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.

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.

Imaging of Pancreatic-Neuroendocrine Tumours: An Outline of Conventional Radiological Techniques.

INTRODUCTION: Pancreatic Neuroendocrine Tumours (p-NETs) are an important disease entity and comprise of peptide-secreting tumours often with a functional syndrome. Accounting for a small percentage of all pancreatic tumours, they have a good overall survival rate when diagnosed early, with surgery being curative. The role of nuclear medicine in the diagnosis and treatment of these tumours is evident. However, the vast majority of patients will require extensive imaging in the form of conventional radiological techniques. It is important for clinicians to have a fundamental understanding of the p-NET appearances to aid prompt identification and to help direct management through neoplastic staging. METHODS: This article will review the advantages and disadvantages of conventional radiological techniques in the context of p-NETs and highlight features that these tumours exhibit. CONCLUSION: Pancreatic neuroendocrine tumours are a unique collection of neoplasms that have markedly disparate clinical features but similar imaging characteristics. Most p-NETs are small and welldefined with homogenous enhancement following contrast administration, although larger and less welldifferentiated tumours can demonstrate areas of necrosis and cystic architecture with heterogeneous enhancement characteristics. Prognosis is generally favourable for these tumours with various treatment options available. However, conventional radiological techniques will remain the foundation for the initial diagnosis and staging of these tumours, and a grasp of these modalities is extremely important for physicians.

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.

A Case Series of Molecular Imaging of Glucagonoma After Initial Therapy-68Ga-DOTATATE PET/CT Reveals Similar Results as in Neuroendocrine Tumors of Other Origin in Follow-up and Re-evaluation.

Glucagonoma is an extremely rare, glucagon-secreting neuroendocrine tumor of the pancreas. Only sparse data are available about the characteristics of this tumor in somatostatin receptor imaging and only for the situation of initial diagnosis. We present a series of 3 glucagonoma patients who underwent at least 1 Ga-DOTATATE PET/CT scan. All patients were diagnosed by either histology and/or elevated serum levels of glucagon. The presented cases suggest that somatostatin receptor-based imaging can probably be used for re-evaluation of disease status in patients with glucagonoma in a similar way as it is already established for neuroendocrine tumors of other origin.

Malignant transformation of glucagonoma with SPECT/CT In-111 OctreoScan features: A case report.

RATIONALE: Glucagonoma is an uncommon disease but it has been associated with a pattern of symptoms defined as glucagonoma syndrome. These symptoms, if promptly recognized, could help to speed up the diagnosing process. PATIENT CONCERNS: We report a case of a 68-year-old woman with a pancreatic glucagonoma. Her symptoms at the onset were typical of the glucagonoma syndrome. DIAGNOSES: After a significant weight loss, she underwent a computer tomography scan of the abdomen, which showed a hypervascular lesion of the tail of the pancreas and hypervascular lesions of the liver. An ultrasound guided biopsy was performed and pathology was consistent with glucagonoma. Her blood glucagon levels were elevated. OUTCOMES: She was treated with chemotherapy and somatostatin analogs. After 4 years, the disease had a malignant transformation, and metastases suddenly started to grow up. She stopped being responsive to treatment and eventually passed away. LESSONS: Due to its rarity, clinical diagnosis is challenging and generally it comes after a long interval since the onset of symptoms. Awareness of physicians and dermatologists of the characteristic necrolytic migratory erythema, and of the other symptoms, often leads to early diagnosis.

Necrolytic migratory erythema associated with glucagonoma syndrome diagnosed by 68Ga-DOTANOC PET-CT.

Necrolytic migratory erythema (NME) is a rare dermatological condition which presents a diagnostic challenge. Repeated negative skin biopsies and non-detection of any pancreatic tumor in conventional imaging modalities like a computed tomography (CT) scan and ultrasonogram (USG) make the diagnosis more difficult. By the time the diagnosis is made, the patient usually presents with metastasis. We present a rare case of difficult to diagnose NME, as repeated skin biopsies and conventional imaging modalities like CT and USG could not detect the underlying glucagonoma. A (68)Ga-DOTANOC positron emission tomography PET-CT was able to detect the underlying cause of NME as glucagonoma of the pancreas and the same investigation confirmed the absence of any metastasis elsewhere in the body. The tumor was excised and patient dramatically improved, and all skin lesions disappeared.

