Lhermitte Duclos Disease - Adolescent girl with daytime sleepiness and prolonged central apneas

We report a patient who at 9 years of age received a brain MRI due to café-au-laît spots as part of a work-up for NF-1. At age of 15 years, she developed daytime sleepiness. Examination showed a macrocephaly (60 cm), café-au-lait spots and fibromas. Polysomnography revealed multiple long-lasting central apneas.

MRI revealed a “tiger-striped” tumour in the left cerebellar hemisphere (Fig.1) and swelling of the left side leading to tonsillar herniation (Fig.1). Patient was admitted to the Neurosurgical Department and a partial resection was performed. Histopathological studies revealed numerous abnormalities which detailed in Figure 2. Altogether these findings were suggestive of Lhermitte Duclos Disease (LDD). Sleep apnea persisted requiring a ventriculoperitoneal shunt. MRI follow-up showed complete resolution of tonsillar herniation (Fig. 1h).  

LDD is a rare benign tumour characterized by alteration of the cerebellar laminar cytoarchitecture [1]. It can occur as an isolated condition, but it can also be associated with a hereditary cancer syndrome called Cowden disease or Cowden syndrome (CS), an autosomal-dominant cancer syndrome caused by a germline mutation in the phosphatase and tensin homolog (PTEN) gene, a tumour suppressor gene [2] leading to dysfunction in the mTOR-signaling pathway. CS is associated with breast, thyroid, colorectal, kidney cell and endometrial cancers stressing the need of early diagnosis and preventive measures [3].

Imaging findings and medical history of cutaneous abnormalities strongly supports a diagnosis of CS. Therefore, the patient will be seen regularly in view of the increased risk of newly developing tumours. The current screening for breast, endometrial and renal malignancies was negative. To confirm the diagnosis, molecular genetic mutation analysis of the PTEN gene is recommended.

Germline mutations in the PTEN gene lead to a group of related disorders including CS, Bannayan-Riley-Ruvalcaba syndrome, adult LDD and autism spectrum disorders associated with macrocephaly. Initially, it was reported that the CS gene is found in up to 80% of patients meeting consortium diagnostic criteria for PTEN hamartoma syndromes [4]. Recently larger cohort studies estimated that at least 11%, probably up to 48% of patients have de novo mutations [5]. Family history revealed that a brother has also cutaneous abnormalities suggesting a genetic background, but further genetic assessment has not yet been performed.

LDD is a rare type of posterior fossa tumour that can either arise as an isolated condition or as a part of CS. Patients with LDD should be evaluated carefully for signs of CS. CS is frequently misdiagnosed, because of the variability of its presentations. Most cases are only recognized in advanced stages, as in the patient presented. As the lesions may contain functional cerebellar tissue and surgical borders are poorly delineated, complete resection can lead to neurological impairment. Potential surgical treatment strategies in symptomatic cases, therefore, involve balancing of complete/partial resection of the lesion, decompression and shunting procedures [6]. According to AWMF Guidelines for diagnosis and management of patients with PTEN hamartoma tumour syndrome molecular genetic testing in patients with two or more major criteria such as LDD, macrocephalus, multiple mucocutaneous lesions or tumour (e.g. breast, thyroid, colorectal, kidney) should be performed [7]. Our case illustrates that MR-imaging is extremely helpful for the diagnosis of “tiger-striped” LDD with important consequences for the patient. It further stresses the need to promote broader knowledge about PTEN hamartoma syndromes to prevent future neoplasms. This case should alert physicians to consider CS in the differential diagnosis of a patient with cutaneous trichilemmomas and posterior fossa space-occupying lesions.