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Thoracic NUT carcinoma: expanded pathologic spectrum with expression of TTF-1 and neuroendocrine markers.

Abstract：

AIMS:NUT carcinoma, a rare aggressive tumor driven by NUTM1 rearrangements, often involves the lung/mediastinum and shows squamous differentiation. We encountered an index patient with a thoracic NUT carcinoma diagnosed by molecular testing, demonstrating extensive pleural involvement and diffuse TTF-1 expressions initially suggestive of lung adenocarcinoma with pseudomesotheliomatous growth. We thus gathered an institutional series of thoracic NUT carcinomas to examine their pathologic spectrum. METHODS AND RESULTS:We queried for thoracic NUT carcinomas in our surgical pathology files and in 2289 consecutive patients with primary thoracic tumors interrogated by RNA-based assays. We performed NUT immunohistochemistry on 425 additional lung adenocarcinomas. Collectively, we identified 6 patients (5 men; 1 woman; age 31-80 years; 4 never-smokers) with thoracic NUT carcinomas confirmed by molecular testing (including 5 with positive NUT immunohistochemistry). They died at 2.3-12.9 (median 2.8) months after presentation. Two patients were diagnosed by histopathologic assessment, whereas the remainder 4 (including the index patient) were recognized by molecular testing. Analysis of the index case revealed expression of multiple neuroendocrine markers along with TTF-1; no ultrastructural evidence of neuroendocrine differentiation was noted in this and 3 additional cases. We found no additional NUT-positive cases by immunohistochemistry screening. CONCLUSIONS:Although NUT carcinoma classically shows squamous differentiation, it can rarely express TTF-1 (even diffusely) and/or multiple neuroendocrine markers. This immunophenotypic spectrum may lead to diagnostic confusion with pulmonary adenocarcinoma, neuroendocrine and other tumors. To circumvent this pitfall, NUT immunohistochemistry and/or NUTM1 molecular testing should be considered in primitive-appearing tumors, regardless of their immunophenotypic features.

journal_name

Histopathology

journal_title

Histopathology

authors

Hung YP,Chen AL,Taylor MS,Huynh TG,Kem M,Selig MK,Nielsen GP,Lennerz JK,Azzoli CG,Dagogo-Jack I,Kradin RL,Mino-Kenudson M

doi

10.1111/his.14306

subject

Has Abstract

pub_date

2020-11-24 00:00:00

eissn

0309-0167

issn

1365-2559

pub_type

杂志文章

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Thoracic NUT carcinoma: expanded pathologic spectrum with expression of TTF-1 and neuroendocrine markers.