INSM1 expression in a subset of thoracic malignancies and small round cell tumors: rare potential pitfalls for small cell carcinoma

Tsai, Harrison; Hornick, Jason L.; Vivero, Marina

doi:10.1038/s41379-020-0517-0

Cited by 30 publications

(23 citation statements)

References 40 publications

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“…Concerning the specificity of the novel neuroendocrine markers, in keeping with the results of Rooper et al (4) and Tsai et al (44), we detected focal expression of INSM1 in 10% of pulmonary adenocarcinomas and 35% of pulmonary squamous cell carcinomas. Although Graff et al (45) reported intracellular granular STX1 immunostaining in 3 of 10 cases of pulmonary adenocarcinomas using the same antibody, STX1 expression was uniformly absent in all 20 pulmonary adenocarcinomas and 20 squamous cell carcinomas tested in the present study.…”

Section: Discussionsupporting

confidence: 91%

The panel of syntaxin 1 and insulinoma‐associated protein 1 outperforms classic neuroendocrine markers in pulmonary neuroendocrine neoplasms

Zombori

Turkevi-Nagy

Sejben

et al. 2021

APMIS

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Syntaxin‐1 (STX1) is a recently described highly sensitive and specific neuroendocrine marker. We evaluated the applicability of STX1 as an immunohistochemical marker in pulmonary neuroendocrine neoplasms (NENs). We compared STX1 with established neuroendocrine markers, including insulinoma‐associated protein 1 (INSM1). Typical carcinoids (n = 33), atypical carcinoids (n = 7), small cell lung carcinomas ([SCLCs] n = 30), and large cell neuroendocrine lung carcinomas (n = 17) were immunostained using tissue microarray for STX1, chromogranin A, synaptophysin, CD56, and INSM1. Eighty‐four of eighty‐seven (96.5%) NENs showed STX1 positivity. Carcinoids and LCNECs typically presented a combined strong membranous and weak cytoplasmic staining pattern; cytoplasmic expression was predominately observed in SCLCs. The sensitivity of STX1 was 90% in SCLCs and 100% in typical carcinoids, atypical carcinoids, and large cell neuroendocrine lung carcinomas. The overall sensitivity of STX1 in pulmonary NENs was 96.6%, and the sensitivity of the other markers was as follows: chromogranin A (85.2%), synaptophysin (85.2%), CD56 (92.9%), and INSM1 (97.7%). STX1 was found to be an excellent neuroendocrine marker of pulmonary NENs, with sensitivity and specificity surpassing that of classic markers. We propose a panel of STX1 and INSM1 for the routine immunohistochemical workup of pulmonary NENs.

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Section: Discussionsupporting

confidence: 91%

The panel of syntaxin 1 and insulinoma‐associated protein 1 outperforms classic neuroendocrine markers in pulmonary neuroendocrine neoplasms

Zombori

Turkevi-Nagy

Sejben

et al. 2021

APMIS

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“…No synovial sarcomas or desmoplastic small round cell tumors were positive for INSM1. Therefore, it is of paramount importance to pay close attention to cytomorphologic features and clinical presentation of thoracic neoplasms in order to avoid diagnostic pitfalls and implement ancillary studies for further characterization of neoplastic cells mimicking NETs [ 49 ]. The lower end of INSM1′s sensitivity and specificity has been found to be 81.5% and 82.7%, respectively; however, INSM1 positivity higher than the minimum diagnostic threshold was observed in rare thoracic tumors that have a morphologic overlap with SCLCs [ 49 ].…”

