Nonfunctioning, small, incidental pancreatic neuroendocrine tumors: Results of a nonoperative approach cohort. / Tumores neuroendocrinos no funcionantes de páncreas incidentales de pequeño tamaño: Resultados de una serie con manejo no quirúrgico.

OBJECTIVE: The availability of new imaging techniques has conditioned an increase in the incidental diagnosis of small nonfunctioning pancreatic neuroendocrine tumors (PNET-NF). The best treatment is controversial, some authors advise a conservative approach in selected cases. Our aim is to analyze the evolution of incidental, small size PNET-NF, treated with clinical follow-up without surgery. METHODS: We performed a retrospective analysis of a prospective database of patients diagnosed incidentally with PNET-NF since November 2007 to September 2015. We include those with PNET-NF ≤2cm and asymptomatic. The diagnosis was performed using imaging tests indicating endoscopic ultrasound-guided fine-needle aspiration in case of doubts in the diagnosis. The follow-up was performed at our center, registering clinical and/or radiological changes. RESULTS: We included 24 patients with a median age of 70 years, and a similar distribution in terms of sex. The diagnosis was made through computed tomography multidetector or magnetic resonance imaging and octreotide scan. The tumors were located mainly in the head and neck (46%), with a mean size of 11,5±3,55mm at diagnosis (5-19mm). In 2 cases endoscopic ultrasound fine needle aspiration was used (8%), confirming the diagnosis of low-grade PNET with Ki67<5%. The median follow-up was 39 months (7-100). In 19 patients (79%) they remained the same size, 21% (5) increased its size with a mean of 2,6±2mm (1-6). No cases had progression of disease. CONCLUSION: In selected patients, non-surgical management of PNET-NF is an option to consider, when they are asymptomatic and ≤2cm. Larger studies with more patients and more time of follow-up are needed to validate this non-operative approach.

Surgical treatment of non-functioning pancreatic neuroendocrine tumours based on three clinical scenarios. / Tratamiento quirúrgico de los tumores neuroendocrinos no funcionantes de páncreas basado en 3 escenarios clínicos.

INTRODUCTION: The treatment of patients with non-functioning pancreatic neuroendocrine tumours (NFPNET) is resection in locally pancreatic disease, or with resectable liver metastases. There is controversy about unresectable liver disease. METHODS: We analysed the perioperative data and survival outcome of 63 patients who underwent resection of NFPNET between 1993 and 2012. They were divided into 3 scenarios: A, pancreatic resection (44patients); B, pancreatic and liver resection in synchronous resectable liver metastases (12patients); and C, pancreatic resection in synchronous unresectable liver metastases (6patients). The prognostic factors for survival and recurrence were studied. RESULTS: Distal pancreatectomy (51%) and pancreaticoduodenectomy (38%) were more frequently performed. Associated surgery was required in 44% of patients, including synchronous liver resections in 9patients. Two patients received a liver transplant during follow-up. According to the WHO classification they were distributed into G1: 10 (16%), G2: 45 (71%), and G3: 8 (13%). The median hospital stay was 11days. Postoperative morbidity and mortality were 49% and 1.6%, respectively. At the closure of the study, 43 (68%) patients were still alive, with a mean actuarial survival of 9.6years. The WHO classification and tumour recurrence were risk factors of mortality in the multivariate analysis. The median actuarial survival by scenarios was 131months (A), 102months (B), and 75months (C) without statistically significant differences. CONCLUSIONS: Surgical resection is the treatment for NFPNET without distant disease. Resectable liver metastases in well-differentiated tumours must be resected. The resection of the pancreatic tumour with unresectable synchronous liver metastasis must be considered in well-differentiated NFPNET. The WHO classification grade and recurrence are risk factors of long-term mortality.

Functional imaging in neuroendocrine tumors: assessment of molecular heterogeneity using [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT.