Role of endoscopic ultrasound in evaluation of pancreatic neuroendocrine tumors--report of 22 cases from a tertiary center in Iran.

BACKGROUND: The pancreatic neuroendocrine tumor (pNET) is relatively rare and generally felt to follow an indolent course. EUS has an important role in detection of pNET. This is a review of clinical and radiological presentation and pathologic reports of 22 patients with pNET. PATIENTS AND METHODS: In this study we analyzed clinical and radiological presentations and pathologic reports of all relevant cases who were referred to Taleghani hospital for 3 years since 2008. RESULTS: A total of 22 patients 28-74 years old (mean=49) were enrolled between 2008 and 2011. Among the total, 13 (59%) were male, 9 (41%) were female and 16 (72.7%) had functional tumors. The results of CT were negative in 12 (54%) cases but EUS was capable of detecting the lesions in these patients, cysts being found in 4 (19%) patients. CONCLUSION: EUS is a highly sensitive procedure for the localization of functional pNETs and especially insulinomas. Nonfunctional tumors were detected in more advanced and late stages and cystic lesions were more common in this group.

An unusual case of subclinical diffuse glucagonoma coexisting with two nodules in the pancreas: characteristic features on computed tomography.

A lesion was discovered in the tail of the pancreas by ultrasonography performed during a health checkup for a 59-year-old Japanese man. Abdominal contrast-enhanced computed tomography (CE-CT) revealed strong enhancement in a 4-cm tumor in the pancreatic tail and in a 1-cm tumor in the pancreatic body. Serum glucagon levels were elevated to 54,405 pg/mL and a preoperative diagnosis of glucagonoma was made. The pancreatic tail and spleen were resected en bloc, along with a protruding tumor in the pancreatic body. However, histopathological evaluation revealed diffuse glucagonoma throughout the pancreas. When we retrospectively reviewed abdominal CE-CT after the operation, the entire pancreas was seen to be enlarged and diffusely enhanced by strong spots. Immunohistochemical examination using anti-CD31 demonstrated rich microvessels in two solid glucagonomas as well as microglucagonoma throughout the entire pancreas, indicating hypervascularity. Enlarged pancreas and diffuse enhancement of the pancreas by strong spots may be characteristic features of diffuse glucagonoma on abdominal CE-CT.

Arterial stimulation and venous sampling for glucagonomas of the pancreas.

BACKGROUND/AIMS: Arterial stimulation and venous sampling (ASVS) is a catheter-based diagnostic technique used to identify the localization of an insulinoma or gastrinoma. The aim of this study was to clarify the clinical significance of ASVS for glucagonomas. METHODOLOGY: Eight patients with pancreatic hypervascular tumors and elevated serum glucagon levels in the peripheral blood were enrolled. Pancreatic angiography was performed and a bolus dose of calcium was injected into a suitable artery. Hepatic venous blood samples were then obtained to measure concentrations of glucagon and insulin. All patients underwent surgical resection, and the resected specimens were investigated immunohistochemically. RESULTS: Compared to insulin, the glucagon levels stabilized after calcium stimulation in four patients, with a 1.2-fold increase or decrease. In the remaining four patients, there was a 1.6- to 5.8-fold increase in glucagon levels. The peak value of glucagon was observed at 90s or 120s which was slower than the insulin peak observed in patients with insulinoma. The patients with elevated glucagon levels during ASVS exhibited positive immunostaining of glucagon in resected specimens. CONCLUSIONS: Increase in glucagon after calcium stimulation was observed in patients with glucagonomas. ASVS for glucagonomas may be useful in determining the most suitable surgical procedure.

Pancreatic endocrine tumors with major vascular abutment, involvement, or encasement and indication for resection.

