UNASSIGNED: To improve the understanding, diagnosis and treatment of bladder large cell neuroendocrine carcinoma (LCNEC).
UNASSIGNED: A clinical case of bladder LCNEC admitted to our hospital was reported. The epidemiology, prognosis, diagnosis and treatment methods of large cell neuroendocrine carcinoma were reviewed. The diagnosis and treatment status and prognosis were discussed based on the literature.
UNASSIGNED: The female patient was admitted to hospital for \"more than 4 years after TURBT and intermittent hematuria for more than 2 years\". She was diagnosed as recurrent bladder cancer and underwent \"radical cystotomy + hysterectomy\". The postoperative pathological findings were high-grade urothelial carcinoma of the bladder neck and large cell neuroendocrine carcinoma of the bladder. The patient recovered well after surgery, but refused radiotherapy and chemotherapy and is still under close follow-up.
UNASSIGNED: Bladder LCNEC is clinically rare, has unique pathological features, is more aggressive than traditional urothelial carcinoma, and has a poor prognosis. Surgery, chemotherapy and radiotherapy should be combined with multi-mode treatment.

Primary bladder large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive neoplasm with high recurrence rates and poor prognosis. Traditional management has heavily relied on radical cystectomy, which, despite its aggressiveness, often results in unsatisfactory outcomes. Emerging evidence suggests the potential for less invasive, bladder-sparing approaches, yet detailed reports and long-term outcomes remain scarce. We report a groundbreaking case of a 59-year-old male diagnosed with primary bladder LCNEC, managed through a pioneering bladder-sparing multimodal treatment. This novel strategy included transurethral resection followed by a tailored chemoradiation protocol, resulting in exceptional disease control and preservation of bladder function over a 20-month follow-up period, without evidence of recurrence. This case underscores the viability of bladder conservation strategies as a legitimate alternative to radical cystectomy for managing LCNEC, presenting a beacon of hope for patients wishing to preserve bladder functionality. It prompts a reevaluation of traditional treatment paradigms and advocates for further research into multimodal, organ-sparing approaches for this challenging malignancy.

暂无摘要。

BACKGROUND: Combined large cell neuroendocrine carcinoma (C-LCNEC) has a poor prognosis and there is no consensus about the treatment regimen for both LCNEC and C-LCNEC patients.
METHODS: The patient was a 47-year-old female who received surgical resection. The postoperative histology and staging of the tumor suggested C-LCNEC with adenocarcinoma and squamous cell carcinoma and T2aN0M0 stage IB. Next-generation sequencing test showed KIF5B/RET fusion mutation without EGFR, ALK, RB1, and TP53 alterations. Adjuvant chemotherapy with 4-cycle docetaxel plus carboplatin was given and brain metastasis occurred after 10 months.
CONCLUSIONS: C-LCNEC with adenocarcinoma and squamous cell carcinoma is rare and highly aggressive cancer. Surgical resection and adjuvant chemotherapy with SCLC regimen may improve the disease-free survival and overall survival. The accumulation of similar cases will clarify the profile and management of the disease.

ALK-positive large-cell neuroendocrine carcinoma (LCNEC) is an exceptionally rare form of lung cancer. The efficacy of ALK inhibitors in treating ALK-positive LCNEC remains unclear. Here, we report a case of ALK-positive LCNEC of the lung, which revealed a sustained clinical benefit (24+ mo of overall survival) after treatment with sequential ALK inhibitors and local therapies. This remarkable improvement in survival underscores the importance of testing metastatic LCNEC for biomarkers, such as ALK rearrangement, using immunohistochemistry or next-generation sequencing, especially in younger patients.

Large cell carcinoma of the lung with null-immunophenotype (LCC-NI) is a diagnostic entity that is especially uncommon now as it does not have any type of cell differentiation or its own molecular alterations. It presents an exceptional diagnostic challenge; indeed, the diagnosis is only possible with complete surgical excision and adequate immunohistochemical and molecular studies. We report the case of a 69-year-old male, with a history of long-term smoking who presented with pleuritic pain. A tumor in the upper lobe of the right lung was detected and removed by lobectomy. Histopathology revealed a neoplasm with large cell morphology without any specific immunophenotype, molecular or genomic rearrangements through next-generation sequencing (NGS) studies, which was diagnosed as LCC-NI.