OBJECTIVE: The aim of the study was evaluate the diagnostic performance of [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT in patients with histologically proven neuroendocrine tumors (NETs), as well as the correlation of the visualized findings with the tumor grade. MATERIAL AND METHODS: We included 50 patients with NETs who underwent both [68Ga]Ga-DOTA-TOC and [18F]FDG PET/TC. The pooled sensitivity of both scans was compared, as well as [68Ga]Ga-DOTA-TOC and [18F]FDG for each tumor grade (grade 1/G1, grade 2/G2 and grade 3/G3). Also, the sensitivity of [68Ga]Ga-DOTA-TOC and [18F]FDG as a function of the continuous variable Ki-67 was investigated. Finally, the number of lesions detected by both PET radiopharmaceuticals for each tumor grade was compared. RESULTS: The pooled sensitivity of both PET/CT (96%) was higher than [68Ga]Ga-DOTA-TOC (84%) and [18F]FDG (44%) separately, with statistically significant differences. The sensitivity of [68Ga]Ga-DOTA-TOC was higher than [18F]FDG in both G1 (p = 0.004) and G2 (p < 0.001). In G3 the performance of both scans detected disease in 100% of this subgroup. The sensitivity of [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT correlated significantly with the Ki-67 proliferative index. In G2 patients the number of lesions detected with [68Ga]Ga-DOTA-TOC was higher than [18F]FDG. CONCLUSIONS: The performance of both PET/CT, particularly in G2 and G3, demonstrates the molecular heterogeneity of metastatic NETs and contributes to the selection of a more appropriate treatment, particularly in those high-grade patients who may benefit from radionuclide therapy (PRRT).

[Neuroendocrine tumor associated with an intestinal cyst: a case report]. / Tumor neuroendocrino asociado con quiste intestinal: presentación de un caso.

Intestinal (tailgut) cysts or retrorectal cystic hamartomas are rare benign lesions that are included in the category of developmental cystic lesions. Their origin is still uncertain, although several hypotheses have been proposed to explain their development. They are located mainly in the presacral (retrorectal) space and predominately affect middle-aged women (40-60 years). Taking into account location and histological characteristics, the main differential diagnoses include epidermoid cysts, duplication cysts and teratomas. Malignant transformation of these lesions is rare and preferentially into adenocarcinoma and neuroendocrine tumors. We present a case of an intestinal cyst associated with a well-differentiated neuroendocrine tumor (G1) in a 63-year-old woman.

Peptide receptor radionuclide therapy with [177Lu]Lu-DOTA-TATE.

This continuing education aims to present in a clear and easy-to-understand way, the biology of neuroendocrine tumors (NETs), the characteristics of somatostatin receptors, the selection of patients for radiolabelled peptide therapy (PRRT), the inclusion criteria to benefit from treatment with the minimum possible adverse effects, the administration protocol, follow-up and response evaluation. The functional imaging studies necessary to explore the biology of the tumor and to individualize the treatment are also carried out, and constitute the cornerstone for the development of teragnosis. Clinical trials are being developed to better define the position of PRRT within the broad therapeutic options, and among the future perspectives, there are several lines of research to improve the objective response rate and survival with PRRT, focused on the development of new agonists and somatostatin receptor antagonists, new radionuclides and radiosensitizing combination therapies. In conclusion, PRRT is a great therapeutic, well-tolerated and safe tool with generally mild and self-limited acute side effects, that must be sequenced at the best moment of the evolution of the disease of patients with NET. Candidate patients for PRRT should always be evaluated by a multidisciplinary clinical committee.

Discrepancy in the Ki67 labeling index of brain and orbital metastatic lesions from gastrointestinal neuroendocrine tumors: A case report.

Proliferative activity examined by Ki67 labeling index (LI) plays pivotal role for managing gastrointestinal neuroendocrine tumor (GI-NET). Few reports indicated the intra-patient heterogeneity of Ki67-LI among metastatic tumor sites. We report a case of brain and orbital metastases from GI-NET that showed discrepancy of the Ki67-LI. A 71 year-old woman who was diagnosed as GI-NET with liver and bone metastases and performed medical therapy, had headache, right exophthalmos, and pain of right eye and was referred to our department. Magnetic resonance image revealed that tumors in the left occipital region and right orbit. We diagnosed as metastatic brain and orbital tumors from GI-NET. Surgical removal of both symptomatic lesions was performed and the diagnosis was pathologically confirmed. Immunohistochemical studies revealed the discrepancy of the Ki67-LI of the lesions (brain tumor: 8% versus orbital tumor: 22%). Sampling of multiple metastatic sites may prevent underestimate tumor proliferative activity.

Discrepancy in the Ki67 labeling index of brain and orbital metastatic lesions from gastrointestinal neuroendocrine tumors: A case report.

