Most nonparotid "acinic cell carcinomas" represent mammary analog secretory carcinomas

Abstract

Acinic cell carcinoma (ACC) is a low-grade salivary gland malignancy characterized by serous acinar differentiation. Most ACCs arise in the parotid gland, but ACCs have been reported to originate in nonparotid salivary glands where serous acini are less abundant. Given the recent discovery of mammary analog secretory carcinoma (MASC)-a salivary malignancy that histologically mimics ACC-a retrospective reevaluation of nonparotid ACCs is warranted. The surgical pathology archives of The Johns Hopkins Hospital were searched for all ACCs arising outside of the parotid gland. For each case, the histologic slides were reviewed; immunohistochemical analysis (mammaglobin, S100 protein) was performed; and confirmatory ETV6 breakapart fluorescence in situ hybridization assay was completed. Demographic and clinical data were obtained from the medical records. Fourteen extraparotid tumors diagnosed as ACC were identified. Eleven of 14 (79%) tumors harbored the ETV6 translocation (oral cavity=9 of 11; submandibular gland=2 of 2). The translocation-positive tumors occurred in 7 women and 4 men ranging in age from 20 to 86 years (mean, 56 y) and usually presented as painless masses. Immunohistochemistry for mammaglobin and S100 was positive in all 11 translocation-positive tumors but negative in the 3 translocation-negative tumors. Histologically, the translocation-positive tumors exhibited uniform cells with vacuolated cytoplasm, microcystic/cystic and papillary architecture, and intraluminal secretions; however, the presence of basophilic cytoplasmic granules was conspicuously absent. Basophilic cytoplasmic granules, indicative of true serous acinar differentiation, were present in the 3 translocation-negative tumors. Of the translocation-positive tumors, only 1 locally recurred, and none metastasized. Most alleged ACCs of nonparotid origin actually represent misclassified MASCs. The impact of diagnostic error is mitigated by the low-grade nature of MASC that, like ACCs, do not appear to be clinically aggressive.

Figure 1

The extra-parotid mammary analogue secretory carcinomas are usually circumscribed, and they frequently exhibit papillary-cystic (A and B) and microcystic (C) growth. Staining for mammaglobin is strong and diffuse (D). ETV6 break apart FISH demonstrates one intact gene (i.e., orange and green together) and one rearranged ETV6 gene (inset of D).

Figure 2

These extra-parotid acinic cell carcinomas exhibit predominantly solid growth (A and B) and well developed cytoplasmic zymogen granules (B). ETV6 break apart FISH demonstrated two intact ETV genes (inset of B).

Figure 3

The translocation positive mammary analogue secretory carcinomas were comprised of uniform cells with lightly eosinophilic and vacuolated cytoplasm (A). The tumor cells lacked the basophilic granules that were evident in the translocation negative acinic cell carcinomas (B).