ABSTRACT

Glucagonomas; is a rare neuroendocrine tumor originating from alpha cells of the pancreas. Glucagonoma syndrome is a paraneoplastic entity known as diarrhea, weight loss, stomatitis, thrombosis, diabetes, and necrotizing migratory erythema. It is difficult to come to mind in the differential diagnosis with the very rarely seen and little known reason. We also wanted to present a patient with bilateral deep vein thrombosis and a new diagnosis of diabetes that we were difficult to diagnose.

Introduction

Neuroendocrine tumors (NETs) are the tumors originating from the neuroendocrine system in any part of the body. NETs are rare tumors that are mostly benign but may also be aggressive. Today, NETs are divided into two groups as pancreatic NETs and other NETs (1). 60-90% of NETs occur in the gastrointestinal tract and pancreatic system. They are rarely seen in other organs (lung, adrenal gland, thymus, bladder, ovary, testis) (2). Pancreatic NETs, 90-95% of which are insulinoma and gastrinoma, constitute 7% of all NETs. Glucagonoma constitutes only 4% of pNETs (3). 80% of glucagonomas are malignant. It is often sporadic and is associated with genetic factors in 20% of cases (MEN1). Glucagonomas may present with migratory necrotic skin rash (dermatitis), diabetes, depression, diarrhea (4D syndrome), glossitis, stomatitis, angular cheilitis and severe weight loss (4). We present the case because it is a rare entity.

Discussion

NET incidence is two per million and constitutes 0.5% of all cancers. It should be noted that NETs may coexist with other solid organ cancers. The gastrointestinal tract is the largest neuroendocrine system in the body, and NETs are often localized here. Gastroenteropancreatic NET (GEP-NET) cells are caused by diffuse endocrine system cells, which are phenotypically similar. These tumors are referred to as Neuroendocrine because they express proteins such as synaptophysin, neuron-specific enolase (NSE) and chromogranin A associated with neural cells. 65% of NETs occur in the gastrointestinal tract, 25% in the lungs, and the rest in other endocrine tissues. Clinical findings vary depending on the location of the NETs and the hormone that they secrete. Diagnosis is made by elevated blood glucagon level. The diagnosis is supported by the measurement of chromogranin-A (CgA) levels, 5-HIAA, CA19-9 and CEA levels. CgA has a sensitivity of 80% and specificity of 90% and has a better diagnostic value than 5-HIAA,  NSE and pancreatic polypeptide. Plasma NSE identifies poorly differentiated NETs with 85% specificity and 70% sensitivity (5). Mitosis rate and ki-67 index are well below 2% in well-differentiated NETs and necrosis is not seen, whereas in poorly differentiated group, these rates increase above 10% and necrosis can be seen (6). Pancreatic NETs are also classified according to the hormones they secrete and they are called insulinoma, gastrinoma, glucagonoma, VIPoma. It can also be classified as local, regional and distant spread according to the extent of the disease. NETs may occur with metastases below 2 cm. Similarly, the rate of metastasis was 50% at the time of diagnosis (7). The metastasis rate is determined by the organ from which the tumor originated. Glucagonomas are located in the distal pancreas at a rate of 85%. In our case, the patient was examined considering GIS malignancy initially because there were weight loss, anemia, and DVT, and Ca19-9 was high (8). Abdominal imaging revealed a mass between the spleen and kidney; therefore, biopsy was performed under endoultrasonography. Meanwhile, basal-bolus insulin therapy for glycemic regulation and coumadin therapy for DVT were performed. After stabilization of the patient, he was discharged for outpatient follow-up. Then, the patient was brought back to the emergency unit due to deterioration of his general condition. Meanwhile, diarrhea and non-necrotic erythematous skin rash on the right leg were added to the complaints. In the immunohistochemical study of the previous biopsy, chromogranin (+), synaptophysin (+), pancytokeratin (+), LCA (-), ki 67 index was less than 1%. Results were evaluated to be consistent with neuroendocrine tumor (Grade I). Glucagon level sent to support the diagnosis was found to be significantly higher (9). Surgical intervention was planned but was not accepted. As a result of the consultation with oncology, lanreotide treatment was planned (10). After the treatment, his general condition recovered and glycemic regulation was achieved. The patient was discharged for follow-up in the outpatient clinics of oncology and general internal medicine.

We wanted to emphasize that glucagonoma should be considered in cases with newly diagnosed diabetes and DVT, erythematous skin lesions, diarrhea and a mass in the abdomen and examinations for it should be performed.