Association between Cowden syndrome and Lhermitte-Duclos disease: report of two cases and review of the literature.

BACKGROUND

The authors describe 2 cases of dysplasic gangliocytoma of the cerebellum or Lhermitte-Duclos disease revealing Cowden disease or multiple hamartoma neoplasia syndrome. Cowden disease is a rare autosomal dominant disorder, now considered as a phakomatosis. Nevertheless, relationships between both conditions still remain unclear, since Lhermitte-Duclos disease can also be sporadic.

METHODS

Two patients, 25 and 27 years old, were admitted to the emergency department for an acute intracranial hypertension. In both cases, magnetic resonance imaging (MRI) scan showed a mass in the cerebellar hemisphere. Pathological examination of surgical resection specimens concluded Lhermitte-Duclos disease. Because of the patients' previous personal and familial medical history, Cowden disease was suspected and confirmed by mutational analysis of the phosphatase and tensin homolog (PTEN) gene. In the first case, a nonsense punctual mutation in exon 8 was found. In the second one, a mutation was revealed in the exon 5, a mutational hot spot encoding the phosphatase catalytic core motif.

CONCLUSIONS

Lhermitte-Duclos disease and Cowden disease can be associated. Germline mutations of PTEN gene are known to be implicated in Cowden disease. This gene, located at chromosome 10q23-3, is a tumor suppressor gene that encodes a protein with phosphatase activity. To date, more than 80 mutations have been reported in Cowden disease. When the diagnosis of either one of these two disorders is established, it is imperative to search for the other one to detect early malignant lesions that occur in Cowden disease. Finally, a long-term follow up of the patient is required and a thorough familial screening is necessary.