Proliferative activity examined by Ki67 labeling index (LI) plays pivotal role for managing gastrointestinal neuroendocrine tumor (GI-NET). Few reports indicated the intra-patient heterogeneity of Ki67-LI among metastatic tumor sites. We report a case of brain and orbital metastases from GI-NET that showed discrepancy of the Ki67-LI. A 71 year-old woman who was diagnosed as GI-NET with liver and bone metastases and performed medical therapy, had headache, right exophthalmos, and pain of right eye and was referred to our department. Magnetic resonance image revealed that tumors in the left occipital region and right orbit. We diagnosed as metastatic brain and orbital tumors from GI-NET. Surgical removal of both symptomatic lesions was performed and the diagnosis was pathologically confirmed. Immunohistochemical studies revealed the discrepancy of the Ki67-LI of the lesions (brain tumor: 8% versus orbital tumor: 22%). Sampling of multiple metastatic sites may prevent underestimate tumor proliferative activity.

Síndrome de Hedinger secundario a Tumor neuroendocrino bronquial. Presentación de un caso

El síndrome carcinoide es un síndrome paraneoplásico que se presenta en tumores neuroendocrinos. Aunque es una entidad infrecuente suele ser la primera manifestación de la enfermedad. La baja incidencia junto a la presentación inespecífica genera retrasos diagnósticos importantes. Se presenta el caso de una paciente con síntomas digestivos y tuforadas que posteriormente agrega insuficiencia cardíaca, logrando mediante un ecocardiograma típico y marcadores analíticos el diagnóstico de síndrome carcinoide. Posteriormente se evidencia que su origen en un tumor neuroendocrino bronquial. Conocer las características de este síndrome es fundamental para mantener una alta sospecha clínica en pacientes con síntomas sugestivos logrando un diagnóstico precoz y adecuado.

Carcinoid syndrome is a paraneoplastic syndrome that occurs in neuroendocrine tumors. Although It is an uncommon entity, it is usually the first manifestation of the disease. The low incidence besides the non-specific presentation generates important diagnostic delays. We present the case of a patient presenting digestive symptoms and flushing that subsequently adds heart failure, achieving though a typical echocardiogram and analytical markers the diagnosis of carcinoid syndrome. Later it is discovered its origin in a bronchial neuroendocrine tumor. Knowing the characteristics of this syndrome is essential to maintain a high clinical suspicion in patients with suggestive symptoms, in order to achieve an early and adequate diagnosis.

El síndrome carcinoide é um síndrome paraneoplásico que ocorre em tumores neuroendócrinos. Embora seja uma entidade rara, geralmente é a primeira manifestação da doença. A baixa incidência, juntamente com a apresentação inespecífica, resulta em atrasos importantes no diagnóstico. Apresentamos o caso de uma paciente com sintomas digestivos e ruborização cutânea, que posteriormente desenvolve insuficiência cardíaca. O diagnóstico de síndrome carcinoide foi estabelecido por meio de um ecocardiograma característico e marcadores analíticos. Posteriormente, foi evidenciada a origem em um tumor neuroendócrino brônquico. Conhecer as características deste síndrome é fundamental para manter uma alta suspeita clínica em pacientes com sintomas sugestivos, permitindo um diagnóstico precoce e adequado.

Neuroendocrine tumor associate with inflammatory bowel disease: two cases report.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) have a higher risk of developing gastrointestinal tumors, the adenocarcinoma is the most frequently associated, and neuroendocrine tumor (NET) the most rare. CLINICAL CASES: We present two patients, one with Crohn's disease and the other with ulcerative colitis, who present nonspecific symptoms, and after resection of an intestinal lesion, a gastrointestinal NET (GINET) is diagnosed. DISCUSSION AND CONCLUSION: The GINET have an insidious clinic and these can be confused with those of the IBD. There could be an association between both pathologies; an important role of the chronic intestinal inflammatory process is suggested. The best treatment for GINET is the resection.

INTRODUCCIÓN: Los pacientes con enfermedad inflamatoria intestinal (EII) tienen mayor riesgo de desarrollar neoplasias gastrointestinales y el adenocarcinoma es el relacionado con más frecuencia y el tumor neuroendocrino (TNE) el más raro. CASO CLÍNICO: Se presentan los casos de dos pacientes, uno con enfermedad de Crohn y otro con colitis ulcerosa, que cursan con clínica inespecífica, y tras resección de la lesión intestinal se diagnostica un TNE gastrointestinal (TNEGI). DISCUSIÓN Y CONCLUSIONES: Los TNEGI tienen una clínica insidiosa y pueden confundirse con los de la EII. Es posible un nexo entre ambas entidades, lo que sugiere un papel importante del proceso inflamatorio crónico intestinal. El tratamiento de elección de los TNEGI es la resección.

