Tratamiento quirúrgico del carcinoma de Merkel facial avanzado. Presentación de un caso / Surgical treatment of advanced facial Merkel cell carcinoma. A case report

Introducción. El carcinoma de Merkel es un tumor maligno poco frecuente, que afecta principalmente a la población caucásica y cuya etiología guarda relación con el poliomavirus de las células de Merkel. Conlleva mal pronóstico, especialmente en estadios finales. Caso clínico. Se expone el caso de una paciente que presentaba un tumor primario facial de grandes dimensiones, con avanzado grado de extensión, afectación linfática cervical y metástasis parotídea derecha. Fue tratada mediante exéresis de la lesión primaria y cobertura con injerto de piel parcial, linfadenectomía cervical y parotidectomía ipsilateral. Resultados. Se logró mejoría importante en la calidad de vida de la paciente y sobrevida de al menos seis meses. Conclusión. Aunque no está claro el manejo óptimo del carcinoma de Merkel avanzado debido a su mal pronóstico, la cirugía favorece una mejoría en la calidad de vida del paciente y puede tener un papel clave en el manejo del carcinoma de Merkel en los estadios avanzados.

Introduction. Merkel carcinoma is a rare malignant tumor that mainly affects the Caucasian population and whose etiology is related to the Merkel cell polyomavirus. It has a poor prognosis, especially in the final stages. Clinical case. The case of a patient who presented a large primary facial tumor, with an advanced degree of extension, cervical lymphatic involvement and right parotid metastasis is described. She was treated surgically by excision of the primary lesion and coverage with partial skin graft, cervical lymphadenectomy, and ipsilateral parotidectomy. Results. A significant improvement was achieved in the patient's quality of life and survival of at least six months.Conclusion. Although the optimal management of advanced Merkel carcinoma is unclear due to its poor prognosis, surgery improves the patient's quality of life and it can play a key role in the management of Merkel carcinoma in advanced stages.

Carcinoma neuroendocrino de la piel: Carcinoma de células de Merkel. Revisión de la Literatura, a propósito de un caso / Neuroendocrine skin carcinoma: Merkel cell carcinoma. Review of literature, about a case

El carcinoma de células de Merkel, también llamado carcinoma neuroendocrino de la piel, es un tipo de cáncer de piel muy poco frecuente que generalmente aparece como un nódulo de color carne o rojo azulado, más frecuentemente en región facial, cabeza y cuello. El carcinoma de células de Merkel se desarrolla principalmente en personas mayores ya que la exposición al sol a largo plazo o un sistema inmunitario débil pueden aumentar el riesgo de desarrollarlo. Las células de Merkel se encuentran en la base de la capa más externa de la piel (epidermis) y están conectadas a las terminaciones nerviosas que son responsables del sentido del tacto. Tiende a crecer rápido y diseminarse a otras partes del cuerpo. Por tanto, las opciones de tratamiento para el carcinoma de células de Merkel dependen de si el cáncer se ha diseminado más allá de la piel

Merkel cell carcinoma, also called neuroendocrine skin of the skin, is a very rare type of skin cancer that generally appears as a bluish meat or red color nodule, more frequently in the facial, head and neck region. Merkel cell carcinoma develops mainly in older people since long -term exposure or a weak immune system can increase the risk of developing it. Merkel cells are at the base of the outermost layer of the skin (epidermis) and are connected to nerve endings that are responsible for the sense of touch. It tends to grow quickly and spread to other parts of the body. Therefore, the treatment options for Merkel cell carcinoma depend on whether cancer has spread beyond the skin

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.

O prognóstico dos diferentes subtipos de carcinomas de esôfago neuroendócrinos: um estudo de base populacional / The prognosis of the different esophageal neuroendocrine carcinoma subtypes: a population-based study

ABSTRACT Background Neuroendocrine neoplasms are extremely rare and account for 0.4% to 2% of all malignant esophageal neoplasms. The burden of the neuroendocrine histological type on the patients' prognosis and survival is poorly debated. This study aimed to compare the survival rates of primary neuroendocrine neoplasms compared with adenocarcinoma and squamous cell carcinoma of the esophagus. Methods This is a retrospective cohort from the Surveillance, Epidemiology, and End Results Program database. Overall survival and cancer-specific survival were evaluated with Kaplan-Meier curves and logrank tests. Proportional Cox regression models were used to evaluate variables related to overall survival. Results After eligibility criteria, 66,528 patients were selected. The mean follow-up was 22.6 months (SD 35.6). Adenocarcinoma was predominant (62%), followed by squamous cell carcinoma (36%). Large cell carcinoma, small cell carcinoma, and mixed adenoneuroendocrine carcinoma each account for less than 1% each. On the long-term overall survival analysis, esophageal adenocarcinoma showed a better prognosis than all the other histologic types (P-value for logrank test <0.001). With adenocarcinoma as a reference, HR was 1.32 for large cell carcinoma (95%CI 1.2 to 1.45) and 1.37 for small cell carcinoma (95%CI 1.23 to 1.53). The HR was 1.22 for squamous cell carcinoma (95%CI: 1.2 to 1.24); and 1.3 for adenoneuroendocrine carcinoma (95%CI 1.01 to 1.66). For multivariate Cox regression analysis, besides age and stage, the neuroendocrine subtypes large cell carcinoma and small cell carcinoma were considered independent prognostic variables. Conclusion In the esophagus, large cell carcinoma and small cell carcinoma show poorer long-term survival rates than squamous cell carcinoma and adenocarcinoma.

