The Decline of Salivary Adenocarcinoma Not Otherwise Specified as a Tumor Entity: Reclassification Using Contemporary Immunohistochemical Profiling and Diagnostic Criteria

Am J Surg Pathol. 2021 Jun 1;45(6):753-764. doi: 10.1097/PAS.0000000000001636.


The classification of salivary gland carcinomas has become increasingly specific over the last decade with the definition of new tumor types, documentation of novel molecular and immunohistochemical findings, and development of more refined diagnostic criteria. In this setting, it is unclear how many salivary tumors still cannot be easily categorized-and whether such tumors represent undifferentiated malignancies or include additional definable entities. Relying largely on current classification schemes and contemporary immunohistochemical panels, we reassessed salivary tumors previously diagnosed as adenocarcinoma, not otherwise specified (ACA NOS) from 2 large academic medical centers. Fifty-seven ACA NOS (72%) could be reclassified as more specific entities including 31 salivary duct carcinomas (39%), 7 polymorphous adenocarcinomas (9%), 5 epithelial-myoepithelial carcinomas (6%), 4 myoepithelial carcinomas (5%), 4 secretory carcinomas (5%), 1 acinic cell carcinoma (1%), 1 basal cell adenocarcinoma (1%), 1 intraductal carcinoma (1%), and 1 clear cell carcinoma (1%) as well as 2 metastatic squamous cell carcinomas (3%). Of reclassified cases, 21 (37%) represented variant histologies within these categories. ACA NOS comprised 11% of salivary malignancies before reclassification, but only 4% after reclassification. The remaining 22 ACA NOS demonstrated heterogeneous features, with an association between histologic grade and clinical outcome. In effect, ACA NOS is becoming a bygone entity as modern classification schemes and ancillary techniques now permit more specific typing of a majority of these tumors, potentially facilitating more specific prognostication and treatment. Additional distinctive entities such as mucinous adenocarcinoma may still be definable within the ACA NOS category.

Publication types

  • Multicenter Study

MeSH terms

  • Adenocarcinoma / chemistry*
  • Adenocarcinoma / classification
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Child
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry*
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Predictive Value of Tests
  • Salivary Gland Neoplasms / chemistry*
  • Salivary Gland Neoplasms / classification
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / pathology
  • Terminology as Topic*
  • Tissue Array Analysis
  • United States
  • Young Adult


  • Biomarkers, Tumor