NON SURGICAL TREATMENT OF CARCINOID LUNGS TUMORS

Typical carcinoid lungs tumors are neuroendocrine bronchopulmonary tumors with a low-grade malignancy, and an atypical carcinoid is an intermediate form of these tumors. Their systemic treatment is greatly influenced by therapeutic evidence derived from the more frequent gastroenteropancreatic neuroendocrine neoplasms. Currently, systemic therapies for lung carcinoids, aiming at controlling tumor growth include long acting somatostatin analogues (SSAs), peptide receptor radionuclide therapy, chemotherapy and molecular-targeted therapy.

Clinicopathologic Features and Lymph Node Metastasis Pattern of the Cervical MiNEN

Purpose: Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare type of cervical tumor. Its clinicopathological features, lymph node(LN) metastatic patterns and outcomes are still unclear. Methods: We have analyzed the clinicopathological information of 26 patients with cervical MiNEN.Results: The median age of onset for cervical MiNEN was 48 years. Macroscopically, polyps and nodules were the main types. The neuroendocrine components included small cell neuroendocrine carcinoma (SCNEC) (14/26 cases), large cell neuroendocrine carcinoma (LCNEC) (10/26 cases), and typical carcinoid (2/26 cases). Non-neuroendocrine components included adenocarcinoma (AC) (12/26, including one case of AC in situ) and squamous cell carcinoma (SC) (10/26) and adeno-squamous cell carcinoma (ASC) (4/26). Of the 16 AC cases, 15 were human papilloma virus (HPV) -associated AC and onewasHPV-independent AC. Except for the case of MiNEN with HPV-independent AC, all cases were diffusely and strongly positive for p16 protein. The lympho-vascular space invasion (LVSI) was seen in 17/26 cases, and the components that invade lymphatic vessels were mainly neuroendocrine carcinomas (NECs) (15/17), followed by SC (1/17) and AC (1/17). Ten patients developed LN metastases, including six in combined SCNECs (6/14) and four in combined LCNECs (4/10); the metastatic component was pure NEC in eight cases (8/10) and SC or AC in two cases (2/10) .Conclusions: NEC component is the key factor that determines the clinical behavior and prognosis of cervical MiNEN.

Lung Carcinoid Tumors and Paraneoplastic Cushing's Syndrome: Diagnostic and Therapeutic Difficulties - A Case Report

Introduction. - Paraneoplastic Cushing's syndrome is a rare cause of endogenous hypercorticism. It is caused by ectopic secretion of ACTH by a non-pituitary endocrine tumor. The aetiological biological and radiological data are often inconclusive, which creates a problem of differential diagnosis with Cushing's disease. In addition, these tumors are often small and their location is extremely variable. As a result, the difficulties of localization require the use of specific imaging techniques.Observation. - We report the observation of a 44-year-old man suffering from diabetes and high blood pressure, presenting a severe and rapidly progressive Cushing syndrome, in connection with a hypercorticism caused by an ectopic ACTH secretion. The thoracic computed tomography performed within the framework of a search for a neoplastic origin objectified a 15 mm nodule isolated at the level of the middle lobe, the scintigraphy with octreotide marked with indium-111 found a significant fixation at the level of the lung nodule. The patient had a middle lobe lobectomy. The outcome was favorable with regression of Cushing's syndrome. Pathological examination was in favor of a typical carcinoid tumor, and the immunohistochemical complement showed tumor cell positivity for ACTH, CD56, chromogranin, and synaptophysin.Conclusion. - This observation illustrates the dilemma between the need to locate an ectopic ACTH secretion and the control of aggressive and threatening Cushing's syndrome. Early use of the octreotide scintigraphy should be considered if a topographic diagnosis of the causative tumor cannot be done through conventional imaging techniques.

Radiation Methods in the Diagnosis and Determination of Surgical Treatment Tactics for Primary Multiple Lung Carcinoid

The early and complete diagnosis of lung carcinoid tumors is of great interest in clinical oncology, since this is the basis for the possibility of using options for organ-sparing surgical treatment. According to the 2015 WHO classification, carcinoids belong to the group of neuroendocrine tumors and are divided into two types: a typical carcinoid and an atypical one. Based on the data available in the literature, there are from 0.2 to 2 cases per 100,000 population. The paper considers the possibilities of radiation studies in the early diagnosis of this tumor, as well as those of determining the tactics, type, and scope of surgical treatment.