RESUMO Contexto As neoplasias neuroendócrinas são extremamente raras e representam 0,4% a 2% de todas as neoplasias malignas do esôfago. A determinação prognóstica e avaliação de sobrevida para o tipo histológico neuroendócrino é pouco debatida. Este estudo teve como objetivo comparar as taxas de sobrevida de neoplasias neuroendócrinas primárias comparadas com adenocarcinoma e carcinoma espinocelular de esôfago. Métodos Este é um estudo coorte retrospectivo do banco de dados do Surveillance, Epidemiology, and End Results Program. A sobrevida global e a sobrevida específica do câncer foram avaliadas com curvas de Kaplan-Meier e testes de logrank. Modelos de regressão de Cox proporcional foram utilizados para avaliar as variáveis relacionadas à sobrevida global. Resultados Após critérios de elegibilidade, foram selecionados 66,528 pacientes. O seguimento médio foi de 22,6 meses (DP 35,6). O adenocarcinoma foi predominante (62%), seguido pelo carcinoma espinocelular (36%). Carcinoma de grandes células, carcinoma de pequenas células e carcinoma adenoneuroendócrino misto representam menos de 1% cada. Na análise de sobrevida global, o adenocarcinoma de esôfago apresentou um prognóstico melhor do que todos os outros tipos histológicos (P valor para teste de logrank < 0,001). Com adenocarcinoma como referência, HR foi de 1,32 para carcinoma de grandes células (IC95% 1,2 a 1,45) e 1,37 para carcinoma de pequenas células (IC95% 1,23 a 1,53). O HR foi de 1,22 para carcinoma espinocelular (IC95%: 1,2 a 1,24); e 1,3 para carcinoma adenoneuroendócrino (IC95% 1,01 a 1,66). Para a análise multivariada da regressão de Cox, além da idade e do estadiamento, os subtipos neuroendócrinos carcinoma de grandes células e carcinoma de pequenas células foram considerados variáveis prognósticas independentes. Conclusão No esôfago, o carcinoma de grandes células e o carcinoma de pequenas células apresentam menores taxas de sobrevida a longo prazo do que o carcinoma espinocelular e o adenocarcinoma.

68Ga-DOTATATE PET/CT versus 111In-octreotide scintigraphy in patients with neuroendocrine tumors: a prospective study / PET/CT com 68Ga-DOTATATE versus cintilografia com 111In-octreotide em pacientes com tumores neuroendócrinos: estudo prospectivo

Abstract Objective: To compare 68Ga-DOTA-DPhe1,Tyr3-octreotate (68Ga-DOTATATE) positron-emission tomography/computed tomography (PET/CT) findings with those of conventional 111In-octreotide scintigraphy in patients with neuroendocrine tumors (NETs). Materials and Methods: This was a single-center prospective study including 41 patients (25 males; mean age, 55.4 years) with biopsy-proven NETs who underwent whole-body 111In-octreotide scintigraphy and whole-body 68Ga-DOTATATE PET/CT. The patients had been referred for tumor staging (34.1%), tumor restaging (61.0%), or response evaluation (4.9%). Images were compared in a patient-by-patient analysis to identify additional lesions, and we attempted to determine the impact that discordant findings had on treatment planning. Results: Compared with 111In-octreotide scintigraphy, 68Ga-DOTATATE PET/CT revealed more lesions, the additional lesions typically being in the liver or bowel. Changes in management owing to the additional information provided by 68Ga-DOTATATE PET/CT occurred in five patients (12.2%), including intermodal changes in three (7.3%) and intramodal changes in two (4.9%). In addition, 68Ga-DOTATATE PET/CT yielded incidental findings unrelated to the primary NET in three patients (7.3%): Hürthle cell carcinoma of the thyroid, bowel non-Hodgkin lymphoma, and a suspicious breast lesion. Conclusion: We conclude that 68Ga-DOTATATE PET/CT is superior to conventional 111In-octreotide scintigraphy for the management of NETs because of its ability to determine the extent of the disease more accurately, which, in some cases, translates to changes in the treatment plan.

RESUMO Objetivo: Comparar os achados da PET/CT com 68Ga-DOTATATE em relação aos da cintilografia com 111In-octreotide em pacientes com tumores neuroendócrinos (TNEs). Materiais e Métodos: Estudo prospectivo unicêntrico incluindo 41 pacientes (25 homens; média de idade: 55,4 anos) com TNEs comprovados por biópsia submetidos a cintilografia de corpo inteiro com 111In-octreotide e PET/CT com 68Ga-DOTATATE. Os pacientes incluídos foram encaminhados para estadiamento do tumor (34,1%), reestadiamento (61,0%) ou avaliação da resposta (4,9%). As imagens foram comparadas para identificar lesões adicionais e o impacto dos achados discordantes no planejamento terapêutico. Resultados: Na comparação com a cintilografia com 111In-octreotide, a PET/CT com 68Ga-DOTATATE revelou mais lesões, mais frequentemente localizadas no fígado e intestino. Mudanças no tratamento devidas às informações adicionais reveladas pela PET/ CT ocorreram em 5/41 pacientes (12,2%), incluindo mudanças intermodalidade em três casos (7,3%) e intramodalidade em dois casos (4,9%). A PET/CT também identificou achados incidentais não relacionados ao TNE em 3/41 pacientes (7,3%), incluindo um carcinoma de células de Hürthle da tireoide, um linfoma não Hodgkin de intestino e uma lesão mamária suspeita. Conclusão: A PET/CT com 68Ga-DOTATATE é superior à cintilografia convencional com 111In-octreotide para o manejo de pacientes com TNEs, em virtude da sua capacidade de detectar a extensão da doença com mais precisão, o que se traduz, em alguns casos, em alterações terapêuticas.

