Giant Malignant Insulinoma Which Developed from a Non-Functioning Pancreatic Tumor Over a Long Period of Time

Sugiyama, Toru; Kouyama, Ryuji; Tani, Yuji; Izumiyama, Hajime; Akashi, Takumi; Kishimoto, Seiji; Arii, Shigeki; Hirata, Yukio

doi:10.2169/internalmedicine.49.3540

Cited by 15 publications

(7 citation statements)

References 25 publications

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“…Since 2001, the mitotic activity, Ki-67 index, and grade have been reported for 17 patients with giant insulinomas (Table 2) [5–7, 12–14, 16–19, 21]. We compared the grade, the rate of metastases and duration of follow-up of 18 cases, including the present case.…”

Section: Discussionmentioning

confidence: 98%

“…The severity of hypoglycemia varies from patient to patient and has no direct relationship with tumor burden [10]. Sugiyama et al [7] suggested that giant insulinoma initially diagnosed as non-functioning pNETs may secondarily become functioning.…”

Section: Discussionmentioning

confidence: 99%

“…Some authors have defined “giant” insulinomas as ≥9 cm in largest dimension [6, 7]. We here report the characteristics and treatment of a giant insulinoma with peripancreatic local invasion and lymph node metastasis and present a review of published reports.…”

Section: Introductionmentioning

confidence: 94%

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Giant insulinoma: report of a case and review of published reports

et al. 2016

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BackgroundLarger insulinomas are reportedly more likely to be malignant; however, their biological behavior has not been clearly elucidated. We here report the characteristics and treatment of a giant insulinoma with local invasion and lymph node metastasis. We also review published reports concerning the clinical features of giant insulinomas and comparing their grading with that of pancreatic neuroendocrine tumors.Case presentationA 71-year-old man was referred to our hospital for investigation of persistent hypoglycemia. On the current presentation, laboratory tests showed serum glucose, immunoreactive insulin, and C peptide concentrations of 45 mg/dL, 17.2 μIU/mL and 4.1 ng/mL, respectively. Dynamic magnetic resonance imaging showed a hypervascular tumor measuring 13.5 cm in the head of the pancreas. Computed tomography scanning demonstrated local invasion and lymph node involvement. He thus had Whipple’s triad, which is associated with malignant insulinoma. No distant metastases having been identified, pancreaticoduodenectomy was performed. Intraoperatively, three separate tumors were identified in the pancreatic head. Pathological examination showed all three tumors were pancreatic neuroendocrine tumors; the tumor cells in the largest mass were strongly immunoreactive for insulin. The Ki-67 index was 2–5% in most parts of the largest tumor and over 20% in the poorly differentiated areas. This tumor was classified as neuroendocrine carcinoma in accordance with the 2010 World Health Organization classification of pancreatic endocrine neoplasms. He remains free of evidence of recurrence 2 years postsurgery.A review of published reports indicated that giant insulinomas are more malignant than smaller ones, and metastatic disease is found on presentation in 56% of patients with giant insulinomas; however, we were unable to identify any correlation between grade of pancreatic neuroendocrine tumor and biological behavior of giant insulinomas.ConclusionsGiant insulinomas more frequently exhibit malignant behavior, such as local invasion, lymph node involvement, and liver metastasis, than smaller ones. However, there was no relationship between grade and rate of metastases or survival in this small case series. Identification of useful biological markers is necessary.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Giant insulinoma: report of a case and review of published reports

et al. 2016

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“…En la primera, es posible que un insulinoma con pobre producción de insulina crezca muy lentamente durante un largo período de tiempo sin causar síntomas, hasta que alcanzan un gran tamaño capaz de producir suficiente insulina para inducir los ataques de hipoglicemia (12,20) . En la segunda, es posible que haya un cambio fenotípico de un TNEP no funcionante que facilite su transformación a un tumor productor de insulina (21) .…”