Section: Insm1 Expression In Pulmonary Netsmentioning

confidence: 99%

“…In one study, 7/38 (18%) of lung adenocarcinomas, 2/17 (12%) of lung squamous cell carcinomas, 4/10 (40%) of thymic carcinomas, 4/12 (33%) of adenoid cystic carcinomas, 1/19 (5%) of diffuse large B-cell lymphomas, 4/11 (36%) of alveolar rhabdomyosarcomas, and 4/23 (17%) of Ewing sarcomas were positive for INSM1.No synovial sarcomas or desmoplastic small round cell tumors were positive for INSM1. Therefore, it is of paramount importance to pay close attention to cytomorphologic features and clinical presentation of thoracic neoplasms in order to avoid diagnostic pitfalls and implement ancillary studies for further characterization of neoplastic cells mimicking NETs[49]. The lower end of INSM1 s sensitivity and specificity has been found to be 81.5% and 82.7%, respectively; however,…”

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confidence: 99%

INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists’ View

Maleki

Nadella

et al. 2021

Diagnostics

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Background: Insulinoma-associated protein 1 (INSM1) has been considered as a novel immunostain for neuroendocrine tumors (NETs) and is hypothesized to be more reliable than first-generation NET biomarkers, such as CGA (chromogranin A), SYP (synaptophysin) and CD56 (neural cell adhesion molecule). In this review, we summarize existing literature on INSM1′s reliability as an immunostain for detection of various NETs, its results in comparison to first-generation NET biomarkers, and its expression in both non-NETs and benign tissues/cells on cytology specimens (cell blocks/smears).

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“…INSM1 is an emerging diagnostic marker for neuroendocrine tumours. 24,25 Whereas INSM1 expression was absent in eight NUT carcinomas in two prior studies, 26,27 we identified one case expressing INSM1 focally, along with TTF-1, synaptophysin, and chromogranin; and an additional tumour with rare tumour cells showing INSM1 expression. Despite the presence of neuroendocrine immunophenotypic features, we could not find ultrastructural evidence of neuroendocrine differentiation in the four cases examined, consistent with prior reports.…”

Section: Discussionmentioning

confidence: 60%

Thoracic nuclear protein in testis (NUT) carcinoma: expanded pathological spectrum with expression of thyroid transcription factor‐1 and neuroendocrine markers

et al. 2021

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Aims Nuclear protein in testis (NUT) carcinoma, an aggressive tumour 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, showing extensive pleural involvement and diffuse thyroid transcription factor‐1 (TTF‐1) expression, initially suggestive of lung adenocarcinoma with pseudomesotheliomatous growth. We thus gathered an institutional series of thoracic NUT carcinomas to examine their pathological spectrum. Methods and results We searched for thoracic NUT carcinomas in our surgical pathology files and in 2289 consecutive patients with primary thoracic tumours investigated with RNA‐based assays. We performed NUT immunohistochemistry on 425 additional lung adenocarcinomas. Collectively, we identified six patients (five men and one woman; age 31–80 years; four never‐smokers) with thoracic NUT carcinomas confirmed by molecular testing (including five with positive NUT immunohistochemistry). They died at 2.3–12.9 months (median, 2.8 months) after presentation. Two patients were diagnosed by histopathological assessment, and the remaining four (including the index patient) were diagnosed by molecular testing. Analysis of the index case revealed expression of multiple neuroendocrine markers and TTF‐1; no ultrastructural evidence of neuroendocrine differentiation was noted. No additional NUT‐positive cases were found by immunohistochemical 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 tumour, and others. To circumvent this pitfall, NUT immunohistochemistry and/or NUTM1 molecular testing should be considered in primitive‐appearing tumours, regardless of their immunophenotypic features.

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INSM1 expression in a subset of thoracic malignancies and small round cell tumors: rare potential pitfalls for small cell carcinoma

Cited by 30 publications

References 40 publications

The panel of syntaxin 1 and insulinoma‐associated protein 1 outperforms classic neuroendocrine markers in pulmonary neuroendocrine neoplasms

The panel of syntaxin 1 and insulinoma‐associated protein 1 outperforms classic neuroendocrine markers in pulmonary neuroendocrine neoplasms

INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists’ View

Thoracic nuclear protein in testis (NUT) carcinoma: expanded pathological spectrum with expression of thyroid transcription factor‐1 and neuroendocrine markers

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