[Mixed adenoneuroendocrine carcinoma: case report]. / Carcinoma adenoneuroendocrino mixto: reporte de caso.

Introducción: Mixed adenoneuroendocrine carcinoma is a rare tumor of the gastrointestinal tract with double differentiation into adenomatous and neuroendocrine carcinoma, each component with at least 30%. Case report: A 60-year-old female with acute abdominal pain. Surgical treatment was decided, finding a tumor at the level of the cecum and ascending colon, a right hemicolectomy and ileostomy were performed. Discussion: Mixed adenoneuroendocrine carcinoma can appear in various organs. They are highly malignant tumors, with a high risk of metastasis. Conclusions: These tumors do not present symptoms or specific radiological or laboratory findings; diagnosis depends on postoperative histopathological and immunohistochemical studies.

Introducción: El carcinoma adenoneuroendocrino mixto es un tumor raro del tracto gastrointestinal con doble diferenciación en carcinoma adenomatoso y neuroendocrino, cada componente con al menos el 30%. Caso clínico: Mujer de 60 años con cuadro de dolor abdominal agudo. Se decide tratamiento quirúrgico, encontrando un tumor a nivel de ciego y colon ascendente, y se realizan hemicolectomía derecha e ileostomía. Discusión: El carcinoma adenoneuroendocrino mixto puede aparecer en diversos órganos. Son tumores muy malignos, con alto riesgo de metástasis. Conclusiones: Estos tumores no presentan síntomas ni hallazgos radiológicos o de laboratorio específicos; el diagnóstico depende de estudios histopatológicos e inmunohistoquímicos posoperatorios.

Neuroendocrine Differentiation of Lung Cancer Cells Impairs the Activation of Antitumor Cytotoxic Responses in Mice.

Lung cancer has the highest mortality among all types of cancer; during its development, cells can acquire neural and endocrine properties that affect tumor progression by releasing several factors, some acting as immunomodulators. Neuroendocrine phenotype correlates with invasiveness, metastasis, and low survival rates. This work evaluated the effect of neuroendocrine differentiation of adenocarcinoma on the mouse immune system. A549 cells were treated with FSK (forskolin) and IBMX (3-Isobutyl-1-methylxanthine) for 96 h to induce neuroendocrine differentiation (NED). Systemic effects were assessed by determining changes in circulating cytokines and immune cells of BALB/c mice immunized with PBS, undifferentiated A549 cells, or neuroendocrine A549NED cells. A549 cells increased circulating monocytes, while CD4+CD8- and CD4+CD8+ T cells increased in mice immunized with neuroendocrine cells. IL-2 and IL-10 increased in mice that received untreated A549 cells, suggesting that the immune system mounts a regulated response against adenocarcinoma, which did not occur with A549NED cells. Cocultures demonstrated the cytotoxic capacity of PBMCs when confronted with A549 cells, while in the presence of neuroendocrine cells they not only were unable to show cytolytic activity, but also lost viability. Neuroendocrine differentiation seems to mount less of an immune response when injected in mice, which may contribute to the poor prognosis of cancer patients affected by this pathology.

Multitarget Molecular Imaging in Metastatic Castration Resistant Adenocarcinoma Prostate Cancer with Therapy Induced Neuroendocrine Differentiation.

Neuroendocrine differentiation of prostate cancer (NEDPC) includes de novo presentation and secondary to epigenetic changes, referred as therapy-induced neuroendocrine prostate cancer (t-NEPC). Molecular imaging with prostate-specific membrane antigen (PSMA) and somatostatin analogues positron emission tomography (PET/CT) in NEDPC have not been validated. 18F-FDG (fluorodeoxyglucose) PET/CT has numerous limitations in prostate cancer (PCa) and the utility in NEDPC has only been reported in a few series of cases. The objective of this study is to compare the lesions detection rate of the three radiotracers in metastatic t-NEPC patients. (1) Material and Methods: Retrospective evaluation of patients with prostate adenocarcinoma treated with androgen deprivation therapy, chemotherapy, a novel androgen receptor pathway inhibitor or a combination of them and a second tumour biopsy confirming t-NEPC was made. All patients underwent 18F PSMA-1007, 18F AlF-NOTA-Octreotide, and 18F-FDG PET/CT. Evaluation of positive lesions was determined and SUVmax of each radiotracer was estimated and correlated with computer tomography (CT) findings. (2) Results: A total of eight patients were included. The mean time from diagnosis of prostate adenocarcinoma to t-NEPC was 28.2 months, with a mean serum specific prostate antigen (PSA) of 16.6 ng/dl at the time of NEPC diagnosis. All patients were treated with antiandrogen therapy and 87.5% with chemotherapy. A total of 273 lesions were identified by CT from which 182 were detected by 18F-FDG PET/CT, 174 lesions by 18F PSMA-1007, and 59 by 18F AlF-NOTA-Octreotide. An interpatient analysis of the lesions was performed and dual tracer 18F-FDG PET/CT and 18F PSMA-1007 PET/CT detected a total of 270/273 lesions (98.9%). (3) Conclusions: NEDPC patients demonstrated wide inter and intrapatient molecular imaging heterogeneity within the three radiotracers. 18F-FDG detected most lesions in t-NEPC among all radiotracers, especially in visceral sites; 18F PSMA-1007 detected more bone lesions. 18F AlF-NOTA-Octreotide showed no significant utility.

Effect of A549 neuroendocrine differentiation on cytotoxic immune response.

