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.

Keywords: Adenocarcinoma; DOG1; Non-intestinal; SOX10; Seromucinous.

Fig. 1

Morphologic spectrum of ITAC. a PTCC-I showing a predominantly papillary growth pattern (H&E, ×40), and stratification of fairly monomorphic nuclei resembling the appearance of a colonic adenoma (inset H&E, ×200). b PTCC-II showing a tubular and cribriform growth with stromal reaction similar to colorectal carcinoma (H&E, ×40), and more cytonuclear atypia and apoptotic debris (inset H&E, ×200). c AGC showing predominantly mucin filled spaces akin to a mucinous adenocarcinoma of colon (H&E, ×40), tumor nests are found floating in the mucin filled spaces (inset H&E, ×200). d PTCC-III showing a solid growth pattern and cytologic atypia (H&E, ×100). e Recurrence of same case showing SRC pattern instead (H&E, ×100)

Fig. 2

Morphologic spectrum of non-ITAC. a SSH-like (minimal deviation) non-ITAC showing a rounded tubulolobular growth similar to SSH, but with larger more confluent tumor nests (H&E, ×40). This tumor is low grade and composed of bland monomorphic tubules with almost no nuclear atypia (inset H&E, ×200). b Tubulopapillary non-ITAC showing columnar cells with nuclear stratification evident even at this magnification (H&E, ×40). This tumor is intermediate grade with nuclear membrane irregularities and prominent nucleoli with some mitotic activity (inset H&E, ×200). c Solid-cribriform non-ITAC with prominent central comedonecrosis (H&E, ×40). This tumor is high grade with prominent nuclear pleomorphism in addition to the necrosis (inset H&E, ×200). d Non-ITAC with tubulopapillary areas and intermediate nuclear grade (H&E, ×100). e The majority of this same case, however, showed solid ribbon like trabecular growth reported in ‘blastomatous’ tumors (H&E, ×100)

Fig. 3

Variant morphologies in tubulopapillary non-ITAC. a Low grade tumor with micro and macrocystic change (H&E, ×100). b Low grade tumor with prominent psammoma-like calcifications (H&E, ×100). c Low grade tumor with lymphoplasmacytic infiltrates in papillae resembling those of salivary Warthin tumor (H&E, ×100)

Fig. 4

Morphologic features of SSH. a SSH tended to be small polypoid lesions (H&E, ×40) with a lobular proliferation of acini, mostly serous (inset H&E, ×200). b A larger SSH with respiratory epithelial adenomatoid hamartoma caliber glandular spaces (H&E, ×40)

Fig. 5

Squamoid morular metaplasia. a Squamoid morular metaplasia in non-ITAC with central cystic change with foamy macrophages (H&E, ×200). b Less mature squamoid morule (arrow) in SSH. (H&E, ×200)

Fig. 6

Immunophenotype of ITAC, non-ITAC, and SSH using classical markers. a ITAC (H&E, ×40 showing. b CK20 (×100). c CDX2 (×100) positivity. d focal CK7 positivity (×100). e Intermediate grade tubulopapillary non-ITAC (H&E, ×40) showing. f CK20 (×100), and g CDX2 (×100) negativity, and h CK7 positivity (×100). i SSH (H&E, ×40) similarly showing j CK20 (×100), and k CDX2 (×100) negativity, and l CK7 positivity (×100). However, a subset of non-ITAC and SSH showed m squamoid morular metaplasia (H&E, ×100) which showed n CDX2 positivity in the morules (×200). o This corresponded to areas of nuclear accumulation of β-catenin (×200)

Fig. 7

Immunophenotype of SSH and non-ITAC using markers of seromucinous differentiation. a SSH (H&E, ×40) showing b S100 positivity in serous acini (×100), c DOG1 apical luminal staining mainly in serous acini (×100), and d SOX10 expression in all acini (×100). e Intermediate grade tubulopapillary non-ITAC (H&E, ×40) showing f focal S100 positivity (×100), g weak DOG1 apical luminal staining (×100), and h SOX10 positivity (×100)