Characteristics and treatment options of glucagonomas: a national study from the French Group of Endocrine Tumors and ENDOCAN-RENATEN network.

OBJECTIVE: Glucagonoma is a very rare functional pancreatic neuroendocrine tumor (PanNET). We aimed to provide data on the diagnosis, prognosis, and management of patients with glucagonoma. DESIGN AND METHODS: In this retrospective national cohort, we included all patients with glucagonoma, defined by at least 1 major criterion (necrolytic migratory erythema [NME] and/or recent-onset diabetes, and/or weight loss ≥ 5 kg) associated with either glucagonemia > 2 × upper limit of normal or positive glucagon immunostaining. Antisecretory efficacy was defined as partial/complete resolution of glucagonoma symptoms. Antitumor efficacy was assessed according to the time to next treatment (TTNT). RESULTS: Thirty-eight patients were included with median age 58.7 yo, primary PanNET located in the tail (68.4%), synchronous metastases (63.2%). Median Ki-67 index was 3%. Most frequent glucagonoma symptoms at diagnosis were NME (86.8%), weight loss (68.4%), and diabetes (50%). Surgery of the primary PanNET was performed in 76.3% of cases, mainly with curative intent (61.5%). After surgery, complete resolution of NME was seen in 93.8% (n = 15/16). The secretory response rates were 85.7%, 85.7%, 75%, and 60% with surgery of metastases (n = 6/7), chemotherapy (n = 6/7), liver-directed therapy (n = 6/8), and somatostatin analogs (n = 6/10), respectively. All lines combined, longer TTNT was reported with chemotherapy (20.2 months). Median overall survival (OS) was 17.3 years. The Ki-67 index > 3% was associated with shorter OS (hazard ratio 5.27, 95% CI [1.11-24.96], P = .036). CONCLUSION: Patients with glucagonoma had prolonged survival, even in the presence of metastases at diagnosis. Curative-intent surgery should always be considered. Chemotherapy, peptide receptor radionuclide therapy, or liver-directed therapy seems to provide both substantial antitumor and antisecretory efficacies.

Glucagonoma Syndrome: A Rare Paraneoplastic Disorder due to Neuroendocrine Tumor of the Pancreas.

Glucagonoma syndrome is an extremely rare paraneoplastic disorder. The key presenting feature is a rash (necrolytic migratory erythema) which can easily be misdiagnosed as a primary skin disorder. Moreover, 50 to 80 % of patients already have metastatic disease at diagnosis. We report a case of a 38-year female presenting with epigastric pain and a skin rash all over the body. Workup revealed a neuroendocrine tumor (NET) of the pancreas, for which she underwent resection, resulting in a complete cure. A follow-up MRI after 8 months showed a hyperintense and arterially enhancing nodular liver lesion which did not show any uptake on the octreotide scan. However, a subsequent biopsy revealed a recurrence of the tumor. This was a unique finding in our case where a highly sensitive octreotide scan failed to identify metastasis, emphasising the importance of biopsy in such cases. Key Words: Glucagonoma, Necrolytic migratory erythema, Alpha-cell adenom.

Necrolytic migratory erythema is an important visual cutaneous clue of glucagonoma.

Glucagonoma is an extremely rare neuroendocrine tumor that arises from pancreatic islet alpha cells. Although glucagonoma is usually accompanied by a variety of characteristic clinical symptoms, early diagnosis is still difficult due to the scarcity of the disease. In this study, we present the cumulative experiences, clinical characteristics and treatments of seven patients diagnosed with glucagonoma during the past 10 years at the First Affiliated Hospital of Xi'an Jiaotong University. The seven patients in our cohort consisted of six females and one male with an average diagnosis age of 40.1 years (range 23-51). The average time from onset of symptoms to diagnosis of glucagonoma was 14 months (range 2-36 months). All the patients visited dermatology first for necrolytic migratory erythema (NME) 7/7 (100%), and other presenting symptoms included diabetes mellitus (DM) 4/7 (57%), stomatitis 2/7 (28%), weight loss 4/7 (57%), anemia 4/7 (57%), diarrhea 1/7 (14%), and DVT1/7 (14%). Plasma glucagon levels were increased in all patients (range 216.92-3155 pg/mL) and declined after surgery. Imaging studies revealed that four of seven patients had liver metastasis. Six of seven patients received surgical resection, and all of them received somatostatin analog therapy. Symptoms improved significantly in 6 out of 7 patients. Three of seven patients died of this disease by the time of follow-up. Our data suggest that if persistent NME is associated with DM and high glucagon levels, timely abdominal imaging should be performed to confirm glucagonoma. Once diagnosed, surgery and somatostatin analogs are effective for symptom relief and tumor control.

