Indications for genetic study in gastro-entero-pancreatic and thoracic neuroendocrine tumors.

Gastro-entero-pancreatic (GEP-NET) and thoracic neuroendocrine tumours (NETs) are one of the most heritable groups of neoplasms in the body, being multiple endocrine neoplasia syndrome type 1 (MEN1), the genetic syndrome most frequently associated with this type of tumours. Moreover, Von Hippel Lindau syndrome, tuberous sclerosis, type 4 multiple neoplasia syndrome, and type 1 neurofibromatosis are associated with an increased risk of developing GEP-NETs. Another important aspect in GEP-NETs and thoracic NETs is the knowledge of the molecular background since the molecular profile of these tumours may have implications in the prognosis and in the response to specific treatments. This review summarizes the main indications for performing a genetic study in patients with GEP-NETs and thoracic NETs, and the methods used to carry it out. Moreover, it offers a description of the main hereditary syndromes associated with these NETs and their molecular background, as well as the clinical implications of the molecular profile.

Sclerosing pneumocytoma with carcinoid tumorlets and neuroendocrine cell hyperplasia.

Sclerosing pneumocytoma is an uncommon pulmonary tumor which generally behaves benignly and occurs predominately in women. Rarely, it is associated with neuroendocrine proliferations such as hyperplasia, tumorlets and carcinoid tumors, which may be observed in relation to the tumor or in the distant lung parenchyma; the mechanism underlying this neuroendocrine differentiation is not clear. We present a case of a 33 year-old male with sclerosing pnemocytoma with coexistent neuroendocrine hyperplasia and combined carcinoid tumorlets. Taking into account the pluripotentiality of the round cells present in the sclerosing pneumocytoma, with positive staining for stem cells markers, it is possible that the different components of this neoplasia share a common origin, in accordance with previously reported findings.

The dark side of pseudoscorpion diversity: The German Barcode of Life campaign reveals high levels of undocumented diversity in European false scorpions.

DNA barcoding is particularly useful for identification and species delimitation in taxa with conserved morphology. Pseudoscorpions are arachnids with high prevalence of morphological crypsis. Here, we present the first comprehensive DNA barcode library for Central European Pseudoscorpiones, covering 70% of the German pseudoscorpion fauna (35 out of 50 species). For 21 species, we provide the first publicly available COI barcodes, including the rare Anthrenochernes stellae Lohmander, a species protected by the FFH Habitats Directive. The pattern of intraspecific COI variation and interspecific COI variation (i.e., presence of a barcode gap) generally allows application of the DNA barcoding approach, but revision of current taxonomic designations is indicated in several taxa. Sequences of 36 morphospecies were assigned to 74 BINs (barcode index numbers). This unusually high number of intraspecific BINs can be explained by the presence of overlooked cryptic species and by the accelerated substitution rate in the mitochondrial genome of pseudoscorpions, as known from previous studies. Therefore, BINs may not be an appropriate proxy for species numbers in pseudoscorpions, while partitions built with the ASAP algorithm (Assemble Species by Automatic Partitioning) correspond well with putative species. ASAP delineated 51 taxonomic units from our data, an increase of 42% compared with the present taxonomy. The Neobisium carcionoides complex, currently considered a polymorphic species, represents an outstanding example of cryptic diversity: 154 sequences from our dataset were allocated to 23 BINs and 12 ASAP units.

Appendiceal Neuroendocrine Tumours - Experience of One Service / Tumores neuroendócrinos do apêndice - Experiência de um serviço

Abstract Tumours of the appendix are rare and tend to be diagnosed incidentally, in cases of acute appendicitis. For some authors, appendiceal neuroendocrine tumours (ANETs) are the most frequent neoplasm of the appendix, observed in 0.3% to 0.9% of cases acute appendicitis. The present is a unicentric retrospective study conducted between January 2005 and March 2017. Out of a total of 3,007 surgeries for appendiceal pathologies performed in the adult population at the hospital where the present study was conducted, there were 70 (2.33%) malignant cases, 20 (28.6%) of which were ANETs. The patients had a median age of 44 years (range: 18 to 85 years), and were predominantly women (there were 1.9 times more women than men). In 16 cases (80%), a simple appendicectomy was performed (1 patient was submitted to a right hemicolectomy later). The cases of ANETs had a good prognosis in our series: 85% of the patients are either alive today or were alive after 5 years of follow-up. Despite the fact that ANETs are described as the most frequent tumor of the appendix, this was not confirmed in our series, in which they only represented 28.6% of the cases; adenocarcinoma was the most frequent tumor (65.7%) among our sample.

