Large cell neuroendocrine carcinoma of cervix: A case report

Neuroendocrine carcinoma of the cervix is a rare aggressive tumor with a poor prognosis. Neuroendocrine carcinomas account for 1–1.5% of cervical cancer and around 12.5% were of large cell types. We report the case of a 55-year-old woman who came with complaints of pain abdomen and was reported as large cell neuroendocrine carcinoma of the cervix on biopsy. Immunohistochemistry was done which confirmed the diagnosis.

Pregnancy-preserving and maternal-fetal management in a patient with rare large cell neuroendocrine carcinoma of the uterine cervix / 南方医科大学学报

OBJECTIVE@#To explore the strategy of pregnancy-preserving and maternal- fetal management in patients with primary gynecologic neuroendocrine tumors (gNETs) during pregnancy.@*METHODS@#We performed whole genome sequencing (WGS) for analyzing maternal and fetal somatic and germline single nucleotide variations (SNVs) and small insertions and deletions (InDels) for a 29-year-old pregnant woman diagnosed with stage IB2 large cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma in the cervix. A systematic literature review was performed to explore the strategies for treatment of such rare histological type while maintaining pregnancy.@*RESULTS@#Global case analysis of cervical NETs during pregnancy suggested that negative lymph node metastasis and an early FIGO stage were potentially associated with a good prognosis of the patients. In the case presented herein, a pregnancy-preserving strategy was adopted and favorable maternal-fetal outcomes were achieved after neoadjuvant chemotherapy, radical surgery and postoperative systemic chemotherapy. At 35@*CONCLUSIONS@#Although gNETs in pregnancy are rare and highly risky, pregnancy-preserving managements of gNETs can still be considered and favorable maternalfetal outcomes are possible with proper assessment of the clinical indications and implementation of multimodal treatments. Precise treatment and follow-up strategies based on the results of WGS for risk-reducing intervention of cancer recurrence or occurrence can potentially benefit the patient and the neonate.

Correlation Analysis of Serum LDH Concentration before and after Operation and Prognosis of Large Cell Neuroendocrine Lung Cancer Patients / 中国肺癌杂志

BACKGROUND@#Studies have shown that elevated serum lactate dehydrogenase (LDH) concentration can lead to poor prognosis in patients with small cell lung cancer and lung adenocarcinoma, but its relationship with the prognosis of patients with lung large-cell neuroendocrine carcinoma (L-LCNEC) is not clear. This study aims to explore the influence of L-LCNEC preoperative serum LDH concentration and postoperative LDH concentration change trend on the disease-free survival (DFS) of patients after surgery, so as to judge the clinical prognosis of L-LCNEC provides new ideas.@*METHODS@#Collected the clinical data. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value, while the Kaplan-Meier and Cox proportional hazard model were used to analyze data.@*RESULTS@#DFS was shortened in patients with high serum LDH concentration before operation and increased LDH concentration after operation (P<0.001, P<0.001). The preoperative LDH concentration and postoperative LDH concentration change trend were independent prognostic factors for patients (P<0.001, P=0.037).@*CONCLUSIONS@#Preoperative LDH concentration and its postoperative concentration change trend in patients with L-LCNEC are independent prognostic factors for DFS of patients.

Advances in Molecular Biomarker for Pulmonary Large Cell Neuroendocrine Carcinoma / 中国肺癌杂志

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a pathological subtype of lung neuroendocrine cancer, which accounts for 2.4%-3.1% in surgical specimens of lung cancer. It is characterized by high invasiveness and poor prognosis, and highly correlated with smoking. There are few relevant studies due to the low incidence and small sample size. Therefore, it is relatively difficult to diagnosis and treatment in clinical practice. In this review, we described molecular subtype, diagnostic and prognostic-related markers about large cell neuroendocrine carcinoma of lung based on the recent progress in genomic sequencing and molecular markers, to find the direction for the next research.
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Research progress on molecular biology for subtyping and clinical treatment of pulmonary large cell neuroendocrine carcinomas / 中国肿瘤临床

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of pulmonary malignant tumors, accounting for

Progress in comprehensive treatment of pulmonary large cell neuroendocrine carcinoma / 中华放射肿瘤学杂志

Large cell neuroendocrine carcinoma is not very common, and it has a high degree of malignancy and invasion, outcome is also poor. Even LCLC is defined as non-small cell lung cancer, its biological and clinical characteristics, prognostic factors are similar to small cell lung cancer. The treatment for LCLC is still controversial. The research progress on comprehensive treatment of lung large cell neuroendocrine carcinoma was reviewed.

