Molecular aspects of prostate cancer with neuroendocrine differentiation

Neuroendocrine differentiation （NED）, which is not uncommon in prostate cancer, is increases in prostate cancer after androgen-deprivation therapy （ADT） and generally appears in castration- resistant prostate cancer （CRPC）. Neuroendocrine ceils, which are found in normal prostate tissue, are a small subset of cells and have unique function in regulating the growth of prostate ceils. Prostate cancer with NED includes different types of tumor, including focal NED, pure neuroendocrine tumor or mixed neuroendocrine-adenocarcinoma. Although more and more studies are carried out on NED in prostate cancer, the molecular components that are involved in NED are still poorly elucidated. We review neuroendocrine cells in normal prostate tissue, NED in prostate cancer, terminology of NED and biomarkers used for detecting NED in routine pathological practice. Some recently reported molecular components which drive NED in prostate cancer are listed in the review.

Neuroendocrine differentiation:The mysterious fellow of colorectal cancer

Neuroendocrine differentiation in sporadic colorectal cancer has been recognized since decades, but its clinical impact is still controversially discussed. Detailed parameter analyses hint at the possibility that probablynot neuroendocrine differentiation itself, but its association with poor grade of tumor differentiation, lymph node metastases, distant metastases and other unfavorable features contribute to worse clinical outcome. However, other studies deny a relationship between neuroendocrine differentiation and prognosis of colorectal cancer. This review elucidates, whether new insights into the origin of neuroendocrine differentiation in the intestinal epithelium, its regulation by m TOR pathway components and its possible link to the intestinal stem cell compartment could determine a role of neuroendocrine cells as prognostic marker and putative therapeutic target in sporadic colorectal cancer.

Prostate tumor neuroendocrine differentiation via EMT: The road less traveled

The long-standing challenge in the treatment of prostate cancer is to overcome therapeutic resistance during progression to lethal disease.Aberrant transforming-growth factor-b(TGF-b)signaling accelerates prostate tumor progression in a transgenic mouse model via effects on epithelial-mesenchymal transition(EMT),and neuroendocrine differentiation driving tumor progression to castration-resistant prostate cancer(CRPC).Neuroendocrine prostate cancer(NEPC)is highly aggressive exhibiting reactivation of developmental programs associated with EMT induction and stem cell-like characteristics.The androgen receptor(AR)is a critical driver of tumor progression as well as therapeutic response in patients with metastatic CRPC.The signaling interactions between the TGF-β mechanistic network and AR axis impact the EMT phenotypic conversions,and perturbation of epithelial homeostasis via EMT renders a critical venue for epithelial derived tumors to become invasive,acquire the neuroendocrine phenotype,and rapidly metastasize.Combinations of microtubule targeting taxane chemotherapy and androgen/AR targeting therapies have survival benefits in CRPC patients,but therapeutic resistance invariability develops,leading to mortality.Compelling evidence from our group recently demonstrated that chemotherapy(cabazitaxel,second line taxane chemotherapy),or TGF-β receptor signaling targeted therapy,caused reversion of EMT to mesenchymal-epithelial transition and tumor re-differentiation,in in vitro and in vivo prostate cancer models.In this review,we discuss the functional contribution of EMT dynamic changes to the development of the neuroendocrine phenotypedthe newly characterized pathological feature of prostate tumors in the context of the tumor microenvironment-navigated cell lineage changes and the role of this neuroendocrine phenotype in metastatic progression and therapeutic resistance.

Clinical relevance of neuroendocrine differentiation in lung adenocarcinoma

Objective:The aim of our study was to investigate the prevalence and clinical relevance of neuroendocrine(NE) differentiation in lung adenocarcinoma.Methods:Eighty-six adenocarcinoma paraffin-embedded specimens and cases which were followed up completely for 3 years,were obtained from 86 patients(35 men and 51 women) who underwent surgical resection for pathologically supported adenocarcinoma in the Cancer Hospital of Tianjin Medical University,from June 2005 to December 2006.Immunohistochemical EnVision two-step method was used to detect the expression of neuron-specific enolase(NSE),synaptophysin(SYN) and chromogranin A(CGA).All data were analyzed using SPSS statistics software and Kaplan-Meier survival curves were constructed,meanwhile,we conducted a Log-rank test.Results:All patients with lung adenocarcinoma,35 cases with NE differentiation(40.7%).The statistical analysis showed that the positive rate of NE differentiation in lung adenocarcinoma was significantly associated with cancer recurrence and histological differentiation.In addition,CGA,NSE and SYN positive rates were 27.9%,50.0%,43.0%,respectively.A statistically significant difference was found between positive expression of SYN and other clinicopathological parameters,such as pathological type,histological differentiation,lymph node metastasis,postoperative recurrence and 3-year survival rate(P = 0.001) and so on.Conclusion:NE differentiation can be used as a metastatic potentially indicator of biological behavior of lung adenocarcinoma,and combined detection of NSE and SYN markers may be recommended to examine NE differentiation of lung adenocarcinoma.Positive expression of SYN indicates poor prognosis.