Resumo Tumores do apêndice são raros, e tendem a ser diagnosticados de forma incidental, em casos de apendicite aguda. Para alguns autores, tumores neuroendócrinos do apêndice (TNEAs) são as neoplasias mais frequentes do apêndice, e são observados em 0,3 a 0,9% de todos os casos agudos de apendicite. Este é um estudo monocêntrico e retrospectivo realizado entre janeiro de 2005 e março de 2017. Entre umtotal de 3.007 cirurgias para patologias do apêndice realizadas na população adulta no hospital em que o estudo foi conduzido, houve 70 (2,33%) casos de malignidade, 20 (28,6%) dos quais eram TNEAs. Os pacientes tinham uma idade média de 44 anos (gama: 18-85 anos), e eram predominantemente mulheres (havia 1,9 vezes mais mulheres do que homens). Em 16 casos (80%), realizou-se uma simples apendicectomia (1 paciente foi submetido a uma hemicolectomia direita mais tarde). Os casos de TNEAs tiveram um bom prognóstico em nossa série: 85% dos pacientes estão vivos hoje, ou estavam após um seguimento de 5 anos. Apesar de os TNEAs serem descritos como os tumores mais frequentes do apêndice, isso não foi confirmado nesta série, na qual eles representaram apenas 28,6% dos casos; adenocarcinoma foi o tumor mais frequente (65,7%) emnossa amostra.

[Diagnostic and therapeutic management of operable bronchopulmonary carcinoid tumours]. / Prise en charge diagnostique et thérapeutique des tumeurs carcinoïdes broncho-pulmonaires opérables.

INTRODUCTION: Bronchial carcinoid tumours (CT), divided into typical carcinoid (TC) or atypical carcinoid (AC), are rare tumours whose therapeutic management remains unspecified. METHODS: Retrospective study collecting cases of bronchial CT operated at the thoracic surgery department of Abderrahmane-Mami hospital of Ariana and recruited from the pneumology departments of Northern Tunisia, during a 12-year period. RESULTS: Ninety patients were collected (74 cases of TC and 16 cases of AC). The mean age was 45 years and the sex ratio H/F=0.5. The chest X-ray was normal in 11 cases, as well as flexible bronchoscopy in seven cases. The tumour was classified: stage IA (10 cases), IIA (28 cases), IIB (31 cases), IIIA (15 cases) and IIIB (six cases). Surgery resulted in a complete resection in 78 patients, an extensive resection in six patients, and a conservative resection in six patients. Adjuvant chemotherapy was given in 10 patients. The survival was 84% at five years and 42% at 10 years. CONCLUSION: The prognosis of CT depends directly on the histological subtype. It is excellent for TC after complete resection, unlike ACs that are similar to well-differentiated bronchial carcinomas.

Benign non-carcinoid neoplasms of the cecal appendix: presentation of 36 cases during the last 17 years in a third level hospital.

BACKGROUND: The tumors of the cecal appendix are a rare and heterogeneous group of neoplasms with variable prognosis and evolution, its incidence is very low. Mucinous tumors are defined as a dilated cecal appendix due to an abnormal accumulation of mucin, which may be benign or malign. Within these we find the mucoceles, which according to the latest consensus and classifications no longer include them. In this article we describe our experience in these tumors, we also propose a group to include the mucoceles and we review the literature. METHOD: Descriptive and retrospective study, analyzing all the surgical pieces of cecal appendix during the last 17 years. RESULTS: We analyzed 4910 surgical pieces. 36 were included in the group of non-carcinoid benign epithelial neoplasms (NEBNC), in this group 16 were low-grade mucinous neoplasms, 14 mucoceles and 6 tubular adenomas. The most frequent presentation's form was simulating an acute appendicitis. Surgical treatment was performed by open approach in 22 cases and by laparoscopic approach in 14 cases. CONCLUSIONS: Symptomatic NEBNC can simulate acute appendicitis but in people with a higher mean age, so this diagnostic should be considered in older patients with nonspecific imaging tests. The recommended treatment is always surgical and it can be possible by laparoscopic approach.