BACKGROUND: Surgery for pancreatic endocrine tumors (PETs) with blood vessel involvement is controversial. HYPOTHESIS: Resection of PETs with major blood vessel involvement can be beneficial. DESIGN: The combined databases of the National Institutes of Health and Stanford University hospitals were queried. MAIN OUTCOME MEASURES: Operation, pathologic condition, complications, and disease-free and overall survival. RESULTS: Of 273 patients with PETs, 46 (17%) had preoperative computed tomography evidence of major vascular involvement. The mean size for the primary PET was 5.0 cm. The involved major vessel was as follows: portal vein (n = 20), superior mesenteric vein or superior mesenteric artery (n = 16), inferior vena cava (n = 4), splenic vein (n = 4), and heart (n = 2). Forty-two of 46 patients had a PET removed: 12 (27%) primary only, 30 (68%) with lymph nodes, and 18 (41%) with liver metastases. PETs were removed by either enucleation (n = 7) or resection (n = 35). Resections included distal or subtotal pancreatectomy in 23, Whipple in 10, and total in 2. Eighteen patients had concomitant liver resection: 10 wedge resection and 8 anatomic resections. Nine patients had vascular reconstruction: each had reconstruction of the superior mesenteric vein and portal vein, and 1 had concomitant reconstruction of the superior mesenteric artery. There were no deaths, but 12 patients had complications. Eighteen patients (41%) were immediately disease free, and 5 recurred with follow-up, leaving 13 (30%) disease-free long term. The 10-year overall survival was 60%. Functional tumors were associated with a better overall survival (P < .001), and liver metastases decreased overall survival (P < .001). CONCLUSION: These findings suggest that surgical resection of PETs with vascular abutment/invasion and nodal or distant metastases is indicated.

Glucagonoma and the glucagonoma syndrome - cumulative experience with an elusive endocrine tumour.

OBJECTIVE: Glucagonoma is a pancreatic neuroendocrine tumour that arises from alpha cells in the pancreas and is often accompanied by a characteristic clinical syndrome. DESIGN: In this report, we present the cumulative experience and clinical characteristics of six patients diagnosed with glucagonoma and the glucagonoma syndrome and treated at our centre during the past 25 years. RESULTS: Although the course of the disease was variable, some features were similar. The median age at diagnosis was 53·5 years; the median time from onset of symptoms to diagnosis was 39 months. Presenting symptoms were as follows: weight loss 5/6 (83%), necrotizing migratory erythema (NME) 5/6 (83%), diabetes mellitus 4/6 (66%) and diarrhoea, weakness and thrombosis 2/6 (33%). Plasma glucagon was elevated in all patients upon diagnosis (range 200-10,000 pm; N < 50). Skin biopsy was diagnostic only in 1/6 specimens obtained, even after revision. Metastatic disease developed in all patients; 4/6 initially presented with hepatic metastasis. All patient symptoms responded to somatostatin analogue therapy. In 4/6, the NME responded to amino acid solutions. Other modes of therapy were as follows: surgery in 3/6 patients, peptide receptor radioligand therapy with (90) Y-DOTATOC (PRRT) in 3/6 patients (two responses) and chemotherapy in three patients (two responded). Four out of six patients died of the disease, and median survival time was 6·25 years (range 2-11) from diagnosis and 8 years (range 8-16) from initial symptoms. Five-year survival was 66%. CONCLUSION: Our data indicate that somatostatin analogues and an aggressive surgical approach offer symptom relief and tumour control. Among other available treatment modalities, PRRT seems to hold the most promise.

Glucagonoma syndrome and necrolytic migratory erythema.

The glucagonoma syndrome is a rare disorder, characterized by necrolytic migratory erythema, elevated serum glucagon levels, abnormal glucose tolerance, weight loss, and anemia in association with a glucagon-secreting alpha-cell tumor of the pancreas. We present a 67-year-old diabetic patient with extensive cutaneous lesions, weight loss, and poor glycemic control. The clinical investigation revealed a pancreatic glucagonoma with resolution of the cutaneous and systemic features after surgical removal. The dermatologic and endocrine approach to this syndrome is discussed here. Early recognition and treatment may prevent metastatic disease and ensure its cure with resolution of the cutaneous and catabolic manifestations.