Humans ; Female ; Uterine Cervical Neoplasms/pathology* ; Carcinoma, Neuroendocrine/pathology* ; Consensus ; Prognosis ; Neoplasm Staging ; Cervix Uteri/pathology*

Neuroendocrine carcinoma (NEC) represents a category of malignant tumors originating from neuroendocrine cells. Given that NEC cells exhibit characteristics of both neural and endocrine cells, they can hijack neuronal signaling pathways and dynamically regulate the expression of neuronal lineage markers during tumor metastasis, thereby constructing a microenvironment conducive to tumor growth and metastasis. Conversely, alterations in the tumor microenvironment can enhance the interactions between neurons and tumor cells, ultimately synergistically promoting the metastasis of NEC. This review highlights recent advancements in the field of cancer neuroscience, uncovering neuronal lineage markers in NEC that facilitate tumor dissemination through mediating crosstalk, bidirectional communication, and synergistic interactions between tumor cells and the nervous system. Consequently, the latest findings in tumor neuroscience have enriched our understanding of the biological mechanisms underlying tumor metastasis, opening new research avenues for a deeper comprehension of the complex biological processes involved in tumor metastasis, particularly brain metastasis. This review provides a comprehensive review of the crosstalk between tumor cells and neural signaling in the metastasis of NEC.
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Humans ; Carcinoma, Neuroendocrine/metabolism* ; Signal Transduction ; Animals ; Neoplasm Metastasis ; Neurons/pathology* ; Tumor Microenvironment ; Cell Communication

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor with unique characteristics, and its treatment regimens are primarily derived from those for small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). In recent years, the incidence rate has been on the rise, and the prognosis are affected by the interaction of multiple factors such as individual, clinical stage and treatment mode, and the heterogeneity is significant. In the study of molecular subtypes, multiple subgroups were divided according to key gene mutations such as RB1 and TP53, and genomic subtypes were associated with survival, chemotherapy response, and efficacy of precision therapy. Targeted therapy excavates multiple targets, and the efficacy of drugs is different. Immunotherapy has made remarkable progress, and immune checkpoint inhibitors (ICIs) have been effective in all stages of chemotherapy alone or in combination with chemotherapy or radiation therapy, but there is a risk of hyperprogressive diseases, and accurate prognostic markers need to be explored urgently. This review reviews the latest research progress in the study of molecular subtypes and precision therapies such as targeted therapy and immunotherapy of pulmonary LCNEC, and points out that pulmonary LCNEC treatment will develop in the direction of precision and individualization in the future.
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Humans ; Lung Neoplasms/drug therapy* ; Carcinoma, Neuroendocrine/drug therapy* ; Precision Medicine ; Immunotherapy ; Carcinoma, Large Cell/drug therapy*

Neuroendocrine carcinoma (NEC), a subtype of neuroendocrine tumors with high proliferative activity, is characterized by strong invasiveness and poor prognosis. This article reports a previously healthy female non-smoker who developed NEC occurring sequentially in different lobes of both lungs. The lesions were pathologically diagnosed by hematoxylin-eosin (HE) staining as large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC), respectively. Next-generation sequencing (NGS) performed on both lesions revealed the presence of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion mutations in both lesions. Notably, the patient achieved a significant therapeutic response to ALK-tyrosine kinase inhibitors (TKIs) targeted therapy.
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Humans ; Oncogene Proteins, Fusion/metabolism* ; Female ; Lung Neoplasms/enzymology* ; Carcinoma, Neuroendocrine/pathology* ; Middle Aged

