Salivary duct carcinoma: new developments--morphological variants including pure in situ high grade lesions; proposed molecular classification

Abstract

Salivary duct carcinoma (SDC) is an aggressive primary salivary malignancy which microscopically resembles high-grade ductal carcinoma of the breast, with both in situ and invasive patterns. It is typically found in older men, most often in the parotid. It can arise de novo or as the malignant component of carcinoma ex pleomorphic adenoma. SDC is generally a hematoxylin and eosin stain-based diagnosis, with special stains and immunohistochemistry acting mainly in a confirmatory role. Other than epithelial markers, SDC expresses androgen receptors in most cases, with true HER2 positivity seen in about 15 %. Based on these data and analogous to similar schemes in the breast, it is suggested that SDCs can be classified into three main groups: luminal androgen receptor positive, HER2+ and basal phenotype. This may form the basis for prognostic information and new therapeutic possibilities. In addition to the usual type of SDC, a few less common morphological variants have been reported: papillary, micropapillary, mucin-rich, sarcomatoid and oncocytic, as well as pure in situ cases.

Fig. 1

Usual type SDC. a DCIS lesion with central comedo-necrosis. b Invasive tubulo-trabecular pattern. c Invasion as single cells in a tumor with more usual SDC areas elsewhere. d Invasive tubules with apocrine-type snouts

Fig. 2

Micropapillary SDC. a Invasive cellular morules each surrounded by a clear space; there is also a small central in situ lesion. b Peripheral “inside-out” staining with EMA

Fig. 3

Mucin-rich SDC. a Both components: area of usual type SDC and an area of colloid carcinoma. b. Group of carcinoma cells surrounded by epithelial mucin

Fig. 4

Sarcomatoid SDC; glandular area and a population of spindle-shaped carcinoma cells

Fig. 5

Pure SDCIS. a Comedocarcinoma with cytological atypia. b Cancerization of acini

Fig. 6

Molecular subtypes: luminal androgen receptor positive. a Typical invasive SDC. b Strong reaction for AR in almost every nucleus

Fig. 7

Molecular subtypes: HER2 positive. a 3+ immunostaining for HER2 protein (with normal negative staining ducts as internal control). b Amplification of the HER2/neu gene (SISH)

Fig. 8

Molecular subtypes: Basal phenotype. SDC invading normal gland (a HE and b CK5/6)