IHC / molecular / translocations

Question 1

What tissues are PAX-8 +?
How would be PAX-8 be useful in the following differentials?
Prostate mesonephric remnant hyperlasia from AC?
endosalpingiosis in axillary nodes from met BRCA?
Upper tract urothelial ca vs. renal collecting duct?

Answer 1

PAX-8 + : renal, mullerian (female gyn tract), thyroid, and thymus

Prostate mesonephric remnant hyperlasia (PAX8+) from AC (PAX8-)
endosalpingiosis (PAX8 +) in axillary nodes from met BRCA (PAX8-)?
Upper tract urothelial ca (PAX8-) vs. renal collecting duct (PAX8+)

Question 2

What are the roles of glypican 3?

Answer 2

1 - It is + in HCC, and neg in other HCC lesions (though focally in some cirrhotic nodules)

2- Yolk sac tumor (GPC3 +) while embryonal carcinoma and other germ cell neoplasms are -

Question 3

What is the role of DOG-1

Answer 3

1 - Can be positive for GISTs that are Ckit negative (stands or Discovered On GIST 1)

2- Also is a marker of acinic cell carcinoma (gives a canalicular pattern on acinic cell - demonstrates acinic and intercalated disk differentiation

Question 4

Hemochromatosis mutation

Answer 4

HFE gene, C282Y

Question 5

Platelet / megakaryocyte markers

Answer 5

CD41, CD61 (loss of these also cause Glanzman’s thrombasthenia

Question 6

Translocations (and genes) in alveolar rhabdomyosarcoma?

Answer 6

t(2:13) PAX3 (on chrom 2) with FOXO1 (on chrom 13)

t(1:13) PAX 7 (on chrom 1) with FOXO1 (on chrom 13)

Question 7

What are the key genetic alterations associated with the main types of liposarcoma?

Answer 7

Well-differ liposarcomas / De differentiated liposarcomas – Both have MDM2 and CDK4 amplification due to amplification of chromosome 12q13-15 (and ring or giant chromosome 12)

myxoid / round cell liposarcoma - t(12;16) translocation between FUS-DDIT3 (TLS-CHOP) and less commonly a t(12;22) translocation between EWSR1-DDIT3

Pleomorphic liposarcoma - complex karyotype

Question 8

What does phosphaturic mesenchymal tumor cause and how?

Answer 8

osteomalacia due to excess secretion of fibroblast growth factor 23 (FGF 23)

Question 9

Translocation for synovial sarcoma?

Important IHC for SS?

Answer 9

t(X;18) SSx gene with SS18

IHC: usually EMA and CK7, CK8/18 focally positive (more so in biphasic epithelial areas)
also bcl-2 positive

Question 10

Solitary fibrous tumor IHC?

Answer 10

CD34+ STAT6+ (nuclear staining needed; most specific)

Question 11

Translocation for high grade ESS?

Also describe usual IHC profile for this

Answer 11

t(10:17) YWHAE-FAM22
lower grade parts are CD10, ER, and PR all positive
higher grade parts are CD10, ER, and PR negative, but positive for cyclin D1

Question 12

Mutation and protein in hereditary diffuse gastric cancer?
How should you test for it?
What other assocated cancers do they get?

Answer 12

CDH1 gene codes for e-cadherin
Must sequence the entire gene b/c >100 mutations can account for phenotype

also get lobular carcinoma of breast and signet ring cell carcinoma of colon