Non-neuroendocrine Carcinoma Research Articles

Primary Neuroendocrine Carcinoma in Oral and Maxillofacial Region: A Comprehensive Study of Twelve Rare Cases Including Mixed Neuroendocrine Non-Neuroendocrine Carcinoma

Primary Neuroendocrine Carcinoma in Oral and Maxillofacial Region: A Comprehensive Study of Twelve Rare Cases Including Mixed Neuroendocrine Non-Neuroendocrine Carcinoma

Neuroendocrine neoplasms of the ovary: a review of 63 cases

ObjectiveTo describe the clinicopathological characteristics and survival outcomes of ovarian neuroendocrine neoplasms from a curated registry.MethodsThis is a retrospective cross-sectional study of patients in our registry with confirmed ovarian neuroendocrine...

A rare clinical case of a patient with mixed neuroendocrine-non-neuroendocrine neoplasms of the ampulla of vater

Background. Neuroendocrine tumors are rare neoplasias accounting for 1 % of all digestive malignancies. In 2010, mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) were classified by the World Health Organization This type of tumor is extremely rare and most commonly occurs in the appendix, colon, and rectum. To date, only 30 clinical cases of MINEN of the major duodenal papilla (MDP) have been described in the available world literature, while we have not found a description of this pathology in the domestic literature.Description of the clinical case. We present a case of a 64-year-old male patient with MiNEN MDP. The first clinical manifestation of the disease was obstructive jaundice. To eliminate the jaundice, papillosphincterotomy, transpapillary stenting of the choledochus with a plastic stent was performed. MDP tumor was verifed as adenocarcinoma by histological examination. The patient underwent gastropancreatoduodenal resection. Postoperative immunohistochemical examination showed the expression of antibodies in tumor cells: Synaptophysin (clone 27G12) +++, Chromogranin A (5H7) +, CD 57 (NK-1) ++, Ki 67 (Mib 1) 80 %.Conclusion: mixed neuroendocrine (G3) non-neuroendocrine carcinoma (G2) of the major duodenal papilla with growth within the wall of the duodenum; metastases of the neuroendocrine component in three lymph nodes, adenocarcinoma metastasis in 1 out of 15 lymph nodes examined; pT2N2M0, MiNEN high grade (classified by S. La Rosa). Conclusion. Mixed neuroendocrine-non-neuroendocrine tumors of MDP are an extremely rare pathology. The accuracy of preoperative morphological diagnostics is not high, therefore, this diagnosis can be easily missed at the preoperative stage. In the morphological study of malignant tumors of MDP, a pathologist should take into account the feasibility of a combination of a neuroendocrine tumor with adenocarcinoma.

Development and validation of a contrast-enhanced CT-based radiomics nomogram for preoperative diagnosis in neuroendocrine carcinoma of digestive system.

To develop and validate a contrast-enhanced CT-based radiomics nomogram for the diagnosis of neuroendocrine carcinoma of the digestive system. The clinical data and contrast-enhanced CT images of 60 patients with pathologically confirmed neuroendocrine carcinoma of the digestive system and 60 patients with non-neuroendocrine carcinoma of the digestive system were retrospectively collected from August 2015 to December 2021 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and randomly divided into a training cohort (n=84) and a validation cohort (n=36). Clinical characteristics were analyzed by logistic regression and a clinical diagnosis model was developed. Radiomics signature were established by extracting radiomic features from contrast-enhanced CT images. Based on the radiomic signature and clinical characteristics, radiomic nomogram was developed. ROC curves and Delong's test were used to evaluate the diagnostic efficacy of the three models, calibration curves and application decision curves were used to analyze the accuracy and clinical application value of nomogram. Logistic regression results showed that TNM stage (stage IV) (OR 6.8, 95% CI 1.320-43.164, p=0. 028) was an independent factor affecting the diagnosis for NECs of the digestive system, and a clinical model was constructed based on TNM stage (stage IV). The AUCs of the clinical model, radiomics signature, and radiomics nomogram for the diagnosis of NECs of the digestive system in the training, validation cohorts and pooled patients were 0.643, 0.893, 0.913; 0.722, 0.867, 0.932 and 0.667, 0.887, 0.917 respectively. The AUCs of radiomics signature and radiomics nomogram were higher than clinical model, with statistically significant difference (Z=4.46, 6.85, both p < 0.001); the AUC difference between radiomics signature and radiomics nomogram was not statistically significant (Z=1.63, p = 0.104). The results of the calibration curve showed favorable agreement between the predicted values of the nomogram and the pathological results, and the decision curve analysis indicated that the nomogram had favorable application in clinical practice. The nomogram constructed based on contrast-enhanced CT radiomics and clinical characteristics was able to effectively diagnose neuroendocrine carcinoma of the digestive system.

