Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

Early adenocarcinoma mixed with a neuroendocrine carcinoma component arising in the gastroesophageal junction: A case report

BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-year-old Chinese man.CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation.Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric cardia.The nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 cm.Immunohistochemically,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and chromogranin.Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 genes.The patient was alive without evidence of the disease 36 mo after ESD.CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.

Clinical analysis of 12 cases of ovarian neuroendocrine carcinoma

BACKGROUND Neuroendocrine neoplasms of the female genital tract are rare.AIM To enhance our clinical understanding of neuroendocrine carcinoma(NEC)of the ovary.METHODS A retrospective review was conducted on 12 patients diagnosed with NEC of the ovary,analyzing clinicopathological characteristics,treatment modalities,and survival status.RESULTS The median age at diagnosis was 34.5 years(range:20 to 62 years).Among the 12 cases,9 were small cell carcinoma of the ovary and 3 were large cell NEC.Five cases were stage I tumors,one case was stage IV,and six cases were stage III.Eleven patients underwent surgery as part of their treatment.All patients received adjuvant chemotherapy.Among the 12 patients,one patient received radiotherapy,and one patient with a BRCA2 mutation was administered PARP inhibitor maintenance after chemotherapy.The median progression-free survival was 13 months,and the median overall survival was 19.5 months.Four cases remained disease-free,while eight cases experienced tumor recurrence,including three cases that resulted in death due to disease recurrence.CONCLUSION NEC of the ovary is a rare condition that is more common in women of childbearing age and is associated with aggressive behavior and poor clinical outcomes.Surgical resection remains the mainstay of treatment,with some patients benefiting from adjuvant chemoradiation therapy.

Neuroendocrine carcinoma of the common hepatic duct coexisting with distal cholangiocarcinoma:A case report and review of literature

BACKGROUND Neuroendocrine carcinoma(NEC)of the extrahepatic bile duct is very rare,and the treatment and prognosis are unclear.Herein,we report the case of a middleaged female with primary large cell NEC(LCNEC)of the common hepatic duct combined with distal cholangiocarcinoma(dCCA).Additionally,after a review of the relevant literature,we summarize and compare mixed neuroendocrine-nonneuroendocrine neoplasm(MiNEN)and pure NEC to provide a reference for selecting the appropriate treatment and predicting the prognosis of this rare disease.CASE SUMMARY A 62-year-old female presented to the hospital due to recurrent abdominal pain for 2 months.Physical examination showed mild tenderness in the upper abdomen and a positive Courvoisier sign.Blood tests showed elevated liver transaminase and carbohydrate antigen 199 levels.Imaging examination revealed node dissection was performed,and hepatic duct tumours were unexpectedly found during surgery.Pathology suggested poorly differentiated LCNEC(approximately 0.5 cm×0.5 cm×0.4 cm),Ki-67(50%),synaptophysin+,and chromogranin A+.dCCA pathology suggested moderately differentiated adenocarcinoma.The patient eventually developed lymph node metastasis in the liver,bone,peritoneum,and abdominal cavity and died 24 months after surgery.Gene sequencing methods were used to compare gene mutations in the two primary bile duct tumours.CONCLUSION The prognosis of MiNEN and pure NEC alone is different,and the selection of treatment options needs to be differentiated.

Neuroendocrine carcinoma of the endometrium concomitant with Lynch syndrome:A case report

BACKGROUND Large-cell neuroendocrine carcinoma(NEC)is an uncommon type of tumor that can occur in the endometrium.This aggressive cancer requires definitive management.Here,we describe the clinical characteristics and treatment of a postmenopausal woman with large cell NEC of the endometrium.CASE SUMMARY A 55-year-old Asian female presented with a 1-year history of postmenopausal vaginal bleeding.Transvaginal ultrasound revealed a thickened endometrium(30.2 mm)and a hypervascular tumor.Computed tomography revealed that the tumor had invaded more than half of the myometrium and spread to the pelvic lymph nodes.The tumor marker,carcinoembryonic antigen,was elevated(3.65 ng/mL).Endocervical biopsy revealed high-grade endometrial carcinoma.She underwent radical hysterectomy,bilateral salpingo-oophorectomy,omentectomy,and bilateral pelvic and para-aortic lymph node dissection.Pathological examination revealed mixed neuroendocrine and endometrioid adenocarcinoma,pT2N0M0,grade 3,and International Federation of Gynecology and Obstetrics stage 2.Immunohistochemistry showed moderate estrogen and progesterone receptor expressions(20%and 1%,respectively),focal CD56 expression(NEC marker),positive staining for vimentin,p53(wild type),and ki67(90%),and loss of expression of PMS2(Lynch syndrome marker).The patient received five cycles of cisplatin and etoposide after surgery.No recurrence was noted after 5 mo.CONCLUSION We report the characteristics and successful management of a rare case of large cell endometrial NEC concomitant with Lynch syndrome.

