Neuroimaging abnormalities in patients with Cowden syndrome: Retrospective single-center study

Abstract

Background: We retrospectively reviewed the neuroimaging findings of patients with Cowden syndrome and determined their frequency in a single cohort.

Methods: Electronic medical records were queried from January 1999 to January 2017 to identify patients who fit the clinical criteria for diagnosis of Cowden syndrome with or without a documented PTEN mutation. Patients with brain MRI examinations were then identified.

Results: We retrospectively identified 44 patients with Cowden syndrome, 22 of whom had neuroimaging for review. Eleven (50%) had Lhermitte-Duclos disease, 4 (18.1%) had meningiomas, 13 (59.1%) had at least one developmental venous anomaly, 3 had cavernous malformations, 2 had evidence of dural arteriovenous fistula, 7 had increased white matter signal abnormalities relative to age (31.8%), 4 had prominent perivascular spaces, cerebellar tonsillar ectopia was present in 7 of 21 (33.3%), and 1 had cortical malformation.

Conclusions: It is important to recognize that in addition to Lhermitte-Duclos disease, other intracranial findings such as multiple venous anomalies, meningiomas, greater than expected white matter signal abnormality, prominent perivascular spaces, and cortical malformations may warrant a thorough evaluation for Cowden syndrome in the appropriate clinical setting. We further recommend that this broader spectrum of intracranial abnormalities be considered for addition to the Cowden syndrome diagnostic criteria at the time of next revision.

Figure 1. Flow chart illustrating the assembly of the clinical cohorts used for brain MRI review

Patients with Cowden syndrome (CS) all met criteria for operational diagnosis, either without or with a documented PTEN mutation. LDD = Lhermitte-Duclos disease.

Figure 2. Associated MRI findings in patients with Cowden syndrome (CS)

(A) The classic striated appearance of Lhermitte-Duclos disease (LDD) (arrows) is well-demonstrated with T2-weighted imaging in a 67-year-old woman. (B) Axial T1 postcontrast MRI illustrates a large left parietal dural-based extra-axial mass (arrowheads), which was pathologically confirmed to represent a meningioma, in a 54-year-old woman. (C) Axial T1 postcontrast MRI demonstrates bilateral frontal developmental venous anomalies (arrows) in a 50-year-old woman. (D) Numerous foci of white matter hyperintensity (arrows), which are greater than expected for age, are identified on an axial T2-weighted fluid-attenuated inversion recovery sequence in a 39-year-old man. (E) As depicted on an axial T2-weighted sequence, multiple abnormally prominent perivascular spaces (arrows) are present in the cerebral white matter of a 61-year-old man. (F) In a 62-year-old woman, susceptibility-weighted imaging reveals multiple foci of magnetic susceptibility (arrows) in the cerebral white matter, which are presumably related to hemosiderin deposition from chronic microhemorrhages or possibly tiny cavernous malformations. (G) As seen on sagittal T1-weighted MRI, low-lying cerebellar tonsils (arrow) reach the upper aspect of the C1 arch in a 61-year-old woman who had CS without LDD. (H) In a 22-year-old woman with CS and LDD, sagittal T1-weighted image demonstrates cerebellar tonsillar ectopia (arrow) and typical striated appearance of the cerebellar gangliocytoma (asterisk). (I) Sagittal T1-weighted sequence depicts thick and irregularly bumpy cortex (arrows) consistent with a coarse pattern of right perisylvian polymicrogyria in an 8-year-old boy. A separate abnormality in the left frontal lobe had imaging features suspicious for cortical dysplasia (not shown).