State of the art of cervical cancer treatment in rare histologies.

The objective of this review is to summarize the current scientific evidence to formulate clinical recommendations regarding the classification, diagnostic approach, and treatment of rare histological subtypes of cervical cancer; neuroendocrine carcinoma, gastric-type mucinous adenocarcinoma, and glassy cell adenocarcinoma. These histological subtypes are generally characterized by their low frequency, aggressive biological behavior, certain chemoradioresistance, and consequently, high recurrence rates with a deleterious impact on survival. Molecular studies have identified several associated mutations in neuroendocrine carcinoma (PIK3CA, MYC, TP53, PTEN, ARID1A, KRAS, BRCA2) and gastric-type adenocarcinoma (KRAS, ARID1A, PTEN) that may serve as molecular targets. While adenocarcinomas are typically treated and classified based on squamous histology across early, locally advanced, and advanced stages, the treatment strategies for neuroendocrine carcinomas in early stages or locally advanced cases differ, particularly in the sequencing of administering chemotherapy, chemoradiotherapy, or surgery. The chemotherapy regimen is based on etoposide plus cisplatin (EP). Unlike squamous cell carcinomas, immune checkpoint inhibitors are yet to establish a standard role in the treatment of recurrent neuroendocrine carcinomas due to the absence of clinical trials. Regarding glassy cell adenocarcinomas and gastric-type adenocarcinoma, the potential use of immunotherapy in advanced stages/disease requires further evaluation through international collaborations, given the limited number of cases.

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 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.

Esophageal Neuroendocrine Carcinoma Presenting After Definitive Chemoradiation of Squamous Cell Carcinoma in the Same Location.

Esophageal neuroendocrine carcinoma is very rare and highly aggressive. An 85-year-old man with a history of esophageal squamous cell carcinoma in remission presented 4 years after definitive chemoradiation with new-onset dysphagia. Endoscopy with biopsy revealed high-grade malignancy consistent with neuroendocrine carcinoma. Treatment options were limited to chemotherapy because of his metastatic disease, and he unfortunately died 14 months after diagnosis. The occurrence of esophageal neuroendocrine carcinoma in a site of prior squamous cell carcinoma is very uncommon, and this likely represents a case of radiation-induced malignancy. Therefore, when undergoing radiotherapy, patients and providers should discuss the possibility of this life-threatening complication.

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.

Clinicopathological and molecular profile of grade 3 gastroenteropancreatic neuroendocrine neoplasms.

The 2019 Word Health Organization (WHO) subclassified grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) into neuroendocrine carcinoma (NEC) or tumours (G3 NET) based on morphology and proliferation. Yet, few data exist on molecular profiles for G3 NEN. We compared clinicopathological and molecular characteristics of these two groups. We retrospectively reviewed consecutive G3 GEP NEN patients and had their tumour tissues reviewed, reclassified as per the WHO 2019, and analyzed by a next-generation sequencing (NGS) panel. Between 2000 and 2019, 43 patients had pathology revision: 29 (67%) were NEC and 14 (33%) were G3 NET, with a 23% change in diagnosis. Median overal survival for G3 NET and NEC patients was 55.6 and 11.9 months, respectively (hazard ratio = 2.78 [95% confidence interval = 1.09-7.11], p = .042), which was confirmed by an adjusted analysis (hazard ratio = 2.90 NEC vs. G3 NET; p = .03). NGS was performed in 32 cases: 21 NEC and 11 G3 NET. Mutations in RB1 and PTEN were exclusively encountered in NEC. Median tumour mutational burden was 5 (0-67) mutations per megabase in NEC and 4.5 (0-9) among G3 NET. Microsatellite instability was found in 3 (14.3%) NEC cases. In conclusion, pathology revision is essential to estimate prognosis and therapeutic plan. G3 GEP NEN generally harbour low tumor mutation burden and fewer actionable mutations, but 14% of NEC cases were microsatellite unstable and could benefit from immune checkpoint inhibitors.

Oral and Maxillofacial Neuroendocrine Carcinoma: A Systematic Review.

The aim of the present study was to integrate the available data published in the literature on oral and maxillofacial neuroendocrine carcinomas concerning the demographic, clinical and histopathological features of this condition. An electronic search with no publication date restriction was undertaken in April 2021 in four databases. Eligibility criteria included reports published in English having enough data to confirm a definite diagnosis, always showing a neuroendocrine marker. Cases originating in the oropharynx, including base of the tongue and tonsils, were excluded. Outcomes were evaluated by the Kaplan-Meier method along with Cox regression. Twenty-five articles (29 cases) from nine different countries were detected. Mean patient age was 56.3 (± 17.5) years, with a slight male predilection. Symptomatology was present in 72.2% of informed cases. Regarding clinical presentation, a non-ulcerated nodule located in the gingiva with a mean size of 3.4 (± 2.0) cm was most frequently reported. Concomitant metastasis was identified in seven individuals. Histopathologically, most neoplasms were of the small cell type, and immunohistochemistry for both epithelial and neuroendocrine differentiation was used in 65.5% cases. Radical surgery was the treatment of choice in almost all cases, with or without adjuvant therapy. Mean follow-up was 20.5 (± 21.2) months, and only four patients developed recurrences. Eleven (44.0%) individuals died due to the disease. Ulcerated lesions were a prognostic factor. This study provides knowledge that can assist surgeons, oncologists, and oral and maxillofacial pathologists with the diagnosis and management of neuroendocrine carcinomas. Our findings demonstrated that the long-term prognosis of this lesion continues to be poor.