Crisis carcinoide como una causa poco frecuente de choque distributivo / Carcinoid crisis as a rare cause of distributive shock

Los tumores neuroendocrinos son neoplasias que suelen tener un comportamiento clínico maligno, son provenientes de células entero cromafines y/o células productoras de gastrina. Según su origen anatómico, se clasifican en tumores del intestino anterior (comprometen estómago, duodeno, pulmones y páncreas), intestino medio (parte distal del duodeno) e intestino posterior (colon transverso hasta el recto). El síndrome carcinoide, presente en la mitad de los casos al momento del diagnóstico, se caracteriza por desencadenar episodios de diarrea, taquicardia, hipotensión, rubor (por el desarrollo de telangiectasias), y según la gravedad, valvulopatías cardiacas. Por otro lado, la crisis carcinoide, una complicación infrecuente, está relacionada con episodios de choque, que cuando ocurren son consecuencia de la liberación en la circulación sistémica de aminas vasoactivas, posterior a un evento desencadenante. A continuación, se presenta el caso de un paciente masculino con antecedente de un tumor neuroendocrino de intestino delgado, quien luego de ser llevado a embolización de metástasis hepáticas, presentó una crisis carcinoide, y finalmente un choque distributivo refractario a tratamientos convencionales, incluyendo octreotide y vasopresores, que culminó con la muerte del paciente. Se realiza la discusión del caso clínico y la presentación de la literatura disponible, donde se describe la epidemiología, patogénesis, diagnóstico, clínica y tratamiento de esta entidad

Neuroendocrine tumors are neoplasms that usually have a malignant clinical behavior. They arise from enterochromaffin-like and/or gastrin-producing cells. According to their anatomical location they can be classified as foregut tumors (af- fecting stomach, duodenum, lungs and pancreas), midgut tumors (affecting distal portion of the duodenum) and hindgut tumors (affecting transverse colon to rectum). Carcinoid syndrome, occurring in half of the cases at the time of diagnosis, is characterized by episodes of diarrhea, tachycardia, hypotension, flushing (due to telangiectasia), and heart valve disease depending on their severity. On the other hand, the carcinoid crisis, a rare complication that is related to episodes of shock, occur as a consequence of the release of vasoactive amines into the systemic circulation after a triggering event. Here we describe a case of a male patient with a history of neuroendocrine neoplasm, who after embolization of hepatic metastatic lesions presented a carcinoid crisis, ending with a vasodilatory shock, refractory to conventional treatment including octreotide and vasopressors, which resulted in the death of the patient. A discussion of the clinical report and a review of the available literature are presented, including the epidemiology, pathogenesis, diagnosis, clinical manifestations and treatment of this entity

Neoplasias neuroendocrinas del intestino: serie de casos / Intestinal neuroendocrine tumors: case series

RESUMEN: Los tumores neuroendocrinos (TNE) intestinales representan el mayor porcentaje de este tipo de lesiones a nivel del aparato digestivo. El tratamiento de elección es la extirpación de la lesión primaria y sus linfonodos regionales. El objetivo de este estudio es reportar el resultado de pacientes portadores de TNE intestinales, tratados quirúrgicamente, en términos de morbilidad postoperatoria (MPO) y mortalidad. Serie de casos de pacientes con TNE intestinales intervenidos de forma consecutiva en Clínica RedSalud Mayor Temuco, entre 2006 y 2020. Las variables resultado fueron MPO y mortalidad. Otras variables de interés fueron localización y diámetro del tumor, tipo de cirugía y estancia hospitalaria. Se utilizó estadística descriptiva. Se trató a 11 pacientes (54,5 % mujeres), con una mediana de edad de 56 años. El 54,5 % de los tumores se localizó en yeyuno-íleon. La mediana del diámetro tumoral, tiempo quirúrgico y estancia hospitalaria fueron 2 cm, 75 min y 4 días, respectivamente. El tipo de resección más frecuente fue hemicolectomía derecha (63,6 %). La MPO fue 9,1 % (seroma en un paciente). No hubo reintervenciones ni mortalidad operatoria. Con una mediana de seguimiento de 18 meses, no se verificaron recurrencias. Los resultados reportados en relación a MPO y mortalidad, son adecuados en relación con la evidencia publicada.

SUMMARY: Intestinal neuroendocrine tumors (INETs) represent the highest percentage of this type of lesion in the digestive system. The treatment of choice is removal of the primary lesion and its regional lymph nodes. The aim of this study is to report the results of patients with INETs treated surgically, in terms of postoperative morbidity (POM) and mortality. Series of cases of patients with intestinal INETs operated consecutively at Clínica RedSalud Mayor Temuco, between 2006 and 2020. Result variables were POM and mortality. Other variables of interest were location and diameter of the tumor, type of surgery, and hospital stay. Descriptive statistics were used. Eleven patients (54.5 %) were treated, with a median age of 56 years. 54.5 % of the tumors were located in the jejunum-ileum. The median tumor diameter, surgical time, and hospital stay were 2 cm, 75 min, and 4 days, respectively. The most frequent type of resection was right hemicolectomy (63.6 %). The MPO was 9.1 % (seroma in one patient). There were no reoperations or operative mortality. With a median follow-up of 18 months, there were no recurrences. Reported results in relation to POM and mortality are adequate in relation to the published evidence.

Tumor neuroendocrino en recto simulando una neoplasia benigna: reporte de caso y revisión de a literatura / Neuroendocrine tumor in the rectum simulating a benign neoplasm: case report and literature review

Los tumores neuroendocrinos se definen como un grupo heterogéneo de neoplasias de origen epitelial, provenientes de células enterocromafines diseminadas por todo el organismo, y representan alrededor del 1 al 4 % de todas las neoplasias. Su mayor distribución se encuentra en el tracto gastrointestinal, donde se localiza el 75 % de los tumores neuroendocrinos, siendo los ubicados en el recto, el 27 % de todos los que afectan el tracto gastrointestinal. A propósito de esta revisión de tema, presentamos el caso de un paciente de 71 años de edad, que consultó por sangrado rectal rojo rutilante, sin otra sintomatología asociada, y se le diagnosticó un tumor neuroendocrino grado 1, que se comportaba como una lesión benigna del recto

Neuroendocrine tumors are defined as a heterogeneous group of neoplasms of epithelial origin from enterochromaffin cells disseminated throughout the body, and represent about 1% to 4% of all neoplasms. Its largest distribution is found in the gastrointestinal tract, where 75% of neuroendocrine tumors are located, being 27% of those in the rectum. We present the case of a 71-year-old patient who consulted for bright red blood per rectum, with no other associated symptoms, and was diagnosed with a grade 1 neuroendocrine tumor, which behaved as a benign lesion of the rectum

