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.

Characterisation of DOG-1 Expression in Salivary Gland Tumours and Comparison with Myoepithelial Markers

“…Staining of duct cells was patchy and weak but widespread luminal staining was evident in all tumours. The majority of SC lacked DOG1 staining, similar to previous reports [6–8, 15, 18], confirming the diagnostic usefulness of DOG-1 in differentiating between ACC and SC.…”

(Mammary Analogue) Secretory Carcinoma of the Nasal Cavity: Report of a Rare Case with p63 and DOG1 Expression and Uncommon Exon 4–Exon 14 ETV6-NTRK3 Fusion Diagnosed with Next Generation Sequencing

“…(Mammary analogue) Secretory carcinoma (SC) was first described in 2010 by Skalova et al in a series of 16 tumors from the parotid gland and minor salivary glands of the oral cavity, with histomorphologic and immunohistochemical features strongly reminiscent of secretory carcinoma of the breast [1]. On immunohistochemistry, SC is typically positive for S100 protein, mammoglobin, GATA3, STAT5 and MUC4, but negative for p63 and DOG1 [2][3][4]. Like secretory carcinoma of the breast, salivary gland SC typically demonstrates a t(12;15) (p13; q25) ETV6-NTRK3 translocation.…”

MUC4 is a valuable marker for distinguishing secretory carcinoma of the salivary glands from its mimics

“…found S100 and mammaglobin coexpression in SC, but not in AciCC (20 of 21 AciCCs were S100‐negative, and 18 of 21 were mammaglobin‐negative). Negativity of AciCC for S100 and mammaglobin has been confirmed by others 42,43 . Conversely, Baghai et al 33 .…”