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.

Gastric Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: A Western Center Case Series.

BACKGROUND: Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) represent a rare tumor composed of adenocarcinoma and neuroendocrine carcinoma components. This study reports a case series of gastric MiNEN and discusses issues related to its diagnosis, management, and outcomes. METHODS: We retrospectively analyzed data from patients with gastric MiNEN who underwent surgical resection at our service from 2009 to 2020. Patients with gastric adenocarcinoma served as a comparison group. Clinical, pathologic, and surgical characteristics were compared. RESULTS: During the selected period, 5 gastric MiNEN patients and 597 patients with gastric adenocarcinoma were included. Among the clinical variables, age, sex, BMI, and laboratory exams were similar between the two groups. Only ASA classification was different (p = 0.015). Pathological variables such as tumor size, lymphovascular invasion, number of retrieved lymph nodes, and pTNM staging were also similar between both groups. Lastly, early surgical outcomes and long-term survival did not differ between gastric MiNEN and adenocarcinoma patients. CONCLUSION: A MiNEN is a rare tumor that represents less than 1% of GC patients undergoing curative treatment, and demonstrated clinicopathological characteristics and outcomes similar to gastric adenocarcinoma.

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

A fat containing combined neuroendocrine carcinoma and hepatocellular carcinoma in the liver: A case report.

A 79-year-old man was admitted to our hospital because of increased hepatobiliary enzyme levels. Dynamic computed tomography and magnetic resonance imaging showed a liver tumor measuring 60mm containing fat foci at the cranial aspect of the tumor. We diagnosed the patient with hypovascular hepatocellular carcinoma (HCC) and fat deposition, and performed a caudate lobe resection. Pathology examination revealed two intermingled components: moderately differentiated HCC with fat deposition and neuroendocrine carcinoma (NEC). Primary combined NEC and HCC is extremely rare. To our knowledge, this is the first report of combined NEC and HCC including a fat component. HCC is the most common primary hepatic malignancy with fat. HCC might include fat, even if HCC coexists with another type of cancer. The imaging characteristics of and HCC with another type of cancer vary depending on the amount of each component. We should not simply diagnose such tumors as HCC, but think about the possibilities of HCC with another type of cancer, because there is a fat component.

Clinical, histopathologic, and immunohistochemical features of 13 cases of canine gallbladder neuroendocrine carcinoma.

In this retrospective descriptive study, we characterized the clinical, histologic, and immunohistochemical features of 13 cases of canine gallbladder neuroendocrine carcinoma (GB-NEC). Immunohistochemical stains for neuroendocrine (neuron-specific enolase [NSE], chromogranin A, synaptophysin) and gastrin markers were evaluated, and clinicopathologic and follow-up data were obtained for all cases. The average age at diagnosis was 8.9 y, and breeds included 6 Boston Terriers, 2 Bichon Frise, 1 Poodle, 1 English Bulldog, 1 French Bulldog, and 2 mixed-breed dogs. Boston Terriers were overrepresented in this cohort, and therefore a breed predilection is possible. Most dogs were presented with emesis and elevated liver enzyme activities: 13 of 13 had elevated alanine aminotransferase and alkaline phosphatase activities; 8 of 13 had elevated aspartate aminotransferase activity; 7 of 13 had elevated gamma-glutamyl transferase activity. Abdominal ultrasound and/or exploratory surgery revealed a gallbladder mass. All neoplasms had similar histologic features and positive immunoreactivity for NSE, chromogranin A, synaptophysin, and gastrin. Vascular invasion was noted in 8 of 13 neoplasms, and metastasis was present in 6 of 13 cases (4 hepatic and 2 pulmonary metastases). The median survival time was 3.7 y in patients who died; 5 of 8 deaths were directly attributed to the GB-NEC, 3 of which had metastatic spread. GB-NECs have the potential to metastasize; however, surgical excision may be curative in a subset of dogs.

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

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.(AU)

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.(AU)

Neuroendocrine Carcinomas of the Canine Mammary Gland: Histopathological and Immunohistochemical Characteristics.