Carcinoma neuroendocrino moderadamente diferenciado (carcinoide atípico) de cavidad nasal: Reporte de un caso y revisión del tema / Moderately differentiated neuroendocrine carcinoma of the nasal cavity, a case report and literature review

Resumen Los carcinomas neuroendocrinos son tumores poco frecuentes en nariz y senos paranasales. Se consideran tumores primitivos y son los menos diferenciados del sistema neuroendocrino difuso. Se discute el caso de una paciente femenina de 49 años quien acude al servicio de otorrinolaringología en el Hospital Central Militar refiriendo masa en cavidad nasal izquierda de crecimiento progresivo en un periodo de 9 meses, así como epistaxis y obstrucción nasal izquierda. Mediante resonancia magnética y tomografía computada se observó tumoración de la cavidad nasal izquierda en su totalidad hasta nasofaringe, con captación heterogénea del medio de contraste. Se decide resección de tumoración mediante abordaje endoscópico (sinusotomía maxilar tipo III, etmoidectomía anterior y posterior izquierda, Draf esfenoidal tipo II izquierdo, Draf IIa del seno frontal izquierdo, así como septectomía posterior). El estudio histopatológico reportó un carcinoma neuroendocrino moderadamente diferenciado, por lo que se trató de forma conjunta con servicio de oncología médica. Este tipo de tumores son un reto diagnostico por la complejidad para diferenciarlos en un estudio histopatológico. La diferenciación efectiva de los mismos puede tener un impacto clínico, por lo que los avances en la intervención terapéutica podrían prolongar la supervivencia del paciente, mejorar la calidad de vida e incluso la cura.

Abstract Neuroendocrine carcinomas are rare tumors of the nose and sinuses. They are considered primitive tumors and are the least differentiated from the diffuse neuroendocrine system. We report a 49-year-old female patient who attends the otolaryngology service at the Central Military Hospital referring mass in the left nasal cavity with a progressive growth over a period of 9 months, including epistaxis, as well as left nasal obstruction. Magnetic Resonance Imaging and Computed Tomography imaging studies showed a tumor occupying the entirety of the left nasal cavity to the nasopharynx, with heterogeneous uptake of the contrast medium. Tumor resection is decided by endoscopic approach (maxillary sinusotomy type III, left anterior and posterior ethmoidectomy, left sphenoid Draf type II, left frontal Draf IIa as well as posterior septectomy). The pathology service reported a moderately differentiated neuroendocrine carcinoma. The treatment was decided joint session with the medical oncology service. These types of tumors are a diagnostic challenge because of the complexity to differentiate them in a histopathological study. Their effective differentiation can have a clinical impact, that's why the advances in therapeutic intervention could prolong patient survival, improve quality of life and even find a cure.

Características clínicas y sociodemográficas de una población adulta con tumores neuroendocrinos

Introducción: Los tumores neuroendocrinos representan un grupo de neoplasias de baja incidencia que derivan de células neuroendocrinas distribuidas en todo el cuerpo en especial sistema respiratorio y gastrointestinal. Objetivo: Determinar las características clínicas y sociodemográficas de una población adulta con padecimiento de tumores neuroendocrinos. Materiales y métodos: Estudio descriptivo transversal, se evaluaron 91 historias clínicas con diagnóstico de tumores neuroendocrinos confirmados por patología entre los años 2013 a 2020. Análisis realizado en Microsoft Excel 2013 y EpiInfo 7.2. Resultados: La media de edad fue 60 años, con predominio en hombres (57%). Los principales antecedentes fueron el tabaquismo (35%), hipertensión arterial (22%) y EPOC (9%). Los principales síntomas fueron el dolor abdominal (43%), pérdida de peso (31%) y tos (26%). Según el origen, fueron más frecuentes los de intestino anterior (75%), predominando los de tracto respiratorio (39,5%). En el 21,9%, el origen fue desconocido. Teniendo en cuenta la clasificación 2019 de la OMS, predominaron los carcinomas neuroendocrinos (56%), de los cuales el más frecuente fue el carcinoma de células pequeñas. Entre los bien diferenciados (44%), fueron más frecuentes los de bajo grado (58%) seguido grado intermedio (24%) y bajo grado (17%). Las metástasis se registraron en 37% de los casos con afectación principalmente hepática (49%), ganglios (21%) y sistema nervioso central (9%). La muerte se presentó en el 24% de los casos. Conclusiones: Los resultados del presente estudio concuerdan con lo reportado a nivel mundial, resaltando el predominio de los tumores de origen pulmonar, como también clínica semejante según los órganos afectados.

Introduction: Neuroendocrine tumors represent a group of low-incidence neoplasms derived from neuroendocrine cells distributed throughout the body, especially the respiratory and gastrointestinal systems. Objective: To determine the clinical and sociodemographic characteristics of an adult population with neuroendocrine tumors. Materials and methods: In a descriptive cross-sectional study, 91 medical records with a diagnosis of neuroendocrine tumors confirmed by pathology were evaluated between the years 2013 and 2020. Analysis carried out in Microsoft Excel 2013 and EpiInfo 7.2. Results: The mean age was 60 years, with a predominance in men (57%). The main antecedents were smoking (35%), arterial hypertension (22%), and COPD (9%). The main symptoms were abdominal pain (43%), weight loss (31%), and cough (26%). According to the origin, those of the foregut were more frequent (75%), predominantly those of the respiratory tract (39.5%). In 21.9%, the origin was unknown. Taking into account 2019 WHO classification, neuroendocrine carcinomas predominated (56%), of which the most frequent was small cell carcinoma. Among the well-differentiated (44%), low-grade (58%) followed by intermediate grade (24%) and low-grade (17%). Metastases were registered in 37% of the cases with mainly liver involvement (49%), lymph nodes (21%), and central nervous system (9%). Death occurred in 24% of cases. Conclusions: The results of the present study coincide with those reported worldwide, highlighting the predominance of tumors of pulmonary origin, as well as similar clinical symptoms according to the affected organs

Calcitonin negative neuroendocrine thyroid carcinoma: Case report and literature review

SUMMARY Medullary thyroid carcinoma (MTC) is a relatively rare neuroendocrine tumor that originates in the parafollicular C cells of the thyroid gland. It is characterized by the synthesis and secretion of calcitonin. Usually, serum calcitonin is used as part of the diagnosis and follow-up of these patients. Few cases of MTC with negative calcitonin have been reported worldwide, whose diagnosis is a clinical challenge.