Pure large cell neuroendocrine carcinoma originating from the endometrium: A case report

BACKGROUND Large cell neuroendocrine carcinoma(LCNEC)of the endometrium is an uncommon and highly aggressive tumor that has not been comprehensively characterized.We report a case of pure endometrial LCNEC and review the current literature of similar cases to raise awareness of the histological features,treatment,and prognosis of this tumor.CASE SUMMARY We report the case of a 73-year-old woman who presented with irregular postmenopausal vaginal bleeding.Ultrasonography showed an enlarged uterus and a 5.1 cm×3.3 cm area of medium and low echogenicity in the uterine cavity.Biopsy by dilatation and curettage suggested poorly differentiated carcinoma.Magnetic resonance imaging revealed a heterogeneously enhanced uterine tumor with diffuse infiltration of the posterior wall of the uterine myometrium and enlarged pelvic lymph nodes.The patient underwent a hysterectomy and bilateral adnexal resection.Gross observation revealed an ill-defined white solid mass of the posterior wall of the uterus infiltrating into the serosa with multiple solid nodules on the serous surface.Microscopically,the tumor cells showed neuroendocrine morphology(organoid nesting).Immunohistochemistry revealed the tumor cells were diffusely positive for the neuroendocrine markers CD56,chromogranin A,and synaptophysin.Thus,the tumor was diagnosed as stage IIIC endometrial LCNEC.CONCLUSION Pathologic findings and immunohistochemistry are essential in making a diagnosis of endometrial LCNEC.

Textbook Outcome as a measure of surgical quality assessment and prognosis in gastric neuroendocrine carcinoma:A large multicenter sample analysis

Objective:Quality assurance is crucial for oncological surgical treatment assessment.For rare diseases,singlequality indicators are not enough.We aim to develop a comprehensive and reproducible measurement,called the"Textbook Outcome"(TO),to assess the quality of surgical treatment and prognosis of gastric neuroendocrine carcinoma(G-NEC)patients.Methods:Data from patients with primary diagnosed G-NEC included in 24 high-volume Chinese hospitals from October 2005 to September 2018 were analyzed.TO included receiving a curative resection,≥15 lymph nodes examined,no severe postoperative complications,hospital stay≤21 d,and no hospital readmission≤30 d after discharge.Hospital variation in TO was analyzed using a case mix-adjusted funnel plot.Prognostic factors of survival and risk factors for non-Textbook Outcome(non-TO)were analyzed using Cox and logistic models,respectively.Results:TO was achieved in 56.6%of 860 G-NEC patients.TO patients had better overall survival(OS),disease-free survival(DFS),and recurrence-free survival(RFS)than non-TO patients(P<0.05).Moreover,TO patients accounted for 60.3%of patients without recurrence.Multivariate Cox analysis revealed non-TO as an independent risk factor for OS,DFS,and RFS of G-NEC patients(P<0.05).Increasing TO rates were associated with improved OS for G-NEC patients,but not hospital volume.Multivariate logistic regression revealed that nonlower tumors,open surgery,and>200 mL blood loss were independent risk factors for non-TO patients(P<0.05).Conclusions:TO is strongly associated with multicenter surgical quality and prognosis for G-NEC patients.Factors predicting non-TO are identified,which may help guide strategies to optimize G-NEC outcomes.

