Thoracic NUT carcinoma: Common pathological features despite diversity of clinical presentations

Fekkar, Amal; Emprou, C.; Lefebvre, Christine; Ferretti, Gilbert; Stephanov, Olivier; Pissaloux, Daniel; Leer, Anne Mc; Toffart, Anne‐Claire; Rousseaux, Sophie; Khochbin, Saadi; Lantuéjoul, Sylvie; Valmary‐Degano, Séverine

doi:10.1016/j.lungcan.2021.06.008

Cited by 6 publications

(10 citation statements)

References 10 publications

(31 reference statements)

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“…This study evaluated 55 patients (36 men and 19 women) among the 35 articles [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ] with a mean age of 41.4 years (range, 6–82). The male to female ratio was approximately 1.89 to 1.…”

Section: Resultsmentioning

confidence: 99%

Diagnosis, Treatment and Prognosis of Primary Pulmonary NUT Carcinoma: A Literature Review

Yuan

Guo

2022

Current Oncology

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NUT carcinoma is a rare, highly lethal cancer characterized with the rearrangement of the nuclear protein in testis (NUT) gene on chromosome 15q14, which primarily occurs in the midline organs. Primary pulmonary NUT carcinoma (NC) lacks characteristic clinical manifestations, which leads to the high rate of misdiagnose and nonstandard treatment. To date, fewer than one hundred cases have been reported worldwide. Here, a comprehensive literature search involving a total of 35 articles with 55 patients was conducted in this paper. We reviewed and analyzed the associated clinical and pathological characteristics, the efficacy of various treatment options and the prognosis. Pulmonary NC mainly occurred in middle young-aged men (median age, 36) with no smoking history (2:1) and would present with symptoms of cough (63.6%), dyspnea (29.5%), chest pain (18.2%) and hemoptysis (18.2%). The initial imaging frequently revealed large and irregular lesions in the lower lobe (46.5%) of the left or right lungs; lymph node metastasis was also prevalent (91.9%). A focal squamous differentiation with abrupt keratinization often occurred in the undifferentiated or poorly differentiated (93.75%) tumor cells, with abundant necrosis and numerous neutrophils infiltrated. The mean overall survival (OS) in patients of this malignant disease was 6.21 months, and the median OS was 4.4 months. According to our results, this disease is sensitive to radiotherapy, and chemoradiotherapy (either concurrent chemoradiotherapy or sequential chemoradiotherapy) was the most efficient therapeutic regimen to prolong the OS of patients with pulmonary NC.

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Section: Resultsmentioning

confidence: 99%

Diagnosis, Treatment and Prognosis of Primary Pulmonary NUT Carcinoma: A Literature Review

Yuan

Guo

2022

Current Oncology

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“…Anti-p63 is less specific than p40 for the diagnosis of squamous cell carcinoma and might be positive in lymphoma, polymorphous carcinomas, and some trophoblastic tumors 6,7. Recently, this pitfall was reported for p63 and p40 in the diagnosis of the rare NUT carcinoma where p40 is negative, focally, or diffusely positive p63 is diffusely positive 3,8. Anti-p40, like anti-p63, can stain urothelial carcinomas but is negative or very focally positive in less than 5% of tumor cells in adenocarcinomas or in prostatic adenocarcinoma 1,2,9.…”

Section: Discussionmentioning

confidence: 99%

“…In thoracic pathology, among the rarer entities, NUT-type carcinomas may express p40, whereas this is not usually found in SMARCA4-deficient carcinomas. 3 The sensitivity and specificity of the anti-p40 antibody for the diagnosis of squamous cell carcinoma of the lung are important, and it is therefore recommended not to perform multiple immunohistochemical markers for this diagnosis, especially on small samples.…”

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confidence: 99%

Challenging Metastatic Melanoma to the Lung With p40 Expression: A Diagnostic Pitfall, Case Report

Thierry

Juberthie

Gyenes

et al. 2022

Applied Immunohistochemistry &Amp; Molecular Morphology

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p40 immunohistochemistry is a cornerstone of histopathological examination for non-small cell lung carcinoma. p40 is an isoform of p63 and is reported to be highly specific for the diagnosis of squamous cell carcinoma. Very rare pitfalls are reported for this antibody, and p40 is typically negative in melanoma. A 66-year-old patient was admitted for multiple hemorrhagic brain tumors evocative of secondary tumors. On imaging, a 26 mm lung tumor was detected, and a biopsy of the lung tumor was performed. The tumor was stained by melanic markers and diffusely stained by p40 and p63. Molecular analysis found a somatic p.Asn581Ser (c.1742A>G) point mutation in exon 15 of BRAF and a p.Arg80Ter (c.238C>T) germline variant of CDKN2A, a predisposing mutation to melanoma. This case report highlights the importance of clinical, pathologic, and molecular correlation.

