Expression of nSATB2 in Neuroendocrine Carcinomas of the Lung: Frequent Immunopositivity of Large Cell Neuroendocrine Carcinoma with a Diagnostic Pitfall

2021 ◽  
pp. 106689692110657
Author(s):  
Hiromichi Inoue ◽  
Jun Matsushima ◽  
Satoru Kobayashi ◽  
Toshimi Sairenchi ◽  
Hirokuni Hirata ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Neuroendocrine Carcinoma ◽  
Past History ◽  
Small Cell Lung Carcinoma ◽  
Strong Relationship ◽  
Large Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Cell Lung Carcinoma ◽  
Diagnostic Pitfall ◽  
The Difference

Small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC) are both classified as lung neuroendocrine carcinoma (NEC). It has recently been reported that the special AT-rich sequence-binding protein 2 (STAB2), known as a colorectal cancer marker, is also expressed in NECs occurring in various organs including the lung. However, few studies have examined any differences of SATB2 immunopositivity between SCLC and LCNEC. We investigated SATB2 expression in 45 SCLC and 14 LCNEC cases using immunohistochemistry as well as the expression of caudal-type homeobox 2 (CDX2) and keratin (KRT) 20. The LCNEC cases were more frequently positive for SATB2 (ten out of 14, 71%) than the SCLC ones (seventeen out of 45, 38%) with a statistically significance (P = 0.035). Furthermore, two LCNEC cases were positive for CDX2 while no positive findings were observed for any SCLC cases, the difference of which, however, was not statistically significant (P = 0.053). KRT20 was negative in all LCNEC and SCLC cases. These results require our attention when we use SATB2 and CDX2 as colorectal cancer markers because their expression in pulmonary NECs can lead to a misdiagnosis that the tumor is of metastatic colorectal adenocarcinoma, especially when the patient has a past history of colorectal cancer. Analyzing the relationship between the demographic/clinical variables and the SATB2 expression in the SCLC cases, just high Brinkman index (≥ 600) was significantly related to the positivity of SATB2 (P = 0.017), which is interesting considering the strong relationship between SCLC and smoking.

scholarly journals Clinical features of large cell neuroendocrine carcinoma: a population-based overview

2015 ◽  
Vol 47 (2) ◽  
pp. 615-624 ◽  
Author(s):  
Jules L. Derks ◽  
Lizza E. Hendriks ◽  
Wieneke A. Buikhuisen ◽  
Harry J.M. Groen ◽  
Erik Thunnissen ◽  
...  
Keyword(s):  
The Netherlands ◽  
Cancer Registry ◽  
Neuroendocrine Carcinoma ◽  
Early Stage ◽  
Small Cell Lung Carcinoma ◽  
Large Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Stage I ◽  
Cell Lung Carcinoma ◽  
Netherlands Cancer Registry

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is an orphan disease and few data are available on its clinical characteristics. Therefore, we analysed LCNEC registered in the Netherlands Cancer Registry, and compared data with small cell lung carcinoma (SCLC), squamous cell carcinoma (SqCC) and adenocarcinoma (AdC).Histologically confirmed LCNEC (n=952), SCLC (n=11 844), SqCC (n=19 633) and AdC (n=24 253) cases were selected from the Netherlands Cancer Registry (2003–2012). Patient characteristics, metastasis at diagnosis (2006 or later), overall survival (OS) including multivariate Cox models and first-line treatment were compared for stage I–II, III and IV disease.The number of LCNEC cases increased from 56 patients in 2003 to 143 in 2012, accounting for 0.9% of all lung cancers. Stage IV LCNEC patients (n=383) commonly had metastasis in the liver (47%), bone (32%) and brain (23%), resembling SCLC. Median OS (95% CI) of stage I–II, III and IV LCNEC patients was 32.4 (22.0–42.9), 12.6 (10.3–15.0) and 4.0 (3.5–4.6) months, respectively. Multivariate-adjusted OS of LCNEC patients resembled that of SCLC patients, and was poorer than those of SqCC and AdC patients. However, frequency of surgical resection and adjuvant chemotherapy resembled SqCC and AdC more than SCLC.Diagnosis of LCNEC has increased in recent years. The metastatic pattern of LCNEC resembles SCLC as does the OS. However, early-stage treatment strategies seem more comparable to those of SqCC and AdC.

