Salivary Gland–like Tumors of the Breast

Overview of Salivary Gland-like Tumors of the Breast

• These tumors are classified by the World Health Organization (WHO) and share features with salivary gland tumors.

• Focus on histologic, immunophenotypic, molecular, and clinical features.

• Triple-negative phenotype (negative for estrogen receptor (ER), progesterone receptor (PR), HER2) yet often better prognosis than standard triple-negative carcinomas.

Special Type Salivary Gland-like Breast Carcinomas

• Types include:

  • Adenoid cystic carcinoma (AdCC)

  • Secretory carcinoma (SC)

  • Mucoepidermoid carcinoma (MEC)

  • Polymorphous adenocarcinoma (PAC)

  • Acinic cell carcinoma (AciCC)

  • Pleomorphic adenoma (PA)

  • Adenomyoepithelioma (AME)

• Key focus on similarities and differences between breast and salivary gland counterparts.

Adenoid Cystic Carcinoma (AdCC)

Histologic and Immunohistochemical Features

• Characterized by biphasic morphology with luminal and basaloid/myoepithelial cell components.

• Luminal cells form ductal structures; basaloid cells form pseudolumina.

• Immunohistochemical markers:

  • Luminal component: CK7, KIT

  • Basaloid/myoepithelial: CK 5/6, p63, smooth muscle actin.

• Different growth patterns observed (tubular, cribriform, trabecular).

Clinical Behavior and Prognosis

• Associated with good prognosis and low metastasis risk post-excision.

• Lack of benefit from chemotherapy despite being triple-negative.

• Solid variant exhibits more aggressive behavior: high local recurrence rates and lymph node involvement.

Molecular Findings

• Associated with recurrent genetic alterations:

  • MYB::NFIB fusion and MYBL1 rearrangements.

  • MYB overexpression linked to cancer development.

  • Solid variant shows NOTCH1 and CREBBP mutations.

Secretory Carcinoma (SC)

Histologic and Immunohistochemical Features

• Characterized by tubules, cords, nests with eosinophilic cytoplasm.

• Typically triple-negative but may express low hormone levels.

• Expresses SOX10, mammaglobin; distinct from its salivary gland counterpart using MUC4 as a marker.

Molecular Findings

• T(12;15) translocation leading to ETV6::NTRK3 fusion.

• Highly sensitive FISH tests developed for diagnosis.

• Pan-TRK immunohistochemistry can support diagnosis and predict sensitivity to TRK inhibitors.

Mucoepidermoid Carcinoma (MEC)

Histologic and Immunohistochemical Features

• Composed of epidermoid, intermediate, and mucous cells.

• Typically negative for ER, PR, and HER2; positive for high & low molecular weight cytokeratins and p63.

• Characterized by multiple different cell types.

Prognosis

• Generally good prognosis compared to triple-negative breast carcinomas; low-grade MECs are particularly indolent.

Molecular Findings

• Associated with t(11;19) forming CRTC1::MAML2 fusion, often seen in low-grade tumors.

• FISH diagnostic assays for confirming rearrangements.

Acinic Cell Carcinoma (AciCC)

Distinctions from Salivary Gland Carcinomas

• Morphologic overlap but different molecular features from salivary AciCC.

• Typical features include eosinophilic cytoplasm with granules and luminal secretions.

Clinical Behavior

• Generally indolent but can be associated with aggressive triple-negative types.

Molecular Findings

• Frequent mutations include TP53, PIK3CA, and low levels of chromosomal instability.

Pleomorphic Adenoma (PA)

Characteristics

• Rare benign tumor with epithelial and myoepithelial components; shows variable morphology.

• Immunohistochemical profile: myoepithelial markers like smooth muscle actin and S100 protein

Molecular Findings

• Some cases harbor rearrangements involving PLAG1 or HMGA2.

• Potential for local recurrence and malignant transformation.

Adenomyoepithelioma (AME)

Features

• Biphasic proliferation of epithelial and myoepithelial cells; can undergo malignant transformation.

• Distinct from salivary EMC in clinical behavior and grading of malignancy.

Polymorphous Adenocarcinoma (PAC)

Rare Type

• Extremely rare with distinct infiltrative growth patterns.

• Key molecular alterations involve PRKD gene mutations.

Conclusions

• Recognition and accurate diagnosis of these tumor types is crucial for determining prognosis and treatment plans.

• Research and diagnostic methods continue to evolve for better understanding of these tumors and their behaviors.