Cowden disease and Lhermitte-Duclos disease: characterization of a new phakomatosis

Lhermitte-Duclos disease, or dysplastic gangliocytoma of the cerebellum, is an unusual hamartomatous lesion that can cause progressive mass effects in the posterior fossa. Cowden disease, or multiple hamartoma-neoplasia syndrome, is a rare autosomal dominant disorder characterized by mucocutaneous hamartomas and high incidences of systemic malignancies. We recently treated a patient with manifestations of both Lhermitte-Duclos disease and Cowden disease, and we were intrigued by the occurrence of these two rare disorders in the same patient. The purpose of the present study was to examine the nature of the association between Lhermitte-Duclos disease and Cowden disease.

The records for all patients who had been diagnosed at our institution as having Lhermitte-Duclos disease were reviewed, to determine whether these patients also exhibited manifestations of Cowden disease. Data were obtained from multiple sources, including patient interviews, correspondence with treating physicians, and chart reviews.

During the past 40 years, five patients were diagnosed at Case Western Reserve University as having Lhermitte-Duclos disease. All five patients exhibited manifestations of Cowden disease. Before this review, Cowden disease had not been diagnosed for three of the patients. In our most recent case, the diagnoses of both disorders were established preoperatively. That patient was observed to have a deletion in the critical portion of Exon 5 of the PTEN gene, the gene associated with Cowden disease.

Inclusion of Lhermitte-Duclos disease in the Cowden disease spectrum suggests that Cowden disease is a true phakomatosis, with hamartomas arising from cutaneous and neural ectoderm. Recent advances in molecular genetics may help to refine the current descriptive classification of the phakomatoses. The association between Lhermitte-Duclos disease and Cowden disease has been under-recognized and under-reported. Recognition of this association has direct clinical relevance, because diligent long-term follow-up monitoring of individuals with Lhermitte-Duclos disease and Cowden disease may lead to the early detection of malignancy.