Brain Magnetic Resonance Imaging in Patients With Cowden Syndrome

Abstract

Cowden syndrome (CS) is a rare autosomal dominant genodermatosis, characterized by multiple hamartomas, particularly of the skin, associated with high frequencies of breast, thyroid, and genitourinary malignancies. Although Lhermitte-Duclos disease (LDD) or dysplastic gangliocytoma of the cerebellum, a slowly progressive unilateral tumor, is a major criterion of CS, its frequency in patients with CS is unknown. Other cerebral abnormalities, especially meningioma and vascular malformations, have also been described, albeit rarely, in these patients. The aim of the current study was to use cerebral magnetic resonance imaging (MRI) to evaluate LDD frequency and to investigate other brain abnormalities in CS patients recruited by dermatologists. A multicenter study was conducted in 8 hospital dermatology departments between January 2000 and December 2003. Twenty patients with CS were included; specific cerebral MRI abnormalities were found in 35% (7/20) of them. Cerebral MRI revealed LDD in 3 patients, a meningioma in 1, and numerous vascular malformations in 6 patients. Five patients had venous angiomas (3 associated with LDD) and 2 patients had cavernous angiomas (1 associated with LDD and a venous angioma). The discovery of asymptomatic LDD in 3 patients and a cavernous angioma in another prompted us to perform neurologic examinations regularly and MRI to estimate the size and the extension of the tumor, and to assess the need for surgery. CS similarities with Bannayan-Riley-Ruvalcaba (BRR) are discussed because some patients could also have the BRR phenotype (for example, genital lentigines, macrocephaly, multiple lipomas) and because BRR seems to have more central nervous system vascular anomalies. Because CS signs can involve numerous systems, all physicians who might encounter this disease should be aware of its neurologic manifestations. Our findings confirm the contribution of brain MRI to detecting asymptomatic LDD, vascular malformations, and meningiomas in patients with CS.

Bannayan-Riley-Ruvalcaba Syndrome: MRI Neuroimaging Features in a Series of 7 Patients

“…23 High frequency of vascular malformations was noted in a study of 20 patients with CS, where 5 patients had venous angiomas (3 associated with Lhermitte-Duclos disease [LDD]) and 2 patients had cavernous angi- omas (1 associated with LDD) with a significant proportion related to LDD. 14 No vascular anomalies were found in our 7 patients, but this probably is an underestimate because none of our patients received contrast material. More recently, congenitally enlarged VR spaces have been described in a case of BRRS.…”

“…19 Published case reports have described rare cases of meningiomas, frontal vascular hamartoma, intracranial lipomatous hamartoma, and malignant intracranial human chorionic gonadotropin-secreting tumor in patients with BRRS. 14,20 The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis. 21 High-flow vascular malformations, 1 including dural AVM, 10 hemangiomata, and vertebral angiomas, 22 may exist in patients with BRRS.…”

“…One follow-up MR imaging study was available for comparison, and the cystic dilation of the VR spaces appeared nonprogressive. Lok et al 14 reported cystic dilation of the VR spaces in 3 (15%) of 20 patients (ages 34 -56 years) with CS. Merks et al 24 described a mother and 3 sons with CS/BRRS and variable phenotype: 1 family member having macrocephaly, normal intelligence, and minimal pigmentation abnormalities; another member with macrocephaly with developmental delay; another with macrocephaly, delay and lipoma; and the last family member having hemimegalencephaly, Jadassohn naevus sebaceous, and neonatal demise.…”

Lhermitte-Duclos disease with neurofibrillary tangles in heterotopic cerebral grey matter

“…To our best knowledge, there is no known link between LDD or PTEN mutations and any of these conditions. However, PTEN mutations are associated with a high rate of vascular malformations [37] and several studies demonstrated cavernous and venous angiomas [22] as well as other developmental vascular abnormalities in LDD [2,27,41]. An association of this mutation with LDD may explain striking hypervascularisation of gangliocytomas observed in one large study [1], and possible contribution to the widespread presence of telangiectasias in our patient.…”

Atypical focal cortical dysplasia in a patient with Cowden syndrome

“…To our knowledge, such brain MRI imaging has not been described previously in Cowden syndrome. 9 Apart from regulating cell growth, the PTEN gene also plays a role in cell migration. It interacts with focal adhesion kinase, which results in the inhibition of cell migration and spread.…”