Secretory Carcinoma (Mammary Analogue Secretory Carcinoma)

• Low- to intermediate-grade malignant salivary gland tumor showing morphologic and molecular resemblance to breast secretory carcinoma.

• Most arise in the parotid, but may occur in minor salivary glands.

• Affects wide age range, including young adults; no strong sex predilection.

• Typically presents as a slow-growing, painless mass.

Driven by ETV6::NTRK3 fusion (classic) → constitutive TRK signaling → promotes secretory differentiation and low-grade tumorigenesis.

Fusion leads to intracellular protein accumulation → secretory, vacuolated cytoplasm and luminal secretions.

Rare alternative fusions involve ETV6 with other tyrosine kinase partners, but clinical behavior is similar.

Architecture: Microcystic, solid, tubular, and papillary-cystic patterns.

Cells: Polygonal cells with eosinophilic to vacuolated cytoplasm, often with bubbly/secretory appearance.

Lumina: Filled with eosinophilic secretions resembling breast secretory carcinoma.

Nuclei: Round to oval, low-grade atypia; small nucleoli.

Stroma: Fibrous; may have focal sclerosis.

• Pearls / Pitfalls:

Cells may resemble acinic cell carcinoma, but lack basophilic zymogen granules.

Abundant eosinophilic secretions are a diagnostic hint.

Key markers (≤5):

• S100: strong, diffuse.

• SOX10: positive.

• Mammaglobin: positive (mirrors breast secretory carcinoma).

• CK7: positive.

• Negative / helpful: Typically DOG1-, which helps exclude acinic cell carcinoma (DOG1+).

• (Supported by IHC tables: SC is S100+/mammaglobin+/SOX10+, DOG1–.)

Molecular:

• ETV6::NTRK3 fusion (canonical).

• Molecular confirmation is highly specific and often performed in equivocal cases.

Acinic Cell Carcinoma (AciCC)

• Basophilic granular cytoplasm (zymogen granules), DOG1+, NR4A3-related.

• Secretory carcinoma has eosinophilic/vacuolated cytoplasm, S100+/mammaglobin+, DOG1–.

Mucoepidermoid Carcinoma (MEC)

• Triphasic mucous / intermediate / squamoid cells; often MAML2 fusion.

• Secretory carcinoma lacks mucous cells and shows ETV6-NTRK3 fusion.

Adenoid Cystic Carcinoma (ACC)

• Cribriform spaces with basement-membrane globules; CD117+, MYB+.

• Secretory carcinoma lacks true basement-membrane globules and is mammaglobin+.

Pleomorphic Adenoma

• Mixed epithelial + myoepithelial components with chondromyxoid stroma; PLAG1/HMGA2 alterations.

• Secretory carcinoma shows uniform epithelial differentiation with secretions.

Low-grade Cribriform Adenocarcinoma of the Tongue

• Distinct site (oropharyngeal tongue base), S100+/SOX10+, but lacks ETV6-NTRK3 fusion and lacks eosinophilic intraluminal secretions.

Parotid gland, excision:

• Secretory carcinoma.

• Comment: Low-grade malignant salivary gland neoplasm with microcystic and papillary-cystic architecture, eosinophilic secretions, and S100/mammaglobin positivity. Molecular testing confirms ETV6-NTRK3 fusion. Margins are negative.