Glucagonoma del páncreas: la piel puede llevarnos al diagnóstico / Pancreatic glucagonoma: observing the skin can lead to diagnosis

Resumen Presentamos el caso de una paciente que tenía un tumor del páncreas -denominado glucagonoma- y cuyo diagnóstico se sospechó por las manifestaciones cutáneas, las cuales nos condujeron realizar una tomografía axial computarizada (TAC). En ella se halló una masa. La paciente se remitió a cirugía y presentó una buena evolución.

Abstract This is a case report of a patient with a pancreatic tumor, known as glucagonoma, whose diagnosis was suspected because of skin manifestations which led to performing a CT scan, finding the mass. She underwent surgery with satisfactory results.

Sweet´s syndrome and pancreatic neoplasm: an atypical association

El síndrome de Sweet es una dermatosis inflamatoria poco común, que se ha asociado a tumores malignos, principalmente de tipo hematológico. Presentamos un caso clínico de síndrome de Sweet asociado con una rara neoplasia pancreática, siendo uno de los pocos casos reportados en la literatura médica acerca de esta asociación.

Sweet's syndrome is an uncommon inflammatory dermatosis, which has been associated with malignant tumors, mainly of hematological type. We report a clinical case of Sweet syndrome associated with a rare pancreatic neoplasm, which is one of the few cases reported in the medical literature about this association.

Diabetes and Endocrine Disease / 임상당뇨병

Impaired insulin secretion and insulin resistance are the two main mechanisms leading to type 2 diabetes mellitus. Insulin exerts multiple effects upon target cells, especially skeletal muscle, liver, and adipose tissue. In general, insulin promotes storage of glucose and inhibits the breakdown of stored glycogen into glucose. The counter regulatory hormones glucagon, catecholamine, cortisol and growth hormone are released during hypoglycemia and under other stress conditions. These hormones have insulin-antagonistic effects both in the liver and in the peripheral tissues. A significant number of endocrine disorders is associated with varying degrees of glucose intolerance, with which sustained excess of these hormones is associated. Indeed, type 2 diabetes is frequently observed in patients with various hormonal diseases including acromegaly, Cushing syndrome, pheochromocytoma, hyperthyroidism, and glucagonoma. In particular, improvement of glycemic control following treatment for these hormonal diseases confirms a causal relationship between excess of these hormones and diabetes. In this review, there will be a discussion over these endocrine diseases in relation to diabetes.

Eritema necrolítico migratorio y glucagonoma pancreático / Necrolytic migratory erythema and pancreatic glucagonoma

El eritema necrolítico migratorio es una dermatosis paraneoplásica infrecuente que puede ser la primera manifestación clínica del glucagonoma, el cual se caracteriza por erupción mucocutánea, intolerancia a la glucosa, hipoaminoacidemia, hiperglucagonemia y glucagonoma pancreático. Se presenta el caso clínico de una mujer de 45 años que presentó pérdida de peso, polidipsia, polifagia, vómito posprandial, caída abundante del cabello y dolor abdominal de dos meses de evolución. Tenía, además, placas eritematosas, descamativas y migratorias en tronco, periné, codos, manos, pies, pliegues submamarios y antecubitales de 20 días de evolución. En la biopsia de piel se observaron células epidérmicas altas con cambio vacuolar notorio, extensa necrosis y delgada capa córnea ortoqueratósica, hallazgos interpretados como eritema necrolítico migratorio. Se sugirió investigar un glucagonoma pancreático. En los exámenes de laboratorio se encontró anemia moderada, hiperglucemia e importante hiperglucagonemia. La ecografía abdominal reveló una masa de 6 x 5 x 5 cm en la cola pancreática, la cual fue resecada. El diagnóstico histopatológico fue de glucagonoma confirmado por inmunohistoquímica. Los síntomas cutáneos desaparecieron a los 10 días de la resección tumoral. Se concluye que los cambios histológicos observados pueden ser claves en la búsqueda de una enfermedad distante de la piel y permiten hacer su diagnóstico. El patrón histológico de vacuolización y necrosis epidérmica subcórnea debe llevar a sospechar la presencia de un glucagonoma pancreático.