ANTECEDENTES: Las tumoraciones del apéndice cecal son un grupo raro y heterogéneo de neoplasias con evolución y pronóstico variables, y tienen una incidencia muy baja. Las tumoraciones mucinosas se definen como aquellas con un apéndice cecal dilatado debido a una acumulación anormal de mucina en su interior; pueden ser benignas o malignas. Dentro de ellas se encuentran los mucoceles, que según los últimos consensos y clasificaciones ya no los incluyen. En este artículo se describe la experiencia de los autores en estas tumoraciones y se propone un grupo en el que incluir los mucoceles; además, se hace una revisión de la literatura. MÉTODO: Estudio descriptivo y retrospectivo en el que se analizan todas las piezas quirúrgicas de apéndice cecal durante los últimos 17 años. RESULTADOS: Se analizaron 4910 piezas quirúrgicas. De ellas, 36 fueron incluidas en el grupo de neoplasias epiteliales benignas no carcinoides (NEBNC): 16 fueron neoplasias mucinosas de bajo grado, 14 mucoceles y 6 adenomas tubulares. La forma de presentación más frecuente fue simulando una apendicitis aguda. El tratamiento quirúrgico fue mediante abordaje abierto en 22 casos y laparoscópico en 14. CONCLUSIONES: Las NEBNC sintomáticas pueden simular cuadros de apendicitis aguda, pero en personas con una mayor edad media, por lo que hay que considerar esta posibilidad diagnóstica en pacientes mayores con pruebas de imagen inespecíficas. El tratamiento recomendable es siempre quirúrgico, y resulta viable su realización mediante abordaje laparoscópico.

Lung and digestive neuroendocrine neoplasms. From WHO classification to biomarker screening: Which perspectives?

The recent classifications of lung and digestive neuroendocrine neoplasms (NENs) make a fundamental distinction between well- and poorly-differentiated neoplasms. Well-differentiated NENs are termed carcinoids in the lung and neuroendocrine tumors in the gastroenteropancreatic sphere; their risk of malignancy is highly variable; histological grading is used to stratify patients into prognostically significant groups. Poorly-differentiated NENs are termed neuroendocrine carcinoma in both the lung and the digestive sphere; they constantly are of high grade of malignancy; two types are recognized on the basis of tumor cell morphology, the small cell and the large cell types. Recent studies have largely uncovered the genetic landscape of several subsets of well-differentiated NENs (lung, pancreas, small intestine) and of poorly-differentiated NENs. Some molecular markers may help to the differential diagnosis between highly proliferative neuroendocrine tumors and neuroendocrine carcinomas, especially in the pancreas. In well-differentiated tumors, MGMT status is proposed as a predictive marker of the response to temozolomide, but remains to be validated. In poorly-differentiated neoplasms, large cell neuroendocrine carcinoma has been shown to be a heterogeneous category, with some cases presenting the same molecular signature than small cell carcinoma and others the same signature than adenocarcinomas of the same body site. Rb protein has been recently shown to be a potential marker of response to platinum salts in neuroendocrine carcinoma. Much remains to be done to translate the rapid progress in the molecular understanding of NENS into diagnostic, prognostic or predictive markers.

Appendiceal neuroendocrine tumors: approach and treatment / Tumores neuroendócrinos do apêndice: abordagem e tratamento

ABSTRACT The incidence of tumors in the appendix has increased over the years, and they are mainly found in the anatomical and pathological examination of appendices operated due to acute appendicitis. The annual incidence of neuroendocrine tumors of the appendix, also called carcinoid tumors, is 0.15-0.16 per 100,000 people. In absolute terms, the incidence of these tumors has increased in the last decade by 70-133%. Appendiceal carcinoid tumors occur more often in women, and are found in 0.3-0.9% of the appendices removed in appendectomies. They appear in the subepithelial neuroendocrine cells and have an indolent course, with the symptoms being indistinguishable from an acute appendicitis. There are two classifications, one presented by the European Neuroendocrine Tumor Society and the other by the American Joint Committee on Cancer. Both classifications use tumor size as a predictor of tumor burden. The classification used by European Neuroendocrine Tumor Society also uses the invasion of the mesoappendix to select the best surgical treatment. However, these classifications require the inclusion of more criteria to define the selection of surgical treatment of tumors between 1 and 2 cm. Thus, along with the size of the tumor and the invasion of the mesoappendix, other factors such as vascular invasion, ki67 index, mitotic index and tumor location should be considered at the time of classification, for a better selection of the treatment and prognostic evaluation.

