation in synovial sarcoma

Answer 6

t(X;18) (p11.2;q11.2) translocation involving the SS18 gene and one of several SSX genes. It is most commonly seen in young adults aged 15 to 40 years, but it can occur in early childhood to late adulthood. Usually, they present as multinodular masses with a cut surface ranging from solid and firm to smooth and glistening. Two major histologic subtypes exist: monophasic spindle type, which is composed entirely of spindle cells, and biphasic subtype, which has a mixture of fibroblast-like spindle cells and epithelial cells that usually form gland-like structures. The tumor is usually positive for cytokeratins, EMA, and TLE1.

Question 7

sarcomatoid neoplasm in kidney as renal cell carcinoma (RCC) with sarcomatoid features (sRCC)
Which immunohistochemical profile would be most supportive of a diagnosis of sRCC?
a) AE1/AE3 (+), PAX8 (+), GATA3 (-)
b) AE1/AE3 (+), PAX8 (-), GATA3 (+)
c) AE1/AE3 (+), PAX8 (-), TLE1 (+)
d) AE1/AE3 (-), HMB45 (+), SMA (+)
e) AE1/AE3 (-), PAX8 (-), STAT6 (+)

Answer 7

Answer: A,
Feedback: The correct answer is A, AE1/AE3 (+), PAX8 (+), GATA3 (-).
Positive staining for AE1/AE3 and PAX8, with negative staining for GATA3, would be most supportive of sRCC. Option B would be most consistent with
sarcomatoid urothelial carcinoma, option C would be most consistent with a synovial sarcoma, option D would be most consistent with an angiomyolipoma, and option E would be most consistent with a solitary
fibrous tumor

Question 8

Which of the following markers best differentiates between cellular schwannoma and MPNST?
a) EMA
b) GFAP
c) H3K27me3
d) S100
e) Tyrosinase

Answer 8

Answer: C,
Feedback: The correct answer is C, H3K27me3. H3K27me3 is a newer marker that is lost in a majority of MPNST but is retained in schwannoma. S100 is often negative in MPNST, but strong and diffuse staining does not rule it out. EMA, GFAP, and tyrosinase are noncontributory in this differential.

Question 9

Which of the following statements is correct regarding schwannoma?
a) A majority demonstrate inactivating mutations of NF2.
b) Malignant transformation is common.
c) Plexiform schwannoma is pathognomonic for neurofibromatosis type 1.
d) Plexiform schwannoma is pathognomonic for neurofibromatosis type 2.
e) They are benign lesions but are often poorly circumscribed.

Answer 9

Answer: A,
Feedback: The correct answer is A, a majority demonstrate inactivating mutations of NF2. Schwannoma is associated with NF2, and 2/3 of sporadic lesions demonstrate inactivating NF2 mutations. They rarely undergo malignant
transformation. Plexiform variants are not indicative of NF1 or NF2. Schwannoma are usually well circumscribed and often encapsulated.

Question 10

Which is the most common genetic alteration in pancreatic ductal adenocarcinoma
(PDAC)?
a) BRCA1 mutation
b) KRAS mutation
c) Microsatellite instability
d) NRAS mutation
e) PTEN mutation

Answer 10

The correct answer is B, KRAS mutation. PDAC commonly harbors activating
mutations in the KRAS oncogene.

Question 11

The most common benign mesenchymal renal neoplasm?

Answer 11

Angiomyolipoma

Question 12

Which immunohistochemical profiles would support a diagnosis of angiomyolipoma?

Answer 12

HMB45 positive, SMA positive

Question 13

Which molecular alterations has been implicated in the
pathogenesis of renal angiomyolipomas?

Answer 13

TSC1 mutations

Question 14

Extra-adrenal paraganglioma standard of care stain

Answer 14

Performance of SDHB immunostain is now considered standard of care, which may reveal an underlying mutation in the SDH gene family.

Question 15

Seminoma is positive for

Answer 15

OCT3/4, SALL4, PLAP, D2-40, CD117, and SOX17.

Question 16

second most common pure testicular germ cell tumor.

Answer 16

Embryonal carcinoma

Question 17

second most common sex cord stromal tumor

Answer 17

Sertoli cell tumor

Question 18

Embryonal carcinoma staining pattern

Answer 18

Cytokeratin AE1/AE3 and CD30 are positive in
embryonal carcinoma. SOX2, in particular, is a specific marker for embryonal carcinoma. Additionally, PLAP, D2-40, CD117, and SOX17 should be negative in embryonal carcinoma.

