A Subset of Sinonasal Non-Intestinal Type Adenocarcinomas are Truly Seromucinous Adenocarcinomas: A Morphologic and Immunophenotypic Assessment and Description of a Novel Pitfall

Abstract

While sinonasal intestinal type adenocarcinoma (ITAC) is defined by an intestinal phenotype, non-intestinal type adenocarcinoma (non-ITAC) is traditionally viewed as a diagnosis of exclusion, despite previous implication of a seromucinous phenotype and similarity to sinonasal seromucinous hamartomas (SSH). We performed a comparison of clinicopathologic and immunophenotypic features of ITAC, non-ITAC and SSH using traditional discriminatory markers and new markers of seromucinous differentiation. Twenty-three non-ITAC, 17 ITAC, and 5 SSH were retrieved (1987-2014). As expected, ITAC occurred predominantly in the nasal cavity in elderly patients (mean age 65 years) with a striking male predilection (15:2). Regardless of grade/subtype, all ITAC were invariably CK20 and CDX2 positive, and many (11/15) showed some CK7 positivity. Non-ITAC occurred in younger individuals (mean age 51 years) with a slight female predilection (male to female ratio: 10:13) and showed diverse morphologic patterns and grades, some with morphologic similarity to SSH. SSH occurred in younger individuals (mean age 33 years). Non-ITAC and SSH were invariably CK7 positive and CK20 negative, however, 4/22 non-ITAC and 2/5 SSH showed squamoid morular metaplasia that aberrantly expressed CDX2 and co-expressed nuclear β-catenin. Markers of seromucinous differentiation (S100, DOG1, and SOX10) were essentially absent in ITAC, but present to varying degrees in the majority of non-ITAC and all SSH. Thus, the term 'seromucinous adenocarcinoma' is the more appropriate designation for non-ITAC. Squamoid morules in non-ITAC and SSH may be an immunophenotypic pitfall given the aberrant CDX2 expression.

Sinonasal Adenocarcinoma: Update on Classification, Immunophenotype and Molecular Features

“…Immunohistochemically, they are constantly positive for CK7, but usually negative for CK20 and CDX-2. Some 20 % of these tumors associate with sinonasal seromucinous hamartomas or respiratory epithelial adenomatoid hamartomas [ 39 , 41 , 42 ]. Due to positivity for markers of seromucinous differentiation such as DOG1, SOX10, and S-100, a subset of these carcinomas was called sinonasal seromucinous adenocarcinomas [ 42 ].…”

Sinonasal Renal Cell-Like Carcinoma: Case Report and Review of the Literature

“…One previous case tested for DOG-1 [10] was reportedly negative, but here it is positive along with SOX-10. DOG-1, a calcium dependent chloride channel, demonstrates moderate apical staining in the sinonasal seromucinous glands [14,15]. Similarly SOX-10 is strongly expressed insinonasal glands [14].…”

Renal cell -like carcinoma of the nasal cavity: a case report and review of the literature

“…At present, the histogenesis of SRCLC remains uncertain. New markers for seromucinous glands, including sinonasal glands, namely DOG1, SOX10 and S100 have been defined [ 20 , 21 ]. DOG1, a calcium-activated chloride channel, initially described in gastrointestinal stromal tumors, but now known to be expressed in normal sinonasal seromucinous glands, it shows moderate apical luminal staining of serous acini with weaker staining in mucous acini.…”

“…Our study shows that tumor cells in SRCLC are positive for two of these three seromucinous markers, suggesting possible seromucinous derivation of SRCLC. It has also been reported that markers of seromucinous differentiation are present to varying degrees in the majority of low-grade non-intestinal-type adenocarcinomas [ 21 ]; a term which has been used synonymously with renal cell -like carcinoma (SRCLC) in the new edition of WHO classification of head and neck tumors [ 22 ]. With a common seromucinous phenotype, we conclude that SRCLC is likely a clear cell variant of sinonasal non-intestinal type adenocarcinoma.…”