RESUMO A incidência de tumores no apêndice tem aumentado ao longo dos anos, principalmente encontrados no exame anatomopatológico dos apêndices operados por apendicite aguda. A incidência anual de tumores neuroendócrinos do apêndice, também designados por tumores carcinoides é de 0,15 a 0,16 por 100.000 pessoas. Em termos absolutos, a incidência destes tumores tem aumentado na última década em 70% a 133%. Os tumores carcinoides do apêndice ocorrem mais em mulheres e são encontrados em 0,3%‒0,9% dos apêndices removidos em apendicectomias. Têm origem nas células neuroendócrinas subepiteliais e apresentam um curso indolente, sendo os sintomas indistinguíveis de uma apendicite aguda. Existem duas classificações, a apresentada pela ENETS (European Neuroendocrin Tumor Society) e da AJCC (American Joint Committee on Cancer). Ambas as classificações utilizam o tamanho do tumor como preditor de carga tumoral. A classificação utilizada pela ENETS recorre ainda à invasão do mesoapêndice para selecionar o melhor tratamento cirúrgico. Contudo, estas classificações necessitam incluir mais critérios para definir a escolha do tratamento cirúrgico de tumores entre 1‒2 cm. Assim, para além do tamanho do tumor e da invasão do mesoapêndice, outros fatores como a invasão vascular, o ki67, o índice mitótico e a localização do tumor devem ser considerados no momento da classificação, para uma melhor seleção do tratamento e avaliação prognóstica.

Tumores neuroendocrinos primarios de colon y recto / Primary neuroendocrine tumors of the colon and rectum

Resumen Introducción La clasificación y el manejo de los tumores neuroendocrinos (TNEs) han cambiado drásticamente en la última década. Se realiza un análisis crítico del manejo de los TENs colorrectales primarios intervenidos en nuestro centro a la luz de la nueva clasificación. Material y Método Análisis retrospectivo de los resultados del tratamiento quirúrgico radical de este tipo de lesiones en un período de 15 años. Resultados Se trata de 10 pacientes, con un promedio de 56 años (extremos 48-76), 6 ubicados cercanos a la válvula ileocecal (VIC) que se presentaron con un cuadro de obstrucción intestinal incompleto y tres en el recto (2 pólipos) y un pólipo en colon sigmoides. La cirugía efectuada incluye cuatro resecciones anteriores y seis colectomías derechas (con resección de una metástasis hepática en 1 caso). La mediana de seguimiento fue de 78,3 meses (extremos 8-180), durante el cual dos pacientes fallecen por metástasis a distancia. Conclusión Los TNEs ubicados en el colon habitualmente se presentaron como grandes masas tumorales cercanos a la VIC, lo que proporcionalmente no ocurre con las lesiones del rectosigmoides que son diagnosticados más precozmente como pólipos o lesiones submucosas. Algunos tumores de bajo grado muestran un compromiso avanzado en la pared y/o los linfonodos regionales lo que justifica la resección radical y/o la quimioterapia adyuvante. A la luz de esta experiencia, es necesario complementar el grado del tumor OMS 2010 (Ki-67 y número de mitosis) con el estadio TNM para caracterizar adecuadamente los TNEs, lo que influye en el manejo multidisciplinario.

Background The nomenclature and staging classification of neuroendocrine tumors (NETs) has changed drastically in the past decade. Objective To do a critical analysis of management of colorectal NETs in our institution in the light of the new classification. Methods We retrospectively reviewed the records of consecutive patients operated on with radical intention due to a colorectal NET in the last 15 years. Results There were 10 patients, median age was 56 years (range 48-76), six of them located near the ileocecal valve, three in the rectum (2 of them polyps) and one polyp in the sigmoid colon. Surgical procedure included four anterior resections and six right colectomy (one with hepatic resection). The median follow up was 78.3 months (range 8-180). Two patients died due to metastatic disease. Conclusion NETs located near de ileocecal valve were diagnosed usually as a big tumor with obstructing symptoms, while NETs of the rectum and sigmoid colon more frequently were detected as polyps or submucosal lesions. Some low grade TENs may invade the colonic wall and/or have metastasis in the regional lymph nodes and those cases need radical resection and/or adjuvant therapy. Combine the grade (Ki-67 and number and/or number of mitosis) of 2010 WHO classification with TNM showed prognostic value for classification and staging colorectal NETs with important therapeutic implications.

Síndrome de Cushing ectópico: revisión de la literatura / Ectopic Cushing Syndrome: A literature review

El síndrome de Cushing es una enfermedad muy rara pero asociada a una morbimortalidad significativa. Se clasifica como dependiente de la hormona adrenocorticotrópica (ACTH: tumores hipofisiarios y ectópicos) o independiente de ACTH (lesiones de origen adrenal). En la mayoría de los casos, las lesiones responsables del síndrome corresponden a tumores hipofisiarios, seguida de lesiones adrenales y por último de tumores ectópicos (5-15% de todos los casos). En este artículo se hará una revisión de los aspectos epidemiológicos, clínicos, diagnósticos y terapéuticos más importantes de los tumores ectópicos causantes del síndrome de Cushing.

