Clinicopathological characteristics of primary lung nuclear protein in testis carcinoma: A single‐institute experience of 10 cases

Abstract

Background Nuclear protein in testis (NUT) carcinoma is a rare tumor associated with NUT rearrangement that can present as poorly differentiated to undifferentiated carcinoma, with or without abrupt squamous differentiation. It is often misdiagnosed as poorly differentiated carcinoma or undifferentiated carcinoma if NUT is not suspected. In this study, we retrospectively analyzed pulmonary NUT carcinoma cases diagnosed with NUT immunohistochemical staining and discuss the differential diagnosis to provide information for this rare and aggressive entity. Methods Cases, diagnosed as “NUT carcinoma” in lung pleura and “metastatic NUT carcinoma from the lung” in lymph nodes were diagnosed between 2017 and 2019 at the Samsung Medical Center (SMC). Clinical features such as age, sex, treatment and follow‐up period, and pathological reports were obtained by reviewing patients’ electronic medical records. Results A total of 10 NUT carcinoma cases were found in the SMC pathology database. Seven patients were men and six were non‐smokers. Tumor cells showed various cellular features such as round, squamoid, and spindle. Some cases had initially been misdiagnosed as spindle cell neoplasm, round cell sarcoma, squamous cell carcinoma and small cell carcinoma. All cases showed diffuse strong nuclear expression of NUT immunohistochemical staining, and some were positive for p63 staining and negative for CD56 staining. Conclusions NUT carcinoma is often misdiagnosed because of its various morphologies. It is important to consider NUT as one of the differential diagnoses when encountering lung biopsy with undifferentiated morphology. Key points Due to various morphological features, NUT carcinoma can be misdiagnosed It is important to consider NUT carcinoma when diagnosing a poorly differentiated or undifferentiated tumor

Immunotherapy and Targeting the Tumor Microenvironment: Current Place and New Insights in Primary Pulmonary NUT Carcinoma

“…The clinical manifestations of primary pulmonary NUT carcinoma are similar to those of lung cancer and are often closely related to tumor size, location, presence or absence of complications or metastases. Some patients are even asymptomatic, only founded in routine physical examination ( 36 ). The common symptoms included cough, chest pain, hemoptysis, wheezing, dyspnea, fever, etc., among which cough is the most common, and dyspnea caused by moderate to large pleural effusion is also frequently present ( 13 , 15 , 36 ).…”

“…Some patients are even asymptomatic, only founded in routine physical examination ( 36 ). The common symptoms included cough, chest pain, hemoptysis, wheezing, dyspnea, fever, etc., among which cough is the most common, and dyspnea caused by moderate to large pleural effusion is also frequently present ( 13 , 15 , 36 ).…”

“…So far, this patient had the longest survival time among the primary pulmonary NUT carcinoma patients retrieved in the literatures, who had received immunotherapy. Two patients received the combination treatment including Pembrolizumab as the first-line treatment, the OS had exceeded 12 months ( 36 ), suggesting that first-line use of Pembrolizumab may improve the prognosis. The OS of two non-surgical patients staging III who had previously received chemoradiotherapy and then received Nivolumab or Pembrolizumab was significantly prolonged [11.6 months ( 39 ), 26.7 months ( 13 ) respectively].…”

“…It is well known that PD-L1 expression level has a certain correlation with the benefit from immunotherapy. Few cases on PD-L1 expression level of primary pulmonary NUT carcinoma have been reported, and PD-L1 TPS (Tumor Proportion Score) varied from 0-80% ( 36 , 73 ). However, due to the uneven quality of cases data, it is impossible to precisely evaluate the relationship between PD-L1 expression level and the benefit from immunotherapy or prognosis in primary pulmonary NUT carcinoma.…”

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

“…Nuclear protein in testis (NUT) carcinomas are very rare, notably among lung cancers, but are very aggressive tumors [276][277][278][279][280][281][282]. These tumors are more frequent in pediatric populations, in particular tumors that develop on the median anatomical axis above the diaphragm [253,283,284].…”