Tuberous sclerosis patient with neuroendocrine carcinoma of the esophagogastric junction:A case report

BACKGROUND Tuberous sclerosis complex(TSC)is a rare inherited disease with non-cancerous tumor growths in the skin,brain,kidneys,heart,and lungs.The co-occurrence of neuroendocrine neoplasm(NEN)with TSC is even rarer.There have been few reports on the relationship between TSC and neuroendocrine tumors(NETs),and fewer on the relationship between TSC and neuroendocrine carcinoma(NEC),a subtype of NEN.This is the first reported case of NEC occurring at the esophagogastric junction in a patient with TSC.CASE SUMMARY A 46-year-old woman visiting our hospital for the treatment of TSC was admitted to the emergency department with tarry stools and dizziness.Computed tomography scans revealed thickness of the gastric cardia,multiple metastatic lesions of the liver,and enlarged lymph nodes near the lesser curvature of the stomach.Esophagogastroduodenoscopy revealed a type 3 tumor located from the esophagogastric junction to the fundus,and the pathological diagnosis by biopsy was NEC.The patient was treated with seven courses of cisplatin+irinotecan,followed by eight courses of ramucirumab+nab-paclitaxel,one course of nivolumab,and two courses of S-1+oxaliplatin.Twenty-three months after the first treatment,the patient died because of disease progression and deterioration of the general condition.CONCLUSION This case of NEC occurring in a patient with TSC indicates a difference in the occurrence of NETs and NECs.

Prognostic value of pretreatment contrast-enhanced computed tomography in esophageal neuroendocrine carcinoma: A multicenter follow-up study

BACKGROUND The rare incidence of esophageal neuroendocrine carcinoma(NEC)and limited treatment experience result in insufficient clinical observations and unsuitable guidelines for its management.AIM To investigate the prognostic value of pretreatment contrast-enhanced computed tomography(CT)characteristics in patients with esophageal NEC.METHODS Seventy-seven esophageal NEC patients who received contrast-enhanced CT at two hospitals were enrolled in this study from June 2014 to December 2019.The clinical features and image characteristics were recorded accordingly.Univariate survival analysis was performed using the Kaplan-Meier method and log-rank test,and multivariate analysis was carried out with a Cox proportional hazards model.RESULTS The multivariate analysis performed using the Cox proportional hazards model showed that N stage,adjuvant chemotherapy,and degree of enhancement were independent prognostic factors for overall survival(OS).Meanwhile,adjuvant chemotherapy was an independent prognostic factor for progression-free survival(PFS).The hazard ratios(HRs)of N stage,adjuvant chemotherapy,and degree of enhancement(mild vs moderate/marked)for OS were 0.426(P=0.024),3.862(P=0.006),and 2.169/0.809(P=0.037),respectively.The HR of adjuvant chemotherapy for PFS was 6.432(P<0.001).Adjuvant chemotherapy was significantly associated with degree of enhancement(P=0.018).CONCLUSION Adjuvant chemotherapy is an independent prognostic factor for OS and PFS.Additionally,N stage and degree of enhancement are prognostic factors for OS in patients with esophageal NEC.

Small-cell neuroendocrine carcinoma of the rectum—a rare tumor type with poor prognosis:A case report and review of literature

BACKGROUND Small-cell neuroendocrine carcinoma(SNEC)of the rectum is a rare tumor associated with poor prognosis.CASE SUMMARY We report a case of a 77-year-old male who came into our hospital because of blood with his stool.An endoscopy revealed a cauliflower-like neoplasm in his rectum.Imaging examination showed that the lesion in the upper rectum was likely rectal cancer,and there was no evidence of metastasis.The patient was treated with surgery.Pathological examination confirmed SNEC of the rectum and an R0 resection was achieved.However,1 mo after the operation,the patient developed intestinal and ureteral obstructions due to peritoneal metastases.Finally,the patient died from renal failure.CONCLUSION SNEC of the rectum is a high-grade carcinoma with an aggressive phenotype,and surgery should be cautiously considered.

Mixed large and small cell neuroendocrine carcinoma of the stomach:A case report and review of literature