Cushing's syndrome is a very rare disease associated with significant morbidity and mortality. It is classified as adrenocorticotropic hormone (ACTH) dependent (Pituitary and ectopic tumors) or ACTH independent (lesions of adrenal origin). In most cases, pituitary tumors are responsible for the Cushing's syndrome, followed by adrenal lesions and finally by ectopic tumors (5-15% of all cases). This article describes the most important epidemiological, clinical, diagnostic and therapeutic aspects of ectopic tumors causing Cushing's syndrome.

[Metastatic bronchial carcinoid tumors]. / Les carcinoïdes bronchiques métastatiques.

Bronchial carcinoids are uncommon pulmonary neoplasms and represent 1 to 2 % of all lung tumors. In early stage of disease, the mainstay and only curative treatment is surgery. Bronchial carcinoids are generally regarded as low-grade carcinomas and metastatic dissemination is unusual. The management of the metastatic stage is not currently standardized due to a lack of relevant studies. As bronchial carcinoids and in particular their metastatic forms are rare, we apply treatment strategies that have been evaluated in gastrointestinal and pancreatic neuroendocrine tumors. However, bronchial carcinoids have their own characteristic. A specific therapeutic feature of these metastatic tumors is that they require a dual approach: both anti-secretory for the carcinoid syndrome, and anti-tumoral.

[Digestive neuroendocrine tumors]. / Tumeurs neuroendocrines digestives.

Digestive neuroendocrine tumors (NETs) are a group of rare tumors with increasing incidence. Pathological analysis is critical to establish the diagnosis and evaluate tumor grade that relies on differentiation and proliferation index. NETs are mostly diagnosed at an advanced stage because of late occurrence of nonspecific symptoms, and can be associated with hormone hypersecretion. Chromogranin A is the main biochemical marker of NETs. Extension workup relies on conventional imaging (CT-scan, MRI) and isotopic imaging including somatostatin-receptor scintigraphy, which should be soon replaced by positron-emitting scintigraphy. The main prognostic factors include tumor stage, metastatic volume, histological differentiation and grade. Hormonal syndromes and poorly differentiated tumors are the two therapeutic emergencies. The treatment of localized well-differentiated tumors relies on endoscopic or surgical resection depending on the location and aggressiveness. Surgical removal is the only potentially curative treatment of metastatic NETs but is rarely feasible and is associated with almost constant relapse. Other antitumor therapies include somatostatin analogs, systemic chemotherapy, liver trans-arterial chemo-embolization, targeted therapies and peptide-receptor radionuclide therapy. Management strategy relies on primary tumor location, tumor aggressiveness, metastatic volume and the presence of extra-hepatic metastases. It must take into account the risk of cumulated toxicity in patients whose survival is often prolonged.

Verrucous Carcinoma - Observations on 4 Cases.

Verrucous carcinoma (VC) is a rare well-differentiated squamous cell carcinoma with the clinical forms: oral florid papillomatosis, epithelioma cuniculatum, papilomatosis cutis and Buschke-Löwenstein tumor. We present four patients and the four clinical forms of CV. The diagnosis we held after clinical examination and histopathological examination of the balance sheet expansion. First described by Ackermanin the oral mucosal, today it has a reported incidence of 1-3 cases per million inhabitants. CV can involve both skin and mucous membranes. Etiopathogenesis is uncertain, but participation HPV is widely accepted. WHO recognizes the CV as a rare form of well-differentiated squamous cell carcinoma with slow and continues evolution, with the invasion of underlying tissues, frequent relapses and very low risk of metastasis. The elective therapy is surgical excision with safety oncological margins. Diagnosis involves corroboration of clinical data with histopathological appearance and evolutive behavior of the tumor. Given the increased risk for recurrence, the patient should be reviewed quarterly to finding healing.