Invasive mammary carcinomas with neuroendocrine differentiation are rare in women and were reported only once in female dogs. For the present study, ten cases of solid mammary carcinoma positive for chromogramin A in immunohistochemistry were selected. Histopathological characteristics of these tumors were described and immunohistochemical evaluation was performed with chromogranin A, synaptophysin, CD56, NSE, PGP 9.5, pancitokeratin, Ki67, estrogen receptor (ER), and progesterone receptor (PR). The average animal age was 13.2 years old and the average tumor size was 4.8 cm. In total, 70% of the neoplasms were classified as grade III and 30% as grade II by the Nottingham histological grade system. High mitotic index was observed with a mean of 27.5 mitoses in 10 high magnification fields. Only one case showed typical carcinoid tumor characteristics. In addition, vascular invasion was shown in 3 tumors. All carcinomas were positive for chromogran A, while only two cases were reactive to synaptophysin. For PGP 9.2, NSE and CD56, we observed positivity of 100, 90, and 70%, respectively, in the samples, being that no tumor was positive for all the neuroendocrine markers. All neoplasms showed ER and PR in at least 10% of neoplastic cells, while Ki67 varied from 29 to 95%, with mean mitotic index of 67%. Four of the ten animals died within 1 year of the tumor diagnosis. Neuroendocrine neoplasms occur in the canine mammary gland and are propably underdiagnosed. This is due to their non-specific morphological characteristics and the low use of neuroendocrine immunohistochemistric markers the diagnostic routine. More studies are necessary to determine the prognosis of this new histological type.

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

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.

Carcinoma neuroendocrino rectal: Una neoplasia infrecuente / Neuroendocrine rectal carcinoma: An infrequent tumor

Resumen El carcinoma neuroendocrino (CNE) es una entidad infrecuente encontrándose usualmente al diagnóstico en estadios avanzados. El tratamiento suele ser combinado, quirúrgico junto a quimiorradioterapia. Presentamos el caso de una mujer de 73 años estudiada por síndrome constitucional y rectorragias. Tras completar estudios fue diagnosticada de CNE rectal pobremente diferenciado a 5 cm del margen anal con adenopatías mesorrectales. Inicio quimioterapia de inducción con respuesta parcial y se realizó resección anterior de recto ultrabaja con anastomosis primaria e ileostomia en asa derivativa, con histología de CNE de células grandes pT2N0 Mx. Posteriormente recibió quimioterapia adyuvante. El CNE rectal es una neoplasia rara, presente entre la 4o-7o década de la vida y con sintomatología similar al adenocarcinoma colorrectal, siendo un tumor poco diferenciado y muy agresivo. El papel de la neo adyuvancia es fundamental dado que suele ser una enfermedad avanzada al diagnóstico, disminuye el tamaño del tumor primario y permite realizar posteriormente resecciones oncológicas.

Abstract Neuroendocrine carcinoma (NC) is an infrequent pathology that is usually found in the advanced stages. The treatment is surgery, and combined chemotherapy andradiotherapy. A 73-year old woman was being studied for constitutional syndrome and rectal bleeding. After which, she was diagnosed with a poorly differentiated rectal NC, 5 cm from de anal margin with mesorectal lymph nodes. Induction chemotheraphy was started with partial response. A low anterior resection of rectum was performed with primary anastomoses and diverting loop ileostomy. The histology result was a large-cell NC, staged as pT2N0 Mx. She then received adjuvant chemotherapy. Rectal NC is infrequent, and usually presents between the fourth and seventh decade of life. Its symptoms are similar to colorectal adenocarcinoma, but it has a lower grade of differentiation, and is more aggressive. Neoadjuvant treatment is essential as it usually a metastatic disease at diagnosis, and helps to decrease the tumor size, and allows oncological surgery to be performed later.

[Prostate carcinoma and syndrome of inappropriate antidiuretic hormone secretion]. / Carcinoma de próstata y síndrome de secreción inadecuada de hormona antidiurética.

Prostate cancer is an extremely rare cause of syndrome of inappropriate antidiuretic hormone (SIADH) secretion. These tend to be aggressive tumors and SIADH can carry serious clinical consequences. A 64 years old patient was diagnosed with Gleason 4+3: 7 prostate adenocarcinoma in December 2014 and received hormonal blockade therapy. By March 2015 he was admitted for symptomatic hyponatremia and SIADH secretion was diagnosed, with no other probable cause than prostate cancer. He suffered a rapid progression of his oncologic disease, surprisingly with PSA in normal range, and died in the short term. There is great clinical and histopathological variability in the cases reported in the literature of association of prostate carcinoma and SIADH. However, they all agree on the aggressiveness of these tumors. This characteristic is present in tumors that have neuroendocrine features. They are frequently resistant to hormonal treatment and may present with paraneoplastic syndromes such as SIADH. The profile of its molecular alterations is under study for the development of target therapies. The association of prostate adenocarcinoma and SIADH is very uncommon and could involve neuroendocrine differentiation. For this reason, it is essential to perform a new biopsy of the tumor or its metastases at the progressive disease in order to conduct an appropriate treatment according to its morphological, immunohistochemical and, in the future, molecular characteristics.