Combined Large Cell Neuroendocrine Carcinomas of the Lung: Integrative Molecular Analysis Identifies Subtypes with Potential Therapeutic Implications.

Simple SummaryIn this manuscript, we offer an integrated molecular analysis of 44 combined large cell neuroendocrine carcinomas (CoLCNECs) in order to deepen the knowledge about these rare histotypes and to clarify their relationship with lung cancers. In the present state of research, molecular studies are still scant, consisting of small and heterogeneous cohorts, and the genomic landscape is poorly characterized. This study shows that CoLCNECs constitute a standalone group of neuroendocrine neoplasm, with three different molecular profiles, two of which overlap with pure LCNEC or adenocarcinoma. CoLCNECs can be considered an independent histologic category with specific genomic and transcriptomic features, different and therefore not comparable to other lung cancers. Indeed, in addition to a histological re-evaluation of lung cancer classification, our study may help to develop a new diagnostic approach for novel and personalized treatments in CoLCNECs.Background: Combined large cell neuroendocrine carcinoma (CoLCNEC) is given by the association of LCNEC with adeno or squamous or any non-neuroendocrine carcinoma. Molecular bases of CoLCNEC pathogenesis are scant and no standardized therapies are defined. Methods: 44 CoLCNECs: 26 with adenocarcinoma (CoADC), 7 with squamous cell carcinoma (CoSQC), 3 with small cell carcinoma (CoSCLC), 4 with atypical carcinoid (CoAC) and 4 napsin-A positive LCNEC (NapA+), were assessed for alterations in 409 genes and transcriptomic profiling of 20,815 genes. Results: Genes altered included TP53 (n = 30), RB1 (n = 14) and KRAS (n = 13). Targetable alterations included six KRAS G12C mutations and ALK-EML4 fusion gene. Comparison of CoLCNEC transcriptomes with 86 lung cancers of pure histology (8 AC, 19 ADC, 19 LCNEC, 11 SCLC and 29 SQC) identified CoLCNEC as a separate entity of neuroendocrine tumours with three different molecular profiles, two of which showed a non-neuroendocrine lineage. Hypomethylation, activation of MAPK signalling and association to immunotherapy signature specifically characterized each of three CoLCNEC molecular clusters. Prognostic stratification was also provided. Conclusions: CoLCNECs are an independent histologic category. Our findings support the extension of routine evaluation of KRAS mutations, fusion genes and immune-related markers to offer new perspectives in the therapeutic management of CoLCNEC.

Expression and clinical significance of a new neuroendocrine marker secretagogin in cervical neuroendocrine carcinoma

AimsTo explore the expression of secretagogin (SCGN) in neuroendocrine carcinoma of the uterine cervix and analyse its relationship with clinicopathological characteristics and prognosis.MethodsFrom January 2010 to December 2017, 44 patients...

Targeted Sequencing of Mixed Neuroendocrine- Non-neuroendocrine Neoplasm of the Gallbladder Suggests a Monoclonal Origin: A Case Report

Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) of the gallbladder is a rare tumor that is defined in the World Health Organization (WHO) 2019 digestive system tumor classification as the presence of a neuroendocrine neoplasm admixed with a non-neuroendocrine carcinoma, each component constituting at least 30% of the neoplasm. The exact pathogenesis of MiNENs remains unclear. We present a case of a 74-year-old Filipino woman who presented with nonspecific clinical and radiologic findings and subsequently underwent cholecystectomy. Histopathologic and immunohistochemical evaluation of the gallbladder confirmed the diagnosis of a mixed well-differentiated adenocarcinoma (30%) and large cell neuroendocrine carcinoma (70%). The adenocarcinoma and neuroendocrine carcinoma components were separately microdissected and submitted for targeted 15-gene sequencing using the Illumina Trusight Tumor 15 (TST15) panel. NGS identified a TP53 missense mutation leading to a stop codon in both components. The finding of similar molecular signatures in the two morphologically distinct components supports the hypothesis that MiNEN arises from a common precursor stem cell capable of divergent phenotypic differentiation.

Clinical characteristics of the mixed form of neuroendocrine tumor in the lung: A retrospective study in 2501 lung cancer cases.