El carcinoma medular de tiroides (MTC) es un tumor neuroendocrino relativamente raro que se origina en las células C para foliculares de la glándula tiroides. Se caracteriza por la síntesis y secreción de calcitonina. Por lo general, la calcitonina sérica se utiliza como parte del diagnóstico y seguimiento de estos pacientes. Se han notificado pocos casos de MTC con calcitonina negativa en todo el mundo, cuyo diagnóstico es un desafío clínico.

Sincronismo colorrectal: adenocarcinoma de colon ascendente y carcinoma neuroendocrino de células pequeñas de recto / Colorectal synchronism: ascending colon adenocarcinoma and small-cell neuroendocrine carcinoma of the rectum

RESUMEN El cáncer colorrectal (CCR) es el tercer cáncer más frecuente en el mundo y la segunda causa de muerte de origen neoplásico. El sincronismo en CCR es de aproximadamente 3-6%. El tracto gastrointestinal es el lugar más frecuente de asiento de neoplasias neuroendocrinas (NNE), y de estos los carcinomas neuroendocrinos (CNE) son poco frecuentes. El tratamiento es un desafío, debido a la agresividad de la neoplasia y la falta de protocolos bien establecidos. Todo esto conlleva a la necesidad de un enfoque multidisciplinario, sin embargo, en la mayoría de casos el pronóstico resulta no ser el mejor. Presentamos el caso de un varón de 83 años que acude a emergencia con historia de 3 meses de diarrea, dolor perianal, pérdida ponderal y hematoquezia. El estudio endoscópico evidenció dos neoplasias y el estudio histológico confirmó la presencia de CNE de células pequeñas de recto y adenocarcinoma de colon ascendente, recibió quimioterapia sistémica sin embargo evolucionó desfavorablemente falleciendo a las 3 semanas.

ABSTRACT Colorectal cancer (CRC) is the third most frequent cancer in the world and the second cause of death of neoplastic origin. Synchronism in CCR is approximately 3-6%. The gastrointestinal tract is the most frequent place where neuroendocrine neoplasms (NNE) settle and a special type of these neuroendocrine carcinomas (CNE) are rare. Treatment is challenging, due to the aggressiveness of the malignancy and the lack of well-established protocols. Therefore a multidisciplinary approach is needed, however, in most cases the result is not the best. We present the case of an 83-year-old man who has an emergency with a 3-month history of diarrhea, perianal pain, weight loss, and hematochezia. The endoscopic study shows evidence of two malignancies and the histological study confirms the presence of CNE in small cells at the rectum and adenocarcinoma in the ascending colon. He underwent systematic chemotherapy, however, he evolved unfavorably, dying after 3 weeks.

Hepatic neuroendocrine neoplasm: imaging patterns / Neoplasia neuroendócrina hepática: padrões de imagem

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors with distinct morphological and biological manifestations, the liver being the main organ affected by its metastases. However, primary hepatic involvement is quite rare. Hepatic NENs can have a variety of radiological presentation forms and can therefore mimic other lesions, making their diagnosis challenging. Nonetheless, certain imaging aspects allow NENs to be included among the main differential diagnoses of hepatic lesions and can guide the search for an extrahepatic primary site when the probable diagnosis is metastases.

As neoplasias neuroendócrinas (NNEs) são um grupo heterogêneo de tumores com manifestações morfológicas e biológicas distintas, sendo o fígado o principal órgão acometido por suas metástases. Por outro lado, o acometimento primário deste órgão é muito raro. Podem-se observar as mais diversas formas de apresentação radiológica das NNEs hepáticas primária e secundária e, em razão dessa variedade e por mimetizar outras lesões, o seu diagnóstico pode se revelar um desafio. No entanto, alguns desses aspectos permitem incluir as NNEs entre os principais diagnósticos diferenciais de lesões hepáticas e, nos casos de metástases, orientar na busca de um eventual sítio primário extra-hepático.

Carcinoid of the gallbladder in two dogs / Carcinoide de vesícula biliar em dois cães

ABSTRACT: A carcinoid is a rare neoplasm derived from neuroendocrine cells that may arise in the hepatobiliary system. This report described two cases of carcinoid of the gallbladder in dogs, with emphasis on the clinical, pathological and immunohistochemical aspects. Case 1 was a 10-year-old female Shih Tzu, with a history of prostration and occasional episodes of diarrhea and vomiting. Case 2 was a 10-year-old male Cocker Spaniel, with a history of diarrhea and abdominal pain. Abdominal ultrasonography suggested a neoplasm of the gallbladder in both cases. The dogs underwent cholecystectomy, and 10% formalin-fixed samples were sent for pathological examination. Histologically, a neoplastic proliferation of neuroendocrine cells was observed in the gallbladder submucosa of both cases. Immunohistochemical labeling for neuroendocrine antibodies, such as synaptophysin, neuron-specific enolase and chromogranin A, confirmed the diagnoses. Carcinoid of the gallbladder is a rare neoplasm in dogs, without specific clinical signs, but should be included in the differential diagnosis of lesions that affect this organ.