Hepatocellular carcinoma with biliary and neuroendocrine differentiation: A case report

BACKGROUND Liver tumors with dual differentiations[combined hepatocellular carcinoma(HCC)and cholangiocarcinoma]are common.However,liver tumors that exhibit hepatocellular,biliary,and neuroendocrine differentiation are exceedingly rare,with only three previous case reports in the literature.CASE SUMMARY A 65-year-old female with a previous history of hepatitis C and a distant history of low grade,well-differentiated rectal neuroendocrine tumor was found to have two liver lesions in segment 4 and segment 7 on imaging.Serum alpha-fetoprotein and chromogranin A were elevated.Biopsy of the larger lesion in segment 4 revealed a high-grade tumor,with morphologic and immunohistochemical features of a neuroendocrine tumor.Given the previous history of rectal neuroendocrine tumor,imaging investigation,serologic markers,and biopsy findings,metastatic neuroendocrine tumor was considered.Subsequent regional resection of these hepatic lesions revealed the segment 4 lesion to be a HCC with additional biliary and neuroendocrine differentiation and the segment 7 lesion to be a cholangiocarcinoma with neuroendocrine differentiation.Follow-up of the patient revealed disease recurrence in the dome of the liver and metastasis in retro-pancreatic lymph nodes.The patient eventually expired due to complications of chemotherapy.CONCLUSION HCC cases with additional biliary and neuroendocrine differentiation are exceedingly rare,posing a diagnostic challenge for clinicians and pathologists.

Neuroendocrine Differentiation in the Progression of Prostate Cancer: An Update on Recent Developments

Neuroendocrine (NE) differentiation, either benign or malignant, is the hallmark of prostate cancer (PCa). Clusters of malignant NE cells are found in most prostate cancer cases. NE differentiation is among the non-mutually exclusive theories proposed to explain the progression to androgen independence of PCa. NE differentiation is usually associated with an increased aggressivity and invasiveness of prostate tumors and a poor prognosis. This review aims to present an overview of current knowledge on neuroendocrine differentiation in PCa to improve our understanding of tumour progression and androgen independence. The NE component represents an important therapeutic axis. Development of new generation of drugs that selectively target NE-like cells may lead to the development of new therapeutic modalities for advanced and hormone-refractory PCa.

Neuroendocrine differentiation in prostate cancer

Hormonal therapy is an important treatment for advanced/metastatic prostate cancer. But it can induce neuroen-docrine(NE) differentiation in prostate cancer cells. These NE cells will secrete manifold neural peptide or hormones which can lead to androgen-independent growth of non-NE tumor cells. When this happens,hormonal therapy becomes useless and indicates bad prognosis. In this paper,the mechanism of neuroendocrine differentiation and its relationship with andro-gen-independent were reviewed.

Neuroendocrine differentiation and the ubiquitinproteasome system in cancer:Partners or enemies?

Neuroendocrine(NE)differentiation of cancer and deregulation of the ubiquitin-proteasome system(UPS)are two processes that have been independently linked to the development of aggressive and treatment-resistant tumors.Striking data suggest a plausible interconnection between these two mechanisms,based on indirect evidence of neuropeptide-induced effects on UPS,reversed by proteasome inhibition and deubiquitinaselike properties of NE markers.Deciphering the model of their exact interactions is one of the keys to targeting the NE malignant phenotype more effectively.

Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation:A case report and review of literature

BACKGROUND Both hepatoid adenocarcinoma of the stomach(HAS)and neuroendocrine differentiation(NED)are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes.HAS with NED is even rarer.CASE SUMMARY Here,we report a 61-year-old man with HAS with NED,as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule.Distal gastrectomy was performed,and pathological examination led to the diagnosis of HAS with NED.However,liver metastases occurred 6 mo later despite adjuvant chemotherapy,and the patient died 27 mo postoperatively.CONCLUSION We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases.We first report the detailed processes of the treatment and development of HAS with NED,providing an important reference for the clinical diagnosis and treatment of this condition.