Tumores carcinoides pulmonares tratados quirúrgicamente valor pronóstico de la 7ª estadificación TNM

Con el objetivo de evaluar el valor pronóstico de la 7a estadificación TNM se analizaron 43 mujeres (61%) y 28 hombres (39%) con diagnóstico de tumor carcinoide tratados quirúrgicamente desde enero/1975 hasta diciembre/2011. Mediana de edad: 38 años (13-67). Presentaron carcinoide típico (CT) 63 (89%) pacientes y 8 (11%) carcinoide atípico (CA). Mediana de seguimiento: 4 años (1 - 24 años). Los estadios correspondientes a CT fueron: IA = 33 (52%), IB = 10 (16%), IIA = 2 (3%), IIB = 2 (3%), IIIA = 12 (19%) y IIIB = 2 (3%); para los CA fueron: IA = 1 (12.5%), IIB = 1 (12.5%), IIIA = 2 (25%) y IIIB = 4 (50%). No hubo diferencia estadísticamente significativa en la supervivencia global a cinco años en el análisis estratificando por estadios (p = 0.689), ni analizando separadamente cada tipo histológico (CT p = 0.547; CA p = 0.592). El intervalo libre de enfermedad fue significativamente menor (CT: 3 años vs CA: 2 años, p = 0.000) y las recaídas más frecuentes en el grupo de carcinoides atípicos (CA: 50% vs CT: 2%, p = 0.000). Los pacientes con CT presentaron buena evolución aun en estadios avanzados, mientras que los que tuvieron CA presentaron menor tiempo de supervivencia e intervalo libre de enfermedad, y mayor frecuencia de recurrencia. El subtipo histológico resultó un factor significativo de pronóstico, mientras que la 7ª estadificación TNM no contribuyó en predecir la supervivencia en los tumores carcinoides.

We analyzed 43 women (61%) and 28 men (39%) surgically treated for carcinoid tumors from Jan/1975 to Dec/2011. Median age: 38 years (13-67). Typical carcinoid (TC) appeared in 63 (89%) patients, 8 (11%) suffered from atypical carcinoid (AC). Median follow-up: 4 years (1-24). TC stages were: IA = 33 (52%), IB = 10 (16%), IIA = 2 (3%), IIB = 2 (3%), IIIA = 12 (19%) and IIIB = 2 (3%); AC stages were: IA = 1 (12.5%), IIB = 1 (12.5%), IIIA = 2 (25%) and IIIB = 4 (50%). TNM classification did not show significant differences on 5-years survival period by stage (p = 0.689), even according to histological type (TC: p = 0.547; AC: p = 0.592). The disease-free survival rate was significantly lower (TC: 3 years vs. AC: 2 years, p = 0.000) and relapses were more frequent in AC (AC: 50% vs. TC: 2%, p = 0.000). The 7th TNM staging was not influential in estimating survival from carcinoid tumours in our population. The histological subtype was a better prognostic factor.

Caso inusual de síndrome de cushing

Objetivo: discutir las dificultades en el diagnóstico y manejo terapéutico de un caso poco frecuente de Síndrome de Cushing (SC). Caso Clínico: se reporta el caso de un paciente femenino, de 24 años, con hipercortisolismo y patrón bioquímico sugestivo de SC dependiente de corticotropina (ACTH). Estudios imagenológicos mostraron agrandamiento de la glándula hipófisis, extensión supraselar y una lesión lateral izquierda, sugestiva de microadenoma. Sometida a cirugía transesfenoidal en dos oportunidades, sin obtenerse la remisión del cuadro. Tomografía computarizada (TC) de tórax demostró la presencia de nódulo pulmonar único izquierdo, hipercaptante en el gammagrama con octreotido. Fue removido quirúrgicamente en forma satisfactoria produciéndose un abrupto descenso en los niveles de ACTH y cortisol pero nuevamente se incrementaron 24 horas después, permaneciendo elevados desde entonces. La inmunohistoquímica fue positiva para ACTH y cromogranina; el estudio anatomapatológico reportó tumor carcinoide típico sin invasión a ganglios linfáticos; sin embargo, la evolución clínica sugirió enfermedad residual. Se inició tratamiento con análogos de somatostatina (octreotido), el cual se ha mantenido por once meses, obteniéndose mejoría significativa del cuadro clínico y control parcial del hipercortisolismo. TC de tórax y gammagrama con octreotido recientemente practicados, revelaron pequeño foco, el cual correspondió a adenopatía mediastinal derecha. Se plantea la hipótesis de que el tumor producía simultáneamente ACTH y hormona liberadora de corticotropina (CRH, por sus siglas en inglés), explicándose de esta manera la hiperplasia hipofisaria. Conclusión: En pacientes con SC dependiente de ACTH hay que tener presente la existencia de incidentalomas que pueden confundir el diagnóstico. Considerar que la hiperplasia hipofisaria puede ser secundaria a una fuente ectópica productora de CRH y aunque en este caso no pudo realizarse inmunohistoquímica para CRH en las células tumorales, es posible suponer que dichas células secretaban conjuntamente CRH y ACTH lo cual explica la hiperplasia hipofisaria.