Necrolytic migratory erythema is a rare paraneoplastic dermatosis that may be the first clinical manifestation of the glucagonoma syndrome, a disorder characterized by mucocutaneous rash, glucose intolerance, hypoaminoacidemia, hyperglucagonaemia and pancreatic glucagonoma. The clinical case of a 45-year-old woman is presented. She had been experiencing weight loss, polydipsia, polyphagia, postprandial emesis, excessive hair loss and abdominal pain for two months. Erythematous, scaly and migratory plaques with 20 days of evolution were found on her trunk, perineum, elbows, hands, feet, inframammary and antecubital folds. The skin biopsy revealed noticeable vacuolar changes in high epidermal cells, extensive necrosis and thin orthokeratotic cornified layer. These findings pointed to a diagnosis of necrolytic migratory erythema. A suggestion was made to investigate a pancreatic glucagonoma. Laboratory tests showed moderate anemia, hyperglycemia and marked hyperglucagonaemia. Abdominal ultrasound revealed a mass in the tail of the pancreas measuring 6 x 5 x 5 cm which was resected. The histopathological findings were compatible with a diagnosis of glucagonoma, as confirmed by immunohistochemistry. Skin symptoms disappeared 10 days after the tumor resection. We can conclude that the histological changes defined may be clues that can lead the search for a distant skin disease and allow for its diagnosis. The histological pattern of vacuolation and epidermal necrosis should arouse suspicion of pancreatic glucagonoma.

Glucagonoma Syndrome: A case report / Journal of the ASEAN Federation of Endocrine Societies

@#A 58-year-old Malay female with underlying diabetes mellitus, presented with chronic skin lesions, associated with weight loss and anemia. There were erosive, scaling skin lesions over the extremities, gluteal region and perioral area. Skin biopsy histopathological examination revealed Necrolytic Migratory Erythema (NME). A CT scan of the abdomen revealed a pancreatic neck and body tumor with possible liver metastases. She was successfully treated with subcutaneous somatostatin and underwent distal pancreatectomy with wedge resection of liver nodule.

Glucagonoma syndrome associated with necrolytic migratory erythema / Síndrome do glucagonoma associado a eritema necrolítico migratório

Summary Introduction: glucagonoma is a pancreatic neuroendocrine tumor derived from alpha-cells of the islets of Langerhans. It is marked by tumoral autonomous production of glucagon and characterized, among other symptoms, by necrolytic migratory erythema, an erythematous circinate lesion with areas of necrosis and sloughing. This is a rare disease with worldwide incidence estimated at 1 case per 20 million people. Case report: we report a case of glucagonoma associated necrolytic migratory erythema in a male patient, 56 years, with signs of skin lesions mainly on his legs and groin, hyperglycemia and weight loss. Biopsies of the skin lesions were performed and imaging of the abdomen showed a mass of 10 x 9 cm, at the pancreatic region. The patient was subjected to body-caudal pancreatectomy and splenectomy with autotransplant of the spleen in the greater omentum. The histopathologic report indicated a tumor in the pancreatic alpha cells. Immunohistochemistry showed expression of glucagon and chromogranin A in most tumor cells, consistent with the diagnosis of glucagonoma. The patient presented 3 years of outpatient follow-up with no complications. Conclusion: the necrolytic migratory erythema is important for the clinical recognition of glucagonoma, and its early diagnosis is essential for a successful curative therapy. .