scholarly journals Diagnosis and Molecular Profiles of Large Cell Neuroendocrine Carcinoma With Potential Targets for Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Helmut Popper ◽  
Luka Brcic
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Large Cell ◽  
Small Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Cell Lung Carcinoma ◽  
Activating Mutations ◽  
Personal Experiences ◽  
Cytological Features ◽  
Oncologic Treatment

Large cell neuroendocrine carcinoma (LCNEC) together with small cell carcinoma (SCLC) and typical and atypical carcinoids form the group of pulmonary neuroendocrine tumors. LCNEC and SCLC are high-grade carcinomas. Although both can be found outside the thoracic cavity, they are most common in the lung. LCNEC differs from SCLC by morphologic pattern, and by cytological features such as nuclear size, nucleoli, chromatin pattern, but also by genetic differences. Originally thought to represent a single entity, it became evident, that three subgroups of LCNEC can be identified at the molecular level: a SCLC-like type with loss of retinoblastoma 1 gene (RB1) and TP53 mutations; a non-small cell lung carcinoma (NSCLC)-like type with wildtype RB1, TP53 mutation, and activating mutations of the phosphoinositol-3 kinase (PI3K-CA), or loss of PTEN; and a carcinoid-like type with MEN1 gene mutation. These subtypes can be identified by immunohistochemical staining for RB1, p53, and molecular analysis for PI3K and MEN1 mutations. These subtypes might also respond differently to chemotherapy. Immuno-oncologic treatment has also been applied to LCNEC, however, in addition to the evaluation of tumor cells the stroma evaluation seems to be important. Based on personal experiences with these tumors and available references this review will try to encompass our present knowledge in this rare entity and provoke new studies for better treatment of this carcinoma.

scholarly journals Molecular Pathology of Pulmonary Large Cell Neuroendocrine Carcinoma: Novel Concepts and Treatments

2021 ◽  
Vol 11 ◽  
Author(s):  
Masayo Yoshimura ◽  
Kurumi Seki ◽  
Andrey Bychkov ◽  
Junya Fukuoka
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Molecular Subtypes ◽  
Small Cell Lung Carcinoma ◽  
Large Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Type I ◽  
Histologic Diagnosis ◽  
Cell Lung Carcinoma ◽  
Genomic Studies ◽  
Poorly Differentiated

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is an aggressive neoplasm with poor prognosis. Histologic diagnosis of LCNEC is not always straightforward. In particular, it is challenging to distinguish small cell lung carcinoma (SCLC) or poorly differentiated carcinoma from LCNEC. However, histological classification for LCNEC as well as their therapeutic management has not changed much for decades. Recently, genomic and transcriptomic analyses have revealed different molecular subtypes raising hopes for more personalized treatment. Two main molecular subtypes of LCNEC have been identified by studies using next generation sequencing, namely type I with TP53 and STK11/KEAP1 alterations, alternatively called as non-SCLC type, and type II with TP53 and RB1 alterations, alternatively called as SCLC type. However, there is still no easy way to classify LCNEC subtypes at the actual clinical level. In this review, we have discussed histological diagnosis along with the genomic studies and molecular-based treatment for LCNEC.

scholarly journals Pulmonary Large Cell Neuroendocrine Carcinoma Associated With Lambert-Eaton Syndrome

2021 ◽  
Vol 14 ◽  
pp. 2632010X2110517
Author(s):  
Pamela Hernandez-Arriaga ◽  
Mauricio Gonzalez-Urquijo ◽  
Daniel Fernando López Altamirano ◽  
Bryan Vaca-Cartagena ◽  
Andres Vergil-Vargas ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Large Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Proximal Muscle ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Autonomic Changes ◽  
Release Of Acetylcholine ◽  
Paraneoplastic Disorder

Lambert-Eaton syndrome is a rare paraneoplastic disorder of the neuromuscular junction, characterized by impaired release of acetylcholine, which causes proximal muscle weakness, depressed tendon reflexes, and autonomic changes. Most cases of Lambert-Eaton syndrome present in small-cell lung carcinoma, and only a few cases have been reported in other lung subtypes. Herein, we report a case of 69 years old male patient with Lambert-Eaton syndrome as a rare association with a pulmonary large-cell neuroendocrine carcinoma, which presented 5 months before neoplasm diagnosis. A lobectomy was auspiciously performed. A review of the literature is also presented.

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