Immunohistochemical neuroendocrine marker expression in primary pulmonary NUT carcinoma: a diagnostic pitfall

Pezzuto, Federica; Fortarezza, Francesco; Mammana, Marco; Pasello, Giulia; Pelosi, Giuseppe; Rea, Federico; Calabrese, Fiorella

doi:10.1111/his.14166

Cited by 16 publications

(17 citation statements)

References 6 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NUT midline carcinoma sometimes expresses neuroendocrine markers to various degrees. Previous studies reported that it was hidden in small cell lung cancer [15,17]. Based on these findings and previous cases with information on neuroendocrine marker expression, including the present case (Additional file 1), we speculated whether pulmonary NUT carcinoma needs to be considered when less than one out of 3 neuroendocrine markers (chromogranin A, synaptophysin, and CD56) are (incompletely) positive in tumors showing a monotonous morphology.…”

Section: Discussionsupporting

confidence: 72%

See 1 more Smart Citation

P63-negative pulmonary NUT carcinoma arising in the elderly: a case report

et al. 2020

View full text Add to dashboard Cite

Background Pulmonary NUT carcinoma is rare, but lethal, thus, must not be overlooked. The definitive diagnosis is made by a NUT monoclonal antibody or gene analysis, but these are not always routinely available. Therefore, the diagnosis depends on this rare disease being suspected from the clinical and pathological findings. Generally, NUT carcinoma of the lung occurs near the hilum in younger adults with severe subjective symptoms. Histologically, it is characterized by the monomorphic growth of small cells which showed positivity of p63 immunohistochemistry. Case presentation An 82-year-old man was referred for an incidental finding of an abnormal shadow at the peripheral apex of the right lung on computed tomography for a regular follow-up examination of renal cancer. Microscopically, small cell carcinoma was initially suspected; however, immunohistochemistry was not typical. NUT carcinoma with BRD4-NUT fusion was ultimately diagnosed using a NUT monoclonal antibody, fluorescence in situ hybridization, and RNA-seq. p63 and p40 protein expression was not detected. Conclusions This is the first case of pulmonary NUT carcinoma to show negativity for p63 and is the oldest among previously reported cases. The present case suggests that NUT carcinoma should be suspected when the morphology of monomorphic growth of small cells without lineage-specific differentiation, regardless of age, clinical symptoms, the tumor location, or p63 expression.

show abstract

Section: Discussionsupporting

confidence: 72%

“…NUT carcinoma may be suspected based on clinical characteristics [15]. However, the present case was not typical of the clinical features of pulmonary NUT carcinoma in age, size, or location.…”

Section: Discussionmentioning

confidence: 56%

P63-negative pulmonary NUT carcinoma arising in the elderly: a case report

et al. 2020

View full text Add to dashboard Cite

show abstract

“…NUT midline carcinoma sometimes expresses neuroendocrine markers to various degrees. Previous studies reported that it was hidden in small cell lung cancer [15,17]. Based on these ndings and previous cases with information on neuroendocrine marker expression, including the present case (Additional le 1), we speculated whether pulmonary NUT carcinoma needs to be considered when less than one out of 3 neuroendocrine markers (chromogranin A, synaptophysin, and CD56) are (incompletely) positive in tumors showing a monotonous morphology.…”

Section: Discussionsupporting

confidence: 63%

P63-Negative Pulmonary NUT Carcinoma Arising in the Elderly: A Case Report.

Numakura

Saito

Motoi³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: We herein describe a rare case of primary pulmonary NUT carcinoma with unusual clinical and pathological presentations. NUT carcinoma of the lung occurs near the hilum in younger adults with severe symptoms and is positive for p63. This is the first case to show negativity for p63 and is the oldest among previously reported cases of pulmonary NUT carcinoma. Case presentation: An 82-year-old man was referred for an incidental finding of an abnormal shadow at the peripheral apex of the right lung on computed tomography for a regular follow-up examination of renal cancer. Microscopically, small cell carcinoma was initially suspected; however, immunohistochemistry was not typical. NUT carcinoma with BRD4-NUT fusion was ultimately diagnosed using a NUT monoclonal antibody, fluorescence in situ hybridization, and RNA-seq. p63 protein expression was not detected. Conclusions: NUT carcinoma is rare, but lethal, and, thus, must not be overlooked. The present case suggests the importance of NUT immunohistochemistry in cases of small round cell tumors without clear lineage-specific differentiation, regardless of age, clinical symptoms, the tumor location, or p63 expression.

show abstract

“…Rather than being indicative of pulmonary glandular differentiation, TTF-1 expression in NUT carcinomas may relate to the presence of neuroendocrine differentiation (see below), analogous to TTF-1 expression in a subset of extrapulmonary highgrade neuroendocrine carcinomas. The expression of the neuroendocrine markers synaptophysin, chromogranin, and/or CD56 has been described in a subset of thoracic NUT carcinomas, 5,12,[21][22][23] including two of six tumours herein. INSM1 is an emerging diagnostic marker for neuroendocrine tumours.…”

Section: Discussionmentioning

confidence: 99%

“…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. 20,28,29 The differential diagnoses of thoracic NUT carcinoma include other poorly differentiated squamous cell carcinomas, high-grade neuroendocrine carcinomas (including large-cell neuroendocrine carcinomas 12,23 and small-cell carcinoma 5,22 ), and other small round blue cell tumours (such as Ewing sarcoma and desmoplastic small round cell tumour). 2,30 Whereas the lack of genuine neuroendocrine histological features is straightforward to discern in resection specimens of NUT carcinomas, distinction from large-cell neuroendocrine carcinoma and small-cell carcinoma can be challenging in biopsies that show TTF-1 and/or neuroendocrine marker expression, as illustrated by Pezzuto et al 23 and herein.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

Immunohistochemical neuroendocrine marker expression in primary pulmonary NUT carcinoma: a diagnostic pitfall

Cited by 16 publications

References 6 publications

P63-negative pulmonary NUT carcinoma arising in the elderly: a case report

P63-negative pulmonary NUT carcinoma arising in the elderly: a case report

P63-Negative Pulmonary NUT Carcinoma Arising in the Elderly: A Case Report.

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

Contact Info

Product

Resources

About