RESUMO: Carcinoide é um neoplasma raro derivado de células neuroendócrinas, que pode surgir no sistema hepatobiliar. Este relato descreve dois casos de carcinoide da vesícula biliar em cães, com ênfase nos aspectos clínicos, patológicos e imuno-histoquímicos. O caso 1 era uma fêmea, Shih Tzu de 10 anos de idade, com histórico de letargia e ocasionais episódios de diarreia e vômito. O caso 2 era um macho, Cocker Spaniel de 10 anos, que apresentava diarreia e dor abdominal. Através da ultrassonografia abdominal foi sugerida neoplasia na vesícula biliar em ambos os casos. Os caninos foram submetidos à colecistectomia e amostras em formol a 10%, seguidamente, foram enviadas para o laboratório de patologia. Histologicamente, observou-se proliferação neoplásica de células neuroendócrinas na submucosa da vesícula biliar nos dois casos. A marcação imuno-histoquímica para os anticorpos neuroendócrinos, como sinaptofisina, enolase específica de neurônios e cromogranina A confirmou o diagnóstico. Carcinoide de vesícula biliar é uma neoplasia rara em cães, sem sinais clínicos específicos, mas deve ser incluída no diagnóstico diferencial das lesões que afetam esse órgão.

Caracterización de pacientes con tumores neuroendocrinos en un hospital de referencia de alta complejidad / Characterization of patients with neuroendocrine tumors in a referral hospital

Introducción. Los tumores neuroendocrinos comprenden una amplia familia tumoral, siendo de mayor frecuencia aquellos localizados en el tracto gastrointestinal, los pulmones, el timo y el páncreas. Ocurren con poca frecuencia y cursan con un comportamiento biológico variable. El objetivo del presente estudio fue describir las características demográficas y clínicas de los pacientes con esta entidad en un hospital de alta complejidad. Métodos. Estudio descriptivo con revisión de historias clínicas correspondientes a pacientes con tumor neuroendocrino, cuya muestra histológica fue analizada en el Departamento de Patología del Hospital Pablo Tobón Uribe, Medellín, Colombia, entre 2010 y 2015. Se describen frecuencias de localización, grado de diferenciación y perfil de inmunohistoquímica. Resultados. Se revisaron 111 historias, de las que el 51,5 % correspondió a pacientes masculinos, con una mediana de edad al momento del diagnóstico de 48 años. Las comorbilidades más frecuentes fueron: hipertensión arterial (38,6 %), hipotiroidismo (15,8 %) y diabetes mellitus (11,9 %). El antecedente de neoplasia estuvo presente en el 13,9 % de los casos. Un 59,4 % de las muestras correspondieron a tumores primarios, el 34,8 % estaban localizados en el páncreas. El hígado fue el órgano más comprometido por metástasis (73,3 %). De los tumores neuroendocrinos, el 27 % correspondió a tumores grado 1 del tracto gastrointestinal o del páncreas, el 36 % a grado 2 y el 27,9 % a grado 3. El 3,6 % correspondió a tumores pulmonares de grado bajo o intermedio y el 5,4 % a tumores pulmonares de alto grado. Los marcadores tumorales con mayor positividad fueron sinaptofisina (97,2 %), citoqueratinas AE1/AE3 (95 %), CD56 (91,3 %) y cromogranina (87,8 %). Discusión. Los tumores neuroendocrinos tienen características clínicas e histopatológicas diversas. Conocer las características de los pacientes afectados permite una aproximación de la epidemiología local aplicable a futuras investigaciones

Introduction. Neuroendocrine tumors comprise a broad family of tumors, the most common being those located in the gastrointestinal tract, lungs, thymus, and pancreas. They occur infrequently and have a variable biological behavior. The objective of this study was to describe the demographic and clinical characteristics of patients with this entity in a highly complex hospital.Methods. Descriptive study with review of medical records corresponding to patients with neuroendocrine tu-mors, whose histological sample was analyzed in the Pathology Department of the Pablo Tobón Uribe Hospital in Medellín between 2010 and 2015. Frequencies of location, degree of differentiation and immune-histochemistry profile are described.Results. One hundred eleven histories were reviewed, of which 51.5% corresponded to male patients, with a median age at diagnosis of 48 years. The most frequent comorbidities were arterial hypertension (38.6%), hypothyroidism (15.8%) and diabetes mellitus (11.9%). Medical history of neoplasia was present in 13.9% of the cases. 59.4% of the samples corresponded to primary tumors, 34.8% were located in the pancreas. The liver was the organ most compromised by metastasis (73.3%). Of the neuroendocrine tumors, 27% corresponded to grade 1 tumors of the gastrointestinal tract or pancreas, 36% to grade 2 and 27.9% to grade 3; 3.6% corresponded to low or intermediate grade lung tumors and 5.4% to high-grade lung tumors. The tumor markers with the highest positivity were synaptophysin (97.2%), cytokeratins AE1/AE3 (95%), CD56 (91.3%) and chromogranin (87.8%).Discusion. Neuroendocrine tumors have diverse clinical and histopathologic features. Knowing the characteristics of affected patients allows an approximation of local epidemiology applicable to future research

The role of conventional echoendoscopy (eus) in therapeutic decisions in patients with neuroendocrine gastrointestinal tumors / O papel da ecoendoscopia convencional nas decisões terapêuticas em pacientes com tumores neuroendócrinos gastrointestinais