Primary neuroendocrine tumor (NET) of bladder is rare. It has four subtypes, and large cell neuroendocrine carcinoma (LCNEC) is the rarest. LCNEC affects mostly men over 60. Most common symptom is gross hematuria. It has no specific treatment. Metastasis is common and once occurred, average survival would be less than three months. Herein we present diagnostic and therapeutic management of a 65-year-old female with LCNEC of bladder and concurrent high-grade urothelial carcinoma. Despite developing early liver metastasis, she achieved a one-year tumor-free survival.

We report a rare case of stage IV pulmonary combined large-cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma (ACA), both demonstrating anaplastic lymphoma kinase (ALK) rearrangement by IHC and FISH. This 61-year-old lifelong nonsmoking Asian woman presented with a cough, and after diagnosis and surgical treatment, completed four cycles of adjuvant cisplatin and etoposide chemotherapy. She subsequently developed recurrence with bony metastases of exclusively ALK-positive LCNEC. Alectinib was started, and the patient experienced a partial response.

BACKGROUND: Neuroendocrine carcinomas (NECs) of the colon are among the rarest types of colorectal cancers. Among these, large cell type neuroendocrine carcinoma (LCNEC) is particularly rare. Colorectal NEC is an aggressive disease, and there are few reports of long-term survivors. Here, we report a case of LCNEC accompanied by disseminated peritoneal leiomyomatosis that was difficult to diagnose.
METHODS: The case involves a 62-year-old female found to be positive for fecal occult blood by medical examination. An endoscopy revealed a tumor in the ascending colon, and the biopsy revealed poorly differentiated cancer. Abnormal FDG accumulation with peritoneal thickening was visible on 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) and suspected to be peritoneal dissemination. Laparoscopic ileocecal resection was performed for the tumor of the ascending colon with abdominal wall invasion. At that time, numerous intra-abdominal nodules were observed, indicating peritoneal dissemination. The pathological diagnosis of the primary lesion was LCNEC, and the patient requested to undergo total peritoneal resection. After one course of chemotherapy with irinotecan plus cisplatin, she underwent total peritoneal resection, uterine annex resection, left inguinal lymph node resection, and intra-abdominal hyperthermic intraperitoneal chemotherapy with mitomycin C. Because a postoperative pathological examination revealed that the intra-abdominal nodules were leiomyomas, we diagnosed the patient with disseminated peritoneal leiomyomatosis. The left inguinal lymph node was diagnosed with a metastatic tumor. In summary, the final diagnosis was LCNEC in the ascending colon with inguinal lymph node metastasis. Postoperative chemotherapy has been administered to date. She is currently 18 months post-primary surgery and 15 months post-peritonectomy without apparent recurrence or metastatic findings.
CONCLUSIONS: We experienced a case of Stage IVa colorectal LCNEC accompanied by disseminated peritoneal leiomyomatosis. Although the prognosis is generally poor, multidisciplinary treatment for advanced colorectal LCNEC may result in a favorable outcome for some patients. If peritoneal dissemination is suspected during operation, sampling of the nodule to confirm the pathological diagnosis is advisable.

Pulmonary neuroendocrine neoplasms (NENs) are subdivided in carcinoids and neuroendocrine carcinomas (small cell lung carcinoma and large cell neuroendocrine carcinoma (LCNEC)), based on the presence of necrosis and mitotic index (MI). However, it is unclear if tumors with well differentiated morphology but high proliferation rate should be regarded as LCNEC or as high grade carcinoids. In previous case series, a longer overall survival then expected in LCNEC has been suggested. We describe 7 of those cases analyzed for pRb expression and overall survival.
Cases with well differentiated morphology, but MI > 10/2mm2 and/or Ki-67 proliferation index >20% were selected based on pathology reports of consecutive NENs in our university medical center (Maastricht UMC+, 2007-2018) and confirmed by pathological review. Immunohistochemistry was performed to assess pRb expression.
Seven stage IV cases were included in this study. Median overall survival was 8 months (95% confidence interval 5-11 months). Cases with well differentiated morphology and preserved pRb expression (4/7) had a median overall survival of 45 months.
A subgroup of pulmonary NENs with well differentiated morphology but high proliferation rate likely exists. pRb staining might be helpful to predict prognosis, but clinical relevance remains to be studied.