[Tumores neuroendocrinos pancreáticos. Nuestra experiencia]. / Pancreatic neuroendocrine tumors. Our experience.

Pancreatic neuroendocrine tumors are rare. It is a heterogeneous group of neoplasms with very different behavior and prognosis. They can appear sporadically or associated with genetic syndromes. They are divided into functioning and non-functioning. A descriptive retrospective study of patients diagnosed with pancreatic neuroendocrine tumor was performed. The incidental diagnosis of these tumors is increasingly. The only curative treatment for these tumors is surgical excision, depending on the location and characteristics of the tumor and the patient. In selected cases a conservative attitude is recommended.

Los tumores neuroendocrinos pancreáticos son poco frecuentes. Es un grupo heterogéneo de neoplasias con comportamiento y pronóstico muy diferentes. Pueden aparecer de manera esporádica o asociados a síndromes genéticos. Se dividen en funcionantes y no funcionantes. Se realizó un estudio retrospectivo descriptivo de los pacientes diagnosticados de tumor neuroendocrino pancreático. Como se refleja en nuestra serie, cada vez es más frecuente el diagnostico incidental de estos tumores. El único tratamiento curativo de estos tumores es la exéresis quirúrgica, según la localización y las características del tumor y del paciente. En casos seleccionados se puede optar por una actitud conservadora.

Laparoscopic approach of the left side of the pancreas. / Abordaje laparoscópico del páncreas izquierdo.

INTRODUCTION: Laparoscopic left-sided pancreatectomy (LLP) is an increasingly used surgical technique for the treatment of benign and malignant lesions of the left side of the pancreas. The results of LLP as a treatment for primary pancreatic lesions of the head and tail of the pancreas were evaluated. METHODS: From November 2011 to November 2017, 18 patients underwent surgery for primary lesions of the pancreas by means of a laparoscopic distal pancreatectomy. An intra-abdominal drain tube was used in all cases, and the recommendations of the International Study Group for Pancreatic Fistula (ISGPF) were followed. RESULTS: The mean age was 66.5years (IQR 46-74). Among the 18 left pancreatectomies performed, four were with splenic preservation, and one was a central pancreatectomy. There were two conversions. The median surgical time was 247.5minutes (IQR 242-275). The median postoperative hospital stay was 7days (IQR 6-8). After 90days, complications were detected in five patients: three gradeII, one gradeIII and one gradeV according to the modified Clavien-Dindo classification. There was one gradeB pancreatic fistula, and four patients had to be readmitted to hospital because of peripancreatic collections. The anatomic pathology diagnosis was malignant neoplasm in 38.9% of cases, all of them with negative resection margins. CONCLUSIONS: LLP can be considered the technique of choice in the treatment of primary benign pancreatic lesions and an alternative to the open approach in selected patients diagnosed with malignant pancreatic lesions.

[Tumor neuroendocrino ano-rectal: desde un pólipo con buen pronóstico hasta un carcinoma letal]. / Ano-rectal neuroendocrine tumour: from a polyp with a good prognosis to a lethal carcinoma.

