Why test for mammaglobin (mammaglobin) in salivary gland pathology?

Mammaglobin Testing in Salivary Gland Pathology

Mammaglobin testing in salivary gland pathology is primarily indicated as an ancillary immunohistochemical marker to help identify mammary analogue secretory carcinoma (MASC), but should not be used alone as a confirmatory test due to its expression in other salivary gland tumors. 1, 2

Role of Mammaglobin in Salivary Gland Tumor Diagnosis

Primary Indication

Mammaglobin testing serves as a useful screening tool in the diagnostic workup of salivary gland tumors, particularly when MASC is suspected. MASC is a relatively recently described salivary gland tumor that shares morphologic features with secretory carcinoma of the breast and harbors the ETV6-NTRK3 translocation.

Diagnostic Algorithm

1. Initial Assessment: Fine needle aspiration biopsy (FNAB) or core needle biopsy (CNB) to distinguish salivary gland cancers from non-malignant lesions 3

2. When Mammaglobin Testing is Indicated:

   • When morphologic features suggest MASC
   • To differentiate MASC from its mimics (especially acinic cell carcinoma)
   • When standard histopathology is inconclusive

3. Interpretation of Mammaglobin Results:

   • Positive mammaglobin staining is highly sensitive for MASC (100% of cases) 2
   • However, mammaglobin positivity is NOT specific to MASC and can be seen in:
     • 60% of polymorphous low-grade adenocarcinomas 1
     • 13.3% of adenoid cystic carcinomas 1
     • 100% of low-grade cribriform cystadenocarcinomas 2
     • 67% of salivary duct carcinomas 2
     • 11% of mucoepidermoid carcinomas 2
     • 6% of pleomorphic adenomas 2

4. Confirmatory Testing:

   • Positive mammaglobin should be followed by ETV6 break-apart fluorescent in situ hybridization (FISH) to confirm MASC diagnosis 2
   • Only tumors with ETV6 translocation are true MASC

Clinical Implications and Best Practices

Strength of Evidence

The 2021 ASCO guideline on management of salivary gland malignancy states that pathologists may perform ancillary testing (including immunohistochemistry) on FNABs and core needle biopsies to support diagnosis and risk of malignancy assessment (weak recommendation, low quality evidence) 3.

Practical Considerations

• Mammaglobin testing should be used strategically as part of a panel approach, not as a standalone test 2
• Consider combining mammaglobin with other markers:
  • S-100 co-expression is common in MASC 1
  • Cytoplasmic p63 staining may help identify tumors worth screening for ETV6 rearrangement 4

Potential Pitfalls

• Major pitfall: Relying solely on mammaglobin positivity to diagnose MASC without ETV6 translocation confirmation 2
• Over-interpretation of mammaglobin positivity in other salivary gland tumors
• Failure to recognize that mammaglobin expression occurs in approximately 15% of non-breast cancers, including some salivary gland tumors 5

Impact on Patient Management

Accurate diagnosis through appropriate use of mammaglobin testing and confirmatory molecular studies helps guide proper surgical management and treatment planning, which directly impacts patient morbidity, mortality, and quality of life. The extent of surgical resection and need for adjuvant therapy differ based on tumor type and grade 3.

In summary, mammaglobin testing in salivary gland pathology is a valuable tool when used appropriately as part of a comprehensive diagnostic approach, but molecular confirmation of ETV6 rearrangement is necessary for definitive MASC diagnosis.