Resumo Introdução: Introdução: o glucagonoma é um tumor neuroendócrino do pâncreas derivado das células alfa das ilhotas de Langerhans. É marcado pela produção tumoral autônoma de glucagon e caracterizado, dentre outros sintomas, por eritema necrolítico migratório (ENM), uma lesão eritematosa circinada com áreas de necrose e descamação. Trata-se de uma doença rara com incidência mundial estimada em 1 caso para cada 20 milhões pessoas. Relato de caso: apresentamos um caso de glucagonoma associado a ENM em um paciente de sexo masculino, 56 anos de idade, com quadro de lesões cutâneas, principalmente em membros inferiores e região inguinal, hiperglicemia e perda ponderal. Biópsias das lesões cutâneas foram realizadas e exames de imagem do abdome evidenciaram uma massa de 10 x 9 cm em região pancreática. O paciente foi submetido à pancreatectomia corpocaudal e esplenectomia total com autoimplante do baço em omento maior. O laudo histopatológico foi de tumor de células alfa pancreáticas. Imuno-histoquímica evidenciou expressão de glucagon e cromogranina A na maioria das células tumorais, compatível com diagnóstico de glucagonoma. O paciente apresentou seguimento de 3 anos em ambulatório sem intercorrências clínicas. Conclusão: o ENM é importante para o reconhecimento clínico do glucagonoma, sendo seu diagnóstico precoce fundamental para uma terapia curativa de sucesso. .

Metastatic glucagonoma presenting with weight loss and necrolytic migratory erythema / Journal of the ASEAN Federation of Endocrine Societies

@#A 42-year-old Filipino female was admitted due to weight loss and recurrent abdominal pain over the past ten years. In 2010, she was diagnosed to have disseminated PTB associated with a liver mass. After 1 year of anti-TB treatment, lung condition was treated but her liver mass has enlarged. She also developed diarrhea, diabetes, and skin lesions with biopsy results showing Necrolytic Migratory Erythema (NME). CT scan showed liver and pancreatic tumors that were biopsied revealing a neuroendocrine tumor. Blood glucagon level was elevated. She was treated as a case of glucagon-secreting tumor with liver metastases with Everolimus and Octreotide. After 3 months of treatment, she gained weight, the skin lesions improved, and the liver mass decreased in size. Many of the initial symptoms of glucagonoma are nonspecific and subtle. As a result, glucagonoma is often diagnosed relatively late in the course of the disease. NME, the characteristic skin lesion of the glucagonoma syndrome, is often the clue that leads to the correct diagnosis.

Pancreatic neuroendocrine tumors: biology, diagnosis,and treatment / 癌症

Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are somewhat understood, but their molecular pathogenesis remains unknown. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is unpredictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally indicate a less favorable prognosis. Endocrine testing, imaging, and histological evidence are necessary to accurately diagnose PNETs. A 4-pronged aggressive treatment approach consisting of surgery, locoregional therapy, systemic therapy, and complication control has become popular in academic centers around the world. The optimal application of the multiple systemic therapeutic modalities is under development; efficacy, safety, availability, and cost should be considered when treating a specific patient. The clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including the novel Mahvash disease, are summarized.

Prolonged Neutropenia after Sunitinib Treatment in a Patient with a Glucagonoma and Multiple Hepatic Metastases / 대한내과학회지

Pancreatic neuroendocrine tumors (PNET) are rare, with approximately 2.2 in 1,000,000 people affected annually. In the classification of neuroendocrine tumors, glucagonomas are a functional PNET and comprise 1.6% of PNET. Glucagonoma syndrome is a paraneoplastic syndrome that is characterized by necrolytic migratory erythema, weight loss, anemia, and diabetes mellitus. Metastatic disease at presentation is common, but is often limited to the liver and regional lymph nodes. Sunitinib malate improves the progression-free and overall survival of PNET. This report presents a 45-year-old Asian woman with prolonged neutropenia after sunitinib treatment of a glucagonoma with multiple hepatic metastases. The severity of the neutropenia after the sunitinib treatment fluctuated from grade 1 to 4 repeatedly, with a non-febrile pattern. Ultimately, the patient did not recover from the neutropenia, even after stopping the sunitinib.

Diagnosis and treatment of glucagonoma: report of one case / 南方医科大学学报

glucagonoma is a rare islet alpha-cell tumor. We report a case of glucagonoma in a 55-year-old male patient with such clinical findings of necrolytic migratory erythema, diabetes mellitus, body weight loss, and anemia. CT examination found a space-occupying lesion in the pancreas, and an elevated serum glucagon level indicate the diagnosis of glucagonoma, which was confirmed postoperatively by pathological examination of the tumor tissue. A definite diagnosis of glucagonoma relies on pathological report, and so far no standard treatment strategy has been available for this tumor. Surgical resection is an effective means for treatment of glucagonoma.