Progress in comprehensive treatment of pulmonary large cell neuroendocrine carcinoma / 中华放射肿瘤学杂志

Large cell neuroendocrine carcinoma is not very common,and it has a high degree of malignancy and invasion,outcome is also poor.Even LCLC is defined as non-small cell lung cancer,its biological and clinical characteristics,prognostic factors are similar to small cell lung cancer.The treatment for LCLC is still controversial.The research progress on comprehensive treatment of lung large cell neuroendocrine carcinoma was reviewed.

A Case of Large Cell Neuroendocrine Carcinoma of the Maxillary Sinus / 대한두경부종양학회지

Large cell neuroendocrine carcinoma is a rare epithelial neuroendocrine malignancy and is preferentially located in gastrointestinal tract and pancreas. Cases of large cell neuroendocrine carcinoma have been reported in many other locations, including the thymus, gallbladder, prostate, larynx, salivary glands, nasopharynx, tonsil and mastoid. However, primary sinonasal large cell neuroendocrine carcinoma never have been reported in Korea. We experienced a case of primary large cell neuroendocrine carcinoma arising from left maxillary sinus recently. A 82-year-old male patient presented with nasal obstruction and epistaxis. The biopsy revealed large cell neuroendocrine carcinoma with poor differentiation. After a general evaluation, the patient was staged as cT3N0M0. The patient was treated by combined radiotherapy and chemotherapy. We report this rare case with literature review.

Large Cell Neuroendocrine Carcinoma of the Colon With Carcinomatosis Peritonei

Colorectal large-cell neuroendocrine carcinomas (NECs) are extremely rare and have very poor prognosis compared to adenocarcinomas. A 74-year-old man presented with abdominal pain, diarrhea and hematochezia. The histopathologic report of colonoscopic biopsy performed at a local clinic was a poorly differentiated carcinoma. An abdominopelvic computed scan revealed irregularly enhanced wall thickening at the sigmoid colon with regional fat stranding and lymphnode enlargement. He underwent a laparoscopic high anterior resection with selective peritonectomy for peritoneal carcinomatosis, intraoperative peritoneal irrigation chemotherapy, and early postoperative intraperitoneal chemotherapy for 5 days. The tumor had a high proliferation rate (mitotic count > 50/10 HPFs and 90% of the Ki-67 index) and lymph-node metastases had occurred. On immunohistochemistry, the tumor cells expressed CD56 and synaptophysin. Large-cell NEC was confirmed. Systemic chemotherapy with cisplatin/etoposide was done. The patient is still alive after 3 years with no evidence of recurrence.

Combined Adenosquamous and Large Cell Neuroendocrine Carcinoma of the Gallbladder

Large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare and usually combined with other type of malignancy, mostly adenocarcinoma. We report an unusual case of combined adenosquamous carcinoma and LCNEC of the gallbladder in a 54-year-old woman. A radical cholecystectomy specimen revealed a 4.3×4.0 cm polypoid mass in the fundus with infiltration of adjacent liver parenchyma. Microscopically, the tumor consisted of two distinct components. Adenosquamous carcinoma was predominant and abrupt transition from adenocarcinoma to squamous cell carcinoma was observed. LCNEC showed round cells with large, vesicular nuclei, abundant mitotic figures, and occasional pseudorosette formation. The patient received adjuvant chemotherapy. However, multiple liver metastases were identified at 3-month follow-up. Metastatic nodules were composed of LCNEC and squamous cell carcinoma components. Detecting LCNEC component is important in gallbladder cancer, because the tumor may require a different chemotherapy regimen and show early metastasis and poor prognosis.

Large cell neuroendocrine carcinoma of urinary bladder and ureter: a case report and review of the literature / 中华泌尿外科杂志

Objective To investigate the clinicopathological features,diagnosis,treatment and prognosis of a case of large cell neuroendocrine carcinoma (LCNEC) in urinary bladder and ureter.Methods The clinical pathological data of a patient with LCNEC in urinary bladder and ureter was retrospectively analyzed and the related literatures were reviewed.It was a male patient,78 years old,presenting with total painless gross hematuria.The ultrasonography showed nodules on the left lateral wall of bladder.Cystoscopy showed 2 cm cauliflower-like mass on the left lateral wall of bladder,and pathologic biopsy showed bladder urothelial carcinoma.Results Transurethral resection of bladder tumor was performed.The tumor cells were large in size,with vesicular nuclei,prominent nucleoli and nested/trabecular architecture.Immunohistochemical analysis demonstrated that tumor cells were positive for synaptophysin,chromogranin A and CD56.The proliferation index evaluated with Ki-67 was about 80％.The pathology report revealed a large cell neuroendocrine bladder tumor with focal areas of high-grade urothelial carcinoma.After intravesical instillation therapy for 2 months,tumor recurrence was detected by CT.Laparoscopic radical cystectomy and ureteral segmental resection was performed.The pathology report revealed a LCNEC with focal areas of highgrade invasive urothelial carcinoma in the bladder and ureter.CT showed tumor recurrence with liver metastasis 1 month after the operation.The overall survival was 9 months.Conclusions The clinical and imaging findings of LCNEC in bladder and ureter are nonspecific.Diagnosis must depend on the pathological and immunohistochemical staining.The tumor is aggressive with high risk of recurrence and metastasis and has a poor prognosis.It is mainly treated with radical resection combined with chemotherapy.

