Cowden disease and Lhermitte Duclos disease, markers of breast carcinoma: Report of two patients

Large data base registries have shown that up to 20% of women with breast cancer have one affected relative and estimate that 5% of breast cancers are attributable to major genes such as BRCA1 or BRCA2 [1]. The management of familial breast cancers requires a specific approach, aiming at early diagnosis, familial surveillance, and specific treatments adjusted to their specific natural history. BRCA1 and BRCA2 linked families have been identified as the commonest genetic condition predisposing to breast cancer but their treatment remain controvertial. Other inherited conditions have been recently identified as risk factors for breast carcinoma. Among them, genodermatosis are of specific interest. These inherited syndromes characterized by hamartomas of ectodermal, endodermal or mesodermal origin affect multiple organs. Most of them have an autosomal dominant pattern of inheritance. The increased incidence of carcinomas reported in these patients gives rise to specific interest. Cowden's disease (CD) and Lhermitte Duclos disease (LDD) are of particular interest, not only for their multisystem abnormalities, but also for their neoplastic risk. CD was initially described in 1962 by Llyod and Denys [2]. Skin, gingival, or digestive papules are considered pathognomonic but thyroid, breast, and the central nervous system can also be involved and need close monitoring [3]. As neurological abnormalities produce non specific symptoms, they appear underdiagnosed. Hydrocephaly, craniomegaly, epilepsy, intracranial hypertension, cerebellar syndrome or LD syndrome have been reported. LDD is a congenital benign cerebellar hamartoma described as a purkinjenoma or a gangliocytoma by Lhermitte and Duclos [4]. The occurrence of fullblown CD with thyroid, digestive or breast lesions in patients with LDD can not be considered as fortuitous. A strong linkage between these two phacomatosis have been commonly accepted. This close association should be recognized and has led to further genetic analysis, resulting in the identification of the Cowden's gene. We report two patients with breast cancer and Cowden or Lhermitte Duclos disease. We will discuss these two congenital disorders, their features, the risk of cancer and recent advances in genetic findings.