NKX3.1 Expression in Salivary Gland “Intraductal” Papillary Mucinous Neoplasm: A Low-Grade Subtype of Salivary Gland Mucinous Adenocarcinoma

Masato Nakaguro, Peter M. Sadow, Rong Hu, Hikaru Hattori, Kyoko Kuwabara, Toyonori Tsuzuki, Makoto Urano, Toshitaka Nagao, William C. Faquin

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Salivary gland intraductal papillary mucinous neoplasm (SG IPMN) is a recently proposed entity characterized by a papillary-cystic proliferation of mucin-producing cells. Because of overlapping histologic features and a clonal AKT1 p.E17K variant, SG IPMN has been presumed to be a precursor or a low-grade subtype of mucinous adenocarcinoma. NKX3.1 is a tumor suppressor gene located on chromosome 8p and is a known immunohistochemical marker of prostate epithelium and mucinous acinar cells of the intraoral salivary glands. Methods: We retrieved 12 SG IPMN cases, and performed histologic and genetic analysis. Given the association of SG IPMN with mucinous acinar cells, we also investigated the performance of NKX3.1 as a marker of this tumor entity. Results: Diffuse and strong NKX3.1 expression was observed in all SG IPMN cases (12/12, 100%) as well as in normal mucinous acinar cells. In contrast, mucoepidermoid carcinoma and pancreatic IPMN cases as well as normal serous acinar cells were negative for NKX3.1. Genetically, 11 of 12 cases (92%) harbored an AKT1 p.E17K variant. A novel PTEN frameshift deletion (p.G36Dfs*18) was detected in the other single case. At least one of the histologic features implying malignant tumors, such as severe cellular atypia, brisk mitotic activity, high Ki-67 proliferating index, lymphovascular invasion, and lymph node metastasis, was detected in 6 SG IPMN cases (50%). Conclusion: The findings suggest that SG IPMN is a low-grade subtype of mucinous adenocarcinoma which may be derived from mucinous acinar cells of the minor salivary gland.

Original languageEnglish
JournalHead and Neck Pathology
DOIs
Publication statusAccepted/In press - 2022

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Otorhinolaryngology
  • Oncology

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