, Volume 16, Issue 4, pp 423–428 | Cite as

Medullary thyroid cancer, leukemia, mesothelioma and meningioma associated with germline APC and RASAL1 variants: a new syndrome?

  • Anna Angelousi
  • Nikolaos Settas
  • Fabio R. Faucz
  • Charalampos Lyssikatos
  • Martha Quezado
  • Narjes Nasiri-Ansari
  • Constantine A. Stratakis
  • Eva KassiEmail author
Case report


Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor hereditary in 35% of cases. The most common syndromic form is in the context of the multiple endocrine neoplasia type 2 (MEN 2) syndromes in association with other tumors and due to germline RET mutations. We describe a 57-year-old female patient diagnosed with sporadic MTC. The patient had a history of other neoplasias, such as acute myeloid leukemia, for which she had received chemotherapy, and two other solid tumors, peritoneal mesothelioma and meningioma. Genetic analyses were carried out including whole exome and Sanger sequencing (WES and SS) and loss-of-heterozygosity (LOH) testing for the respective loci. Immunohistochemistry (IHC) was used for the detection of proteins of interest. WES showed two germline variants in the APC and RASAL1 genes confirmed by SS. In MTC tissue only there was a RET variant identified by SS; germline studies did not show any RET sequence changes. The pattern of tumors in this patient is unusual for either one of the APC- or RASAL1-associated neoplasms and her non-MEN 2-associated MTC contained a RET variant like other sporadic MTCs. As in other patients with more than one genetic variant predisposing to tumors, it is possible that this case represents a unique association.

Key words

Acute myeloid leukemia Medullar thyroid carcinoma Meningioma MEN2 Peritoneal mesothelium RET 


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Copyright information

© Hellenic Endocrine Society 2017

Authors and Affiliations

  • Anna Angelousi
    • 1
    • 2
  • Nikolaos Settas
    • 2
  • Fabio R. Faucz
    • 2
  • Charalampos Lyssikatos
    • 2
  • Martha Quezado
    • 3
  • Narjes Nasiri-Ansari
    • 4
  • Constantine A. Stratakis
    • 2
  • Eva Kassi
    • 1
    • 4
    Email author
  1. 1.1st Department of Internal Medicine, Laiko Hospital, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  2. 2.Section on Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)National Insitutes of Health (NIH)BethesdaUSA
  3. 3.Laboratory of PathologyNational Cancer Institute (NCI), NIHBethesdaUSA
  4. 4.Department of Biological ChemistryNational and Kapodistrian University of AthensAthensGreece

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