Third reported case of rare necrolytic migratory erythema associated with bacteraemia due to severe zinc deficiency after revisional Roux-En-Y gastric bypass: case report and literature review.

INTRODUCTION: Obesity is a risk factor for zinc deficiency. After bariatric surgery, non-compliance to diet/vitamin supplements, surgical complications leading to vomiting/diarrhea, poor follow-up and malabsorption can precipitate or exacerbate pre-existing zinc deficiency. CASE REPORT: We report a patient with rare necrolytic migratory erythema associated with bacteraemia due to severe zinc deficiency after revisional Roux-en-Y gastric bypass (following primary laparoscopic sleeve gastrectomy). CONCLUSION: Bariatric teams should screen patients before bariatric surgery for nutritional deficiencies and continue surveillance of their nutritional status after surgery. They should maintain a high index of suspicion for zinc deficiency in patients with skin rash after bariatric surgery. LEVEL OF EVIDENCE: Level V, case report.

[Necrolytic migratory erythema in a patient with a glucagonoma]. / Een man met erythema migrans necroticans.

This case concerns an 81-year-old man with weight loss and erythematosquamous plaques, with central clearing and atrophy. Due to a CT scan and blood test the diagnosis necrolytic migratory erythema as a paraneoplastic manifestation of glucagonoma was made. The pathogenesis is not completely elucidated. Early recognition of symptoms is important.

Treatment of Glucagonoma-Related Necrolytic Migratory Erythema With Peptide Receptor Radionuclide Therapy.

ABSTRACT: Glucagonomas are rare types of pancreatic neuroendocrine tumors. They may present with a clinical entity called glucagonoma syndrome, which includes necrolytic migratory erythema as a skin component. Here we present a 26-year-old woman experiencing ongoing skin lesions, excessive weight loss, and nausea. She was diagnosed with metastatic glucagonoma. Her 68Ga-DOTATATE PET/CT showed increased uptake at the primary pancreatic lesion and hepatic metastases. She received 2 cycles of peptide receptor radionuclide therapy and had a partial response with a near-complete regression of her skin lesions.

Glucagonoma syndrome with atypical necrolytic migratory erythema.

Necrolytic migratory erythema is most commonly associated with glucagonoma syndrome. We report a rare case of glucagonoma syndrome with necrolytic migratory erythema presenting as pruritic papules and follicular pustules in a 57-year-old woman; showing eosinophilic infiltration on histology. However, the final diagnosis was confirmed by demonstrating neuroendocrine tumour on histopathological examination of the liver metastases. Nutrition therapy was administered as a palliative treatment. This case also highlights the atypical clinical features and nonspecific histology of necrolytic migratory erythema which makes the diagnosis difficult.

Pseudoglucagonoma syndrome: Description of an 'Idiopatic' case.

A case of pseudoglucagonoma syndrome, that is necrolytic migratory erythema, in a patient with no coexistent glucagonoma, is described. The patient was a 59-year-old man with waxing and waning dermatitis of the buttocks, characterised by arciform erythematous papulo-squamous lesions with micro-pustulation. Histopathology was characteristic for necrolytic migratory erythema, but no other underlying disease was detected. Other cases of pseudoglucagonoma syndrome described in literature are briefly reviewed.

Case of autoimmune progesterone dermatitis presenting as necrotic migratory erythema successfully controlled by danazol.

Autoimmune progesterone dermatitis (APD) is a rare cutaneous disorder with cyclic skin eruptions during the luteal phase of the menstrual cycle. Patients can present with various clinical manifestations, including urticaria and angioedema, erythema multiforme, eczema, fixed drug eruption and centrifugal erythema annulare. In our case, however, the patient's skin lesions mimic necrotic migratory erythema (NME) which is most commonly associated with glucagonoma and rarely with liver disease, inflammatory bowel disease, malnutrition and other tumors. To our knowledge, this is the first case of NME-like APD and is successfully controlled by danazol. This also sheds lights on the etiologic diversity of NME.