INTRODUCCIÓN: Aunque los tumores neuroendocrinos rectales son neoplasias poco frecuentes, su incidencia está aumentando en las tres últimas décadas. El objetivo de este trabajo es el estudio del comportamiento de dichos tumores basándonos en sus variables clínicas, diagnósticas, terapéuticas y anatomopatológicas en un hospital terciario. MÉTODO: Estudio retrospectivo de los tumores neuroendocrinos rectales desde el año 2000 hasta el año 2017 en nuestro hospital. Se realizó una búsqueda informatizada en el programa SNOMED del servicio de anatomía patológica, empleando los criterios «tumor neuroendocrino¼ y «tumor carcinoide¼. RESULTADOS: Se hallaron 16 pacientes con tumor neuroendocrino ano-rectal. El 75% eran varones. La mediana de edad fue de 53 años (rango: 34-83). El diagnóstico fue incidental en el 62,5%. El tratamiento fue endoscópico en 13 (81%) pacientes y quirúrgico en 3 (19%). El 75% de las lesiones fueron T1. El 68,7% de los tumores presentaban un grado de agresividad G1. La media de seguimiento fue de 29 meses; no hubo recidivas. Durante el seguimiento fallecieron 3 (18,5%) pacientes, todos ellos con tumor G3 metastásico, y la supervivencia media fue de 8 meses. CONCLUSIONES: Los tumores neuroendocrinos rectales son cada vez más frecuentes y presentan unos patrones variables, cuyo pronóstico dependerá de su agresividad histológica. El aumento de su incidencia puede deberse a una mayor concienciación de la existencia de estos tumores, a las campañas de cribado del cáncer colorrectal, al aumento del número de colonoscopias realizadas y a la generalización de los estudios histológicos con marcadores neuroendocrinos. BACKGROUND: Although rectal neuroendocrine tumours are rare neoplasms, their incidence is increasing in the last three decades. The objective of this work is to study the behaviour of these tumours based on their clinical, diagnostic, therapeutic, and pathological variables in a tertiary hospital. METHOD: Retrospective study of rectal neuroendocrine tumours from 2000 to 2017 in our hospital. A computerized search was performed in the SNOMED program of the pathological anatomy service, using the criteria "neuroendocrine tumour" and "carcinoid tumour". RESULTS: We found 16 patients with ano-rectal neuroendocrine tumour; 75% were male. The median age was 53 years (range: 34-83). The diagnosis was incidental in 62.5%, with endoscopic treatment in 13 patients (81%) and surgical treatment in 3 (19%). 75% of the lesions were T1. 68.7% of the tumours showed a degree of G1 aggression. The mean follow-up was 29 months; no recurrences. During follow-up, three patients died (18.5%), all of them with metastatic G3 tumour and the mean survival was 8 months. CONCLUSIONS: The rectal neuroendocrine tumours are increasingly frequent and present variable patterns, whose prognosis will depend on their histological aggressiveness. The increase incidence may be due to a greater awareness of the existence of these tumours, to colorectal cancer screening, to the increase in the number of colonoscopies performed and to the generalization of histological studies with neuroendocrine markers.

Divertículo de Meckel con tumor neuroendocrino: presentación inusual / Meckel's diverticulum with neuroendocrine tumor: unusual presentation

El divertículo de Meckel es una malformación congénita que suele presentarse como un hallazgo incidental asintomático. Puede complicarse por procesos inflamatorios o tumores, cursando con sintomatología abdominal sumamente inespecífica, lo que complica su diagnóstico oportuno. Aunque la incidencia de neoplasias malignas en estos divertículos es baja, los tumores neuroendocrinos son los más representativos. Presentamos el caso de una paciente de 72 años que consultó por dolor abdominal y deposiciones melénicas, con múltiples nódulos intrahepáticos sugestivos de tumores neuroendocrinos y hallazgo intraoperatorio incidental de diverticulitis aguda de Meckel con metástasis peridiverticular de un tumor neuroendocrino. (AU)

Meckel's diverticulum is a congenital malformation that usually presents as an incidental finding. It can be complicated by inflammatory processes or tumors, with non-specific abdominal symptoms which delay its timely diagnosis. Although the incidence of malignant neoplasms in these diver-ticula is low, neuroendocrine tumors are the most representative. We present the case of a 72-year-old female patient who consulted for abdominal pain and melenic bowel movements, with multiple intrahepatic nodules suggestive of neuroendocrine tumors and an incidental intraoperative finding of acute Meckel's diverticulitis with peridiverticular metastasis of a neuroendocrine tumor. (AU)

[Polymetastatic highly aggressive Small Cell Undifferentiated Neuroendocrine Carcinoma of Ascending Colon]. / Carcinoma neuroendocrino indiferenciado polimetástatico altamente agresivo de células pequeñas de colon ascendente.

Neuroendocrine carcinoma (NEC) of the colon is a rare and very aggressive tumor with poor prognosis. The current case report presents a 53-year-old male with a 6 cm × 10 cm ascending colon carcinoma, causing large intestine obstruction, with simultaneous multiple hepatic metastases and peritoneal carcinomatosis. Surgical resection of the primary tumor was performed, because of the bowel obstruction, to ameliorate the symptoms before the onset of chemotherapy. Histopathology revealed that the tumor was a small-cell undifferentiated NEC. During the post0operative period, the patient presented pulmonary metastases, and on the 36th post-operative day, death occurred due to respiratory failure.

