Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature

Abstract

Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and favorable clinical behavior with an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma. LG-SDC is composed of multiple cysts, cribriform architecture with "Roman Bridges", "pseudocribriform" proliferations with floppy fenestrations or irregular slits, micropapillae with epithelial tufts, fibrovascular cores, and solid areas. Most of the tumor cells are small to medium sized with pale eosinophilic cytoplasm, and round to oval nuclei, which may contain finely dispersed or dark condensed chromatin. Foci of intermediate to high grade atypia, and invasive carcinoma or micro-invasion have been reported in up to 23 % of cases. The neoplastic cells have a ductal phenotype with coexpression of keratins and S100 protein and are surrounded by a layer of myoepithelial cells in non-invasive cases. The main differential diagnosis of LG-SDC includes cystadenoma, cystadenocarcinoma, sclerosing polycystic adenosis, salivary duct carcinoma in situ/high-grade intraductal carcinoma, and papillary-cystic variant of acinic cell carcinoma. There is no published data supporting the continuous classification of LG-SDC as a variant of cystadenocarcinoma. Given that most LG-SDC are non-invasive neoplasms; the terms "cribriform cystadenocarcinoma" and LG-SDC should be replaced by "low-grade intraductal carcinoma" (LG-IDC) of salivary gland or "low-grade intraductal carcinoma with areas of invasive carcinoma" in those cases with evidence of invasive carcinoma.

Fig. 1

Low power appearance of LG-SDC showing cysts of various sizes and diameters with a large central cyst surrounded by smaller ones. Note the cribriform architecture with “Roman bridges” and epithelial tufts lining the cysts

Fig. 2

LG-SDC with round “rigid” cribriform, oval, and slit-like fenestrated spaces. The neoplastic cells are heterogeneous with elongated cells with small dark nuclei, and larger cells with moderate to abundant eosinophilic cytoplasm with round nuclei with visible nucleoli. Apical cytoplasmic blebs characteristic of apocrine metaplasia are readily seen. No distinctive myoepithelial cells are noted

Fig. 3

LG-SDC with “pseudocribriform” architecture. The ducts and lobules are occupied by a relatively monotonous ductal forming round spaces along with irregular fenestrated secondary lumina. Apocrine metaplasia can be observed in the lower left corner

Fig. 4

LG-SDC with anastomosing and filigreed epithelial tufts. The tumor cells and exhibit dark nuclei or finely dispersed chromatin. Without immunohistochemical stains it is difficult to see a distinctive myoepithelial layer

Fig. 5

LG-SDC with streaming elongated cells with dark nuclei or nuclei with fine chromatin and small nuclei. The peripheral myoepithelial cells are barely visible

Fig. 6

Cellular heterogeneity and cytologic progression in LG-SDC. Most of the neoplastic ductal cells are small with round nuclei containing fine chromatin; however, larger cells with vesicular chromatin and clearly visible nucleoli are also present

Fig. 7

Calponin highlighting a thin myoepithelial cell layer at the periphery of ducts and cysts in LG-SDC

Fig. 8

Diffuse expression of S100 protein in a LG-SDC with “pseudocribriform” architecture