Prevalence of Delta-Like Protein 3 in a Consecutive Series of Surgically Resected Lung Neuroendocrine Neoplasms

Delta-like protein 3 (DLL3) is a protein of the Notch pathway, and it is a potential therapeutic target for high-grade lung neuroendocrine tumors (NETs), i.e., small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). However, DLL3 prevalence in lung NETs and its association with clinicopathological characteristics and prognosis remained unclear. We analyzed the immunohistochemical expression of DLL3 and its prognostic role in a consecutive series of 155 surgically resected lung NETs, including typical carcinoid (TC), atypical carcinoid (AC), LCNEC, and SCLC patients. The DLL3 expression was categorized as high (>50% positive tumor cells) or low (<50%). In addition, tumors were categorized by H-score (i.e., percentage of positive cells by staining intensity, ≥150 vs. <150). DLL3 staining was positive in 99/155 (64%) samples, and high DLL3 expression was frequently observed in high-grade tumors. In detail, 46.9% and 75% of SCLC and 48.8% and 53.7% of LCNEC specimens showed a high DLL3 expression by using H-score and percentage of positive tumor cells, respectively. Regarding low-grade NETs, only 4.9% and 12.2% TCs and 19.5% and 24.4% ACs had high DLL3 expression considering H-score and percentage of positive tumor cells, respectively. High DLL3 expression was associated with advanced American Joint Committee on Cancer (AJCC) stage, peripheral location, and chromogranin A expression in high-grade tumors (p < 0.05). In low-grade NETs, high DLL3 expression was associated with female sex, peripheral location, a higher number of mitoses, higher Ki-67 index, presence of necrosis, and pleural infiltration (p < 0.05). No association was observed between high DLL3 expression and overall survival (OS) and disease-free survival (DFS) in high-grade NETs, whereas high DLL3 expression was associated with lower DFS in ACs (p = 0.01). In conclusion, our study demonstrated a high prevalence of DLL3 expression in high-grade lung NET patients and its association with aggressive clinicopathological features. These findings confirm that DLL3 could represent a useful biomarker for target therapy in high-grade tumors. Our results also suggest that the DLL3 expression could identify a subset of AC tumors with more aggressive behavior, thus providing the basis for new therapeutic options in this group of patients.

Long-term broncocele anamnesis, triggered by typical carcinoid

The paper presents a case of a single bronchocele (bronchogenic retention cyst) caused by a typical carcinoid that was observed for a long time. During the initial complex examination, including computed tomography with intravenous contrast, fibrobronchoscopy, and immunological and bacteriological examinations of tuberculosis, there were no changes for the oncological and infectious nature. The changes were interpreted as the result of a postponed nonspecific inflammatory process. Most of them were monitored using chest X-ray and the changes were stable. After 15 years, a control chest X-ray revealed an increase in the size of the compaction in the lung and the appearance of a mass with calcification in the medial sections of the compaction zone. Additional examination, including computed tomography with biopsy, determined that the obstruction of the bronchus was caused by a neoplasm [according to histological examination (typical carcinoid)]. It should be noted that the initial detection of negative study results requires oncological alertness and periodic examinations in dynamics.

Clinicopathological and Prognostic Significance of CD47 Expression in Lung Neuroendocrine Tumors

Background. Lung neuroendocrine tumors account for approximately 15% of all lung cancer cases. LNET are subdivided into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small-cell lung cancer (SCLC). The Ki-67 index has been used for decades to evaluate mitotic counts however, the role of Ki-67 as a biomarker for assessing prognosis and guiding therapy in metastatic LNET still lacks feasible clinical validation. Recent clinical trials have indicated that inhibition of CD47 with anti-CD47 antibodies exerts a promising antitumor effect against several human malignancies, including NSCLC, melanoma, and hematologic malignancies. However, the clinical relevance of CD47 expression in LNET has remained unclear. Methods. We performed a retrospective study in which we analyzed tumor biopsies from 51 patients with a confirmed diagnosis of LNET that received treatment at our hospital. Then, we analyzed if there was any correlation between CD47 expression with any clinical or pathological characteristic. We also analyzed the prognostic significance of CD47, assessed as progression-free survival and overall survival. Results. A total of 51 patients with LNET were enrolled in our study. The mean age at diagnosis was 57.6 (±11.6) years; 30 patients were women (59%). 27.5% of patients were positive for CD47 expression, and 72.5% of patients showed a CD47 expression of less than 1% and were considered as negatives. In patients with high-grade tumors (this time defined as Ki ‐ 67 > 40 % ), the positive expression of CD47 was strongly associated with an increased PFS. Albeit, these differences did not reach statistical significance when analyzing OS. Conclusion. Contrary to what happens in a wide range of hematologic and solid tumors, a higher expression of CD47 in patients with LNET is associated with a better progression-free survival, especially in patients with a Ki ‐ 67 ≥ 40 % . This “paradox” remains to be confirmed and explained by larger studies.