El carcinoma neuroendocrino del colon es un tumor raro y muy agresivo, con mal pronóstico. Se presenta el caso de un hombre de 53 años con un carcinoma de colon ascendente de 6 × 10 cm que causa obstrucción del intestino grueso, con metástasis hepáticas múltiples simultáneas y carcinomatosis peritoneal. Se realizó la resección quirúrgica del tumor primario, debido a la obstrucción intestinal, para mejorar los síntomas antes del inicio de la quimioterapia. La histopatología reveló que el tumor era un carcinoma neuroendocrino indiferenciado de células pequeñas. Durante el posoperatorio, el paciente presentó metástasis pulmonares y el día 36 posoperatorio se produjo la muerte por insuficiencia respiratoria.

[Synchronous well differentiated ileal neuroendocrine tumour and colonic adenocarcinoma. A case report and a review of the literature]. / Tumor neuroendocrino bien diferenciado ileal y adenocarcinoma de colon sincrónicos: a propósito de un caso y revisión de la literatura.

Synchronous colonic adenocarcinoma and well-differentiated ileal neuroendocrine tumour are infrequent and are usually incidental findings on autopsies or resected surgical specimens. Only rarely are they detected on colonoscopies or during surgery. We present a case of a synchronous caecal adenocarcinoma and well-differentiated ileal neuroendocrine tumour, undetected during colonoscopy, with carcinoid metastasis in one regional lymph node not associated with adenocarcinoma metastasis. A review of the literature shows that the association of non-synchronous second primary malignancies in patients with gastrointestinal carcinoid tumours is reported in more than 50% of cases; however, synchronous tumours are found in only 1-8%. It would appear that well-differentiated ileal neuroendocrine tumour could be a predisposing factor for the development of a second malignancy.

Primary well differentiated neuroendocrine tumor of the filum terminale. Case report and literature review. / Tumor neuroendocrino bien diferenciado intradural-extramedular primario del filum terminale. Presentación de un caso y revisión de la literatura.

OBJECTIVE: To present a case of a well-differentiated primary intradural-extramedullary neuroendocrine tumor of the filum terminale and to conduct a literature review. CASE: A 68-years old patient was assessed after presenting lower back pain and sciatica with ineffective pain relief. The patient presented an intradural-extramedullary lumbar lesion arising from the filum terminale, which was partially resected. The pathology diagnosis was a well-differentiated primary neuroendocrine tumor (carcinoid tumor). After a multidisciplinary evaluation, fractionated stereotactic radiotherapy was administered. No progression or metastatic spread was observed in successive assessments. DISCUSSION: Neuroendocrine tumors are heterogeneous neoplasms derived predominantly from enterochromaffin cells, in which chemotherapy plays a very limited role. In contrast, radiotherapy has been described in partially resected lesions. CONCLUSION: Well-differentiated primary neuroendocrine tumors with intradural-extramedullary lumbosacral location are an exceptional rarity. Isolated surgical resection, or associated with an adjuvant radiotherapy treatment in subtotal resections, could be considered an effective therapeutic strategy.

Ectopic Cushing syndrome: Report of 9 cases. / Síndrome de Cushing ectópico: descripción de 9 casos.

INTRODUCTION: Ectopic Cushing's syndrome (ECS) is a rare condition caused by ACTH secretion by extrapituitary tumors. Its low frequency makes it difficult to acquire experience in its management. The aim of this study was to describe patients with ECS seen at the endocrinology department of a tertiary hospital over 15 years. METHODS: This was a retrospective study of the clinical, biochemical and radiographic data, treatment, and course of patients with ECS seen from 2000 to 2015. RESULTS: Nine patients (6 of them female) with a mean age of 47 years were included in the study. The clinical syndrome developed in less than 3 months in all cases but one, and most patients also had edema, hyperpigmentation and/or hypokalemia. Mean urinary free cortisol and ACTH levels were 2,840µg/24h and 204pg/mL respectively. The ectopic origin was confirmed by a combination of dynamic non-invasive tests and radiographic studies in most cases. The tumor responsible could be identified in 8 cases, and 7 patients had metastatic dissemination. Primary treatment was surgery in one patient, surgery combined with systemic therapy in 3, and chemotherapy in the other 3 patients. Bilateral adrenalectomy was required in 4 patients to control hypercortisolism. After a mean follow-up of 40 months, 3 patients died, 5 were still alive, and one had been lost to follow-up. CONCLUSIONS: Our study confirms that ECS covers a wide spectrum of tumors of different aggressiveness and nature. The ectopic origin of Cushing's syndrome can usually, be suspected and confirmed in most cases without the need for invasive tests. Control of both hypercortisolism and the tumor requires multiple treatment modalities, and multidisciplinary management is recommended.

