Challenges in Diagnostic and Systemic Treatment of Metastatic Lung Atypical Carcinoid: a Case Report

Neuroendocrine lung tumors are rare neoplasms, with an increasing incidence in the last thirty years. Metastatic disease is rarely curable. We present the case of a 65-year-old male patient with atypical functional carcinoid of the lung and synchronous liver metastases beginning with carcinoid syndrome treated with somatostatin analogues, chemotherapy and peptide receptor radionuclide therapy, with a good clinical response and remission of the carcinoid syndrome.

Effects of KEAP1 Silencing on the Regulation of NRF2 Activity in Neuroendocrine Lung Tumors

Background. The KEAP1/NRF2 pathway has been widely investigated in tumors since it was implicated in cancer cells survival and therapies resistance. In lung tumors the deregulation of this pathway is mainly related to point mutations of KEAP1 and NFE2L2 genes and KEAP1 promoter hypermethylation, but these two genes have been rarely investigated in low/intermediate grade neuroendocrine tumors of the lung. Methods. The effects of KEAP1 silencing on NRF2 activity was investigated in H720 and H727 carcinoid cell lines and results were compared with those obtained by molecular profiling of KEAP1 and NFE2L2 in a collection of 47 lung carcinoids. The correlation between methylation and transcript levels was assessed by 5-aza-dC treatment. Results. We demonstrated that in carcinoid cell lines, the KEAP1 silencing induces an upregulation of NRF2 and some of its targets and that there is a direct correlation between KEAP1 methylation and its mRNA levels. A KEAP1 hypermethylation and Loss of Heterozygosity at KEAP1 gene locus was also observed in nearly half of lung carcinoids. Conclusions. This is the first study that has described the effects of KEAP1 silencing on the regulation of NRF2 activity in lung carcinoids cells. The epigenetic deregulation of the KEAP1/NRF2 by a KEAP1 promoter hypermethylation system appears to be a frequent event in lung carcinoids.

A COMPLEX CASE OF DIFFERENTIAL DIAGNOSIS OF PULMONARY TUBERCULOSIS AND A NEUROENDOCRINE TUMOR

Pathomorphosis of tuberculosis and other lung diseases that have a similar clinical radiological and morphological picture leads to considerable difficulties and mistakes in the differential diagnosis of pulmonary processes. In particular, there are difficulties in the differential diagnosis of neuroendocrine lung tumors (NET) and pulmonary tuberculosis.A clinical case of timely diagnosis of a neuroendocrine tumor in a young female patient without clinical symptoms typical for NETs has been described. The main manifestations revealed by chest CT scanning were single focal consolidations. The diagnosis was confirmed by histological studies of surgery samples.

NUCLEAR LOCALIZATION OF CRABP1 IN NEUROENDOCRINE LUNG TUMORS IS ASSOCIATED WITH THE DEGREE OF TUMOR MALIGNANCY

Bronchopulmonary neuroendocrine tumors (NETs) refer to malignant epithelial neoplasms of neuroendocrine origin, which form highly heterogeneous group with respect to biological behavior and clinical manifestations. Three main categories of different grades of malignancy are distinguished in the diagnosis of lung NETs: typical carcinoids (TK), atypical carcinoids (AK) and the most aggressive low-differentiated tumors including small-cell and large-cell neuroendocrine lung carcinomas. These groups differ in terms of disease prognosis and therapeutic approaches, but the criteria currently used do not always allow clear boundaries between different histological variants. The search for additional diagnostic parameters and individual prognosis markers is currently actual for the grading and optimal classification of NETs. For the first time we studied the expression of Retinoic Acid Binding Protein-1 (CRABP1) in different variants of lung NETs. IHC analysis of 43 samples of lung NETs with various degrees of differentiation and grades revealed the statistically significant correlation between nuclear localization of CRABP1 and proliferation index «Ki-67» and tumor grade. The results pointed on the involvement of CRABP1 in the pathogenesis of lung NETs and indicated the need for further investigation of the relationship of the nuclear CRABP1 with clinical parameters and patient survival to determine whether this protein can be used as a marker for differential diagnosis and/or disease prognosis.