Re-evaluating historic cohort of salivary acinic cell carcinoma with new diagnostic tools

Abstract

Mammary analogue secretory carcinoma (MASC) was recently identified as a distinct salivary gland neoplasm, morphologically resembling intercalated duct cell predominant acinic cell carcinoma (AciCC). To determine how frequently MASC has mimicked an intercalated duct cell predominant AciCC, we reviewed AciCC diagnosed from 1956 to 1975. Nine AciCC consecutively diagnosed in that period were identified. Based on morphologic examination, one case diagnosed as AciCC in a male patient in 1960 was re-classified as MASC [confirmed by fluorescence in situ hybridization (FISH) showing ETV6 translocation]. Another case diagnosed as AciCC of the palate in a female patient in 1975 was re-classified as mucoepidermoid carcinoma (based on the lack of acinar differentiation, presence of mucous cells, and confirmed by FISH showing MAML2 translocation). In this proof-of-principle study, we show that 1 in 9 cases historically designated as AciCC represents a MASC. "Intercalated duct cell predominant AciCC", especially among male patients, most likely represent examples of MASC. For anatomic sites outside of the parotid glands, broader differential diagnoses should be considered before accepting morphologic variants of AciCC as the final diagnosis.

Fig. 1

a Classic acinic cell carcinoma. Tumor cells (left half of the field) are well demarcated from normal parotid gland tissue (right half of the field) and show serous acinar cells with abundant zymogen granules, H&E, 200×. b Acinic cell carcinoma, a subset of cells demonstrate cytoplasmic clearing, H&E, 200×

Fig. 2

a Mammary analogue secretory carcinoma with nodular growth, well-defined border, and combination of microfollicular growth (lower half of the image) with more solid growth, H&E, 40×. b Mammary analogue secretory carcinoma, glands are filled with colloid-like secretions. The cytoplasm is vacuolated and shows no basophilic zymogen granules. The lymphoid infiltrate in the left upper corner is part of a moderate tumor-associated lymphoid response. H&E, 400×. c Neoplastic cells express S100, immunohistochemistry, 100×. dETV6 (12p13) FISH with break-apart probes. ETV6 translocation is indicated by the split of red and green signals. Chromosomes with intact ETV6 gene show a yellow signal (overlapping of green and red signals)

Fig. 3

a Mucoepidermoid carcinoma. The cystic lesion involves the hard palate, original H&E prepared in 1975, 40×. b The intermediate cells show vacuolated cytoplasm with a subtle basophilic tint, mimicking zymogen granules of acinic cell carcinoma. However, rare unequivocal mucocytes can be identified (black arrow). cMAML2 FISH with break-apart probe. MAML2 translocation is indicated by the split of red and green signals. Chromosomes with intact MAML2 gene show a yellow signals (overlapping of green and red signals)