The genomic and microenvironmental factors affecting neuroendocrine differentiation in prostate cancer induced by androgen deprivation therapy

Although advanced prostate cancer(PCa)can be initially controlled by androgen deprivation therapy(ADT),recurrence normally occurs due to the appearance of castration-resistant prostate cancer(CRPC).Neuroendocrine differentiation(NED)in PCa can be partly explained the androgen resistance and progression to CRPC.NED normally associates with more aggressive clinical behaviour and poor outcomes in PCa.Although more and more studies are performed on NED in PCa recent decades,the molecular profiles that are implicated in NED are still poorly elucidated.Of these studies,signaling factors involved in genomic and microenvironmental components are deeply researched and most likely to provide the potential therapeutic targets for advanced PCa with NED.In this article,we review the hypothesis about the origin of NE cells and the molecular mechanisms driving NED from the point of genomic and environmental views.In addition,we discuss the current potential therapeutic targets and ongoing clinical trails associated with these molecular factors for the treatment of NED patients induced by ADT.

Value of Texture Analysis of Intravoxel Incoherent Motion Parameters in Differential Diagnosis of Pancreatic Neuroendocrine Tumor and Pancreatic Adenocarcinoma

Objective To evaluate the value of texture features derived from intravoxel incoherent motion(IVIM) parameters for differentiating pancreatic neuroendocrine tumor(pNET) from pancreatic adenocarcinoma(PAC).Methods Eighteen patients with pNET and 32 patients with PAC were retrospectively enrolled in this study. All patients underwent diffusion-weighted imaging with 10 b values used(from 0 to 800 s/mm2). Based on IVIM model, perfusion-related parameters including perfusion fraction(f), fast component of diffusion(Dfast) and true diffusion parameter slow component of diffusion(Dslow) were calculated on a voxel-by-voxel basis and reorganized into gray-encoded parametric maps. The mean value of each IVIM parameter and texture features [Angular Second Moment(ASM), Inverse Difference Moment(IDM), Correlation, Contrast and Entropy] values of IVIM parameters were measured. Independent sample t-test or Mann-Whitney U test were performed for the betweengroup comparison of quantitative data. Regression model was established by using binary logistic regression analysis, and receiver operating characteristic(ROC) curve was plotted to evaluate the diagnostic efficiency.Results The mean f value of the pNET group were significantly higher than that of the PAC group(27.0% vs. 19.0%, P = 0.001), while the mean values of Dfast and Dslow showed no significant differences between the two groups. All texture features(ASM, IDM, Correlation, Contrast and Entropy) of each IVIM parameter showed significant differences between the pNET and PAC groups(P = 0.000-0.043). Binary logistic regression analysis showed that texture ASM of Dfast and texture Correlation of Dslow were considered as the specific imaging variables for the differential diagnosis of pNET and PAC. ROC analysis revealed that multiple texture features presented better diagnostic performance than IVIM parameters(AUC 0.849-0.899 vs. 0.526-0.776), and texture ASM of Dfast combined with Correlation of Dslow in the model of logistic regression had largest area under ROC curve for distinguishing pNET from PAC(AUC 0.934, cutoff 0.378, sensitivity 0.889, specificity 0.854). Conclusion Texture analysis of IVIM parameters could be an effective and noninvasive tool to differentiate pNET from PAC.

Comprehensive treatment for metastatic castration-resistant prostate cancer with neuroendocrine differentiation:a case report

Retrospective analysis of the progression of a case of metastatic castration-resistant prostate cancer with neuroendocrine differentiation:the patient was a 65 year old man with prostate adenocarcinoma on prostate biopsy,Gleason 4+4 score=8,70%,ISUP4 group,localized invasion of nerves.Progressed to metastatic castration-resistant prostate cancer after 8 months of novel endocrine therapy,persistent elevated PSA after endocrine therapy,chemotherapy,and radiation,abdominal metastasis,brain metastasis,gastric metastasis,and staging as neuroendocrine differentiation after second prostate biopsy,which is a highly malignant subtype and has been concerned as a mechanism of resistance to targeted therapies.We discuss how to choose a more optimal treatment plan and outline the patient's diagnostic and therapeutic course.We provide a reflection for the clinical study of metastatic castration-resistant prostate cancer with neuroendocrine type.