BACKGROUND Gastric neuroendocrine carcinoma(GNEC)is a rare histological subtype of gastric cancer,which is categorized into small cell and large cell neuroendocrine carcinomas.It is characterized by strong invasiveness and poor prognosis.Mixed large and small cell neuroendocrine carcinoma(L/SCNEC)is an extremely rare pathological type of gastric cancer,and there have been no reports on this situation until now.CASE SUMMARY Herein,we first present a 57-year-old patient diagnosed with L/SCNEC of the stomach.A 57-year-old Chinese male presented with epigastric discomfort.Outpatient gastroscopic biopsy was performed,and pathological examination revealed that the cardia was invaded by adenocarcinoma.The patient underwent laparoscopic-assisted radical proximal subtotal gastrectomy and was diagnosed with L/SCNEC.He refused adjuvant treatment and was followed up every 3 mo.Eight months after the operation,the patient showed no evidence of local recurrence or distant metastasis.CONCLUSION We advocate conducting further genomic studies to explore the origin of gastric large cell and small cell neuroendocrine carcinoma and using different chemotherapy schemes according to large or small cell neuroendocrine carcinoma of the stomach for clinical research to clarify the heterogeneity of GNEC and improve the prognosis of patients with GNEC.

Endoscopic submucosal dissection combined with adjuvant chemotherapy for early-stage neuroendocrine carcinoma of the esophagus:A case report

BACKGROUND Neuroendocrine carcinoma(NEC)of the esophagus is rare and highly aggressive,and lacks biological features.Currently,there are no established standard treatments for this cancer.In this report,we describe a patient with large-cell NEC of the esophagus who was successfully treated using endoscopic submucosal dissection(ESD)combined with adjuvant chemotherapy.CASE SUMMARY A 55-year-old woman presented with intermittent mild dysphagia for 2 mo.Gastroscopy revealed a disc-shaped protruding lesion about 18 mm×18 mm in size on the upper esophagus.Endoscopic ultrasonography demonstrated that the bulged lesion originated from the muscularis mucosa.We assessed en bloc resections using ESD for therapeutic diagnosis to devise a safe and appropriate treatment.Histopathological examination revealed a poorly differentiated neoplasm comprising of large cells with marked nuclear atypia and multifocal necrosis.In addition,the specimens had a negative horizontal margin and vertical margins.Depth of invasion was classified as submucosa 2(SM2)without lymphovascular invasion.These histopathological results were consistent with a diagnosis of esophageal NEC,large cell type.Adjuvant therapy has been considered for ESD patients with SM2/SM3 lesions and patients with poorly differentiated lesions.After comprehensive consideration,we initiated combination treatment,i.e.,ESD plus adjuvant chemotherapy.The patient remained disease-free at the 2-year follow-up.CONCLUSION En bloc resection approach using ESD may play a vital role as a diagnostic and therapeutic modality for esophageal NEC.

Collision tumor of squamous cell carcinoma and neuroendocrine carcinoma in the head and neck:A case report

BACKGROUND There are many disputes about the definition,diagnosis,therapy,and prognosis of collision tumors.CASE SUMMARY We describe a rare patient with a collision tumor consisting of neuroendocrine carcinoma(NEC)and squamous cell carcinoma(SCC)in the nasal cavity and paranasal sinus.She received operation,concurrent chemoradiotherapy,and then two cycles of palliative chemotherapy.Follow-up at 12 mo after diagnosis showed that this patient experienced a complete response with no signs of recurrence or metastasis.A literature review of previous 26 cases diagnosed with collision tumor of NEC and SCC in the head and neck was also undertaken.CONCLUSION It is challenging to manage collision tumors because there are two morphologically and etiologically distinct tumors.Well-designed multimodality therapy including surgery and chemoradiotherapy might lead to a long survival in these patients.

Pancreatic neuroendocrine carcinoma in a pregnant woman:A case report and review of the literature

BACKGROUND Portal venous thromboembolism caused by malignant pancreatic neuroendocrine tumor metastasis,as the initial presentation of portal hypertension and upper gastrointestinal bleeding,is a rare entity.To our knowledge,there are no reports of this entity in pregnant women.We describe a case of pancreatic neuroendocrine carcinoma during pregnancy with hematemesis and hematochezia as the initial presentation and review the literature to analyze the demographic,clinical,and pathological features to provide a reference for clinical diagnosis and treatment.CASE SUMMARY A 40-year-old woman presented with hematemesis and hematochezia at 26-wk gestation;she had no other remarkable medical history.The physical examination revealed normal vital signs,an anemic appearance,and lower abdominal distension.Abdominal color Doppler ultrasonography showed portal vein thrombosis,splenomegaly,intrauterine pregnancy,and intrauterine fetal death.Esophagogastroduodenoscopy revealed esophageal and gastric varicose veins and portal hypertensive gastropathy.Contrast-enhanced computed tomography demonstrated multiple emboli formation in the portal and splenic veins,multiple round shadows in the liver with a slightly lower density,portal vein broadening,varicose veins in the lower esophagus and gastric fundus,splenomegaly,bilateral pleural effusion,ascites and pelvic effusion,broadening of the common bile duct,and increased uterine volume.According to the results of Positron emission tomography-computed tomography and immunohistochemical staining,the final diagnoses were that the primary lesion was a pancreatic neuroendocrine tumor and that there were secondary intrahepatic metastases and venous cancer thrombogenesis.CONCLUSION Upper gastrointestinal bleeding in a pregnant woman may be caused by portal hypertension due to a malignant pancreatic neuroendocrine tumor.

