Secretory Carcinoma of the Parotid: Making the Correct Diagnosis of a Rare Salivary Gland Carcinoma When Molecular Biology Testing Is Not Available

Table 2

Key elements in the differential diagnosis of secretory carcinoma.

	Secretory carcinoma	Acinic cell carcinoma	Intraductal carcinoma (low-grade cribriform cystadenocarcinoma)	Low-grade mucoepidermoid carcinoma
Location	Parotid gland (75%); present in minor salivary glands, more frequently than ACC, and in the oral cavity	Parotid (90%); very rarely in minor salivary glands	Parotid, most frequently; tongue (posterior region) and minor salivary glands	Parotid (50%) and oral cavity (palate and oral mucosa); very rarely (1-2%) in the submandibular gland; Also described in the lacrimal gland, larynx, nose, and paranasal sinuses
Prevalence by sex	Slight male predominance	Female predominance	The same for both sexes	The same for both sexes
Morphological growth patterns	Predominantly tubular, microcystic, and solid; More frequently cystic-papillary than in ACC	Common: solid, follicular, and microcystic; Rare: cystic-papillary	Encapsulated and cystic, with cribriform and papillary patterns	Heterogeneous pattern: solid and cystic with hydropic degeneration and metaplastic changes
Cell morphology	Epithelial, without acinar differentiation	Acinar and basophilic	Monotonous, with ductal, cuboidal, and apocrine characteristics	Morphologically bland epidermoid, mucinous, and intermediate cells that are oncocytic, clear, or columnar/polygonal
Cytoplasm	Eosinophilic, granular, or vacuolated; no zymogen granules	PAS positive zymogen granules	Eosinophilic, very infrequently with iron pigment	Abundant, clear (mucicarmine, Alcian blue, and PAS-diastase positive), eosinophilic, and foamy
Nuclei	Round or oval	Monomorphic	Clear vesicular nuclei with the appearance of frosted glass that overlap one another	Small hyperchromatic nuclei
Immunohistochemistry	S-100 protein and mammaglobin positive; Usually positive for STAT5a and DOG-1; p63 negative	Mammaglobin and p63 negative; S-100 protein usually negative; DOG-1 intensely positive with apical pattern	S-100 protein, vimentin, and mammaglobin positive; p63- and calponin-positive myoepithelial cells	Positive p63 staining in epidermoid foci and usually S100 and mammaglobin negative
Molecular Alteration	t(12;15) ETV6-NTRK3, 80% of cases; Rearrangements in the ETV6 gene, 99% of cases (ETV6-RET and ETV6-MET fusion reported)	HTN3-MSANTD3 fusion described in a subset of cases [31]	NCOA4-RET and TRIM27-RET fusion genes [32, 33]	t(11;19) CRTC1-MAML2; t(11;15) CRTC3-MAML2

There is a type of acinic cell carcinoma whose cells contain few zymogen granules. In these cases, the differential diagnosis of SC relies mainly on molecular analysis.