Endocrinol Metab.  2014 Jun;29(2):146-153. 10.3803/EnM.2014.29.2.146.

Genetic Analysis of Multiple Endocrine Neoplasia Type 1 (MEN1) Leads to Misdiagnosis of an Extremely Rare Presentation of Intrasellar Cavernous Hemangioma as MEN1

Affiliations
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Gachon Univeristy School of Medicine, Incheon, Korea. shleemd@gachon.ac.kr

Abstract

BACKGROUND
Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder characterized by the simultaneous occurrence of endocrine tumors in target tissues (mainly the pituitary, endocrine pancreas, and parathyroid glands). MEN1 is caused by mutations in the MEN1 gene, which functions as a tumor suppressor and consists of one untranslated exon and nine exons encoding the menin protein. This condition is usually suspected when we encounter patients diagnosed with tumors in multiple endocrine organs, as mentioned above.
METHODS
A 65-year-old woman who underwent surgery for a pancreatic tumor (serous cystadenoma) 5 years previously was referred to our hospital due to neurologic symptoms of diplopia and left ptosis. Brain magnetic resonance imaging revealed a 3.4-cm lesion originating from the cavernous sinus wall and extending into the sellar region. It was thought to be a nonfunctioning tumor from the results of the combined pituitary function test. Incidentally, we found that she also had a pancreatic tumor, indicating the necessity of genetic analysis for MEN1.
RESULTS
Genomic analysis using peripheral leukocytes revealed a heterozygous c.1621G>A mutation in the MEN1 gene that was previously reported to be either a pathogenic mutation or a simple polymorphism. We pursued a stereotactic approach to the pituitary lesion, and microscopic findings of the tumor revealed it to be an intrasellar cavernous hemangioma, a rare finding in the sellar region and even rarer in relation to oculomotor palsy. The patient recovered well from surgery, but refused further evaluation for the pancreatic lesion.
CONCLUSION
There is great emphasis placed on genetic testing in the diagnosis of MEN1, but herein we report a case where it did not assist in diagnosis, hence, further discussion on the role of genetic testing in this disease is needed. Also, in cases of pituitary tumor with cranial nerve palsy, despite its low prevalence, intrasellar cavernous hemangioma could be suspected.

Keyword

Multiple endocrine neoplasia type 1; MEN1 gene; Intrasellar cavernous hemangioma

MeSH Terms

Aged
Brain
Cavernous Sinus
Cranial Nerve Diseases
Diagnosis
Diagnostic Errors*
Diplopia
Exons
Female
Genetic Testing
Hemangioma, Cavernous*
Humans
Islets of Langerhans
Leukocytes
Magnetic Resonance Imaging
Multiple Endocrine Neoplasia Type 1*
Neurologic Manifestations
Paralysis
Pituitary Function Tests
Pituitary Neoplasms
Prevalence

Figure

  • Fig. 1 (A, B) Preoperative magnetic resonance imaging. A 3.4-cm enhanced mass (arrows) with lobulated contour at the cavernous sinus extending into the sellar region (A, axial view; B, coronal view). (C, D) Three months after radiosurgery, the enhanced mass exhibits a decrease in the extent of the lobulated contour at the cavernous sinus extending into the sellar region (C, axial view; D, coronal view).

  • Fig. 2 A 2.5-cm arterial wall enhancing mass with distal p-duct dilatation in the pancreas body (arrows).

  • Fig. 3 (A, B) On histologic examination, the mass was composed of dilated vessels occasionally containing thrombi (A, H&E stain, ×100; B, H&E stain, ×400). (C) Immunohistochemically, these endothelial cells were fully reactive in CD31 (CD31, ×400). These findings were indicative of cavernous hemangioma.

  • Fig. 4 Polymerase chain reaction-direct sequencing demonstrates the tumor's heterogeneous pattern and variant allele, suggesting that a change occurred to the nucleotide sequence from the GCA to ACA (alanine to threonine).

  • Fig. 5 PolyPhen-2 is a tool for prediction of the possible impact of amino acid substitutions on the structure and function of human proteins. The PolyPhen-2 report indicates that the heterogeneous c.1621G>A (Ala541Thr) mutation is predicted to be benign.


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