Palisading Adenocarcinoma: Several New Inherited Cases in Six Patients of a Familial Cohort.

Abstract

Introduction: The past two decades have seen the introduction of several new variants of established salivary gland tumors, along with occasional, entirely novel entities. Palisading adenocarcinoma was described in 2023 with a handful of subsequent additional case reports. We encountered several seemingly inherited cases of palisading adenocarcinoma in a familial cohort.

Methods: Within the affected family, all available archival surgical pathology and cytopathology material was retrieved and reviewed. Clinical history was obtained through chart review. Whole-exome sequencing was performed on two cases.

Results: Six patients were affected by palisading adenocarcinoma. The patients ranged from 33 to 72 years (mean, 52.3 years) and were all women. Each patient had ≥ 2 documented tumors, and the locations of involvement were: parotid gland (n = 7), floor of mouth (n = 4), submandibular gland (n = 3), neck (n = 2), orbit (n = 1), and maxilla (n = 1). Although not every clinically documented case was available for histologic review, all cases that were evaluated demonstrated the features described for palisading adenocarcinoma, including two cell populations of ducts with polygonal neuroendocrine-like cells arranged as trabeculae with palisading, and strong positivity for CD56 but not other neuroendocrine markers. Whole-exome sequencing did not reveal any recurrent alterations.

Conclusion: We present 18 new cases of palisading adenocarcinoma, including 12 documented pathologically, occurring in women in the same family. This series doubles the published experience of this emerging tumor. While most of the previously published features of palisading adenocarcinoma were confirmed (female predominance, Asian population, sublingual and submandibular location), this series expands what is known about this neoplasm with novel sites (with parotid gland being most common) and apparent inheritability, a very rare characteristic among salivary gland neoplasms. While we were unable to uncover its molecular driver, this potential inheritability is a clue that may allow for future studies to unravel the genetics of palisading adenocarcinoma.