MEN I pancreas: A histological and immunohistochemical study

Thompson, Norman W.; Lloyd, Ricardo V.; Nishiyama, Ronald H.; Vinik, Aaron I.; Strodel, William E.; Allo, Maria D.; Eckhäuser, Frederic E.; Talpos, Gary B.; Mervak, Tim

doi:10.1007/bf01654938

Cited by 154 publications

(117 citation statements)

References 40 publications

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“…The evidence for this tendency comes from surgical and autopsy series showing that preneoplastic changes are present in virtually all the MEN 1 patients and throughout the pancreas. 8,32 Evidence for this tendency has also been found in the study by the Ann Arbor group of 39 MEN 1 patients with pancreaticoduodenal tumors, in which 15 (39%) required reoperation after a median follow-up time of 9.9 years, and 12 (31%) had biochemical or imaging evidence of recurrence at a median follow-up of 6.3 years.…”

mentioning

confidence: 70%

Epidemiology Data on 108 MEN 1 Patients From the GTE With Isolated Nonfunctioning Tumors of the Pancreas

Triponez

Dosseh²,

Goudet³

et al. 2006

Annals of Surgery

223

256

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Objective: To analyze the penetrance and clinical course of isolated nonfunctioning tumors of the pancreas (NFTP) in MEN 1 patients, and to propose a strategy for managing them. Summary Background Data: Pancreaticoduodenal tumors develop in a majority of MEN 1 patients and are a major cause of death. The natural history of NFTP is poorly defined, and no clear-cut guidelines have been widely accepted regarding treatment. Methods: Data on 108 patients with isolated NFTP among 579 MEN 1 patients from the French Endocrine Tumor Study Group (GTE) were analyzed. Survival rates were calculated using the Kaplan-Meier method. Results: The penetrance of NFTP was 34% at age 50, making it the most frequent pancreaticoduodenal tumor in MEN 1 patients. Fortythree patients (40%) underwent surgery, 32 of them curatively. No patient died because of surgery. Average life expectancy for patients with NFTP was shorter than that for MEN 1 patients who did not have pancreaticoduodenal tumors. Thirteen patients died during follow-up, 10 due to NFTP. Tumor size was correlated with the risks of metastasis and death. These risks were low for patients with tumors Յ20 mm. Conclusions: NFTP are currently the most common tumors of the pancreaticoduodenal region in patients with MEN 1. Prevention of tumor spread by surgery should be balanced with potential operative mortality and morbidity. We do not recommend routine surgery for NFTP Յ20 mm. (Ann Surg 2006;243: 265-272) M ultiple endocrine neoplasia type 1 (MEN 1) is a rare autosomal dominant condition characterized by the development of endocrine parathyroid, pancreaticoduodenal, and pituitary tumors. In addition, MEN 1 patients are also prone to developing adrenal tumors, neuroendocrine tumors (in particular of the thymus or bronchus), dermal lesions, thyroid disease, and meningeal tumors. 1-7Pancreaticoduodenal tumors are often multiple, have been shown at autopsy to have developed in up to 80% of patients with MEN 1, and are a major cause of premature death in these patients. 8 -12 Most pancreaticoduodenal tumors are functioning tumors, the most frequent of which are gastrinomas and insulinomas, followed by the rare glucagonomas, VIPomas, GRFomas, and somatostatinomas. Surgical resection is the treatment of choice for functioning tumors of the pancreas, although controversy exists regarding the timing of surgery for gastrinomas. [13][14][15][16][17][18] In the absence of hormonal symptoms, nonfunctioning tumors of the pancreas (NFTP) have been recognized as a separate entity whose penetrance in the MEN 1 population is not well known. 19,20 In addition, because large surgical series of patients presenting with isolated NFTP are lacking and few clinical series have followed patients with NFTP, no clear-cut treatment guidelines have been widely accepted. Some authors have recommended a conservative approach for asymptomatic NFTP less than 1, 2, or 3 cm. [21][22][23][24] Others have recommended early surgical excision of all tumors as soon as they are found on imaging studies, or even ea...

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mentioning

confidence: 70%

Epidemiology Data on 108 MEN 1 Patients From the GTE With Isolated Nonfunctioning Tumors of the Pancreas

Triponez

Dosseh²,

Goudet³

et al. 2006

Annals of Surgery

223

256

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“…The hallmark of dpNETs in MEN1 is multiplicity, which is in contrast to the mostly solitary sporadic dpNETs (Thompson et al 1984, Pipeleers-Marichal et al 1993, Crippa et al 2012. All histologic subtypes can occur in MEN1.…”

Section: Dpnets In Men1mentioning

confidence: 99%

“…All histologic subtypes can occur in MEN1. At pathology, all MEN1 patients have multiple micro-adenomas (pNETs !5 mm without clinical syndrome) dispersed throughout the pancreas associated with one or more NETs R5 mm (Thompson et al 1984, Kloppel et al 1986, Le Bodic et al 1996, Anlauf et al 2006b). These multiple dpNETs in MEN1 arise from independent clonal events, as demonstrated by different allelic deletion and retention patterns in synchronous tumors (Debelenko et al 1997b, Hessman et al 1999, Perren et al 2007.…”

