Multiple endocrine neoplasia type 1: Atypical presentation, clinical course, and genetic analysis of multiple tumors

Alexander O. Vortmeyer, Irina A. Lubensky, Monica Skarulis, Guang Li, Young Wan Moon, Won Sang Park, Robert Weil, Carrolee Barlow, Allen M. Spiegel, Stephen J. Marx, Zhengping Zhuang

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38 Scopus citations

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is characterized by the development of endocrine tumors of the parathyroid and pituitary glands, pancreas, and duodenum. Less frequently occurring tumors associated with MEN1 include non-endocrine tumors such as lipomas and angiofibromas. An increased incidence of thyroid neoplasms, leiomyomas, adrenal cortical hyperplasia, hepatic focal nodular hyperplasia, and renal angiomyolipoma has been noted in the MEN1 population. The pathogenesis of non-neuroendocrine tumors in MEN1 is unknown. We report a complex clinical course and a detailed morphologic and genetic analysis of a series of tumors that developed in a patient with MEN1. All tumors were microdissected and analyzed for loss of heterozygosity of the MEN1 gene. A germline mutation of the MEN1 gene was detected, and deletions of the MEN1 gene were consistently detected in multiple neuroendocrine tumors involving the parathyroid glands and the pancreas and a hepatic neuroendocrine tumor metastasis, as predicted by Knudson's 'two hit' hypothesis. Two hits of the MEN1 gene were also detected in esophageal leiomyoma tissue, suggesting that tumorigenesis was directly related to the patient's underlying MEN1. In contrast, follicular thyroid adenoma, papillary thyroid carcinoma, hepatic focal nodular hyperplasia, and adrenal cortical hyperplasia consistently showed retained heterozygosity of the MEN1 gene with flanking markers and an intragenic marker. Therefore, these tumors appear to develop along pathogenetic pathways that are different from classical MEN1- associated tumors.

Original languageEnglish (US)
Pages (from-to)919-924
Number of pages6
JournalModern Pathology
Volume12
Issue number9
StatePublished - Sep 1 1999

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Keywords

  • Adrenal cortical hyperplasia
  • Hepatic focal nodular hyperplasia
  • Leiomyoma
  • Loss of heterozygosity
  • MEN1
  • Neuroendocrine tumors
  • Thyroid neoplasms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Vortmeyer, A. O., Lubensky, I. A., Skarulis, M., Li, G., Moon, Y. W., Park, W. S., Weil, R., Barlow, C., Spiegel, A. M., Marx, S. J., & Zhuang, Z. (1999). Multiple endocrine neoplasia type 1: Atypical presentation, clinical course, and genetic analysis of multiple tumors. Modern Pathology, 12(9), 919-924.