Clinicopathological characteristics and prognosis of 232 patients with poorly differentiated gastric neuroendocrine neoplasms

BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incidence has increased over the past few decades.However,the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.AIM To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs.METHODS The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.RESULTS Among the 232 patients with PDGNENs,191(82.3%)were male,with an average age of 62.83±9.11 years.One hundred and thirteen(49.34%)of 229 patients had a stage III disease and 86(37.55%)had stage IV disease.Three(1.58%)of 190 patients had no clinical symptoms,while 187(98.42%)patients presented clinical symptoms.The tumors were mainly(89.17%)solitary and located in the upper third of the stomach(cardia and fundus of stomach:115/215,53.49%).Most lesions were ulcers(157/232,67.67%),with an average diameter of 4.66±2.77 cm.In terms of tumor invasion,the majority of tumors invaded the serosa(116/198,58.58%).The median survival time of the 232 patients was 13.50 mo(7,31 mo),and the overall 1-year,3-year,and 5-year survival rates were 49%,19%,and 5%,respectively.According to univariate analysis,tumor number,tumor diameter,gastric invasion status,American Joint Committee on Cancer(AJCC)stage,and distant metastasis status were prognostic factors for patients with PDGNENs.Multivariate analysis showed that tumor number,tumor diameter,AJCC stage,and distant metastasis status were independent prognostic factors for patients with PDGNENs.CONCLUSION The overall prognosis of patients with PDGNENs is poor.The outcomes of patients with a tumor diameter>5 cm,multiple tumors,and stage IV tumors are worse than those of other patients.

Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: A systematic review

BACKGROUND Approximately 20%of patients with neuroendocrine tumours(NETs)develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion.Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs(GEP-NETs),other causes to consider include pancreatic enzyme insufficiency(PEI),bile acid malabsorption and small intestinal bacterial overgrowth.If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea,these treatments may be ineffective against the diarrhoea,risking detrimental effects to patient quality of life.AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.METHODS Electronic databases(MEDLINE,Embase and the Cochrane Library)were searched from inception to September 12,2018 using terms for NETs and diarrhoea.Congresses,systematic literature review bibliographies and included articles were also hand-searched.Any study designs and publication types were eligible for inclusion if relevant data on a cause(s)of diarrhoea in patients with GEP-NETs were reported.Studies were screened by two independent reviewers at abstract and full-text stages.Framework synthesis was adapted to synthesise quantitative and qualitative data.The definition of qualitative data was expanded to include all textual data in any section of relevant publications.RESULTS Forty-seven publications(44 studies)were included,comprising a variety of publication types,including observational studies,reviews,guidelines,case reports,interventional studies,and opinion pieces.Most reported on PEI on/after treatment with somatostatin analogs;9.5%-84%of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI.Where reported,14.3%–50.7%of patients received pancreatic enzyme replacement therapy.Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption(80%),small intestinal bacterial overgrowth(23.6%-62%),colitis(20%)and infection(7.1%).Diagnostic approaches included faecal elastase,breath tests,tauroselcholic(selenium-75)acid(SeHCAT)scan and stool culture,although evidence on the effectiveness or diagnostic accuracy of these approaches was limited.Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation.From the identified evidence,if diarrhoea is assumed to be CS diarrhoea,consequences include uncontrolled diarrhoea,malnutrition,and perceived ineffectiveness of CS treatment.Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team,including gastroenterologists.CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use.This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches,to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.

Clonality analysis of neuroendocrine cells in gastric adenocarcinoma

AIM:To achieve a better understanding of the origination of neuroendocrine(NE)cells in gastric adenocarcinoma.METHODS:In this study,120 cases of gastric adenocarcinoma were obtained.First,frozen section-immunohistochemistrical samples were selected from a large quantity of neuroendocrine cells.Second,laser capture microdissection was used to get target cells from gastric adenocarcinoma and whole genome amplification was applied to get a large quantity of DNA for further study.Third,genome-wide microsatellite abnormalities[microsatellite instability(MSI),loss of heterozygosity (LOH)]and p53 mutation were detected by polymerase chain reaction(PCR)-single-strand conformation polymer-phism-silver staining and PCR-sequencing in order to identify the clonality of NE cells.RESULTS:The total incidence rate of MSI was 27.4%,while LOH was 17.9%.Ten cases had a highest concordance for the two types of cells.The other samples had similar microsatellite changes,except for cases 7 and10.Concordant p53 mutations exhibited in sample 4,14,21 and 27,and there were different mutations between two kinds of cells in case 7.In case 17,mutation took place only in adenocarcinoma cells.p53 mutation was closely related with degree of differentiation,tumor-node-metastasis stage,vessel invasion and lymph node metastasis.In brief,NE and adenocarcinoma cells showed the same MSI,LOH or p53 mutation in most cases(27/30).In the other three cases,different MSI,LOH or p53 mutation occurred.CONCLUSION:NE and the gastric adenocarcinoma cells may mainly derive from the same stem cells,but the remaining cases showing different origin needs further investigation.

Oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor: A case report

Gastric adenocarcinoma is one of the most common malignancies worldwide.Histochemical and immunohistologic analyses classify the phenotypes of gastric adenocarcinoma into several groups based on the variable clinical and pathologic features.A new and rare variant of gastric adenocarcinoma with chief cell differentiation(GA-CCD)has recently been recognized.Studies reporting the distinct clinicopathologic characteristics proposed the term oxyntic gland polyp/adenoma because of the benign nature of the GACCD.Typically,GA-CCD is a solitary mucosal lesion that develops either in the gastric cardia or fundus.Histologically,this lesion is characterized by tightly clustered glands and anastomosing cords of chief cells.Immunohistochemically,GA-CCD is diffusely positive for mucin(MUC)6 and negative for MUC2and MUC5AC.However,other gastric tumors such as a gastric neuroendocrine tumor or fundic gland polyp have been difficult to exclude.Because GA-CCD tends to be endoscopically misdiagnosed as a neuroendocrine tumor or fundic gland polyp,comprehensive assessment and observation by an endoscopist are strongly recommended.Herein,we report a rare case of oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor that was successfully removed by endoscopic mucosal resection.

Expression of PKC Iota Affects Neuronal Differentiation of PC12 Cells at Least Partly Independent of Kinase Function

Atypical PKC (aPKC) plays a role in establishing cell polarity and has been indicated in neuronal differentiation and polarization, including neurite formation in rat pheochromocytoma PC12 cells, albeit by unclear mechanisms. Here, the role of the aPKC isoform, PKC iota (PKCι), in the early neuronal differentiation of PC12 cells, was investigated. NGF-treated PC12 cells with stably expressed exogenous wild-type PKCι showed decreased expression of a neuroendocrine marker, increased expression of a neuronal marker and increased neurite formation. Stable expression of a kinase-inactive PKCι, but not constitutively active PKCι lacking a regulatory domain, had similar though less potent effects. Pharmacological inhibition of endogenous aPKC kinase activity in parental PC12 cells did not inhibit neurite formation, suggesting that some of the observed effects of PKCι expression on neuronal differentiation are kinase-independent. Interestingly, exogenous expression of wild-type and kinase-inactive PKCι had little effect on overall PKCι activity, but caused a decrease in PKC zeta (PKCζ) kinase activity, suggesting an interplay between the two isoforms that may underlie the observed results. Overall, these findings suggest that in PC12 and perhaps other neuroendocrine precursor cells, PKCι influences an early differentiation decision between the neuroendocrine (chromaffin) and sympathetic neuron cell lineages, potentially by affecting PKCζ function.

Prognostic importance of lymph node yield after curative resection of gastroenteropancreatic neuroendocrine tumours

