SMARCB1(INI1)-deficient sinonasal basaloid carcinoma: a novel member of the expanding family of SMARCB1-deficient neoplasms

Abstract

Poorly differentiated sinonasal carcinomas are a heterogenous group of aggressive neoplasms that encompasses squamous cell carcinoma including basaloid variant, lymphoepithelial carcinoma, sinonasal undifferentiated carcinoma, and neuroendocrine-type small cell carcinoma. We herein describe 3 cases of a hitherto unreported variant combining features of basaloid carcinoma with variable intermingled rhabdoid cells. Patients were 2 women (aged 28 and 35) and a man (52 y) who presented with sinonasal masses. All had advanced local disease with bone involvement (pT4). None had a history of irradiation or a family history of rhabdoid tumors. Treatment was surgery and adjuvant chemoradiation. One patient developed liver, lung, pleural, and pericardial metastases (63 mo) and is currently (70 mo) alive under palliative treatment. Another developed recurrent cervical lymph node metastases and died of disease 8.5 years later. The youngest patient was disease-free at last follow-up 7 years later. Histologic features were very similar in all 3 cases and showed intimate admixture of compact basaloid cell nests with peripheral palisading, perivascular pseudorosettes, and a few scattered rhabdoid cells. Rhabdoid cells were more extensive in the metastasis in 1 case but formed a minor inconspicuous component in the primary tumors in all cases. Striking features common to all cases were (1) basaloid "blue" appearance at low power, (2) papilloma-like exophytic component, (3) extensive pagetoid surface growth with prominent denuding features, and (4) replacement of underlying mucous glands mimicking an inverted papilloma. Clear-cut origin from benign papilloma and overt squamous differentiation were lacking. Diffuse (2) or partial (1) p16 expression was noted, but all cases lacked human papillomavirus DNA by molecular tests. In situ hybridization was negative for Epstein-Barr virus. Immunohistochemistry showed diffuse expression of pancytokeratin. CK5 and vimentin showed intermingling of CK5/vimentin basaloid and CK5/vimentin rhabdoid cells. Complete loss of nuclear SMARCB1 expression was seen in all cases including also the denuding carcinoma in situ-like surface lesions. To our knowledge, this variant of sinonasal carcinoma has not been reported before. The identical features in all 3 cases suggest a specific disease rather than a nonspecific dedifferentiated phenotype. Awareness of this rare variant and thus reporting of additional cases is necessary for defining its full morphologic and biological spectrum.

FIGURE 1

Representative magnetic resonance tomography of case 1 showed a mass in the right anterior ethmoid cells extending into both frontal sinuses with destruction of the frontal bone and the right medial orbital wall. The lesion has a salt and pepper–like appearance on both postcontrast T1w images (A, B, D) and T2w images (C). Infiltration of the extraconal space and displacement of the right eye ball were noted.

FIGURE 2

Histologic appearance of SMARCB1-negative sinonasal carcinomas. A, Characteristic papillary superficial pattern in the primary tumor of case 1. B, Same case showed prominent rhabdoid cells amid “blue” basaloid cells. C, Monotonous basaloid pattern in case 2. D, Angiocentric growth with perivascular pseudorosettes was seen in all cases. Note monotonous cell morphology and inversed polarity of nuclei. E, Prominent rhabdoid inclusions were seen in the basal layers in this area from case 3 (arrows; note dsycohesive central areas mimicking squamoid cells). F, Area with high-grade nuclear features and necrosis (case 3).

FIGURE 3

Spectrum of surface changes seen in the mucosa overlying SMARCB1-negative sinonasal carcinomas. A, Dyscohesive “denuding” atypical neoplastic cells covered the papillary fronds (case 3). B, These cells are negative for SMARCB1 (stromal and endothelial cells in the papillary cores stained positive). C, Pagetoid spread (long black thin arrows) was seen beneath ciliated respiratory epithelium (thick arrow; case 1). C inset, This case strongly expressed p16 in the invasive tumor (right) and in the pagetoid surface component (left), note scattered p16-negative residual normal epithelial cells on top of staining cells (arrow heads). D, Case 2 showed superficial flat-papillary growth closely mimicking Schneiderian papilloma with spreading along deep submucosal glands. E, Residual lumen is seen indicating preexistent normal gland (uninvolved part of the gland is also seen on the left). This case was initially misinterpreted as inverted papilloma. F, Case 3 showed areas of plump fused papillae resulting in pleomorphic basaloid CIS-like appearance.

FIGURE 4

Immunohistochemical findings in SMARCB1-negative sinonasal carcinomas. A, Pancytokeratin (KL-1) was expressed in almost all tumor cells in all cases and showed diffuse or punctate perinuclear cytoplasmic pattern. B, Vimentin expression varied from diffuse (right) to partial/hybrid pattern (left). Note characteristic paranuclear dot-like pattern highlighting rhabdoid cells. C, CK5 showed an inverse pattern compared with that of vimentin indicating a dual population of CK5⁺/vimentin⁻ (basaloid) and CK5⁻/vimentin⁺ (rhabdoid) cells. D, Complete loss of nuclear SMARCB1/INI1 expression (case 1, note strong staining in inflammatory and endothelial cells).