Proceedings of the North American Society of Head and Neck Pathology Companion Meeting, New Orleans, LA, March 12, 2023: Classification of Salivary Gland Tumors: Remaining Controversial Issues?

Although much has been learned about this IDC in the recent years, unanswered questions remain. Most controversial issue is the terminology and the biological potential of IDC. For example, the description of frankly invasive and metastasizing IDCs with canonical NCOA4::RET fusion casts doubt on its current name “intraductal carcinoma”.

Intraductal papillary mucinous neoplasms (IPMNs) were recently described as a distinct minor salivary gland tumor entity. Mucinous adenocarcinoma (MA) shows variable morphology and is defined as a primary salivary gland carcinoma that displays prominent intracellular and/or extracellular mucin. IPMN, however, shares many similarities with low-grade, papillary-cystic forms of MA, including the identical activating AKT1 p.Glu17Lys (alias p.E17K) gene mutation, and therefore, it was originally proposed as a subtype within the spectrum of low-grade MA in the 5th edition of the WHO Classification of Head and Neck Tumours. Consensus has not been reached, and after a difficult discussion of the WHO Editorial Board, finally IPMN was not included. It is a matter of controversy if IPMN represents a low-grade form of MA, a non-invasive precursor neoplasm, or distinct entity.

Salivary pathology is a rapidly evolving field in which novel molecular discoveries have driven multiple changes in the tumor classification. While in most instances, the discovery of the molecular changes have helped clarify the classification, in certain instances, they had the opposite effect of obscuring the boundaries between entities and creating controversies. This is well illustrated in the case of IPMN versus MA, which both share the same AKT1 p.E17K mutation, which can be interpreted as supportive of merging these entities under one umbrella or as simply a case of two separate entities having the same mutation. Similarly, the molecular testing has allowed reclassification of most oncocytic carcinomas into other salivary carcinoma types leading to an unresolved question of whether there are any true oncocytic salivary carcinomas, and thus, if the entity should be retained as a standalone entity in the classification. Since the answer to this question is unknown, the entity has been placed in the emerging and provisional entities chapter for now. In case of IDC, the molecular discoveries suggest that it is a heterogenous group of tumors; however, whether they should all be considered subtypes of IDC or as separate entities remain to be seen. Finally, the recent molecular profiling of SCS suggests that the entity is likely a carcinoma ex-PA (CEPA) with sarcomatous transformation rather than a true sarcoma in most if not all cases, and this may lead to its reclassification as a variant of CEPA in the future editions of the WHO classification.