BACKGROUND The prognostic significance of lymph nodes(LNs)metastases and the optimum number of LN yield in gastroenteropancreatic neuroendocrine tumours(GEP NETs)undergoing curative resection is still debatable.Many studies have demonstrated that cure rate for patients with GEP NETs can be improved by the resection of the primary tumour and regional lymphadenectomy AIM To evaluate the effect of lymph node(LN)status and yield on relapse-free survival(RFS)and overall survival(OS)in patients with resected GEP NETs.METHODS Data on patients who underwent curative resection for GEP NETs between January 2002 and March 2017 were analysed retrospectively.Grade 3 tumours(Ki67>20%)were excluded.Univariate Cox proportional hazard models were computed for RFS and OS and assessed alongside cut-point analysis to distinguish a suitable binary categorisation of total LNs retrieved associated with RFS.RESULTS A total of 217 patients were included in the study.The median age was 59 years(21-97 years)and 51%(n=111)were male.Primary tumour sites were small bowel(42%),pancreas(25%),appendix(18%),rectum(7%),colon(3%),gastric(2%),others(2%).Median follow up times for all patients were 41 mo(95%CI:36-51)and 71 mo(95%CI:63–76)for RFS and OS respectively;50 relapses and 35 deaths were reported.LNs were retrieved in 151 patients.Eight or more LNs were harvested in 106 patients and LN positivity reported in 114 patients.Three or more positive LNs were detected in 62 cases.The result of univariate analysis suggested perineural invasion(P=0.0023),LN positivity(P=0.033),LN retrieval of≥8(P=0.047)and localisation(P=0.0049)have a statistically significant association with shorter RFS,but there was no effect of LN ratio on RFS:P=0.1 or OS:P=0.75.Tumour necrosis(P=0.021)and perineural invasion(P=0.016)were the only two variables significantly associated with worse OS.In the final multivariable analysis,localisation(pancreas HR=27.33,P=0.006,small bowel HR=32.44,P=0.005),and retrieval of≥8 LNs(HR=2.7,P=0.036)were independent prognostic factors for worse RFS.CONCLUSION An outcome-oriented approach to cut-point analysis can suggest a minimum number of adequate LNs to be harvested in patients with GEP NETs undergoing curative surgery.Removal of≥8 LNs is associated with increased risk of relapse,which could be due to high rates of LN positivity at the time of surgery.Given that localisation had a significant association with RFS,a prospective multicentre study is warranted with a clear direction on recommended surgical practice and follow-up guidance for GEP NETs.

Primary testicular neuroendocrine tumor with liver lymph node metastasis: A case report and review of the literature

BACKGROUND Primary testicular neuroendocrine tumors(TNETs)are sporadic,accounting for only 0.23%of all testicular tumors.Few cases have been reported in the literature,and no uniform treatment protocol exists.We report a case of a primary TNET with liver lymph node metastasis diagnosed at the age of 24 years and discuss its clinicopathological features,diagnosis,differential diagnosis,treatment,and prognosis.CASE SUMMARY We report the case of a 24-year-old patient with a primary TNET with liver lymph node metastasis.The patient was found to have a right testicular swelling of about 3 cm×4 cm in size with unclear borders and no testicular pressure pain seven years ago without any examination or treatment.One month ago,an ultrasound examination was performed for persistent enlargement of the right testis,which showed an occupying lesion of the right testis approximately 110 mm×102 mm×82 mm in size.Magnetic resonance imaging scan of the testis(plain scan)showed that the right testis was an occupying lesion with inhomogeneous density and mixed signal,the boundary was still clear,and the possibility of seminoma was considered;chest X-ray and computed tomography did not show any apparent abnormalities.The patient underwent radical orchiectomy,and the pathological examination suggested a right TNET with a typical carcinoid tumor histological type.One month after the surgery,the patient received nine cycles of lanreotide chemotherapy at a dose of 90 mg/mo without adverse effects.No distant lymph node or other organ metastases were detected at follow-up.He is in good physical condition and attends regular follow-up visits.CONCLUSION Neuroendocrine tumors are rare in clinical practice,and the diagnosis mainly relies on the characteristics of microscopic tumor cells and immunohistochemical features.Treatment involves radical orchiectomy.If it is accompanied by distant lymph node metastasis and the metastatic lesion can be resected,it should be surgically removed;if it cannot be resected,growth inhibitor analog octreotide or lanreotide chemotherapy can be administered to obtain good results,with close postoperative follow-up to prevent recurrence and metastasis.

Esophagogastric junctional neuroendocrine tumor with adenocarcinoma:A case report

BACKGROUND At present,cases of esophageal neuroendocrine tumors combined with cardia adenocarcinoma are extremely rare worldwide,and there are no clinical reports.Herein,we describe such a case for clinical reference.CASE SUMMARY The presence of cardia cancer and esophageal neuroendocrine tumors in a single patient has not yet been reported.The patient in this case underwent prompt endoscopic treatment and additional surgical resection.Pathology revealed the following:The distance between the cardia cancer and the esophageal neuroendocrine tumors was small,approximately 3 mm.Vascular invasion was observed.The esophageal neuroendocrine tumor was determined to be grade G3.According to the treatment guidelines,after the patient received an explanation of their condition,additional surgical procedures were provided in a timely manner.Early detection and early treatment can successfully prolong survival and improve the quality of life of patients.CONCLUSION Early detection and early treatment can successfully prolong survival and improve the quality of life of such patients.