BackgroundA neuroendocrine tumor (NET) is a special kind of epithelial tumor with predominant neuroendocrine differentiation, which arises throughout the body, including the lung. A subpopulation of lung cancer patients suffer from the mixed (combined) form of NET with components of non-neuroendocrine carcinoma. However, the clinical characteristics of the mixed form of NET are not well established.MethodsWe analyzed 2501 consecutive cases of primary lung cancer from 2009 to 2011. The diagnosis, histology, therapy, and outcome were collected.ResultsA total of 22 patients were enrolled. The occurrence rate of lung cancer was 0.9%. Neither gender (1.2% and 0.3% for male and female, respectively, P = 0.35) nor age (0.6% and 1.3% for patients aged ≤60 and >60, respectively, P = 0.13) was associated with the onset of this disease; however it has become more frequent in recent years (0.6% and 1.6% at the time ≤ and >2010 respectively, P = 0.03). This cohort of 22 patients had a median survival of 60.0 months (95% confidence interval: 14.3–105.6 months). Patients with metastatic disease (60 months and not reached [NR], P = 0.18) or a small-cell lung cancer component tended to have a shorter survival (35 months and NR, P = 0.16). Patients who underwent surgery had a significantly longer survival period (NR and 17.0 months, P = 0.001).ConclusionsA mixed form of NET in the lung is a rare disease. While stage and histology might influence prognosis, surgery is the critical factor for long-term survival.

Metastatic lesions to the liver: Surgical indications and techniques

Background: Although there is an established agreement on the advantage of liver resection for metastatic colorectal and neuroendocrine tumours, the role of hepatic surgery in patients with liver metastases from non-colorectal and non-neuroendocrine carcinoma is not well defined. In recent years, despite the poor results, liver metastases suitable for surgery have been treated with resection. The results reported in recent studies support a developing trend toward surgery in this setting. Also, as there are no data that in fact suggest the utility of alternative treatments for these lesions, the role of surgery is reinforced. Methods: A systematic search of English and non-English literature using MEDLINE on the outcomes of patients after surgical treatment of liver metastases from different solid tumours was undertaken. A summary of current surgical techniques used to improve their resectability has been added. Results: All papers reporting median survival and 5-year survival have been selected and presented in tables for most of the primary tumours reviewed. Conclusions: Apart from patients with colorectal and neuroendocrine tumours, liver resection may offer a significative survival advantage in selected patients, mainly those with metastases coming from breast, gastrointestinal stromal tumours, testis, ovary and kidney.

Extrapulmonary neuroendocrine small and large cell carcinomas: a review of controversial diagnostic and therapeutic issues

Extrapulmonary neuroendocrine carcinoma (EPNEC) is a heterogeneous and rare group of high-grade neoplasms occurring in different organs. They usually share a poor prognosis, but diagnostic and therapeutic options still include several controversial issues, due to the rarity of this condition and to differences in architecture and cell size, being some cases pure small cell carcinomas, other pure large cell neuroendocrine carcinomas and some others combined/mixed neuroendocrine carcinomas with a conventional non-neuroendocrine carcinoma. In addition, the therapeutic strategy varies in different organs (surgery and/or chemotherapy and/or radiation therapy and/or targeted treatments), and clinicians and pathologists are asked to interact to reach an accurate classification of every single case, as well as the most appropriate selection of the treatment options, even considering different time points of each EPNEC natural history. This overview highlights controversial pathological and clinical issues and summarizes possible solutions to most of such EPNEC-related problems.

Resection of metastases from pancreatic and periampullary nonneuroendocrine tumors.

e14683 Background: The survival benefit from resection of hepatic metastases from colorectal and neuroendocrine tumors has been well documented in the literature. There are limited studies examining the role of metastasectomy in patients with nonneuroendocrine pancreatic or periampullary primary tumors. Methods: We performed a retrospective chart review of 983 patients who underwent resections for pancreatic and periampullary tumors at our institution between 1991 and 2009. Survival was defined in two ways: overall survival was defined as time from primary resection to death or last follow-up, while metastasectomy-survival was defined as time from metastasectomy to death or last follow-up. Results: We identified 15 patients who underwent metastasectomy for nonneuroendocrine tumors, including adenocarcinoma (n = 14) and acinar cell carcinoma (n = 1). The majority of patients underwent resection of hepatic metastases (n = 9), followed by lung (n = 3) and ovarian (n = 3) metastases. Four patients had periamp...

Multicentric Basaloid Carcinoma of Lung Clinically Mimicking Metastatic Carcinoma: A Case Report

Basaloid carcinoma of lung is a highly aggressive form of non-small cell and non-neuroendocrine pulmonary carcinoma. It may exist in pure form or may admixed with other types of non-small cell lung carcinoma. A unique case of a multicentric basaloid carcinoma of lung is reported in this study. The patient was an 81-year-old male who was found to have 2 separate nodules of the left lung on computed tomography scan. He underwent wedge resection of both nodules. The morphology of the lesions was identical and consistent with basaloid carcinoma. Extensive workup to detect a possible extrapulmonary primary site was negative. Loss of heterozygosity studies performed on the 2 tumors were consistent with multicentric rather than metastatic nature.