Hypercalcemia appeared in a patient with glucagonoma treated with octreotide acetate long-acting release / 中国医学科学杂志(英文版)

PABCREATIC neuroendocrine tumours are uncommon neoplasms of the pancreas. They may cause a clinical syndrome due to hormone overproduction. Glucagonoma is a rare kind of pancreatic tumors. Here we report a case of glucagonoma. Hypercalcemia occurred when the patient underwent octreotide acetate long-acting release.

Tumores neuroendocrinos del páncreas / Pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors are infrequent and slow-growing neoplasms. They are classified basedon their clinical presentation as functioning and nonfunctioning tumors. The most common functionaltumors are the insulinoma and gastrinoma. They can be sporadic or be part of hereditary forms as MEN-1.The diagnosis is based on the detection of the specific clinical syndrome in association of high levels of the substance secreted by the tumor and conventional imaging studies or others such as stimulation tests, somatostatin receptor scintigraphy and endoscopic ultrasound. In general, these tumors have a better prognosis than the pancreatic adenocarcinoma and they can show metastasis to the liver and infrequently, in bones. The treatment can be managed medically diminishing the inappropriate secretion of the substances by the tumor using, for example, the somatostatin analogs. Surgery should be always considered, especially in case of insulinomas, small non-functioning tumors, and small gastrinomas that can be managed with surgery enucleation. More advanced resective surgery, such as Whipple resection, are not routinely recommended and they should be limited to selected patients. In advanced tumors, there are other treatment alternatives, for example, hepatic resection, radiofrequency, chemotherapy and new agents such as sunitinib and everolimus.

Los tumores neuroendocrinos pancreáticos son infrecuentes y de crecimiento lento. Se clasifican en tumores funcionantes o no funcionantes (TNEP-NF), de acuerdo a la presentación clínica. Los tumores funcionantes más frecuentes son los insulinomas y los gastrinomas. Pueden ocurrir en forma esporádica o asociados a síndromes hereditarios como la NEM- 1, entre otros. El diagnóstico se basa en la detección del síndrome clínico específico asociado a la demostración de niveles elevados de la sustancia secretada y exámenes imagenológicos convencionales u otros más específicos como de estimulación, cintigrafía de receptores de somatostatina y endosonografía. En general, tienen mejor pronóstico que los adenocarcinomas pancreáticos y pueden dar metástasis hepáticas y con menor frecuencia, óseas. El tratamiento puede ser médico disminuyendo la secreción inapropiada de las sustancias producidas por el tumor como los análogos de somatostatina. La cirugía siempre debe ser considerada, especialmente en caso de insulinomas, pequeños TNEP-NF, y gastrinomas pequeños, que pueden ser tratados con enucleación quirúrgica. Las cirugías resectivas más avanzadas, como la operación de Whipple no están recomendadas en forma rutinaria y sólo deben ser utilizadas en pacientes seleccionados. En casos de tumores avanzados, existen alternativas de tratamiento, como la resección hepática, radiofrecuencia, quimioterapia, y terapia con nuevos agentes en estudio como el sunitinib y everolimus.

Retrospective review of cross sectional imaging findings of pancreatic non functional islet cell tumor [NFICT] and its hepatic metastases

Review and correlate the computed tomography [CT] imaging features of pancreatic Non Functional Islet Cell Tumors [NFICT] and its hepatic metastases. CT examinations of 28 patients with pathologically proven diagnosis of pancreatic NFICT and no clinical symptoms or signs attributed to hormone overproduction, performed at Mallinkrodt Institute of Radiology, Saint Louis, Missouri, USA between March 2002-July 2006, were retrospectively reviewed by two abdominal radiologists. The imaging findings were analyzed and summarized. Pancreatic NFICT size ranged from 1.2-13 cm. The commonest pattern of enhancement was hypervascular and heterogenous enhancement. The spleen was the commonest invaded nearby local structure. The commonest pattern of enhancement noted in the metastatic liver lesions was hypervascular heterogenous enhancement. 26% of the liver metastatic lesions were associated with invasion/encasement of nearby vessels. Imaging features of pancreatic NFICT can overlap with other pancreatic neoplasms. Therefore combining the imaging features of pancreatic NFICT and its hepatic metastases helps in narrowing the differential diagnosis

