PMID- 10496602
OWN - NLM
STAT- MEDLINE
DCOM- 19991022
LR  - 20041117
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 12
IP  - 9
DP  - 1999 Sep
TI  - Multiple endocrine neoplasia type 1: atypical presentation, clinical course, and 
      genetic analysis of multiple tumors.
PG  - 919-24
AB  - 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.
FAU - Vortmeyer, A O
AU  - Vortmeyer AO
AD  - Laboratory of Pathology, National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland 20892, USA.
FAU - Lubensky, I A
AU  - Lubensky IA
FAU - Skarulis, M
AU  - Skarulis M
FAU - Li, G
AU  - Li G
FAU - Moon, Y W
AU  - Moon YW
FAU - Park, W S
AU  - Park WS
FAU - Weil, R
AU  - Weil R
FAU - Barlow, C
AU  - Barlow C
FAU - Spiegel, A M
AU  - Spiegel AM
FAU - Marx, S J
AU  - Marx SJ
FAU - Zhuang, Z
AU  - Zhuang Z
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (DNA, Neoplasm)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - Chromosomes, Human, Pair 11/genetics
MH  - DNA, Neoplasm/genetics
MH  - Esophageal Neoplasms/genetics/pathology
MH  - Female
MH  - Humans
MH  - Leiomyoma/genetics/pathology
MH  - Loss of Heterozygosity
MH  - Microsatellite Repeats
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/*pathology
MH  - Neoplasm Proteins/genetics
MH  - Pancreatic Neoplasms/genetics/pathology
MH  - Parathyroid Neoplasms/genetics/pathology
MH  - *Proto-Oncogene Proteins
MH  - Thyroid Neoplasms/genetics/pathology
EDAT- 1999/09/25 00:00
MHDA- 1999/09/25 00:01
CRDT- 1999/09/25 00:00
PHST- 1999/09/25 00:00 [pubmed]
PHST- 1999/09/25 00:01 [medline]
PHST- 1999/09/25 00:00 [entrez]
PST - ppublish
SO  - Mod Pathol. 1999 Sep;12(9):919-24.