Utility of mammaglobin immunohistochemistry as a proxy marker for the ETV6-NTRK3 translocation in the diagnosis of salivary mammary analogue secretory carcinoma

Justin A. Bishop, Raluca Yonescu, Denise Batista, Shahnaz Begum, David W. Eisele, William H. Westra

Research output: Contribution to journalArticle

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Abstract

Summary Mammary analogue secretory carcinoma is a recently described salivary gland neoplasm defined by ETV6-NTRK3 gene fusion. Mammary analogue secretory carcinoma's morphology is not entirely specific and overlaps with other salivary gland tumors. Documenting ETV6 rearrangement is confirmatory, but most laboratories are not equipped to perform this test. As mammary analogue secretory carcinomas are positive for mammaglobin, immunohistochemistry could potentially replace molecular testing as a confirmatory test, but the specificity of mammaglobin has not been evaluated across a large and diverse group of salivary gland tumors. One hundred thirty-one salivary gland neoplasms were evaluated by routine microscopy, mammaglobin immunohistochemistry, and ETV6 break-apart fluorescent in situ hybridization. The cases included 15 mammary analogue secretory carcinomas, 44 adenoid cystic carcinomas, 33 pleomorphic adenomas, 18 mucoepidermoid carcinomas, 10 acinic cell carcinomas, 4 adenocarcinomas not otherwise specified, 3 polymorphous low-grade adenocarcinomas, 3 salivary duct carcinomas, and 1 low-grade cribriform cystadenocarcinoma. All 15 mammary analogue secretory carcinomas harbored the ETV6 translocation and were strongly mammaglobin positive. None of the 116 other tumors carried the ETV6 translocation; however, mammaglobin staining was present in 1 (100%) of 1 low-grade cribriform cystadenocarcinoma, 2 (67%) of 3 polymorphous low-grade adenocarcinomas, 2 (67%) of 3 salivary duct carcinomas, 2 (11%) of 18 mucoepidermoid carcinomas, and 2 (6%) of 33 pleomorphic adenomas. Mammaglobin is highly sensitive for mammary analogue secretory carcinoma, but immunostaining can occur in a variety of tumors that do not harbor the ETV6 translocation. Strategic use of mammaglobin immunostaining has a role in the differential diagnosis of salivary gland neoplasms, but it should not be indiscriminately used as a confirmatory test for mammary analogue secretory carcinoma.

Original languageEnglish (US)
Pages (from-to)1982-1988
Number of pages7
JournalHuman Pathology
Volume44
Issue number10
DOIs
StatePublished - Oct 1 2013

Fingerprint

Proxy
Immunohistochemistry
Salivary Gland Neoplasms
Cystadenocarcinoma
Salivary Ducts
Mucoepidermoid Carcinoma
Pleomorphic Adenoma
Adenocarcinoma
Glandular and Epithelial Neoplasms
Acinar Cell Carcinoma
Carcinoma
Adenoid Cystic Carcinoma
Gene Fusion
Mammary Analogue Secretory Carcinoma
Fluorescence In Situ Hybridization
Microscopy
Neoplasms
Differential Diagnosis
Staining and Labeling

Keywords

  • Acinic cell carcinoma
  • ETV6-NTRK3
  • Mammaglobin
  • Mammary analogue secretory carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Utility of mammaglobin immunohistochemistry as a proxy marker for the ETV6-NTRK3 translocation in the diagnosis of salivary mammary analogue secretory carcinoma. / Bishop, Justin A.; Yonescu, Raluca; Batista, Denise; Begum, Shahnaz; Eisele, David W.; Westra, William H.

In: Human Pathology, Vol. 44, No. 10, 01.10.2013, p. 1982-1988.