Objective: to discuss the diagnostic and therapeutic difficulties of a rare case of Cushing´s syndrome. Case Report: we describe a case of a 24-year-old female patient who developed symptoms compatible with hypercortisolism; the biochemical pattern was suggestive of ACTH dependent Cushin´s Syndrome. Imaging studies showed pituitary enlargement with suprasellar extension and a lesion suggestive microadenoma on the left side. Transsphenoidal surgery was performed in two occasions without remission. Subsequent explorations showed the presence of a single left lung nodule, positive to octreoscan. It was successfully operated and, a sharp decline on ACTH and cortisol levels was seen immediately after operation, increasing again 24 hours later and, remained elevated since then. Inmunohistochemestry studies were positive for ACTH and chromogranin and although the pathology was compatible with typical carcinoid, and no lymph node invasion was seen, the clinical evolution suggested the presence of residual disease. Treatment with somatostatin analogues (Octreotide) was started and has being maintained for eleven months, up to the present. A significant improvement of the clinical picture and partial control of the hypercortisolism has being obtained. Chest CT and octreoscan recently performed, revealed small focus, which corresponded to a right mediastinal adenopathy. We hypothesize that the tumor was simulta-neously producing ACTH and CRH, explaining in this way the pituitary hyperplasia. Conclusion: In patients with ACTH dependent Cushing the existence of incidentalomas could confuse the diagnosis and should be ruled out. Pituitary hyperplasia might be secondary to an ectopic CRH source. Although in our case immunohistochemostry for CRH was not performed, we assume that tumor cells secreted both, CRH and ACTH, explaining the pituitary hyperplasia.

Quantificação do ácido 5-hidroxi-indolacético urinário por técnica caseira do nitrosonaftol comparada com ensaio de nitrosonaftol em microcoluna de cromatografia e imunoensaio enzimático / Quantification of urinary 5-hydroxyindoleacetic acid by in-house nitrosonaphthol reaction compared with nitrosonaphthol micro column chromatography and enzyme-linked immunosorbent assay

The aim of this study was to compare the colorimetric "kit" and enzyme-linked immunosorbent assay (ELISA) methods to quantify urinary 5-hydroxyindoleacetic acid through the Goldenberg's technique, exploring the potential of replacing it. 24-hour urine samples were tested by Goldenberg's assay and compared with kits. The agreement was almost perfect for the comparison of Goldenberg's assay with both colorimetric kit, and with ELISA kit, considering ≤ 7.5 mg/24h normal cutoff value. Therefore, both "kits" would be good alternatives to Goldenberg's technique due to practicality and agreement between values...

O objetivo deste estudo foi comparar métodos por kit colorimétrico e por ensaio imunossorvente ligado à enzima (ELISA) para quantificar o ácido 5-hidroxi-indolacético urinário com a técnica de Goldenberg, explorando o potencial de substituí-la. Amostras de urina de 24 horas foram testadas pela técnica de Goldenberg e com os kits. A concordância foi quase perfeita, tanto para a comparação do ensaio de Goldenberg com o kit colorimétrico quanto para com o kit ELISA, considerando normal o valor de corte de ≤ 7.5 mg/24h. Portanto, ambos os kits seriam boa alternativa para a técnica de Goldenberg devido à praticidade e à concordância entre os valores...

Tumores carcinoides gastrointestinales, experiencia en Médica Sur: Gastrointestinal carcinoid tumors, experience in ''Médica Sur''

Objetivo: Evaluación de los casos de tumores carcinoides gastrointestinales en el Hospital y Fundación Clínica Médica Sur y confrontarlos con la literatura. Sede: Hospital y Fundación Clínica Médica Sur (centro de atención de tercer nivel). Diseño: Estudio retrospectivo, transversal, descriptivo, observacional. Análisis estadístico: Porcentaje como medida de resumen para variables cualitativas. Material y métodos: Se revisaron 19 casos de muestras de patología del Hospital y Fundación Clínica Médica Sur. Resultados: En este trabajo presentamos 19 casos de pacientes diagnosticados con tumores carcinoides gastrointestinales encontrados en toma de biopsias por endoscopia o piezas postquirúrgicas. Histológicamente se observaron células tumorales similares, con escaso citoplasma granular eosinófilo o núcleo redondeado moteado. Las variaciones de tamaño nuclear y celular fueron mínimas y las mitosis raras. El crecimiento celular fue predominantemente submucoso con extensión a capa muscular y serosa en algunos casos. Doce correspondieron al sexo femenino y siete, al masculino. El promedio de edad fue de 47 años. El órgano con más frecuencia de aparición fue el estómago y el apéndice cecal y los de menor frecuencia fueron el duodeno y el hígado. Conclusión: El sexo femenino predominó, constituyendo el 63% de los casos, la edad media para las mujeres fue de 49 años, coincidiendo con lo revisado en la literatura. Se encontró una incidencia aumentada en tumores de estómago y apéndice.

