Low Grade Papillary Sinonasal (Schneiderian) Carcinoma: A Series of Five Cases of a Unique Malignant Neoplasm with Comparison to Inverted Papilloma and Conventional Nonkeratinizing Squamous Cell Carcinoma

Abstract

There have been a few case reports and one small series of low grade papillary sinonasal (Schneiderian) carcinomas (LGPSC) which mimic papillomas but have overtly invasive growth and which occasionally metastasize. We describe the morphologic, clinical, immunohistochemical, and molecular features of five patients with LGPSC compared with eight cases each of inverted papilloma (IP) and conventional nonkeratinizing squamous cell carcinoma (SCC) with papillary growth. All LGPSC were nested with predominantly pushing invasion, no stromal reaction, and frequent surface papillary growth. All consisted of one cell type only, with polygonal cells with round nuclei, no (or limited) cytologic atypia, low mitotic activity, and prominent neutrophilic infiltrate. One patient had slightly more infiltrative bone invasion, another lymphovascular, perineural, and skeletal muscle invasion, and a third nodal metastasis after 17 years. By comparison, IPs had bland cytology, neutrophilic microabscesses, mixed immature squamous, goblet cell, and respiratory epithelium, and extremely low mitotic activity. Nonkeratinizing SCCs had basaloid-appearing cells with nuclear pleomorphism, brisk mitotic activity, and apoptosis. All LGPSC were p63 positive. Mitotic activity and Ki67 indices were significantly higher for LGPSCs than IPs and significantly lower than NKSCCs, while p53 immunohistochemistry in LGPSC was identical to nonkeratinizing SCC and higher than for IP. Sequencing showed all five tumors to harbor a MUC6 mutation, one tumor to harbor CDKN2A and PIK3R1 mutations, and one tumor to harbor a NOTCH1 mutation. All LGPSC lacked EGFR and KRAS mutations and lacked copy number variations of any main cancer genes. At a median follow up of 12 months, two LGPSC recurred locally, and one patient died after massive local recurrences and nodal metastases. LGPSC is a distinct, de novo sinonasal carcinoma that can be differentiated from papillomas by morphology and selected immunohistochemistry.

Keywords: Human papillomavirus; Low grade papillary sinonasal carcinoma; Nonkeratinizing squamous cell carcinoma; Papilloma; Sinonasal; p16.

Fig. 1

Low power histologic features of LGPSC with a mixture of papillary, surface ribbony, and solid nested tumor. A LGPSC #1 at first presentation showing papillary, exophytic growth pattern of stratified epithelium (× 2 magnification) B LGPSC #1 at recurrence with nearly solid central growth with rounded nests pushing together (× 10 magnification) C LGPSC #3 with large, inter-anastomosing solid ribbons of surface tumor with smooth edges (× 2 magnification) D LGPSC #2 with solid, rounded nests of cells in a fibrous stroma (× 10 magnification) E LGPSC #4 with solid, rounded nests of cells in a fibrous stroma with occasional open spaces (× 4 magnification) F LGPSC #5 with surface involvement with papillary, exophytic fronds of discohesive tumor cells (× 10 magnification)

Fig. 2

Medium power histologic features of LGPSC. A LGPSC #5 showing ribbons and rounded nests of bland cells with brisk neutrophil-rich inflammation and lacking stromal desmoplastic reaction (× 10 magnification) B LGPSC #3 with large, rounded nests of bland cells lacking stromal desmoplastic reaction despite the invasive growth. (× 10 magnification) C LGPSC #2 showing extensive bone invasion (× 8 magnification)

Fig. 3

High power features of LGPSC demonstrating the cytomorphology. A LGPSC #1 with surface involvement with discohesive, polygonal cells with eosinophilic cytoplasm, monomorphic, round to irregular nuclei, and prominent neutrophil infiltrate (× 40 magnification) B LGPSC #3 with solid nests of polygonal cells with moderate to abundant, eosinophilic cytoplasm, well-defined cell borders, and monomorphic, round to irregular nuclei (× 40 magnification) C LGPSC #5 with surface papillary growth, discohesive, polygonal cells with round nuclei, small but prominent nucleoli, and a brisk neutrophil infiltrate (× 20 magnification)

Fig. 4

Histologic features of inverted papilloma. A Low power view showing large, rounded nests of cells, some solid and some with luminal spaces, pushing into the loose underlying submucosa (× 4 magnification). B Thickened lining epithelium with immature squamoid cells with round, bland nuclei and mixed surface ciliated respiratory cells (× 20 magnification)

Fig. 5

Histologic features of conventional nonkeratinizing SCC. A Low power view showing large, solid, ribbony and pushing nests of basaloid tumor cells (× 2 magnification). B An extensively papillary nonkeratinizing SCC showing papillae lined by basaloid tumor cells (× 4 magnification). C High power view of nonkeratinizing SCC consisting of full thickness surface involvement by basaloid tumor cells with minimal cytoplasm, angulated hyperchromatic nuclei, and prominent mitotic activity and apoptosis (× 20 magnification)

Fig. 6

Immunohistochemical stains for Ki-67 and p53. A Inverted papilloma showing low (15%) Ki-67 expression with a distinctly zonal (basal) distribution of staining (× 10 magnification) B Inverted papilloma showing low (10%) p53 expression (× 10 magnification). C Nonkeratinizing SCC showing diffuse Ki-67 expression (98%) (× 4 magnification). D Nonkeratinizing SCC showing prominent nuclear p53 expression (50%) (× 10 magnification). E LGPSC showing modest Ki-67 expression with no apparent zonal pattern even in areas of surface epithelial involvement (× 10 magnification). F LGPSC showing prominent (60%) nuclear p53 expression (× 10 magnification)