Question 19

What is the most useful microscopic feature of SDH-deficient renal cell carcinoma (RCC) that distinguishes it from other low-grade oncocytic renal neoplasms?

Answer 19

Flocculent intracytoplasmic inclusions

Question 20

SDH-RCC is associated with

Answer 20

hereditary paraganglioma-pheochromocytoma
syndrome, an autosomal dominant mutation in genes encoding SDH complex proteins that causes patients to develop tumors including pheochromocytoma,
paraganglioma, pituitary adenoma, and GIST

Question 21

newly added “molecularly defined” category of renal
tumors in the 5th edition WHO classification

Answer 21

Succinate dehydrogenase-deficient renal cell carcinoma (SDH-RCC), TFE3-rearranged renal cell carcinoma, TFEB-altered renal cell carcinoma, ELOC (formerly TCEB1)-mutated
renal cell carcinoma, fumarate hydratase-deficient renal cell carcinoma, ALK-rearranged renal cell carcinoma, and SMARCB1-deficient renal medullary carcinoma.

Question 22

one of the closest morphologic
mimickers of SDH-RCC

Answer 22

Chromophobe renal cell carcinoma (chRCC) is one of the closest morphologic mimickers of SDH-RCC, due to the shared large nested to solid growth of eosinophilic cells. Key features supporting the diagnosis of chRCC are the presence of prominent cell borders (“vegetable cells”), nuclear membrane irregularities (“raisinoid nuclei”), and peri-nuclear clearing resembling koilocytes.

Question 23

TFE3-rearranged renal cell carcinoma (TFE3 RCC)

Answer 23

(TFE3 RCC) is a molecularly defined renal cell carcinoma that occurs in both pediatric and adult patients. Morphologically, these tumors typically exhibit some degree of papillary architecture with large cells with
abundant clear to eosinophilic cytoplasm. Psammoma bodies may be present. Melan-A and HMB45 may be expressed in TFE3 RCC and are useful in the initial
workup of a suspected case; however, the gold standard for diagnosis is TFE3 break-apart FISH

Question 24

Microscopically, conventional (localized/nodular) NF

Answer 24

hypo- to moderately cellular lesions characterized by a proliferation of uniform spindle cells with elongated wavy nuclei and wire-like collagen (“shredded carrot” appearance) embedded in a fibrous to myxoid stroma. Nuclear pleomorphism is absent, and mitotic activity is usually not seen. Mast cells are commonly present.

Question 25

Macroscopically, plexiform NF

Answer 25

multinodular tumors with a “bag of worms” appearance (intermingling expanded nerve fascicles).

Question 26

atypical neurofibroma/atypical neurofibromatosis neoplasm of uncertain biological potential (AN/ANNUBP) in the setting of NF1

Answer 26

AN/ANNUBP are Schwann cell neoplasms with at least 2 of the 4 following features: cytologic atypia, loss of NF architecture, hypercellularity, and <1.5 mitoses /mm2 (<3 mitotic figures per 10 high-power fields (HPF)

Question 27

gene fusion in Dermatofibrosarcoma protuberans (DFSP)

Answer 27

Dermatofibrosarcoma protuberans (DFSP) are rare locally aggressive cutaneous soft tissue tumors characterized by a COL1A1::PDGFB gene fusion.

Question 28

Giant cell fibroblastoma

Answer 28

Giant cell fibroblastoma is a locally aggressive fibroblastic neoplasm that typically occurs in children, has a male predominance, and is closely related to
dermatofibrosarcoma protuberans (DFSP). Forming within the subcutaneous tissue, they infiltrate the dermis in a honeycomb pattern, sparing adnexal structures. There is variable cellularity with spindled and stellate neoplastic cells, evenly distributed
multinucleated giant cells, and irregularly branching pseudovascular spaces. There is often a predominance of hypocellular areas having myxoid or collagenous stroma. Mitoses and necrosis are rare. Similar to DFSP, these lesions are positive for CD34 and demonstrate rearrangement of chromosomes 17 and 22, resulting in a COL1A1::PDGFB fusion.

Question 29

Which genetic alteration confirms giant cell tumor (GCT) of soft tissue versus metastatic GCT of bone?

Answer 29

Lack of a H3F3A mutation