Case 4
A 34-year-old male presented with a slow growing, painless tumour of the parotid gland. The lesion was biopsied and revealed a neoplasm with microcystic, solid and trabecular architecture. The clinicopathologic findings were suggestive of secretory carcinoma of the parotid gland/mammary analogue secretory carcinoma (MASC).
NTRK gene fusion testing
Despite clinicopathologic findings being suggestive of MASC, pan-TRK IHC was negative for TRK protein expression in tumour cells. Further testing for ETV6 was performed via FISH. An ETV6 structural rearrangement was identified.
H&E (Left-Hand Panel) and Pan-TRK (Right-Hand Panel) IHC of Adult Patient with Parotid Gland Tumour
Antibody for IHC: clone EPR17341 available from Abcam, Cambridge, MA, USA(www.abcam.com)
TRK inhibitor treatment
The patient was treated with the TRK inhibitor larotrectinib.
Clinical interpretation and impact of NTRK gene fusion testing
This case demonstrates a limitation of the sensitivity of pan-TRK IHC. While initial studies have demonstrated a relatively high sensitivity, rare NTRK3 fusion-positive cases have failed to show pan-TRK expression [1, 2]. These cases tend to involve ETV6-NTRK3 fusions. When clinicopathologic suspicion is high (for cases such as secretory carcinoma or infantile fibrosarcoma), and pan-TRK IHC is negative, the performance of alternative methods (specifically NTRK3 FISH) of fusion testing may be indicated.
References
- Rudzinski ER, Lockwood CM, Stohr BA et al. Pan-Trk Immunohistochemistry Identifies NTRK Rearrangements in Pediatric Mesenchymal Tumors. Am J Surg Pathol 2018; 42: 927-935.
- Hechtman JF, Benayed R, Hyman DM et al. Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions. Am J Surg Pathol 2017; 41: 1547-1551.