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.

[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.

Eritema necrolítico migratorio asociado a glucagonoma / Glucagonoma-related necrolytic migratory erythema

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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.

Spleen-preserving distal pancreatectomy and lymphadenectomy for glucagonoma syndrome: A case report.

RATIONALE: Glucagonoma is a rare type of functional pancreatic neuroendocrine tumor that is characterized by distinctive clinical manifestations; among these, necrolytic migratory erythema represents the hallmark clinical sign of glucagonoma syndrome and is usually presented as the initial complaint of patients. PATIENT CONCERNS: A 30-year-old male patient was admitted to our hospital with a complaint of diffuse erythematous ulcerating skin rash for more than 10 months. He also complained of hyperglycemia and a weight loss of 15 kg in those months. DIAGNOSIS: This patient underwent a contrast-enhanced computed tomography scan which showed a pancreatic body mass measuring approximately 6 cm with low density accompanied by partial calcification in plain scanning images and uneven enhancement in strengthening periods. In addition, laboratory tests indicated elevated fasting blood glucagon (1109 pg/mL, normal range: 50-150 pg/mL) levels. Glucagonoma syndrome was ultimately diagnosed in clinical. INTERVENTION: Spleen-preserving distal pancreatectomy was conducted and postoperative pathology revealed the presence of glucagonoma. OUTCOMES: The patient recovered uneventfully with the glucagonoma syndrome disappeared soon after surgery, and the postoperative plasma glucagon decreased to a normal level. Follow-up showed no recurrence for 5 years since the surgery. LESSONS: The treatment of glucagonoma should be directed according to the stage at which the disease is diagnosed. Surgery is currently the only method available to cure the tumor, although medications are given to patients who present with advanced glucagonoma and who are not candidates for operation. Multidisciplinary therapy and multimodality treatment are advised, although these have been systematically evaluated to a lesser degree.

Glucagonoma syndrome with severe erythematous rash: A rare case report.

RATIONALE: Glucagonoma is a rare neuroendocrine tumor of the pancreas. Glucagonoma syndrome is often misdiagnosed as other skin lesions by clinicians due to a typical clinical sign of necrolytic migratory erythema (NME) with severe erythematous rash. PATIENT CONCERNS: A 48-year-old female patient was admitted to our department because she presented with unclear recurrent severe erythematous rash. The patient was diagnosed as skin disease. DIAGNOSES: Histopathologic examination revealed a pancreatic glucagonoma. Immnohistochemical staining of tumor tissue was positive for glucagon. INTERVENTIONS: The distal pancreatectomy plus splenectomy was performed in 2017. OUTCOMES: The skin lesions disappeared after surgery. She was followed up and showed no recurrence until now. LESSONS: Clinicians should consider the diagnosis of glucagonoma according to the typical initial symptoms. Early diagnosis is very important to provide a better prognosis. A multidisciplinary approach is effective in patients with unresectable metastatic tumors.

Resolution of necrolytic migratory erythema with somatostatin analogue in a patient diagnosed with pancreatic glucagonoma.

A 70-year-old man reported progressive weight loss, fatigue and a generalised rash. The rash was consistent with necrolytic migratory erythema, further investigations were performed and the patient was diagnosed with a mass in the tail of the pancreas, in keeping with a localised glucagonoma. Somatostatin analogue therapy was started for symptom control, leading to complete resolution of the skin rash and an improvement in constitutional symptoms. Subsequently, the pancreatic lesion was excised, and pathology assessment confirmed the diagnosis of well-differentiated neuroendocrine tumour with high expression of glucagon compatible with glucagonoma.

Glucagonoma-Associated Necrolytic Migratory Erythema: The Broad Spectrum of the Clinical and Histopathological Findings and Clues to the Diagnosis.

Necrolytic migratory erythema (NEM) is associated with glucagonoma, an endocrine malignancy of the pancreas. It is a rare and a likely underrecognized paraneoplastic dermatitis. A 38-year-old woman presented to our clinic with a 3-year history of reocurring pruritic skin rashes with increasing intensity. The skin lesions presented with active annular borders, central scaling, and postinflammatory hyperpigmentation, but also with erosions, pustules, and crusted lesions. Multiple skin biopsies were taken. The workup of the patient revealed a tumor localized in the head of the pancreas, and glucagon serum levels were elevated. Clues to the diagnosis of NEM were the waxing and waning of serpiginous erythemas with active borders localized on extremities, intertriginous areas, and face. On histopathology, dyskeratosis in all layers of the epidermis were an early feature of NEM, and long-standing lesions typically showed psoriasiform hyperplasia with pallor and necrosis of upper epidermal layers. Clinicians and histopathologists need to be aware of the wide spectrum of skin manifestations in glucagonoma. Early diagnosis of the tumor is crucial for patients.