Partial Hepatectomy for Metastases From Noncolorectal, Nonneuroendocrine Carcinoma

Partial Hepatectomy for Metastases From Noncolorectal, Nonneuroendocrine Carcinoma

Partial Hepatectomy for Metastases From Noncolorectal, Nonneuroendocrine Carcinoma

To define perioperative and long-term outcome and prognostic factors in patients undergoing hepatectomy for liver metastases arising from noncolorectal and nonneuroendocrine (NCNN) carcinoma. Hepatic resection is a well-established therapy for patients with liver metastases from colorectal or neuroendocrine carcinoma. However, for patients with liver metastases from other carcinomas, the value of resection is incompletely defined and still debated. Between April 1981 and April 2002, 141 patients underwent hepatic resection for liver metastases from NCNN carcinoma. Patient demographics, tumor characteristics, treatment, and postoperative outcome were analyzed. Thirty-day postoperative mortality was 0% and 46 of 141 (33%) patients developed postoperative complications. The median follow up was 26 months (interquartile range [IQR]) 10-49 months); the median follow up for survivors was 35 months (IQR 11-68 months). There have been 24 actual 5-year survivors so far. The actuarial 3-year relapse-free survival rate was 30% (95% confidence interval [CI], 21-39%) with a median of 17 months. The actuarial 3-year cancer-specific survival rate was 57% (95% CI, 48-67%) with a median of 42 months. Primary tumor type and length of disease-free interval from the primary tumor were significant independent prognostic factors for relapse-free and cancer-specific survival. Margin status was significant for cancer-specific survival and showed a strong trend for relapse-free survival. Hepatic resection for metastases from NCNN carcinoma is safe and can offer long-term survival in selected patients. Hepatic resection should be considered if all gross disease can be removed, especially in patients with metastases from reproductive tract tumors or a disease-free interval greater than 2 years.

Histidine Decarboxylase Expression as a New Sensitive and Specific Marker for Small Cell Lung Carcinoma

Histidine decarboxylase is one of the enzymes of the amine precursor uptake and decarboxylation system and is known to be distributed in mast cells and enterochromaffin-like cells. With the hypothesis that histidine decarboxylase expression is a marker for neuroendocrine differentiation, we studied the immunoreactivity of histidine decarboxylase in neuroendocrine cells and tumors of the thyroid gland, adrenal medulla, lung, and gastrointestinal tract. Formalin-fixed paraffin sections were subjected to immunohistochemistry using anti-histidine decarboxylase antibody, and the sensitivity and specificity were compared with those of conventional neuroendocrine markers (CD56, chromogranin A, synaptophysin, and neuron-specific enolase). Enterochromaffin or enterochromaffin-like cells, adrenal chromaffin cells, and thyroid C-cells were positive for histidine decarboxylase, and related tumors (carcinoid tumor, pheochromocytoma, medullary carcinoma) showed a high percentage of positive staining. Furthermore, we used the antibody to distinguish small cell lung carcinoma from non-neuroendocrine lung carcinoma and also to detect neuroendocrine differentiation in large-cell neuroendocrine carcinoma and gastrointestinal small-cell carcinoma. The anti-histidine decarboxylase antibody stained most small cell lung carcinoma (18 of 23, sensitivity 0.78), and was rarely reactive with non-neuroendocrine lung tumors (2 of 44; specificity, 0.95). These values were close to those obtained from CD56 staining (sensitivity/specificity, 0.87/0.98). Histidine decarboxylase was also positive for 6 of 12 large cell neuroendocrine carcinomas and 4 of 7 gastrointestinal small cell carcinomas. In conclusion, we demonstrated that histidine decarboxylase is useful to distinguish between small cell lung carcinoma and non-neuroendocrine carcinoma and to demonstrate neuroendocrine differentiation.

Lung tumors with mixed histologic pattern. Clinico-pathologic characteristics and prognostic significance.