Objective: To evaluate the cases of gastrointestinal carcinoid tumors in the Hospital y Fundación Clínica Médica Sur, and to compare them with reports in the literature. Setting: Hospital y Fundación Clínica Médica Sur (third level health care center). Design: Retrospective, cross-sectional, descriptive, observational study. Statistical analysis: Percentage as summary measure for qualitative variables. Material and methods: We reviewed 19 cases of pathology samples from the Hospital y Fundación Clínica Médica Sur. Results: In this report we present 19 cases of patients diagnosed with gastrointestinal carcinoid tumors found in endoscopically taken biopsy samples or in postsurgical pieces. Histologically, similar tumor cells were observed with scarce granular eosinophilic cytoplasm or rounded spotted nucleus. Variations in nuclear and cellular size were minimal and mitoses were rare. Cell growth was predominantly submucous extending to the muscular and serosa layer in some cases. Twelve corresponded to women and seven to men. Average age was of 47 years. The organs most frequently affected were the stomach and the cecal appendix, the least frequent ones were the duodenum and the liver. Conclusion: Women predominated, constituting 63% of cases, mean age of women was of 49 years, coinciding with the literature. We found an increased incidence of tumors in the stomach and appendix.

Apudomas pancreáticos: um desafio para clínicos e cirurgiões / Pancreatic apudomas: a challenge for surgeons and physicians

OBJETIVO: O propósito do presente estudo é analisar as dificuldades quanto ao diagnóstico, avaliação prognóstica e conduta em sete pacientes portadores de tumores neuroendócrinos do pâncreas (apudomas), estudados na última década, comparando os resultados com aqueles discutidos na literatura. MÉTODO: A idade dos pacientes variou de 15 a 66 anos, com média de 38,4 anos. Todos foram submetidos a alguma forma de ressecção pancreática por tumores neuroendócrinos. Os exames histológicos foram feitos pelas técnicas tradicionais e por imuno-histoquímica. RESULTADOS: Três pacientes tiveram um diagnóstico inespecífico de tumor neuroendócrino; dois de vipoma e dois de gastrinoma. As síndromes não se manifestaram claramente, ainda que cada caso tenha tido um rótulo diagnóstico. Os exames por imuno-histoquímica demonstraram a presença de múltiplos hormônios, mas por falta de sintomas clínicos, as correlações ficaram prejudicadas na maioria dos casos, havendo correlação somente em caso de gastrinoma. Um paciente faleceu no pós-operatório; um sobreviveu sete anos e cinco estão vivos, com sobrevida variando entre três e cinco anos. CONCLUSÕES: Não houve uma manifestação sindrômica evidente, porém a sobrevida dos pacientes tem sido compatível com os dados de literatura.

BACKGROUND: The purpose of the present study is to analyze the difficulties concerning diagnostic, prognostic and clinical conduct of seven patients with pancreatic neuroendocrine tumors (APUDomas), evaluated over the past decade. METHODS: Patients varied in age from 15 to 66 years old, with a mean age of 38.4 years. All patients underwent some type of pancreatic resection as treatment of the neuroendocrine tumor. The histological sections were submitted to traditional and imunohistochemical examination. RESULTS: Three patients were diagnosed with unspecific neuroendocrine tumor, two with VIPoma and two with Gastrinoma. Syndromes were not clearly manifested, although every case had a differential diagnosis. Imunohistochemistry showed the presence of multiple hormones, but due to the lack of clinical symptoms, correlation was harmed in most cases, however one Gastrinoma showed typical clinical symptoms. One patient died in the post-operative period, one survived for 7 years and five are still alive, with a life expectancy varying from 3 to 5 years. CONCLUSIONS: We observed a lack of typical clinical syndromes for most cases, but life expectancy was compatible with the one described in the literature.