Section: Discussionunclassified

Insulinoma pancreático gigante

et al. 2016

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ResumenLos insulinomas son los tumores neuroendocrinos pancreáticos más frecuentes y típicamente son benignos y pequeños. Los insulinomas gigantes de páncreas son tumores raros. Reportamos el caso de un paciente varón de 67 años, quien presentaba síntomas y signos de hipoglicemia. Subsecuentes estudios de laboratorio y radiológicos establecieron el diagnóstico de un insulinoma de 13,5 cm. Fue sometido a pancreaticoduodenectomía. A pesar del tamaño, en la evaluación patológica no se identificó invasión local ni metástasis. Además de la descripción de la presentación clínica y los hallazgos operatorios, se realiza una revisión de las opciones para la localización y manejo de los insulinomas. Palabras clave. Insulinoma, Gigante; Páncreas, Neoplasias; Tumores Neuroendocrinos. Abstract Insulinomas are the most common pancreatic neuroendocrine tumors and are typically small and benign. Giant pancreatic insulinomas are rare pancreatic tumors. We report a 67 year old man who presented with signs and symptoms of hypoglycemia. Subsequent laboratory and radiologic studies established the diagnosis of a 13.5 cm insulinoma. The patient underwent a pancreatoduodenectomy. Despite the size, neither local invasion nor metastatic disease was identified on pathological evaluation. In addition to describing the clinical presentation and operative findings, localization and management options of insulinomas are reviewed. Los tumores neuroendocrinos de páncreas (TNEP) tienen una incidencia estimada en 1 por 100 000 habitantes (1,2) y se dividen en dos grupos: aquellos asociados con un síndrome funcional debido a la secreción ectó-pica de una sustancia activa biológica (tumores funcionantes) y aquellos que no están asociados con un síndrome funcional (usualmente llamados no funcionantes) (1,2) . Los TNEP funcionantes incluyen a los insulinomas, gastrinomas, VIPomas, somatostatinomas, glucagonomas, TNEP que causan liberación de la hormona de crecimiento y un grupo menos común de TNEP que secretan ACTH (ACTHomas) y causan síndrome de Cushing, TNEP que causan síndrome carcinoide, TNEP que causan hipercalcemia y muy raramente TNEP ectópicos que secretan hormona luteinizante, renina o eritropoyetina. Los TNEP (funcionantes y no funcionantes) secretan también otras sustancias (cromogranina, sinaptofisina, enolasa neuronal específica, subunidades de la gonadotropina coriónica humana, neurotensina, grhelina), sin embargo, estas no causan un síndrome hormonal especifico (2,3) . Los insulinomas son los TNEP funcionantes más frecuentes, con una incidencia reportada de 4 casos por millón de habitantes por año, con un pico de incidencia específica en la quinta década de la vida y con una leve predilección por el sexo femenino (4) .Más del 90% de los insulinomas son tumores pequeños y únicos; aproximadamente 10% son múltiples, menos del 10% son malignos (clásicamente determinada por la evidencia de invasión local o metástasis) y del 5% al 10% están asociados con la neoplasia endocrina múltiple tipo 1 (NEM -1) (4-6) o síndrome de Wermer, desorden au...

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“…The natural history of insulinomas suggests that malignant transition from benign disease is rare [17]. Other trigger factors for such transition or de-novo occurrence of insulinomas are currently only speculative and not too well known.…”

Section: Glucocorticoidsmentioning

confidence: 99%

Severe Refractory Hypoglycaemia in an Acutely Ill Elderly Man with Type 2 Diabetes Mellitus

Govindan¹,

Singh²,

Kamath³

et al. 2013

J Diabetes Metab

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Background: Hypoglycaemia in elderly Type 2 diabetes mellitus (T2DM) patients causes significant morbidity as the elderly are more prone to the effects of neuroglycopenia and are unable to mount a rapid and effective counter response. Rarely an insulinoma may occur in elderly T2DM subjects and may cause refactory hypoglycaemia.Case report and management: An octagenarian man with T2DM, Parkinson's disease and atrial fibrillation was admitted with leg cellulitis and was treated appropriately. He then developed Klebsiella pneumoniae pneumonia and septicaemia and an acute coronary syndrome. However his stay in hospital was characterized by multiple, frequent, symptomatic and distressing hypoglycaemia requiring ferquent intravenous glucose.Elevated serum insulin and C peptide levels during hypoglycaemia (plasma glucose 1.8 mmol/l), high chromogranin A, and a 2.5 cm low density lesion in the pancreatic head with a liver secondary confirmed a metastatic insulinoma. He was unsuitable for invasive investigations. His hypoglycaemia was refractory to high dose diazoxide, prednisolone and octereotide. Conclusions:We report a malignant insulinoma in an elderly, T2DM patient whose disease was punctuated by distressing hypoglycaemia. A palliative approach was adopted with close involvement of the patient and his family. Severe Refractory Hypoglycaemia in an Acutely IntroductionType 2 diabetes mellitus (T2DM) is common in the elderly with an estimated crude prevalence of 16.7% in 60-74 year olds in the USA [1]. Hypoglycaemia is dangerous in them because of a heightened susceptibility to neuroglycopenia [2] and their inability to mount a prompt and strong neuroendocrine response to it [3]. Amongst the common causes of hypoglycaemia, agents such as sulphonylureas, insulin secretagogues and insulin, or drugs potentiating their effects (e.g. incretins), are important. If responsible, these drugs should be withdrawn promptly. In the absence of incriminating drugs, other rarer but well recognised causes should be considered (Table 1).The rare insulin secreting neuroendocrine tumour (NET), the insulinoma, which occurs mainly in young and middle aged individuals, is one of them [4]. The hallmark of an insulinoma is hypoglycaemia. The majority of them are benign but rare malignant insulinomas present a complicated problem because of refractiory hypoglycaemia and the complexities of tumour resection -many have already metastasized at presentation [5]. Newer therapeutic modalities have been used but they are currently essentially palliative e.g. the tyrosine kinase inhibitor sunitinib and the mTOR inhibitor evorolimus [6,7]. Interestingly, insulinomas may very rarely complicate pre-existing diabetes mellitus although there appears to be no causal relationship [8][9][10]. The aetiology of the condition in T2DM is speculative but the effects of chronic hyperinsulinaemia do not seem to play a role because of the paucity of insulinomas in T2DM.We present an octagenarian T2DM subject who developed refractory severe hypoglycaemia durin...

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Giant Malignant Insulinoma Which Developed from a Non-Functioning Pancreatic Tumor Over a Long Period of Time

Cited by 15 publications

References 25 publications

Giant insulinoma: report of a case and review of published reports

Giant insulinoma: report of a case and review of published reports

Insulinoma pancreático gigante

Severe Refractory Hypoglycaemia in an Acutely Ill Elderly Man with Type 2 Diabetes Mellitus

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