Neoplasms characterized by the expression of markers of neuroendocrine differentiation in neoplastic cells are defined as neuroendocrine neoplasms. A case of neuroendocrine carcinomas (NECs) with a small amount of papillary adenocarcinoma and significantly vacuolar nucleus at the esophagogastric junction was reported in this article. A 77-year-old male had dysphagia for one week. Endoscopy revealed early-stage esophagogastric junction carcinoma, and biopsy was diagnosed as poorly differentiated carcinoma. Endoscopic submucosal dissection was performed. Histologically, the papillary adenocarcinoma progresses from typically branching papillary structures (well-differentiated) to hyperplasia of the lining epithelium of the papilla to form a cribriform structure (moderately differentiated), to solid area lacking papillary structures (poorly differentiated). There was a continuous process, and during this process, the vacuoles in the nuclei of tumor cells showed progressive changes from mild to obvious and finally to significant vacuoles. The tumor was mainly composed of solid areas (about 95%), with single cell, large cell, round or oval to irregular nuclei, and significantly vacuolar nuclei, nuclei with larger vacuoles appeared in a loop, a few thin weakly basophilic or weakly eosinophilic fine particles could be seen in the vacuoles, and the vacuoles had rough edges. The nucleus chromatin at the outer edge of the vacuoles was fine particles, and mitosis was common (20-30/mm²), atypical mitosis could be seen, and nucleoli could be seen easily, the cytoplasm was weakly eosinophilic, and the boundaries of cells were unclear. The cells were arranged in a nested, trabecular, or diffuse sheet shape, with some arranged in a glandular tube shape. Tumor thrombus was found in the vein of submucosa; the interstitial tissue rich in capillaries within the tumor was accompanied by a large number of neutrophil infiltration. Immunohistochemical staining showed that the solid area of the tumor was positive for synaptophysin (Syn) and chromogranin A (CgA), while papillary adenocarcinoma was negative. Mucin 5AC (MUC5AC) was diffusely positive in papillary adenocarcinoma, while the proportion of positive cells in the solid area of the tumor was about 10% to 15%. In a word, this case showed the extreme situation of the vacuolar nuclear characteristics of NECs, extremely rare, in a sense, this case expanded the boundary of the morphological spectrum of NECs. Understanding the extreme vacuolar features of this nucleus is helpful to make a correct pathological diagnosis.
Humans ; Male ; Esophagogastric Junction/pathology* ; Aged ; Carcinoma, Neuroendocrine/pathology* ; Vacuoles/pathology* ; Esophageal Neoplasms/pathology* ; Cell Nucleus/pathology* ; Adenocarcinoma, Papillary/pathology* ; Stomach Neoplasms/pathology*

Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections ; Carcinoma, Small Cell ; Nasopharynx/pathology* ; Carcinoma, Neuroendocrine/pathology* ; Nasopharyngeal Neoplasms/pathology*

Female ; Humans ; Teratoma/pathology* ; Ovarian Neoplasms/pathology* ; Carcinoma, Small Cell/surgery* ; Carcinoma, Squamous Cell/pathology* ; Carcinoma, Neuroendocrine/surgery*

Male ; Humans ; Prostatic Neoplasms ; Cell Line, Tumor ; Cell Differentiation ; Carcinoma, Neuroendocrine

Neuroendocrine carcinoma(NEC) is a malignant tumor derived from neuroendocrine cells, with distinct clinical, morphological and immunohistochemical characteristics. Neuroendocrine carcinoma of the head and neck is very rare in clinic. Larynx is the most common affected site, and the root of the tongue is extremely rare. The clinical manifestations are mainly eating pain, cauliflower like mass in the mouth, and ulcerative lesions that have not healed for a long time. Maxillofacial MRI and contrastenhanced CT are the most commonly used examination tools for such diseases, which can detect the spaceoccupying lesions of tumors. Neuroendocrine granules found in the cytoplasm under pathological light microscope can be diagnosed as neuroendocrine carcinoma. However, for most cases, it is difficult to make a diagnosis only under light microscope, and it is often necessary to make a diagnosis by means of immunohistochemistry and other technical means. This paper reports a case of neuroendocrine carcinoma of the root of the tongue, introduces its characteristics, diagnosis and treatment, and reviews the relevant literature of this case.
Humans ; Carcinoma, Neuroendocrine/pathology* ; Tongue ; Neck/pathology* ; Larynx/pathology* ; Mouth/pathology*

Humans ; Carcinoma, Small Cell/pathology* ; Urinary Tract/pathology* ; Carcinoma, Neuroendocrine/pathology* ; Kidney Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Ureter/pathology*