Recent Update of Radiologic Findings and Interventional Methods of Pancreas Endocrine Tumor / 대한내과학회지

Pancreatic endocrine tumors (PET) are rare neoplasms of the pancreas accounting for less than 5% of all primary pancreatic malignancies. Insulinomas, gastrinomas, glucagonomas and somatostatinomas is included in PET. PETs are usually classified into functioning and non-functioning tumors and presents with a range of benignity or malignancy. It is very important to accurate diagnose the PET location and to predict the benignity or malignancy of PET in terms of the treatment strategy, because PET have higher respectability, better response to chemotherapy and better prognosis compared to that of pancreatic adenocarcinoma. The utility and reliability of different imaging modalities depends on the characteristics of PETs, specifically their size. Functioning PET tend to be small (less than 2 cm), well circumscribed, homogeneous, and usually shown as strong enhancement on contrast enhanced CT or MR imaging. Non-functioning PET tend to be larger (4~10 cm), heterogeneous, and may contain the cystic areas of degeneration and necrosis. In this article, we present the various imaging findings of PET according to recent WHO classification.

case of gllucagonoma and a review the literature

Glucagonoma is a rare islet cell tumor [alpha cell tumor] of the pancreas, when active it produces a syndrome characterized by necrolytic migratory erythema, diabetes mellitus, weight loss, anemia, glossitis, thromboembolism, neuropsychatric disturbances and hyperglucagonaemia. We present a case of a large pancreatic head tumor with diabetes mellitus [DM], anemia, weight loss and muscle wasting. After complete resection of the pancreatic tumor, the hyperglycaemia subsided. Peviewing 120 cases of glucagonoma in the literature the average tumor diameter was 3.6 cm. Most of the tumors [90%] occurred in the body and the tail. Two thirds of the reported glucagonomas were malignant and 53.3% metastasizes to other organs. Necrolytic migratory erythema [NME] is not a prerequisite for the diagnosis of Glucagonoma syndrome, where anemia, hyperglycemia, muscle wasting and weight loss may be the presenting features

Eritema necrolítico migratorio: a propósito de un caso / Necrolytic migratory erythema: a case report

Presentamos el caso de una paciente de 62 años con un cuadro de tres años de evolución, caracterizado por placas y pápulas eritematosas arciformes que comenzaron en cara, extendiéndose luego al resto del cuerpo, asociado a baja de peso y depresión. Después de un completo estudio y dos biopsias de piel se diagnóstica eritema necrolítico migratorio (ENM). El ENM junto con estomatitis/glositis, baja de peso, diarrea, diabetes y anemia forman el síndrome paraneoplásico asociado al tumor de células a pancreáticas, llamado síndrome del glucagonoma, El ENM corresponde a lesiones maculopapulares, coalescentes, de borde serpiginoso, acompañadas de una bula central que se erosiona y forma costras. La biopsia cutánea muestra hiperplasia psoriasiforme y espongiótica, paraqueratosis y separación de las capas superficiales de la epidermis. La resección del tumor conduce a la resolución del ENM. Presentamos este caso y revisión del tema por la baja frecuencia de esta enfermedad y para reforzar lo importante de su sospecha temprana.

We report the case of o 62 year old woman with a 3 year history of erythematous arciform plaques and papules that began in the face and spread to the rest of the body. These lesions were associated with depression and weight loss. After a comprehensive study and two skin biopsies, necrolytic migratory erythema (NME) was diagnosed together with glossitis/stomatitis, weight loss, diarrhea, diabetes and anemia, NME is part of the paraneoplastic syndrome associated with a cell pancreatic tumor, known as glucagonoma syndrome NME lesions are characterized by a coalescent maculopapular rash with a serpiginous edge and a central bulla that erodes and become crusted. Histological studies show a psoriasiform and spongiotic hyperplasia, porakeratosis, and detachment of the superficial layers of the epidermis. ENM usually resolves after tumor resection. We present this case and a review of the literature because of the low frequency of this disease and to reinforce the importance of its early suspicion.