Carcinoma neuroendocrino de canal anal: presentación de un caso y revisión bibliográfica

Introducción: Los carcinomas neuroendocrinos (NEC) de canal anal son neoplasias extremadamente raras, representando del 1 a 1,6% de la totalidad de los tumores neuroendocrinos (NET). Suelen ser poco diferenciados, muy agresivos y con alta tendencia a metastatizar. Caso clínico: Mujer de 52 años diagnosticada de fisura anal. Durante la esfinterotomía lateral interna (ELI) se evidencia un pólipo milimétrico aparentemente hiperplásico. Biopsia: NEC de alto grado. En el estudio de extensión se observa engrosamiento de la mucosa del canal anal que invade el esfínter interno, sin enfermedad a distancia. Se realiza amputación abdominoperineal laparoscópica donde se objetiva infiltración del tabique rectovaginal, por lo que se realiza resección y vaginoplastia. AP: NEC con estadio PT4B N2A, por lo que se indica quimioterapia adyuvante. Discusión: La presentación clínica de los NEC de canal anal es inespecífica, diferenciándose de otros tumores colorrectales en que hasta el 67% de los pacientes presentan metástasis al diagnóstico, siendo la supervivencia media de 11 meses. Si diagnosticamos un NEC localizado de forma incidental, es fundamental la celeridad en su tratamiento, dada su agresividad.

Introduction: Neuroendocrine carcinomas (NEC) of the anal canal are extremely rare neoplasms, representing 1 to 1.6% of all neuroendocrine tumors (NET). They are usually poorly differentiated, very aggressive and with a high tendency to metastasize. Clinical case: A 52-year-old woman diagnosed with anal fissure. During the LIS, an apparently hyperplastic millimetric polyp is evidenced. Biopsy: high-grade NEC. The imaging study shows thickening of the mucosa of the anal canal that invades the internal sphincter, without metastases. We performed a laparoscopic abdominoperineal amputation, and noticed an infiltration of the rectovaginal septum, so resection and vaginoplasty was performed. Pathology: NEC with stage PT4B N2A, for which adjuvant chemotherapy is indicated. Discussion: The clinical presentation of NEC of the anal canal is nonspecific, differing from other colorectal tumors in that up to 67% of patients have metastases at diagnosis, with a median survival of 11 months. When an incidentally localized NEC is diagnosed, prompt treatment is essential, given its aggressiveness.

Tumores neuroendócrinos pancreáticos: revisão histopatológica / Pancreatic neuroendocrine tumors: histopathological review

Introdução: Os tumores neuroendócrinos pancreáticos são considerados raros. Eles são classificados em funcionantes e não funcionantes. Objetivo: Definir e classificar tumores neuroendócrinos pancreáticos de acordo com sua avaliação histopatológica e imunoistoquímica, associado aos critérios diagnósticos. Método: Trata-se de revisão narrativa sobre publicações encontradas no PubMed, SciELO e Google Acadêmico. Resultados: Esses tumores podem ser bem ou pouco diferenciados e apresentam características microscópicas distintas. As células bem diferenciadas têm formato pequeno, núcleos uniformes redondos ou ovais, citoplasma finamente granular indicando forte capacidade secretória e mantêm a estrutura organoide. A presença de necrose tumoral, atividade mitótica aumentada e índice de Ki-67 elevado indicam alta probabilidade de neoplasia neuroendócrina. Cromogranina A e sinaptofisina favorecem o diagnóstico do bem diferenciado. Já a marcação positiva do BCL 10 em conjunto com a ausência de expressão da cromogranina A e da sinaptofisina mostram a precária diferenciação tumoral. A presença de marcação positiva para as expressões hormonais não define o tumor como funcionante. Conclusão: Houve aumento do diagnóstico de tumores neuroendócrinos pancreáticos com o uso de técnicas de imagem e a conscientização sobre a doença. A análise histopatológica com imunoistoquímica, especialmente quando há sintomas consumptivos, podem indicar o tipo do carcinoma e induzir ao mais adequado tratamento.