The present study was designed to determine the effects of factors secreted by the lung adenocarcinoma cell line with the neuroendocrine phenotype, A549NED, on cytotoxic T lymphocytes (CTLs) activity in vitro A perspective that integrates the nervous, endocrine and immune system in cancer research is essential to understand the complexity of dynamic interactions in tumours. Extensive clinical research suggests that neuroendocrine differentiation (NED) is correlated with worse patient outcomes; however, little is known regarding the effects of neuroendocrine factors on the communication between the immune system and neoplastic cells. The human lung cancer cell line A549 was induced to NED (A549NED) using cAMP-elevating agents. The A549NED cells showed changes in cell morphology, an inhibition of proliferation, an overexpression of chromogranin and a differential pattern of biogenic amine production (decreased dopamine and increased serotonin [5-HT] levels). Using co-cultures to determine the cytolytic CTLs activity on target cells, we showed that the acquisition of NED inhibits the decrease in the viability of the target cells and release of fluorescence. Additionally, the conditioned medium of A549NED and 5-HT considerably decreased the viability and proliferation of the Jurkat cells after 24 h. Thus, our study successfully generated a neuroendocrine phenotype from the A549 cell line. In co-cultures with CTLs, the pattern of secretion by A549NED impaired the proliferation and cytotoxic activity of CTLs, which might be partly explained by the increased release of 5-HT.

Carcinoma en tejido mamario ectópico axilar con diferenciación neuroendocrina: reporte de un caso / Carcinoma in ectopic axillary breast tissue with neuroendocrine differentiation: case report

Presentar un caso de carcinoma en tejido mamario ectópico axilar. Paciente femenina de 38 años de edad, quien consultó por aumento de volumen y nódulo en región axilar de un año de evolución y punción aspiración por aguja fina previa no diagnóstica. En la evaluación se observó mamas axilares bilaterales, palpando en la derecha tumor duro de superficie irregular, se realizó mamografía, C y biopsia por aguja gruesa. Por el diagnóstico de la biopsia por aguja gruesa, se practicaron estudios de extensión y se trató con neoadyuvancia y cirugía. El estudio histopatológico de la pieza quirúrgica concluyó carcinoma ductal infiltrante con patrón neuroendocrino y metástasis en 2 de 18 ganglios, recibió adyuvancia y se mantiene libre de enfermedad

A case of female patient 38 years of age, who consulted for increased volume and axillary node in a year of evolution and prior non-diagnostic FNA. The evaluation noted bilateral axillary breasts, feeling hard lump on the right an irregular surface, we performed mammography, PAAF and core needle biopsy. For the diagnosis of the biopsy needle, extension studies were performed and treated with neoadjuvant therapy and surgery. Histopathological examination of the surgical specimen concluded infiltrating ductal carcinoma neuroendocrine pattern and metastatic in 2 of 18 nodes, received adjuvant therapy and remains free of disease

Diferenciación neuroendocrina y marcadores de proliferación celular en adenocarcinoma de próstata en un grupo de casos con antígeno prostático específico normal vs elevado / Neuroendocrine differentiation and markers of cell proliferation in a group of patients with prostate adenocarcinoma and normal or high serum prostate-specific antigen levels

Objetivo. Investigar la población de células neuroendocrinas y sus características morfológicas en pacientes con cáncer de próstata y antígeno sérico normal versus antígeno sérico elevado. Material y métodos. En 13 años se identificaron 372 casos de cáncer de próstata de los cuales 19 (5.1%) con antígeno sérico normal (Grupo I). Se seleccionaron 16 grupos controles con antígeno sérico elevado y características histopatológicas similares (Grupo II). Se evaluaron porcentaje de necrosis tumoral, invasión vascular y perineural, inmunohistoquímica: sinaptofisina, enolasa neuroespecífica, antígeno prostático específico, Ki-67 y p53. Resultados. En el grupo I, se obtuvieron 61 % de casos positivos para antígeno tisular, 28.6 % sinaptofisina, 7.1 % para enolasa neuroespecífica, 50 % para p53 y 78.6 % para Ki-67. En el grupo II, los resultados fueron: sinaptofisina 13.3%, enolasa-neuroespecífica 26.6%, antígeno tisular 93%, p53 46.6% y Ki-67 66.7%. Con punto de corte de antígeno tisular expresado en < 80% de células neoplásicas, en el grupo I se encontraron 69.2% de casos, y en el grupo II 21.4% (p = 0.02). Conclusiones. El único dato histológico que mostró diferencia significativa fue la expresión tisular de antígeno prostático específico en < 80% de las células neoplásicas en el grupo I. Se asoció el incremento de las células neuroendocrinas con el menor número de células productoras de antígeno tisular; esta situación podría ser más visible al estudiar un mayor número de pacientes con características semejantes.

OBJECTIVE: Study the morphologic characteristics of neuroendocrine cells in prostate cancer with normal versus elevated prostate specific antigen (PSA). MATERIALS AND METHODS: 372 cases of prostate cancer were identified during a 13 year period, of which 19 displayed normal PSA (group I). Sixteen controls with elevated PSA and similar histopathological characteristics (group II) were included. We studied the degree of tumor necrosis, vascular and perineural invasion. Synaptophysin (SP), neuron specific enolase (NSE), PSA, Ki-67 and p53 inmunoreactivity were also analyzed. RESULTS: Group I positive findings were 61% PSA, 28.6% SP. 7.1% NSE, 50%p53, and 78.6% Ki-67. Group II positive findings were 93% PSA, 13.3% SP, 26.6% NSE 46.6% p53, and 66.7% Ki-67. When we used a <80% cut off point for PSA immunoreactivity in tumor cells, 69.2% of group I and 21.4% of group II were found. CONCLUSIONS: The sole histopathological finding that showed statistical significance was the tissular expression of the specific prostatic antigen in 80% of neoplasic cells in group I. The increase of neuroendocrine cells was associated with a smaller number of tissular antigen producing cells, a finding that could be more apparent if we were to study a larger sample size.