ABSTRACT Background: Gastrointestinal neuroendocrine tumors are rare, usually presented as subepithelial or polypoid tumors. Accurate diagnosis and indication of the type of resection are still challenging. Aim: To determine the effectiveness of echoendoscopy in determining the depth of the lesions (T) identified by endoscopy in order to evaluate surgical and/or endoscopic indication, and to evaluate the results of endoscopic removal in the medium term. Methods: Twenty-seven patients were included, all of whom underwent echoendoscopy for TN tumor staging and the evaluation of possible endoscopic resection. The parameters were: lesion size, origin layer, depth of involvement and identified perilesional adenopathies. The inclusion criteria for endoscopic resection were: 1) high surgical risk; 2) those with NET <2 cm; 3) absence of impairment of the muscle itself; and 4) absence of perilesional adenopathies in echoendoscopy and in others without distant metastases. Exclusion criteria were TNE> 2 cm; those with infiltration of the muscle itself; with perilesional adenopathies and distant metastases. The techniques used were: resection with polypectomy loop; mucosectomy with saline injection; and mucosectomy after ligation with an elastic band. The anatomopathological study of the specimens included evaluation of the margins and immunohistochemistry (chromogranin, synaptophysin and Ki 67) to characterize the tumor. Follow-up was done at 1, 6 and 12 months. Results: Resections with polypectomy loop were performed in 15 patients; mucosectomy in five; mucosectomy and ligation with elastic band in three and the remaining four were referred for surgery. The anatomopathological specimens and immunohistochemical analyzes showed positive chromogranin and synaptophysin, while Ki 67 was less than 5% among all cases. The medium-term follow-up revealed three recurrences. The average size of tumors in the stomach was 7.6 mm and in the duodenum 7.2 mm. Well-demarcated, hypoechoic, homogeneous lesions occurred in 75%; mucous layer in 80%; and the deep and submucosal mucosa in 70%. Conclusions: Echoendoscopy proved to be a good method for the study of subepithelial lesions, being able to identify the layer affected by the neoplasm, degree of invasion, echogenicity, heterogeneity, size of the lesion and perilesional lymph node involvement and better indicate the treatment option.

RESUMO Racional: Tumores neuroendócrinos gastrointestinais são raros geralmente apresentados como tumores subepiteliais ou polipoides. O diagnóstico preciso e a indicação do tipo de ressecção ainda são desafiadores. Objetivo: Determinar a eficácia da ecoendoscopia em determinar a profundidade das lesões (T) identificadas pela endoscopia com objetivo de avaliar indicação cirúrgica e/ou endoscópica, e avaliar os resultados da remoção endoscópica em seguimento em médio prazo. Métodos: Foram incluídos 27 pacientes todos submetidos à ecoendoscopia para estadiamento tumoral TN e à avaliação de possível ressecção endoscópica. Os parâmetros estudados foram: tamanho da lesão, camada de origem, profundidade do acometimento e adenopatias perilesionais identificadas. Os critérios de inclusão para ressecção endoscópica foram: 1) risco cirúrgico elevado; 2) aqueles com TNE <2 cm; 3) ausência de comprometimento da muscular própria; e 4) ausência de adenopatias perilesionais na ecoendoscopia e em outros sem metástases à distância. Os critérios de exclusão foram TNE >2 cm; os com infiltração da muscular própria; com adenopatias perilesionais e metástases à distância. As técnicas utilizadas foram: ressecção com alça de polipectomia; mucosectomia com injeção de solução salina; e mucosectomia após a ligadura com banda elástica. O estudo anatomopatológico dos espécimes incluiu avaliação das margens e imunoistoquímica (cromogranina, sinaptofisina e Ki 67) para caracterizar o tumor. O seguimento foi feito com 1, 6 e 12 meses. Resultados: Ressecções com alça de polipectomia foram realizadas em 15 pacientes; mucosectomia em cinco; mucosectomia e ligadura com banda elástica em três e os quatro restantes foram encaminhados para cirurgia. O anatomopatológico dos espécimes e as análises imunoistoquímicas mostraram cromogranina e sinaptofisina positivas, enquanto que o Ki 67 foi menor que 5% dentre todos os casos. O seguimento em médio prazo revelou três recidivas. A média de tamanho dos tumores no estômago foi de 7,6 mm e no duodeno 7,2 mm. As lesões bem demarcadas, hipoecóicas, homogêneas ocorreram em 75%; da camada mucosa em 80%; e da mucosa profunda e submucosa em 70%. Conclusões: A ecoendoscopia mostrou ser bom método para o estudo de lesões subepiteliais podendo identificar a camada acometida pela neoplasia, grau de invasão, ecogeneicidade, heterogeneidade, tamanho da lesão e acometimento linfonodal perilesional e melhor indicar a opção de tratamento.

Distribución Topográfica y Manejo de Tumores Neuroendocrinos del Tubo Digestivo / Topographic Distribution and Management of Neuroendocrine Tumors of the Digestive Tube

Introducción: Los tumores neuroendocrinos (TNE) son un grupo de neoplasias que se originan a partir de células enterocromafínicas, especialmente ubicadas en el tubo digestivo. El objetivo del presente estudio es escribir la distribución topográfica, el manejo multidisciplinario y diagnóstico patológico según la OMS de los tumores neuroendocrinos del tubo digestivo. Métodos: El presente es un estudio descriptivo, retrospectivo de los casos con diagnóstico anatomopatológico confirmado de tumor neuroendocrino localizados en el tubo digestivo entre enero del 2011 a diciembre del 2018 en el Instituto Oncológico Nacional del Ecuador- SOLCA de Guayaquil. Se describe topografía y tipo de tratamiento establecido con frecuencias y porcentajes. Resultados: Ingresaron al estudio 21 casos. La localización más frecuente fue el apéndice cecal n = 8 (38 %), en estómago n=4 (19 %), intestino delgado n=3 (14 %). El diagnóstico patológico en estadio G1 (65 %); G2 (24%) y G3 (12%). La primera línea de tratamiento fue la cirugía con intención curativa n=19 (90.5 %) y tratamiento endoscópico n=2 (9.5 %). Los pacientes sometidos a cirugía, n=16/19; (84 %) obtuvieron niveles de resección 0 (R0) y permanecieron en observación clínica, los demás sujetos en el estudio recibieron tratamiento adyuvante con somatostatina sola n=1 (4.8 %) o combinación de somatostatina y radioterapia n=2 (9.5 %). Conclusión: El diagnóstico de tumor neuroendocrino de tubo digestivo es una etiología oncológica poco frecuente. El tratamiento quirúrgico en esta serie de casos está enfocada en una acción curativa de tipo quirúrgico.