Research output: Contribution to journalArticle

Bishop, Justin A. ; Yonescu, Raluca ; Batista, Denise ; Begum, Shahnaz ; Eisele, David W. ; Westra, William H. / Utility of mammaglobin immunohistochemistry as a proxy marker for the ETV6-NTRK3 translocation in the diagnosis of salivary mammary analogue secretory carcinoma. In: Human Pathology. 2013 ; Vol. 44, No. 10. pp. 1982-1988.
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abstract = "Summary Mammary analogue secretory carcinoma is a recently described salivary gland neoplasm defined by ETV6-NTRK3 gene fusion. Mammary analogue secretory carcinoma's morphology is not entirely specific and overlaps with other salivary gland tumors. Documenting ETV6 rearrangement is confirmatory, but most laboratories are not equipped to perform this test. As mammary analogue secretory carcinomas are positive for mammaglobin, immunohistochemistry could potentially replace molecular testing as a confirmatory test, but the specificity of mammaglobin has not been evaluated across a large and diverse group of salivary gland tumors. One hundred thirty-one salivary gland neoplasms were evaluated by routine microscopy, mammaglobin immunohistochemistry, and ETV6 break-apart fluorescent in situ hybridization. The cases included 15 mammary analogue secretory carcinomas, 44 adenoid cystic carcinomas, 33 pleomorphic adenomas, 18 mucoepidermoid carcinomas, 10 acinic cell carcinomas, 4 adenocarcinomas not otherwise specified, 3 polymorphous low-grade adenocarcinomas, 3 salivary duct carcinomas, and 1 low-grade cribriform cystadenocarcinoma. All 15 mammary analogue secretory carcinomas harbored the ETV6 translocation and were strongly mammaglobin positive. None of the 116 other tumors carried the ETV6 translocation; however, mammaglobin staining was present in 1 (100{\%}) of 1 low-grade cribriform cystadenocarcinoma, 2 (67{\%}) of 3 polymorphous low-grade adenocarcinomas, 2 (67{\%}) of 3 salivary duct carcinomas, 2 (11{\%}) of 18 mucoepidermoid carcinomas, and 2 (6{\%}) of 33 pleomorphic adenomas. Mammaglobin is highly sensitive for mammary analogue secretory carcinoma, but immunostaining can occur in a variety of tumors that do not harbor the ETV6 translocation. Strategic use of mammaglobin immunostaining has a role in the differential diagnosis of salivary gland neoplasms, but it should not be indiscriminately used as a confirmatory test for mammary analogue secretory carcinoma.",
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AB - Summary Mammary analogue secretory carcinoma is a recently described salivary gland neoplasm defined by ETV6-NTRK3 gene fusion. Mammary analogue secretory carcinoma's morphology is not entirely specific and overlaps with other salivary gland tumors. Documenting ETV6 rearrangement is confirmatory, but most laboratories are not equipped to perform this test. As mammary analogue secretory carcinomas are positive for mammaglobin, immunohistochemistry could potentially replace molecular testing as a confirmatory test, but the specificity of mammaglobin has not been evaluated across a large and diverse group of salivary gland tumors. One hundred thirty-one salivary gland neoplasms were evaluated by routine microscopy, mammaglobin immunohistochemistry, and ETV6 break-apart fluorescent in situ hybridization. The cases included 15 mammary analogue secretory carcinomas, 44 adenoid cystic carcinomas, 33 pleomorphic adenomas, 18 mucoepidermoid carcinomas, 10 acinic cell carcinomas, 4 adenocarcinomas not otherwise specified, 3 polymorphous low-grade adenocarcinomas, 3 salivary duct carcinomas, and 1 low-grade cribriform cystadenocarcinoma. All 15 mammary analogue secretory carcinomas harbored the ETV6 translocation and were strongly mammaglobin positive. None of the 116 other tumors carried the ETV6 translocation; however, mammaglobin staining was present in 1 (100%) of 1 low-grade cribriform cystadenocarcinoma, 2 (67%) of 3 polymorphous low-grade adenocarcinomas, 2 (67%) of 3 salivary duct carcinomas, 2 (11%) of 18 mucoepidermoid carcinomas, and 2 (6%) of 33 pleomorphic adenomas. Mammaglobin is highly sensitive for mammary analogue secretory carcinoma, but immunostaining can occur in a variety of tumors that do not harbor the ETV6 translocation. Strategic use of mammaglobin immunostaining has a role in the differential diagnosis of salivary gland neoplasms, but it should not be indiscriminately used as a confirmatory test for mammary analogue secretory carcinoma.

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KW - Mammaglobin

KW - Mammary analogue secretory carcinoma

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