SMARCB1 (INI-1)-Deficient Adenocarcinoma of the Sinonasal Tract: A Potentially Under-Recognized form of Sinonasal Adenocarcinoma with Occasional Yolk Sac Tumor-Like Features

Abstract

The classification of sinonasal adenocarcinoma (SNAC) is complex. The high-grade, non-intestinal SNAC group is particularly heterogeneous, with tumors showing widely variable morphology. SMARCB1 (INI-1)-deficient sinonasal carcinoma is a newly described, aggressive tumor that usually resembles sinonasal undifferentiated carcinoma (SNUC) or non-keratinizing squamous cell carcinoma; however, glandular differentiation has been rarely reported and this feature may be under-recognized. We present a dedicated series of 12 SMARCB1-deficient SNACs. All tumors had an oncocytoid/plasmacytoid cytomorphology with variable degrees of glandular differentiation consisting of tubules and cribriform structures with foci of intracellular or intraluminal mucin. Three of 12 tumors exhibited foci of yolk sac tumor-like histologic features. The tumors were uniformly high-grade, with nuclear pleomorphism, elevated mitotic rates and frequent necrosis. By immunohistochemistry, all tumors were entirely SMARCB1-deficient, and 10 of 12 were CK7-positive. Occasional expression of CDX2 (4 of 12), CK20 (3 of 12), and p40 (3 of 10) was seen. Expression of yolk sac markers was variably present in tumors that harbored yolk sac-like areas but also tumors that did not: glypican-3 (10 of 11), SALL4 (6 of 11), HepPar-1 (4 of 11), PLAP (1 of 10), and AFP (1 of 11). SMARCB1-deficient sinonasal carcinoma, particularly the oncocytoid/plasmacytoid form, can demonstrate variable degrees of glandular differentiation. This unexpected morphology combined with variable immunohistochemical results may lead to misdiagnoses of high-grade intestinal or non-intestinal SNAC, myoepithelial carcinoma, or even yolk sac tumor or metastatic hepatocellular carcinoma.

Keywords: Adenocarcinoma; INI-1; SMARCB1; SMARCB1-deficient sinonasal carcinoma; Sinonasal; Yolk sac tumor.

Fig. 1

The SMARCB1-deficient sinonasal adenocarcinomas were made up of oncocytoid/plasmacytoid tumor cells in rounded nests with cribriform architecture and myxoid stromal changes (a–b). Overt glandular differentiation was seen in the form of punched-out luminal spaces (c–d). A mucicarmine stains confirms the presence of intracytoplasmic mucin (inset)

Fig. 2

Oncocytoid/plasmacytoid cytomorphology was seen in all cases not only in the glandular tumor component (a), but also the non-glandular areas (b) of the SMARCB1- deficient sinonasal adenocarcinomas. Uncommon features included basaloid (c) and spindle cell (d) patterns, each seen in one case

Fig. 3

Three of the SMARCB1-deficient sinonasal adenocarcinomas exhibited yolk sac tumor-like morphology, here in the form of microcystic and reticular growth patterns in a myxoid stroma (a). These tumors were strongly positive for yolk sac markers like SALL4 (b) and glypican-3 (c). One tumor was reminiscent of the secretory endometrium-like pattern of yolk sac tumor, and a structure resembling a Schiller-Duvall body was identified (d)

Fig. 4

By immunohistochemistry, the SMARCB1-deficient sinonasal adenocarcinomas were consistently negative for SMARCB1 (12 of 12 cases) with retained expression in benign lymphocytes and stromal cells (a), and positive for CK7 (11 of 12 cases) (b), but were otherwise highly variable, with occasional expression of CK20 (c), p40 (d), and other markers