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Κυριακή 8 Νοεμβρίου 2020

Oncocytic Intraductal Carcinoma of Salivary Glands: A Distinct Variant with TRIM33‐RET Fusions and BRAF V600E mutations

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Abstract

Aims

Salivary gland intraductal carcinoma (IDC) is a complex ductal neoplasm surrounded by a layer of myoepithelial cells. Recent insights have shown that there are 3 different types: intercalated duct‐like, with frequent NCOA4‐RET fusions; apocrine, with salivary duct carcinoma‐like mutations; and mixed intercalated duct‐like/apocrine with RET fusions including TRIM27‐RET. In addition, an oncocytic IDC was described, but it remains unclear if it represents a fourth variant or simply oncocytic metaplasia of another IDC type.

Methods and Results

Six IDCs with oncocytic changes were retrieved from the authors' archives, from 3 men and 3 women ranging from 45‐75 years (mean, 63). Five arose in the parotid, with one in an accessory parotid gland. Four patients with follow‐up were free of disease after 1‐23 months. Several immunostains (S100, mammaglobin, androgen receptor, p63/p40) and molecular tools (RNA sequencing, RET fluorescence in situ hybridization, BRAF V600E VE1 immunohistochemistry and Sanger sequencing) were performed. Histologically, tumors were variably cystic with solid intracystic nodules often difficult to recognize as intraductal. In all, tumor ducts were positive for S100 and mammaglobin, negative for androgen receptor, and completely surrounded by myoepithelial cells positive for p63/p40. Molecular analysis revealed TRIM33‐RET in 2/6, NCOA4‐RET in 1/6, and BRAF V600E in 2/6 cases. One case had no identifiable alterations.

Conclusions

Oncocytic IDC shares similarities with intercalated duct‐like IDC. While additional verification is needed, the oncocytic variant appears to be sufficiently unique to be regarded now as the fourth distinct subtype of IDC. Because of its indolent nature, oncocytic IDC should be distinguished from histologic mimickers.

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