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“…Biphasic tumors composed of mixed epithelial and mesenchymal components have been reported [ 31 ]. Neutrophilic infiltration has been described in some tumors of thoracic primary [ 47 ]. Therefore, a tumor with any of these features should raise suspicion for NUT carcinoma, and trigger additional confirmational studies.…”

Section: Histologic and Immunohistochemical Diagnosismentioning

confidence: 99%

“…NUT carcinoma can show positivity for TTF1 [ 35 , 56 , 57 ] or PAX8 [ 56 , 57 ], potentially causing confusion with lung, thyroid, and Mullerian carcinomas, etc. NUT carcinoma frequently express neuroendocrine markers, including synaptophysin and CD56 [ 35 ], and may thus enter into the differential diagnosis with other tumors with neuroendocrine differentiation, and may also show positivity for markers suggestive of PNET including GFAP and synptophysin [ 13 ]; Ewing sarcoma markers FLI1, CD99, and cytoplasmic glycogen [ 45 ]; melanoma marker preferentially expressed antigen in melanoma (PRAME) [ 56 ]; vascular markers FLI1 and CD34 [ 30 ]; germ cell tumor markers CD30, PLAP, and SALL4 [ 58 ]; muscular markers desmin and calponin focally [ 55 ]; and hematolymphoid markers CD56 [ 58 , 59 ], CD30 [ 58 ], CD34, CD43 [ 47 ], CD138 [ 47 ], and CD45 [ 47 ]. Therefore, caution is advised in interpreting the results of the relatively nonspecific immunohistochemical markers.…”

Section: Histologic and Immunohistochemical Diagnosismentioning

confidence: 99%

NUTM1-Rearranged Neoplasms—A Heterogeneous Group of Primitive Tumors with Expanding Spectrum of Histology and Molecular Alterations—An Updated Review

et al. 2021

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Nuclear protein of testis (NUT), a protein product of the NUTM1 gene (located on the long arm of chromosome 15) with highly restricted physiologic expression in post-meiotic spermatids, is the oncogenic driver of a group of emerging neoplasms when fused with genes involved in transcription regulation. Although initially identified in a group of lethal midline carcinomas in which NUT forms fusion proteins with bromodomain proteins, NUTM1-rearrangement has since been identified in tumors at non-midline locations, with non-bromodomain partners and with varied morphology. The histologic features of these tumors have also expanded to include sarcoma, skin adnexal tumors, and hematologic malignancies that harbor various fusion partners and are associated with markedly different clinical courses varying from benign to malignant. Most of these tumors have nondescript primitive morphology and therefore should be routinely considered in any undifferentiated neoplasm. The diagnosis is facilitated by the immunohistochemical use of the monoclonal C52 antibody, fluorescence in situ hybridization (FISH), and, recently, RNA-sequencing. The pathogenesis is believed to be altered expression of oncogenes or tumor suppressor genes by NUT-mediated genome-wide histone modification. NUTM1-rearranged neoplasms respond poorly to classical chemotherapy and radiation therapy. Targeted therapies such as bromodomain and extraterminal domain inhibitor (BETi) therapy are being developed. This current review provides an update on NUTM1-rearranged neoplasms, focusing on the correlation between basic sciences and clinical aspects.

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Thoracic NUT carcinoma: Common pathological features despite diversity of clinical presentations

Cited by 6 publications

References 10 publications

Diagnosis, Treatment and Prognosis of Primary Pulmonary NUT Carcinoma: A Literature Review

Diagnosis, Treatment and Prognosis of Primary Pulmonary NUT Carcinoma: A Literature Review

Challenging Metastatic Melanoma to the Lung With p40 Expression: A Diagnostic Pitfall, Case Report

NUTM1-Rearranged Neoplasms—A Heterogeneous Group of Primitive Tumors with Expanding Spectrum of Histology and Molecular Alterations—An Updated Review

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