Glucagonoma syndrome

Glucagonoma syndrome is a rare disease in which necrolytic migratory erythema is often one of the early symptoms. Weight loss and diabetes mellitus are two other characteristics of this syndrome. Necrolytic migratory erythema is typically characterized on skin biopsies by necrolysis of upper epidermis with vacuolated keratinocytes. Persistent hyperglucagonemia in excessive stimulation of basic metabolic pathway which in turn in diabetes mellitus at the expense of tissue glycogen stores. Deficiencies of various essential nutrients and vitamin B lead to dermatosis. Due to rarity of glucagonoma, it is quite difficult to diagnose this syndrome at early stages

A Case of a Cutaneous Metastasis from an Endocrine Pancreatic Carcinoma / 대한피부과학회지

Pancreatic endocrine tumors (PET) are rare neoplasms of the pancreas and account for less than 5% of all primary pancreatic malignancies. Included in this group are insulinomas, gastrinomas, glucagonomas and somatostatinomas. Collectively, these neoplasms are classified as functional PETs. When a PET is not associated with a clinical syndrome due to hormone oversecretion, it is referred to as a non-functional PET. Non-functionalPETs are pancreatic tumors with endocrine differentiation but lack a clinical syndrome of hormone hypersecretion. Although a pancreatic carcinoma shows aggressive biological behavior, a cutaneous metastasis from a pancreas carcinoma is rare. We report a case of a case of a cutaneous metastasis from an endocrine pancreatic carcinoma in a 50-year-old female that clinically manifested as a painful firm nodule on the back.

Clinical experience in diagnosis and treatment of glucagonoma / 中华外科杂志

<p><b>OBJECTIVE</b>To study the diagnosis and treatment of glucagonoma.</p><p><b>METHODS</b>A retrospective review of glucagonoma cases was committed between June 1993 and July 2008 in Peking Union Medical College Hospital. It was measured by sex, age, misdiagnosis, clinical symptoms, laboratory data, imaging studies, diagnosis, treatment procedures and so on.</p><p><b>RESULTS</b>The tumors of eleven cases were found in the tail, and one case was in the head of the pancreas at the same time. Ten had solitary lesion, one had multiple lesions. The average diameter of the lesions was 3.9 cm. Nine patients had the metastasis out of pancreas and all of them had the liver metastasis. One case was a member of multiple endocrine neoplasia type 1 (MEN-1) syndromes. Eight patients being treated with operation had the detailed pathological reports. The glucagon was detected by immunohistochemistry and was positive in five patients. Six patients were pathologically malignant. Multimodal treatments included tumor resection, chemoembolization, treated with somatostatin analogues and (or) radionuclides and so on were applied to all patients.</p><p><b>CONCLUSIONS</b>Glucagonoma is a rare pancreatic endocrine tumor. Radical tumor surgery is used as the first choice. Multimodal approach may improve the prognosis.</p>

Manifestaciones anatomoclínicas de las enfermedades cutáneas metabólicas y sistémicas misceláneas: Parte II / Anatomoclinical manifestations of metabolic and systemic diseases: Part II

Numerosas enfermedades sistémicas y metabólicas tienen manifestaciones cutáneas, muchas de estas manifestaciones pueden favorecer su diagnóstico. Dado el gran número de estas patologías, esta revisión no pretende ser un análisis exhaustivo de todas ellas, sino que presenta un análisis clínico-patológico de algunas enfermedades metabólicas y sistémicas seleccionadas.

Numerous systemic and metabolic diseases have coetaneous manifestations, many of these manifestations can favor diagnosis Due to the great number of these conditions, this review does not try to be a comprehensive analysis of all of them, but present a clinicopathological analysis of some selected metabolic and systemic diseases.