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.

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.

Silent advanced large cell neuroendocrine carcinoma with synchronous adenocarcinoma of the colon:A case report

BACKGROUND Large cell neuroendocrine carcinoma(LCNEC)accounts for about 0.25%of colorectal cancer patients.Furthermore,synchronous LCNEC and adenocarcinoma coexistence in the colon is very rare.LCNEC are usually aggressive and have a poor prognosis.Usually,colorectal LCNEC patients complain of abdominal symptoms such as pain,diarrhea or hematochezia because it is often diagnosed as an advanced disease that accompanies metastatic lesions.CASE SUMMARY We describe a case of relatively asymptomatic synchronous LCNEC and colon adenocarcinoma.A 62-year-old male patient visited our hospital due to anemia detected by a local health check-up.He did not complain of melena,hematochezia or abdominal pain.Physical examination was unremarkable and his abdomen was soft,nontender and nondistended with no palpable mass.Laboratory tests revealed anemia with hemoglobin 5.1 g/dL.Colonoscopy revealed an ulcerofungating lesion in the ascending colon and about a 1.5 cm-sized large sessile polyp in the sigmoid colon.Endoscopic biopsy of the ascending colon lesion revealed the ulcerofungating mass that was LCNEC and endoscopic mucosal resection at the sigmoid colon lesion showed a large polypoid lesion that was adenocarcinoma.Multiple liver,lung,bone and lymph nodes metastasis was found on chest/abdominal computed tomography and positron emission tomography.The patient was diagnosed with advanced colorectal LCNEC with liver,lung,bone and lymph node metastasis(stage IV)and synchronous colonic adenocarcinoma metastasis.In this case,no specific symptom except anemia was observed despite the multiple metastases.The patient refused systemic chemotherapy and was discharged after transfusion.CONCLUSION We report a case of silent LCNEC of the colon despite the advanced state and synchronous adenocarcinoma.

Solitary pituitary metastasis resulting from pulmonary large cell neuroendocrine carcinoma

Solitary pituitary metastasis is a rare phenomenon in human neoplasms. We report a case of lung cancer with the initial manifestation of endocrinopathy resulting from pituitary metastasis. The patient's initial diagnosis was a poorly differentiated carcinoma, however, morbid anatomy revealed a definite diagnosis of large cell neuroendocrine carcinoma(LCNEC). Clinical physicians should be aware of potential initial manifestations such as endocrine abnormalities including panhypopituitarism and diabetes insipidus due to solitary pituitary metastasis. This case demonstrates that an endocrine abnormality such as panhypopituitarism could be an initial manifestation of LCNEC.

Case report of a mixed pulmonary large cell neuroendocrine carcinoma

A 57 year-old male patient was found to have a lesion in the middle lobe of his right lung using chest computed tomography(CT).Tumor cells were detected,and surgical excision was performed.The patient was diagnosed with mixed large cell neuroendocrine carcinoma,and underwent six cycles of a chemotherapy regimen comprising etoposide combined with cisplatin.Genetic testing revealed an EGFR mutation,which prompted oxitinib-targeted therapy.To date,no signs of recurrence or metastasis have been reported.

Primary large cell neuroendocrine carcinoma of the bladder:A case report

BACKGROUND Large cell neuroendocrine carcinoma(LCNEC)of the bladder is a rare nonurothelial tumor of the bladder.The treatment of LCNEC of the bladder is different from that of urothelial carcinoma(UC);therefore,early and accurate diagnosis is particularly important.As LCNEC of the bladder is rare and its clinical symptoms and radiographic features are similar to those of urothelial tumors,the clinical diagnosis of the disease remains challenging.CASE SUMMARY We report a 72-year-old female patient who presented with gross hematuria for 3 mo.A solitary tumor located in the anterior wall of the bladder was found by cystoscopy.Pathological examination after biopsy suggested UC of the bladder in the absence of immunohistochemical assessment.The patient underwent partial cystectomy and was finally diagnosed with LCNEC(pT2bN0M0)based on the results of postoperative immunohistochemical examination.During the 10-mo follow-up,no signs of tumor recurrence or metastasis were found.CONCLUSION Immunohistochemical examination is essential for diagnosing LCNEC of the bladder.Accurate diagnosis and multidisciplinary treatment in the early stage of the disease are crucial for improving the prognosis.

Large cell neuroendocrine carcinoma transformation:A novel acquired drug resistance mechanism in colorectal adenocarcinoma

Acquired resistance is a major problem limiting the clinical efficacy of treatments for metastatic colorectal cancer(mCRC).Histological transformation is an important mechanism underlying the acquired resistance of non-small cell lung cancer and prostate cancer to targeted therapy.However,no report has examined the role of histological transformation in mCRC.Here,we report the first case of histologically transformed large cell neuroendocrine carcinoma from primary colon adenocarcinoma during antiangiogenesis and anti-PD-1 combination therapy.The histologic conversion was confirmed by the observation that the transformed large cell neuroendocrine carcinoma lesion retained the original mutational signature found in the primary tumor.Sequential tumor biopsy and dynamic changes in tumor markers demonstrated the transformed process.The histological transformation not only resulted in discordant responses to the same treatment but also significantly shortened overall survival.This case calls for more attention to histological transformation in mCRC.Tumor rebiopsy upon disease progression and monitoring dynamic changes in tumor markers would help to identify such cases.

A case of large-cell neuroendocrine carcinoma harboring rare ALK fusion with initial response to the ALK inhibitor crizotinib and acquired F1174L mutation after resistance

A 51-year-old,male,non-smoker with a 3.4 cm mass in the right middle lobe was diagnosed with large cell neuroendocrine carcinoma(LCNEC).Fluorescence in situ hybridization revealed anaplastic lymphoma kinase(ALK)gene translocation,in agreement with the immunohistochemistry result obtained with use of ALK-Ventana.Radiographic examinations showed both bone and brain metastasis.After two cycles of chemotherapy consisting of etoposide and cisplatin,the patient achieved stable disease,and was subsequently switched to crizotinib.Both computed tomography and magnetic resonance imaging revealed partial response after 4 months of crizotinib,but progressed after treatment for 10 months,when several hard lymph nodes were palpable in the left supraclavicular fossa.Lymph node biopsy showed similar histology of tumor cells and targeted next-generation sequencing revealed ALK F1174L on exon 23 with two rare forms of ALK rearrangements.This case provides evidence of responsiveness of ALK inhibitors for a rare pattern of ALK-rearranged LCNEC,and suggests that F1174L,a common resistant mutation found in non-small-cell lung cancer,also causes crizotinib resistance in LCNEC.