Utility of Immunohistochemistry and ETV6 (12p13) Gene Rearrangement in Identifying Secretory Carcinoma of Salivary Gland among Previously Diagnosed Cases of Acinic Cell Carcinoma

Abstract

Objective. Secretory carcinoma is a recently described entity with characteristic immunoprofile and ETV6 (12p13) rearrangement. Before its initial description, it was generally diagnosed as acinic cell carcinoma (ACCi). We evaluated immunoprofile and ETV6 rearrangement in cytological and surgical cases of previously diagnosed ACCi, in an attempt to identify any misclassified SC. Methods. Fifteen cytology and surgical cases of ACCi diagnosed over a 13-year period were retrieved and subjected to immunohistochemistry for S-100, mammaglobin, GATA-3 and DOG-1 as well as FISH for ETV6 (12p13). Results. Of the 8 cytology cases, only 1 was positive for S100, GATA-3, and mammaglobin, and negative for DOG-1. It also demonstrated ETV6 rearrangement and was reclassified as SC. The same immunoprofile was present in 2 of the 13 surgical cases. ETV6 rearrangement characterized by 3' interstitial deletion was detected in one of these cases and was reclassified as SC. Immunohistochemistry and ETV6 rearrangement were useful in identifying 2 (13.3%) cases misclassified as ACCi. Conclusions. Characteristic immunoprofile and ETV6 gene rearrangement may prove useful in identifying cases of SC. The presence of ETV6 3' interstitial deletion in one of our cases suggests that there may be additional ETV6 related genetic alterations contributing to the pathogenesis of SC.

Figure 1

ETV6-NTRK fusion transcript (case 6) translocation seen by FISH.

Figure 2

Cell block section (case 6) showing tumor cells with immunopositivity for S100 (a), mammaglobin, (b) and GATA-3 (c).

Figure 3

Fine needle aspiration of secretory carcinoma. (a) Arborizing papillary fragments with fibrovascular cores in a granular and cystic background (Diff-Quik Stain, ×200), (b) single cells with vacuolated cytoplasm (Diff-Quik stain ×1000), and (c) cell block showing tumor cells with prominent cribriform configuration and eosinophilic secretions (H and E, ×200).

Figure 4

Cell block section from a case of acinic cell carcinoma exhibiting prominent cribriform configuration of tumor cells (H and E, ×200).

Figure 5

((a)–(c)) Histologic features of secretory carcinoma. (a) Tumor is well circumscribed (H and E, ×20); (b) tumor cells exhibited clear cytoplasm, were focally vacuolated, and lacked zymogen granules (H and E, ×200); (c) cribriform pattern was also noted with eosinophilic secretion in the glands (H and E, ×200).

Figure 6

Histologic features of acinic cell carcinoma. (a) Prominent microcystic and papillary pattern (H and E, ×200); (b) tumor cells with zymogen granules (H and E, ×200); (c) PAS with diastase (PAS-D) stain highlighting the zymogen granules (×200); (d) DOG-1 positive tumor cells (×200).