Introduction: Pancreatic neuroendocrine tumors are considered rare. They are classified into functioning and non-functioning. Objective: To define and classify pancreatic neuroendocrine tumors according to their histopathological and immunohistochemical evaluation, associated with diagnostic criteria. Method: This is a narrative review of publications found in PubMed, SciELO and Google Scholar. \Results: These tumors can be well or poorly differentiated and have distinct microscopic characteristics. Well-differentiated cells are small in shape, have uniform round or oval nuclei, finely granular cytoplasm indicating strong secretory capacity, and maintain the organoid structure. Presence of tumor necrosis, increased mitotic activity and high Ki-67 index indicate a high probability of neuroendocrine neoplasia. Chromogranin A and synaptophysin favor the diagnosis of well-differentiated. The positive staining of BCL 10 together with the absence of expression of chromogranin A and synaptophysin show poor tumor differentiation. The presence of positive staining for hormone expressions does not define the tumor as functioning. Conclusion: There was an increase in the diagnosis of pancreatic neuroendocrine tumors with the use of imaging techniques and awareness of the disease. Histopathological analysis with immunohistochemistry, especially when there are consuming symptoms, can indicate the type of carcinoma and lead to the most appropriate treatment.

Paciente positiva a la COVID-19 operada de un insulinoma

RESUMEN Introducción: El insulinoma es una neoplasia neuroendocrina considerada una de las más raras. Surge en las células beta de los islotes de Langerhans, produce insulina de forma constante, por lo que provoca hipoglucemia. Su diagnóstico se basa en criterios clínicos, analíticos y pruebas de imagen. El tratamiento curativo es la cirugía, mediante la enucleación del tumor, la pancreatectomía parcial o total o duodenopancreatectomía cefálica. La actual pandemia dio a lugar a nuevos protocolos de actuación, con el fin de adaptar los recursos sanitarios sin comprometer la seguridad de los pacientes y el personal de salud. Objetivo: Presentar un caso clínico de una paciente con diagnóstico de insulinoma, que requirió tratamiento quirúrgico en el curso de la COVID-19. Caso clínico: Paciente femenina de 48 años de edad, con episodios de hipoglucemia intensa y dificultad para seguimiento clínico adecuado. Se le diagnosticó insulinoma y la COVID-19; esta última empeoró la sintomatología, de forma que resultó imposible el adecuado control metabólico. Se decidió tratamiento quirúrgico; se llevó a cabo la enucleación del tumor, sin complicaciones. Conclusiones: La cirugía es el tratamiento definitivo para lograr la curación en el caso de los tumores neuroendocrinos y la COVID-19 empeora el pronóstico. La decisión del tratamiento quirúrgico, debe ser tomada en discusión multidisciplinaria con el fin de evitar complicaciones postoperatorias.

ABSTRACT Introduction: Insulinoma is a neuroendocrine neoplasm considered one of the rarest, it arises in the beta cells of the islets of Langerhans, it produces insulin constantly, thus causing hypoglycemia. Its diagnosis is based on clinical, analytical and imaging criteria. Curative treatment is surgery, through enucleation of the tumor, partial or total pancreatectomy, or cephalic pancreaticoduodenectomy. The current pandemic gave rise to new action protocols, in order to adapt health resources without compromising the safety of patients and health personnel. Objective: To present a clinical case of a patient diagnosed with insulinoma who required surgical treatment in the course of COVID-19. Clinical case: 48-year-old female patient, with episodes of severe hypoglycemia and difficulty in proper clinical follow up. She was diagnosed with insulinoma and COVID-19, the latter worsened the patient's symptoms in such a way that adequate metabolic control was impossible. Surgical treatment was decided. The tumor was enucleated, without complications. Conclusions: Surgery is the definitive treatment to achieve cure in the case of neuroendocrine tumors, COVID-19 worsens the prognosis of patients with this tumor. Therefore, the decision of surgical treatment must be made in a multidisciplinary discussion in order to avoid postoperative complications.