To analyze and compare clinico-pathologic characteristics and survival between lung tumors with mixed histologic pattern and our population of resected lung tumors with single histology in the same period. From January 1993 to December 1999, 1158 patients received resection for lung tumors. Of these, 59 (5.1%) presented a mixed histologic pattern on the surgical specimen. There were 48 men and 11 women (mean age 64 years, range 43-79). Three groups of tumors were identified: adenosquamous carcinoma, combined neuroendocrine + non-neuroendocrine carcinoma (NNEC) and biphasic tumors (epithelial + mesenchymal malignant components) represented by carcinosarcoma and blastoma. The combined neuroendocrine tumors were further divided in small cell lung carcinoma (SCLC) + large cell neuroendocrine carcinoma (LCNEC)/NNEC and other neuroendocrine tumors/NNEC. Clinico-pathologic characteristics, pTNM and survival were analyzed and compared to our population of resected lung tumors with single histology. There were 33 adenosquamous carcinomas, 19 combined SCLC+LCNEC/NNEC, two other neuroendocrine tumors/NNEC and five biphasic tumors (three carcinosarcomas and two blastomas). Among adenosquamous carcinomas, high cell grading (G2 or G3), advanced stage (IIIa or higher) and intratumoral perineural invasion were significantly more evident than in the single histology population. Among combined neuroendocrine/NNEC, high cell grading (G3) and intratumoral vascular invasion were significantly more evident than in the single histology population. Among biphasic tumors, all were at early stages and showed high cell grading (G3). Three-year survival rates were 46% in the single histology group, 28% in the adenosquamous group and 21% in the combined SCLC + LCNEC/NNEC. The difference among the three groups was significant (P = 0.013). Median survival of biphasic tumors was 19 months (range 8-37). Lung tumors with mixed histologic pattern are rare tumors. Adenosquamous carcinoma and combined SCLC + LCNEC/NNEC present a more aggressive clinico-pathologic behaviour and reduced survival as compared to the single histology population of resected lung tumors.

Surgical treatment of hepatic and pulmonary metastases from non-colorectal and non-neuroendocrine carcinoma.

Surgical resection is standard treatment for colorectal and neuroendocrine liver metases provided the tumor can be removed completely. The same is true for isolated pulmonary metastases. To date, only few reports have addressed the value of surgical resection of organ metastases from other solid tumors. The literature was searched by Medline, conference proceedings and cross-referencing of published articles for information pertaining to the long-term results of surgical treatment of non-colorectal and non-neuroendocrine (NCNN) liver or lung metastases. Resection of hepatic and pulmonary metastases is increasingly performed in non-colorectal and non-neuroendocrine malignancies. Mortality and morbidity of hepatic and pulmonary resection are low and 5 year survival can be expected to reach some 20-30 percent, irrespective of the histological type of the primary tumor. Resection of hepatic or pulmonary metastasis should be considered in all patients with low operative risk provided that complete resection is possible.

Correlative Immunohistochemical and Reverse Transcriptase Polymerase Chain Reaction Analysis of Somatostatin Receptor Type 2 in Neuroendocrine Tumors of the Lung

Somatostatin receptors type 2 (sst2) have been frequently detected in neuroendocrine tumors and bind somatostatin analogues, such as octreotide, with high affinity. Receptor autoradiography, specific mRNA detection and, more recently, antisst2 polyclonal antibodies are currently employed to reveal sst2. The aim of the present study was to investigate by three different techniques the presence of sst2 in a series of 26 neuroendocrine tumors of the lung in which fresh frozen tissue and paraffin sections were available. It was possible, therefore, to compare, in individual cases, RNA analysis studied by reverse transcriptase polymerase chain reaction (RT-PCR), in situ hybridization (ISH), and immunohistochemistry. A series of 20 nonneuroendocrine lung carcinoma samples served as controls. RT-PCR was positive for sst2 in 22 of 26 samples, including 15 of 15 typical carcinoids, 5 of 6 atypical carcinoids, and 2 of 5 small-cell carcinomas. The sst2 mRNA signal obtained by RT-PCR was strong in the majority (87%) of typical carcinoids and of variable intensity in atypical carcinoids and small-cell carcinomas. A weakly positive signal was observed in 5 of 20 control samples. In immunohistochemistry, two different antibodies (anti-sst2) were employed, including a monoclonal antibody, generated in the Department of Pathology, University of Turin. In the majority of samples a good correlation between sst2 mRNA (as detected by RT-PCR) and sst2 protein expression (as detected by immunohistochemistry) was observed. However, one atypical carcinoid and one small-cell carcinoma had focal immunostaining but no RT-PCR signal. ISH performed in selected samples paralleled the results obtained with the other techniques. A low sst2 expression was associated with high grade neuroendocrine tumors and with aggressive behavior. It is concluded that 1) neuroendocrine tumors of the lung express sst2, and there is a correlation between the mRNA amount and the degree of differentiation; 2) immunohistochemistry and ISH are reliable tools to demonstrate sst2 in these tumors; and 3) sst2 identification in tissue sections may provide information on the diagnostic or therapeutic usefulness of somatostatin analogues in individual patients with neuroendocrine tumors.