Neuroendocrine carcinoma of gallbladder: report of 2 cases

BACKGROUND: Neuroendocrine carcinoma of the gall- bladder is rare. Its best treatment is not known. METHODS: Two patients underwent surgery earlier: one for suspected cholecystitis and the other for cholelithiasis. Magnetic resonance cholangiopancreatography ( MRCP ) showed residual lesions in the livers. The two patients un- derwent revision surgery followed by chemotherapy. RESULTS; Both patients tolerated the second stage surgery well, which was followed by chemotherapy with paclitaxel, ifosphamide and cisplatin for 6 cycles. They were treated this way for 8 months and 12 months post treatment, re- spectively. CONCLUSIONS: A proper diagnosis of neuroendocrine carcinoma is made often after surgery. As it is a slow grow- ing tumor and not very chemotherapeutically, sensitive sur- gery offers the best local control.

Pancreatic neuroendocrine tumors G3 and pancreatic neuroendocrine carcinomas: Differences in basic biology and treatment

In 2017 the World Health Organization revised the criteria for classification of pancreatic neuroendocrine neoplasms(p NENs) after a consensus conference at the International Agency for Research on Cancer. The major change in the new classification was to subclassify the original G3 group into well-differentiated pancreatic neuroendocrine tumors G3(p NETs G3) and poorly differentiated pancreatic neuroendocrine carcinomas(p NECs), which have been gradually proven to be completely different in biological behavior and clinical manifestations in recent years. In 2019 this major change subsequently extended to NENs involving the entire digestive tract. The updated version of the p NENs grading system marks a growing awareness of these heterogeneous tumors. This review discusses the clinicopathological, genetic and therapeutic features of poorly differentiated p NECs and compare them to those of well-differentiated p NETs G3. For p NETs G3 and p NECs(due to their lower incidence), there are still many problems to be investigated. Previous studies under the new grading classification also need to be reinterpreted. This review summarizes the relevant literature from the perspective of the differences between p NETs G3 and p NECs in order to deepen understanding of these diseases and discuss future research directions.

Three-in-one incidence of hepatocellular carcinoma,cholangiocellular carcinoma,and neuroendocrine carcinoma:A case report

BACKGROUND Primary hepatic neuroendocrine carcinoma(NEC)is rare,and a combination with hepatocellular carcinoma(HCC)and cholangiocarcinoma(CCA)is extremely rare.To date,only four combination cases have been reported.The present paper describes the fifth patient.CASE SUMMARY A 32-year-old Chinese man with chronic hepatitis B was hospitalized for persistent upper abdominal pain.Abdominal computed tomography(CT)examination revealed a liver mass.The tumor was located in the 7th and 8th segments of the liver,and CT and magnetic resonance imaging findings were consistent with the diagnosis of HCC.Laboratory examinations revealed the following:Alanine aminotransferase,243 U/L;aspartate aminotransferase,167 U/L;alpha-fetoprotein,4519μg/L.Laparoscopic right lobe hepatectomy was performed on the liver mass.Postoperative pathology showed low differentiation HCC plus medium and low differentiation CCA combined with NEC.One month after the surgery,the patient suffered from epigastric pain again.Liver metastasis was detected by CT,and tumor transcatheter arterial chemoembolization was performed.Unfortunately,the liver tumor was progressively increased and enlarged,and after 1 mo,the patient died of liver failure.CONCLUSION This is a rare case,wherein the tumor is highly aggressive,grows rapidly,and metastasizes in a short period.Imaging and laboratory tests can easily misdiagnose or miss such cases;thus,the final diagnosis relies on pathology.