Section: Dpnets In Men1mentioning

confidence: 99%

“…These multiple dpNETs in MEN1 arise from independent clonal events, as demonstrated by different allelic deletion and retention patterns in synchronous tumors (Debelenko et al 1997b, Hessman et al 1999, Perren et al 2007. Apart from these tumors other lesions such as islet cell hyperplasia/enlargement, nesidioblastosis, and atypical or monohormonal endocrine cell clusters are frequently observed in the MEN1 pancreas, leading to different theories as to the cell of origin for pNETs (Thompson et al 1984, Le Bodic et al 1996, Vortmeyer et al 2004, Perren et al 2007. Normal pancreatic islets and alternatively ductal/acinar cells are proposed to be the precursor cells for pNETs (Vortmeyer et al 2004, Perren et al 2007.…”

Section: Dpnets In Men1mentioning

confidence: 99%

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Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis

Pieterman¹,

Conemans²,

Dreijerink³

et al. 2014

Endocrine-Related Cancer

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Mutations of the multiple endocrine neoplasia type 1 (MEN1) gene lead to loss of function of its protein product menin. In keeping with its tumor suppressor function in endocrine tissues, the majority of the MEN1-related neuroendocrine tumors (NETs) show loss of heterozygosity (LOH) on chromosome 11q13. In sporadic NETs, MEN1 mutations and LOH are also reported, indicating common pathways in tumor development. Prevalence of thymic NETs (thNETs) and pulmonary carcinoids in MEN1 patients is 2-8%. Pulmonary carcinoids may be underreported and research on natural history is limited, but disease-related mortality is low. thNETs have a high mortality rate. Duodenopancreatic NETs (dpNETs) are multiple, almost universally found at pathology, and associated with precursor lesions. Gastrinomas are usually located in the duodenal submucosa while other dpNETs are predominantly pancreatic. dpNETs are an important determinant of MEN1-related survival, with an estimated 10-year survival of 75%. Survival differs between subtypes and apart from tumor size there are no known prognostic factors. Natural history of nonfunctioning pancreatic NETs needs to be redefined because of increased detection of small tumors. MEN1-related gastrinomas seem to behave similar to their sporadic counterparts, while insulinomas seem to be more aggressive. Investigations into the molecular functions of menin have led to new insights into MEN1-related tumorigenesis. Menin is involved in gene transcription, both as an activator and repressor. It is part of chromatin-modifying protein complexes, indicating involvement of epigenetic pathways in MEN1-related NET development. Future basic and translational research aimed at NETs in large unbiased cohorts will clarify the role of menin in NET tumorigenesis and might lead to new therapeutic options.

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“…Recently, precursor lesions giving rise to pancreatic neuroendocrine tumors (PNETs) have drawn much attention and become more understood. It is well known now that diffuse precursor lesions including endocrine cell hyperplasia, dysplasia, and microadenomas are present in the pancreata of patients with familial tumor syndromes such as multiple endocrine neoplasia syndrome type 1 (MEN1) and von Hippel-Lindau disease, and of animal models of PNETs [12][13][14][15][16] . In the pancreata of patients with MEN1 and mice with heterozygous MEN1 inactivation, the hyperplastic endocrine cells are polyclonal and multihormonal and contain the normal menin allele, while microadenomas have to first lose the normal menin allele [17,18] .…”

Section: Introductionmentioning

confidence: 99%

Elusive liver factor that causes pancreatic α cell hyperplasia: A review of literature

Zheng

Lucas

et al. 2015

WJGP

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Tumors and cancers of the gastrointestinal tract and pancreas are commonly derived from precursor lesions so that understanding the physiological, cellular, and molecular mechanisms underlying the pathogenesis of precursor lesions is critical for the prevention and treatment of those neoplasms. Pancreatic neuroendocrine tumors (PNETs) can also be derived from precursor lesions. Pancreatic α cell hyperplasia (ACH), a specific and overwhelming increase in the number of α cells, is a precursor lesion leading to PNET pathogenesis. One of the 3 subtypes of ACH, reactive ACH is caused by glucagon signaling disruption and invariably evolves into PNETs. In this article, the existing work on the mechanisms underlying reactive ACH pathogenesis is reviewed. It is clear that the liver secretes a humoral factor regulating α cell numbers but the identity of the liver factor remains elusive. Potential approaches to identify the liver factor are discussed. lesions. One of the precursor lesions, reactive pancreatic α cell hyperplasia is caused by glucagon signaling disruption and invariably evolves into pancreatic neuroendocrine tumors. In this article, the existing work on the mechanisms underlying the novel precursor lesion is reviewed. It is clear that the liver secretes a humoral factor regulating pancreatic α cell numbers but the identity of the liver factor remains elusive. Potential approaches to identify the liver factor are discussed.Yu R, Zheng Y, Lucas MB, Tong YG. Elusive liver factor that causes pancreatic α cell hyperplasia: A review of literature. World J Gastrointest Pathophysiol 2015; 6(4): 131-139 Available from:

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MEN I pancreas: A histological and immunohistochemical study

Cited by 154 publications

References 40 publications

Epidemiology Data on 108 MEN 1 Patients From the GTE With Isolated Nonfunctioning Tumors of the Pancreas

Epidemiology Data on 108 MEN 1 Patients From the GTE With Isolated Nonfunctioning Tumors of the Pancreas

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis

Elusive liver factor that causes pancreatic α cell hyperplasia: A review of literature

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