Introduction: Neuroendocrine tumors (NETs) are a group of neoplasms that originate from enterochromaffin cells, especially located in the digestive tract. The objective of the present study is to write the topographic distribution, the multidisciplinary management and pathological diagnosis according to the WHO of the neuroendocrine tumors of the digestive tract. Methods: This is a descriptive, retrospective study of the cases with a confirmed anatomopathological diagnosis of neuroendocrine tumor located in the digestive tract between January 2011 to December 2018 at the National Oncology Institute of Ecuador- SOLCA of Guayaquil. The topography and type of treatment established with frequencies and percentages are described. Results: 21 cases were entered into the study. The most frequent location was the cecal appendix n = 8 (38%), stomach n = 4 (19%), small intestine n = 3 (14%). The pathological diagnosis in stage G1 (65%); G2 (24%) and G3 (12%). The first line of treatment was surgery with curative intent n = 19 (90.5%) and endoscopic treatment n = 2 (9.5%). Patients undergoing surgery, n = 16/19; (84%) obtained resection levels 0 (R0) and remained under clinical observation, the other subjects in the study received adjuvant treatment with somatostatin alone n = 1 (4.8%) or combination of somatostatin and radiotherapy n = 2 (9.5%). Conclusion: The diagnosis of neuroendocrine tumor of the digestive tract is a rare oncological etiology. The surgical treatment in this series of cases is focused on a surgical action of a surgical type.

Tumor Neuroendocrino del Ciego: Reporte de Caso / Ciego Neuroendocrine Tumor: Case Report

El carcinoma neuroendocrino (Neuroendocrine carcinoma ­ NEC) del colon es un tumor raro y muy agresivo, generalmente diagnosticado de forma incidental y durante la resolución de complicaciones como perforación u obstrucción. Se presenta el caso de un paciente masculino de 58 años quien fue intervenido quirúrgicamente por presentar cuadro de peritonitis localizada secundario a un tumor neuroendocrino de ciego perforado. Se realizó hemicolectomía derecha con resección ganglionar D2 y anastomosis primaria íleo ­ transversa. El examen histopatológico describió un carcinoma neuroendocrino bien diferenciado de células pequeñas, sin infltración vascular ni neuronal. Al momento el paciente se encuentra en espera de quimioterapia sin necesidad revisión quirúrgica secundaria

Neuroendocrine carcinoma (NEC) of the colon is a rare and very aggressive tumor, generally diagnosticated in an incidental way and during resolution of complications such as perforation or intestinal obstruction. The case of a 58-year-old male patient who was surgically intervened for presenting localized peritonitis pedhora scan to a perforated blind neuroendocrine tumor. Right hemicolectomy whit ganglion D2 resection and ileo ­ transverse primary anastomosis was performed. Histopathological examination described a well-differentiated neuroendocrine carcinoma of small cells, with no vascular or neuronal infltration. Now the patient is awaiting chemotherapy without the need for secondary surgical review

Carcinoma neuroendocrino de mama con diferenciación pulmonar. Reporte de un caso / Neuroendocrine breast carcinoma with pulmonary differentiation. A case report

Resumen ANTECEDENTES: Los carcinomas neuroendocrinos de mama son neoplasias malignas poco frecuentes, con incidencia de 2%. El diagnóstico es difícil de establecer debido a sus características clínicas y morfológicas inespecíficas. La inmunohistoquímica es un estudio útil para identificar marcadores neuroendocrinos. Es importante descartar los casos de metástasis relacionados con algún origen primario distinto, para de esta forma prescribir el tratamiento adecuado. CASO CLÍNICO: Paciente de 37 años, procedente de otra institución con diagnóstico sugerente de carcinoma de alto grado de células medianas, con diferenciación neuroendocrina, afectación de los tres niveles de Berg y adenopatías supraclaviculares patológicas. Después de los estudios de imagen y determinación de marcadores tumorales específicos de la enfermedad se estableció el diagnóstico de carcinoma neuroendocrino de mama. Se indicó tratamiento neoadyuvante con cisplastino y etoposido, con el que se observó reacción parcial de 50%. Posteriormente se efectuó la mastectomía radical, con vaciamiento de los tres niveles de Berg y extirpación de los ganglios supraclaviculares, sin complicaciones aparentes. En la actualidad, la paciente permanece estable, en tratamiento con quimioterapia coadyuvante. CONCLUSIÓN: Lo importante en estos casos es determinar los marcadores tumorales asociados con los carcinomas neuroendocrinos de mama y así poder establecer el diagnóstico certero e implementar el tratamiento adecuado, que puede variar en función de su origen. Hasta la fecha no existe un consenso de tratamiento, por lo que cada caso debe individualizarse. Se requieren estudios adicionales para ampliar el conocimiento de esta variante tumoral.

Abstract BACKDROUND: Neuroendocrine carcinomas are infrequent breast neoplasms representing less than 2% of breast neoplasms. The diagnosis is difficult, since their clinical and morphological characteristics do not help to differentiate them from other types of breast neoplasms. The immunohistochemistry that will determine the characterization of the tumor by the presence of neuroendocrine markers. It is important to rule out a cases of metastasis related to a different primary origin, in order to prescribe the appropriate treatment for the patient. CLINICAL CASE: A 37-year-old patient from another institution with a diagnosis suggestive of high-grade carcinoma of medium cells, with neuroendocrine differentiation, involvement of the 3 levels of Berg and pathological supraclavicular adenopathies. After performing the imaging studies and determining the specific tumor markers of the disease, the diagnosis of breast neuroendocrine carcinoma. Neoadjuvant treatment with cisplastin and etoposide is indicated, with the same partial reaction of 50%. Subsequently, the radical mastectomy was performed, with the emptying of the 3 levels of Berg and the removal of the supraclavicular nodes without apparent complications. Currently remains stable in the treatment with adjuvant chemotherapy. CONCLUSIONS: It is important to determine the tumor markers associated with breast neuroendocrine carcinomas, with the aim of establishing accurate diagnosis and implementing the appropriate treatment, which may vary depending on its origin. To date there is no consensus of treatment, so each case must be individualized. Additional studies are required to expand the knowledge of this tumor variant.