Large cell neuroendocrine carcinoma of the ampulla of Vater

BACKGROUND: Neuroendocrine tumors of the ampulla of Vater are extremely rare, and few cases of large cell neuroendocrine carcinoma (LCNEC) of the ampulla have been reported. METHODS: A 48-year-old male with obstructive jaundice was admitted to our hospital. On examination the patient was found to have a periampullary growth and subsequently underwent the Whipple's procedure. RESULTS: Histopathological examination and immunohistochemistry revealed features of LCNEC of the ampulla of Vater. The patient developed multiple liver metastases 6 months after Whipple's procedure. CONCLUSION: LCNEC of the ampulla of Vater is rare and highly aggressive, with a dismal prognosis.

Intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma:A case report

BACKGROUND The ampulla of Vater is an anatomically and histologically complex region giving rise to a heterogenous group of tumors.This is,to the best of our knowledge,the first case of intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma reported in the literature.CASE SUMMARY A 61-year-old woman presented to the emergency department for evaluation of painless jaundice.Contrast-enhanced computed tomography(CT)of the abdomen and chest showed a periampullary tumor mass measuring 15 mm×12 mm×14 mm,with no evidence of locoregional and distant metastases,for which she underwent pancreatoduodenectomy.Histopathologic examination of a resected specimen revealed an intra-ampullary papillary tubular neoplasm with highgrade dysplasia in combination with poorly differentiated grade 3 neuroendocrine carcinoma with a mitotic count of more than 20 mitoses per 10 high power fields and Ki-67 index of 100%.No positive lymph nodes were identified.Her postoperative course was uneventful.Postoperatively,she remained under close surveillance.Multiple liver metastases were observed on follow-up CT 8 mo after the surgery,so systemic therapy with cisplatin and etoposide was initiated.CONCLUSION The simultaneous occurrence of neuroendocrine and non-neuroendocrine tumors in the ampulla of Vater is rare and the pathogenesis of such tumors is largely unknown.Due to unpredictable clinical behavior and lack of solid evidence on optimal treatment strategy,close patient surveillance is advised after radical resection of the primary tumor.

S-1 plus temozolomide as second-line treatment for neuroendocrine carcinoma of the breast:A case report

BACKGROUND Neuroendocrine carcinoma of the breast(NECB)is a rare type of malignant tumor.Due to the rarity of NECB,the relevant literature mostly comprises case reports.Available data on treatment options for NECB are very limited.CASE SUMMARY A 62-year-old woman presented to our hospital in October 2016 for intermittent vomiting and diarrhea and masses in the liver found on abdominal computed tomography(CT)imaging.She was diagnosed in July 2012 with neuroendocrine carcinoma of the right breast in local hospital.The patient initially presented with a painful lesion of the right breast.She then undergone surgical resection and adjuvant chemotherapy with pirarubicin and paclitaxel for four cycles as well as endocrine therapy.She was regularly followed every 3 mo after surgery.Enhanced abdominal CT imaging at our hospital revealed multiple suspicious masses in the liver with the largest lesion measuring 8.4 cm×6.3 cm.Chest CT revealed masses in the anterior chest wall and lung.Core needle biopsy of the lesion revealed liver metastases of NECB.A bone scan showed right second anterior rib metastases.Upper endoscopy and colonoscopy did not provide any evidence of another possible primary tumor.She stopped receiving endocrine therapy and then received etoposide and cisplatin(EP)chemotherapy as a firstline treatment regimen for six cycles at our hospital after liver,bone,and lung metastases.On October 2017,the chemotherapy regimen was changed to S-1(40mg twice daily,days 1-14)combined with temozolomide(200 mg once daily,days 10-14)(STEM)every 21 d as a second-line treatment regimen due to disease progression.Progression-free survival(PFS)and adverse effects after treatment were analyzed,and the efficacy of the STEM regimen was assessed using RECIST version 1.1.This patient achieved a partial response after using the STEM regimen,with a PFS of 23 mo.Adverse effects included only grade 1 digestive tract reactions with no need for a reduction in chemotherapy.CONCLUSION This case report suggests that the STEM regimen may be effective and well tolerated as the second-line treatment for advanced NECB.STEM is still highly effective in patients who show disease progression with the EP regimen.More evidence is needed to prove the validity of STEM.