Evidence map›Paper›PMID 36746884›Full record

ArticleHead and neck pathology2023

NKX3.1 Expression and Molecular Characterization of Secretory Myoepithelial Carcinoma (SMCA): Advancing the Case for a Salivary Mucous Acinar Phenotype.

Simmi Patel, Abigail I Wald, Jassem M Bastaki, Simon I Chiosea, Aatur D Singhi, Raja R Seethala

Open access · greenAbstract read
In one paragraph

Article in Head and neck pathology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
3.8field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Chromophobe thyroid carcinoma: a distinct entity associated with TSC gene alterations.Virchows Archiv : an international journal of pathology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Simmi PatelDepartment of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. patelsj@upmc.edu.ORCID http://orcid.org/0000-0002-4330-0199
Abigail I WaldDepartment of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Jassem M BastakiAl-Sabah Hospital and Kuwait Cancer Control Center, Ministry of Health, Kuwait City, Kuwait.
Simon I ChioseaDepartment of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Aatur D SinghiDepartment of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Raja R SeethalaDepartment of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
University of Pittsburgh Medical Center · USKuwait Cancer Control Center · KW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSecretory myoepithelial carcinomas (SMCA) are rare, mucinous, signet ring predominant tumors with primitive myoepithelial features. While many mucinous salivary gland tumors have now been molecularly characterized, key drivers in SMCA have yet to be elucidated. Recently, NKX3.1, a homeodomain transcription factor implicated in salivary mucous acinar development was also shown in a subset of salivary mucinous neoplasms, salivary intraductal papillary mucinous neoplasms (SG-IPMN). To date, NKX3.1 expression has not been characterized in other mucinous salivary lesions. Here, we report molecular and extended immunophenotypic findings in SMCA and NKX3.1 expression in the context of other head and neck lesions.

methodsWe retrieved 4 previously reported SMCA, performed additional immunohistochemical and targeted next-generation sequencing (NGS). We also investigated the use of NKX3.1 as a marker for SMCA in the context of its prevalence and extent (using H-score) in a mixed cohort of retrospectively and prospectively tested head and neck lesions (n = 223) and non-neoplastic tissues (n = 66).

resultsNKX3.1 positivity was confirmed in normal mucous acini as well as in mucous acinar class of lesions (5/6, mean H-score: 136.7), including mucinous adenocarcinomas (3/4), SG-IPMN (1/1), and microsecretory adenocarcinoma (MSA) (1/1). All SMCA were positive. Fluorescence in situ hybridization for SS18 rearrangements were negative in all successfully tested cases (0/3). NGS was successful in two cases (cases 3 and 4). Case 3 demonstrated a PTEN c.655C>T p.Q219* mutation and a SEC16A::NOTCH1 fusion while case 4 (clinically aggressive) showed a PTEN c.1026+1G>A p.K342 splice site variant, aTP53 c.524G>A p.R175H mutation and a higher tumor mutation burden (29 per Mb). PTEN immunohistochemical loss was confirmed in both cases and a subset of tumor cells showed strong (extreme) staining for P53 in Case 4.

conclusionDespite a partial myoepithelial phenotype, SMCA, along with mucinous adenocarcinomas/SG-IPMN and MSA, provisionally constitute a mucous acinar class of tumors based on morphology and NKX3.1 expression. Like salivary mucinous adenocarcinomas/SG-IPMN, SMCA also show alterations of the PTEN/PI3K/AKT pathway and may show progressive molecular alterations. We document the first extramammary tumor with a SEC16A::NOTCH1 fusion.

Indexed as

AdenocarcinomaAdenocarcinoma, MucinousMyoepitheliomaPancreatic Intraductal NeoplasmsSalivary Gland NeoplasmsBiomarkers, TumorBreast NeoplasmsCarcinomaEndoplasmic ReticulumGolgi ApparatusHomeodomain ProteinsHumansIn Situ Hybridization, FluorescencePhenotypePhosphatidylinositol 3-KinasesRetrospective StudiesBiomarkers, TumorHomeodomain ProteinsNKX3-1 protein, humanPhosphatidylinositol 3-KinasesTranscription FactorsVesicular Transport ProteinsNKX3.1PTEN/PI3K/AKT pathwaySalivary mucinous adenocarcinomaSecretory myoepithelial carcinoma (SMCA)

Identifiers

PMID36746884
PMCPMC10293155
OpenAlexW4319303880

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.