Multiple Meningiomas in a Patient with Cowden Syndrome

Abstract

Background Cowden syndrome is a rare, multisystem disease manifesting with increased hamartomas and neoplasms. Though meningioma has been documented in patients with Cowden syndrome, the relationship between these two phenomena is still unclear.

Case Description We report a case of a 43-year-old female patient with a known PTEN mutation and clinical history of Cowden syndrome. A workup of headache demonstrated two skull base meningiomas. At the time of surgery, several additional tiny meningiomas were detected in the same region.

Conclusions The development of multiple meningiomas in a patient with predisposition for tumor is more than coincidental. Though PTEN mutations and deletions have not been shown to be critical for meningioma development, this case challenges that conclusion. In light of recent genetic advances in meningioma molecular pathogenesis, the role of the PTEN/AKT/PI3K pathway is discussed.

Keywords

Cowden syndrome - PTEN - meningioma

• References

• 1 Lloyd II KM, Dennis M. Cowden's disease. A possible new symptom complex with multiple system involvement. Ann Intern Med 1963; 58: 136-142
• 2 Liaw D, Marsh DJ, Li J , et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 1997; 16 (1) 64-67
• 3 Nelen MR, van Staveren WC, Peeters EA , et al. Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. Hum Mol Genet 1997; 6 (8) 1383-1387
• 4 Pilarski R, Burt R, Kohlman W, Pho L, Shannon KM, Swisher E. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst 2013; 105 (21) 1607-1616
• 5 Yu W, He X, Ni Y, Ngeow J, Eng C. Cowden syndrome-associated germline SDHD variants alter PTEN nuclear translocation through SRC-induced PTEN oxidation. Hum Mol Genet 2015; 24 (1) 142-153
• 6 Bennett KL, Mester J, Eng C. Germline epigenetic regulation of KILLIN in Cowden and Cowden-like syndrome. JAMA 2010; 304 (24) 2724-2731
• 7 Lok C, Viseux V, Avril MF , et al; Cancerology Group of the French Society of Dermatology. Brain magnetic resonance imaging in patients with Cowden syndrome. Medicine (Baltimore) 2005; 84 (2) 129-136
• 8 Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol 2012; 13 (5) 283-296
• 9 Chung JH, Eng C. Nuclear-cytoplasmic partitioning of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) differentially regulates the cell cycle and apoptosis. Cancer Res 2005; 65 (18) 8096-8100
• 10 Gimm O, Perren A, Weng LP , et al. Differential nuclear and cytoplasmic expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid tumors. Am J Pathol 2000; 156 (5) 1693-1700
• 11 Arslantas A, Artan S, Oner U , et al. The importance of genomic copy number changes in the prognosis of glioblastoma multiforme. Neurosurg Rev 2004; 27 (1) 58-64
• 12 Rasheed A, Herndon JE, Stenzel TT , et al. Molecular markers of prognosis in astrocytic tumors. Cancer 2002; 94 (10) 2688-2697
• 13 Choy W, Kim W, Nagasawa D , et al. The molecular genetics and tumor pathogenesis of meningiomas and the future directions of meningioma treatments. Neurosurg Focus 2011; 30 (5) E6
• 14 Peters N, Wellenreuther R, Rollbrocker B , et al. Analysis of the PTEN gene in human meningiomas. Neuropathol Appl Neurobiol 1998; 24 (1) 3-8
• 15 Miller Jr R, DeCandio ML, Dixon-Mah Y , et al. Molecular Targets and Treatment of Meningioma. J Neurol Neurosurg 2014; 1 (1)
• 16 Terzi A, Saglam EA, Barak A, Soylemezoglu F. The significance of immunohistochemical expression of Ki-67, p53, p21, and p16 in meningiomas tissue arrays. Pathol Res Pract 2008; 204 (5) 305-314
• 17 Clark VE, Erson-Omay EZ, Serin A , et al. Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science 2013; 339 (6123) 1077-1080
• 18 Brastianos PK, Horowitz PM, Santagata S , et al. Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet 2013; 45 (3) 285-289
• 19 El-Habr EA, Levidou G, Trigka EA , et al. Complex interactions between the components of the PI3K/AKT/mTOR pathway, and with components of MAPK, JAK/STAT and Notch-1 pathways, indicate their involvement in meningioma development. Virchows Arch 2014; 465 (4) 473-485
• 20 Weary PE, Gorlin RJ, Gentry Jr WC, Comer JE, Greer KE. Multiple hamartoma syndrome (Cowden's disease). Arch Dermatol 1972; 106 (5) 682-690
• 21 Starink TM. Cowden's disease: analysis of fourteen new cases. J Am Acad Dermatol 1984; 11 (6) 1127-1141
• 22 Fritsch P, Pechlaner R, Czarnecki N, Hintner H. [The multiple hamartoma syndrome (Cowden syndrome)]. Hautarzt 1981; 32 (6) 285-291
• 23 Lyons CJ, Wilson CB, Horton JC. Association between meningioma and Cowden's disease. Neurology 1993; 43 (7) 1436-1437
• 24 Rimbau J, Isamat F. Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease) and its relation to the multiple hamartoma syndrome (Cowden disease). J Neurooncol 1994; 18 (3) 191-197
• 25 Lindboe CF, Helseth E, Myhr G. Lhermitte-Duclos disease and giant meningioma as manifestations of Cowden's disease. Clin Neuropathol 1995; 14 (6) 327-330
• 26 Staal FJ, van der Luijt RB, Baert MR , et al. A novel germline mutation of PTEN associated with brain tumours of multiple lineages. Br J Cancer 2002; 86 (10) 1586-1591
• 27 Rademaker J, Kim YJ, Leibecke T, Raman SS, Voit C. Cowden disease: CT findings in three patients. Abdom Imaging 2005; 30 (2) 204-207
• 28 Isobe N, Oki S, Murakami T, Ooyama S, Kureshima M, Kurokawa Y. [A case of atypical meningioma with Lhermitte-Duclos disease]. No Shinkei Geka 2005; 33 (12) 1229-1235
• 29 Vasovčák P, Senkeříková M, Hatlová J, Křepelová A. Multiple primary malignancies and subtle mucocutaneous lesions associated with a novel PTEN gene mutation in a patient with Cowden syndrome: case report. BMC Med Genet 2011; 12: 38
• 30 Walsh S, Carter M, Tubridy N, McDermott EW. Lhermitte-Duclos and Cowden diseases: breast cancer as an unusual initial presentation of these overlapping conditions. BMJ Case Rep 2011; 2011