Role of postoperative chemotherapy in patients with early-stage pulmonary large-cell neuroendocrine carcinoma after resection / 中国肿瘤临床

Objective:To investigate the efficacy of postoperative chemotherapy in patients with early-stage pulmonary large cell neu-roendocrine carcinoma (LCNEC) after resection. Methods:A cohort of 50 patients who underwent resection and systematic nodal dissection for LCNEC between January 2008 and December 2014 in our institution was retrospectively reviewed. The patients were divided into adjuvant chemotherapy group (32 cases) and non-chemotherapy group (18 cases). Follow-up information was investigated. Results:The median survival and the 5-year survival rate were 48 months and 72.5%for the adjuvant chemotherapy group whereas 29 months and 35.6%for the non-adjuvant chemotherapy group, respectively. Univariate and multivariate analyses using Cox's proportional hazard models showed that postoperative chemotherapy was a signifi cant prognostic factor for OS (P=0.005;hazard ratio=0.281, P=0.008, respectively). Conclusion:Postoperative chemotherapy is beneficial to patients with early-stage pulmonary LCNEC after complete resection.

Manifestación inusual de carcinoma neuroendocrino de células no pequeñas / Unusual presentation of a neuroendocrine lung non small cells carcinoma

El dolor lumbar ocupa la primera causa de consulta por afección músculo-esquelética en el primer nivel de atención, siendo de suma importancia la enfermedad actual y los hallazgos al examen físico. Se presenta un caso clínico de un hombre de 60 años de edad con manifestaciones lumbares de alarma, al cual se le diagnosticó un carcinoma neuroendocrino de células no pequeñas de pulmón en etapa avanzada. Se discuten las características generales e histogénesis del tumor, así como las estrategias de tratamiento, teniendo en cuenta que esta enfermedad es infrecuente y representa un difícil diagnóstico(AU)

Lumbar pain is the first cause of consultation for musculoskeletal affections in the primary level of attention. The history and findings on physical examination are very important. We present a case of a sixty years-old man with lumbar alarming manifestations. He was diagnosed with a neuroendocrine carcinoma of non-small lung cells at an advanced stage. The assessment and histogenesis of the tumor are discussed, as well as the treatment strategies(AU)

A Case of Mixed Small and Large Cell Neuroendocrine Carcinoma of the Uterine Cervix

A rare case of mixed carcinoma of the cervix is reported, composed of a small and large cell neuroendocrine carcinoma. Neuroendocrine cervical carcinomas are very rare and aggressive. The prognosis is very poor despite multimodal treatment. Earlier reports have shown that the majority of patients present with advanced stage disease, have lymph node metastasis, and are at a high risk for recurrence and disease progression. In this study, we report the case of a 26-year-old woman with composite small and large cell neuroendocrine carcinoma of the cervix. A woman presented with vaginal bleed since 2 months of presentation. Gynecologic examination revealed cervical enlargement, and punch biopsy of the cervical lesion was performed. The biopsy was disclosed a large cell neuroendocrine carcinoma. The patient underwent a radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. The final histopathologic findings are mixed small and large cell neuroendocrine carcinoma of cervix.

Interobserver Variability in Diagnosing High-Grade Neuroendocrine Carcinoma of the Lung and Comparing It with the Morphometric Analysis

BACKGROUND: Distinguishing small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung is difficult with little information about interobserver variability. METHODS: One hundred twenty-nine cases of resected SCLC and LCNEC were independently evaluated by four pathologists and classified according to the 2004 World Health Organization criteria. Agreement was regarded as "unanimous" if all four pathologists agreed on the classification. The kappa statistic was calculated to measure the degree of agreement between pathologists. We also measured cell size using image analysis, and receiver-operating-characteristic curve analysis was performed to evaluate cell size in predicting the diagnosis of high-grade neuroendocrine (NE) carcinomas in 66 cases. RESULTS: Unanimous agreement was achieved in 55.0% of 129 cases. The kappa values ranged from 0.35 to 0.81. Morphometric analysis reaffirmed that there was a continuous spectrum of cell size from SCLC to LCNEC and showed that tumors with cells falling in the middle size range were difficult to categorize and lacked unanimous agreement. CONCLUSIONS: Our results provide an objective explanation for considerable interobserver variability in the diagnosis of high-grade pulmonary NE carcinomas. Further studies would need to define more stringent and objective definitions of cytologic and architectural characteristics to reliably distinguish between SCLC and LCNEC.

