Immunohistochemistry Using a Pan‐TRK Antibody Distinguishes Secretory Carcinoma of Salivary Gland from Acinic Cell Carcinoma

Abstract

Aims

Secretory carcinoma (previously known as mammary analog secretory carcinoma) is characterized by ETV6 rearrangements, most often ETV6‐NTRK3 fusion. Given its histologic overlap with other salivary gland tumors, secretory carcinoma can be difficult to diagnose without genetic confirmation. A recently developed pan‐TRK antibody shows promise for identifying tumors with NTRK fusions. This study evaluated the utility of pan‐TRK immunohistochemistry in distinguishing secretory carcinoma from mimics.

Methods and Results

We examined whole‐tissue sections from 86 tumors including 14 secretory carcinomas (12 parotid and 1 buccal primary, 1 metastasis; 5 with ETV6 rearrangement confirmed by fluorescence in situ hybridization, 1 ETV6‐NTRK3 and 1 ETV6‐RET fusion detected by targeted sequencing), 14 acinic cell carcinomas, 18 polymorphous adenocarcinomas, 20 low‐grade mucoepidermoid carcinomas, and 20 pleomorphic adenomas. Immunohistochemistry was performed using a pan‐TRK rabbit monoclonal antibody. Pan‐TRK staining was detected in 9 (64%) secretory carcinomas, all with nuclear pattern and 4 with diffuse staining (>50% of cells). Of other tumor types, pan‐TRK immunoreactivity was observed in all (100%) pleomorphic adenomas (particularly myoepithelial cell‐rich, myxoid areas), 15 (83%) polymorphous adenocarcinomas, and 4 (20%) low‐grade mucoepidermoid carcinomas, all with predominantly membranous/cytoplasmic immunoreactivity; only 6 cases showed focal (<10%) nuclear staining. All acinic cell carcinomas were entirely negative.

Conclusions

While pan‐TRK expression is not entirely sensitive or specific for secretory carcinoma, nuclear staining distinguishes secretory carcinoma from mimics. Acinic cell carcinomas are negative for pan‐TRK, though membranous expression of TRK is common in other salivary gland neoplasms. The lack of pan‐TRK immunoreactivity in a subset of secretory carcinomas may suggest non‐NTRK fusion partners.

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