Syndrome of Inappropriate Antidiuretic Hormone Secretion in a Patient with Large Cell Neuroendocrine Carcinoma

The syndrome of inappropriate antidiuretic hormone secretion has only been reported in a few patients with large cell neuroendocrine carcinoma (LCNEC); however, it has never been reported in a patient with LCNEC of the lung, whose serum sodium levels were normalized after surgical resection of the mass. A 63-year-old male presented with a two-day history of dizziness and recent memory loss. On admission, his serum sodium level was 113 mEq/L with a serum osmolality of 236 mosm/kg, a urine osmolality of 441 mosm/kg, and a urine sodium level of 65 mEq/L. His chest computed tomography revealed a 2.7x2.3 cm-sized mass in the left lower lobe. After surgical removal of the mass, his serum sodium concentrations were normalized, and histopathology of the mass revealed LCNEC.

Large Cell Neuroendocrine Carcinoma of the Thymus: A Two-Case Report

A large cell neuroendocrine carcinoma (LCNEC) of the thymus is a very rare malignant tumor that has a very poor prognosis. The detailed clinical features of LCNEC are still unknown, including the long term prognoses and the definitive modalities of the treatment for LCNEC of the thymus. We are reporting 2 cases of an enlarged LCNEC of the thymus, both of which were diagnosed and treated by surgical resection followed by postoperative adjuvant chemoradiation therapy. Although recurrences and metastases of the LCNEC were noticed 1 and 4 years postoperatively for each case, aggressive surgical resection and adjuvant chemoradiation therapy may be helpful for a patient's long term survival.

Ovarian Large Cell Neuroendocrine Carcinoma Associated with Endocervical-like Mucinous Borderline Tumor: A Case Report and Literature Review

Ovarian large cell neuroendocrine carcinoma is a rare tumor that is usually associated with surface epithelial tumors. Mucinous tumors are most common surface epithelial component identified in reported cases. Ovarian mucinous tumor associated with large cell neuroendocrine carcinoma is almost always an intestinal type. However, large cell neuroendocrine carcinoma associated with pure mucinous borderline tumor of endocervical-like type has not been described previously. The present case report describes a large cell neuroendocrine carcinoma associated with endocervical-like mucinous borderline tumor of the ovary in a 35-year-old woman. The tumor was confirmed by histopathology and immunohistochemistry. A review of the pertinent literature is included.

A Case of a Collision Tumor in the Ampulla of Vater with an Adenocarcinoma and a Large Cell Neuroendocrine Carcinoma / 대한소화기내시경학회지

Most tumors affecting Vater's ampulla are adenocarcinomas, but a neuroendocrine carcinoma in the ampulla of Vater is extremely rare. The coexistence of these two tumors has been reported in only a few cases. Here, we report a rare case of a collision tumor of the ampulla of Vater with an adenocarcinoma and a large cell neuroendocrine carcinoma.

Distinction of Pulmonary Large Cell Neuroendocrine Carcinoma from Small Cell Lung Carcinoma Using a Panel of Bcl-2, p63, and 34betaE12

BACKGROUND: Making the distinction between large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) is difficult in some samples of biopsy tissues, but we have to separate LCNEC from SCLC because the two types of cancer may need different therapy and they have different prognostic implications. Thus far, there are no specific immunohistochemical markers that allow distinguishing these two kinds of tumors. METHODS: We performed an immunohistochemical analysis to study the expressions of p63, Bcl-2, and 34betaE12 and to investigate whether these 3 molecules have correlations in LCNEC and SCLC. We also evaluated the expression of the neuroendocrine markers chromogranin, synaptophysin and CD56. RESULTS: A statistical analysis was performed for p63, Bcl-2, and 34betaE12 in separate and combined panels. According to the combinations of p63, Bcl-2, and 34betaE12, there were frequent expressions of p63-/Bcl-2+ or Bcl-2+/34betaE12- in the SCLC, and there was a superior proportion of them in the SCLC rather than that in the LCNEC. The p63-/Bcl-2+ and Bcl-2+/34betaE12- antibody combinations showed higher specificities compared to any single antibody for diagnosing SCLC. CONCLUSIONS: Bcl-2 and selective p63 or 34betaE12 made up a most useful panel of markers for making the differential diagnosis of LCNEC and SCLC.