Elsevier

World Neurosurgery

Volume 104, August 2017, Pages 398-406
World Neurosurgery

Original Article
Lhermitte-Duclos Disease (Dysplastic Gangliocytoma of the Cerebellum) and Cowden Syndrome: Clinical Experience From a Single Institution with Long-Term Follow-Up

https://doi.org/10.1016/j.wneu.2017.04.147Get rights and content

Background

Adult-onset Lhermitte-Duclos disease (LDD) and Cowden syndrome (CS) are considered a single phakomatosis that belongs to PTEN hamartoma tumor syndrome (PHTS) now. There is still controversy regarding the diagnosis and treatment. The authors describe the clinical features of LDD and CS with long-term follow up.

Methods

From January 2001 to January 2017, 18 patients were admitted to the neurosurgery department of Beijing Tiantan Hospital. The authors analyzed the medical records of each patient and followed every case.

Results

Seventeen of 18 patients underwent surgery to remove the tumor. The results of pathologic analysis revealed LDD. There was obvious enhancement on magnetic resonance imaging (MRI) in 2 patients who received gamma knife and radiotherapy before surgery. During surgery, it is difficult to determine the exact margin. Tumors were removed gross totally in 9 patients, partially in 6 patients, and only subtotally in 2 patients. CS was diagnosed in 11 patients. Two patients received DNA analysis, revealing heterozygous mutation of exon 5 in an 11-year-old girl. There was no recurrence of the tumor during follow-up.

Conclusions

LDD has the unique appearance on T2-weighted MRI. The most difficult aspect of surgery is determining the actual margins of the tumor. Total resection is difficult in some patients. There was no tumor recurrence after long-term follow-up in our case series. For pediatric LDD patients, DNA analysis should be performed to rule out CS.

Introduction

Lhermitte-Duclos disease (LDD; dysplastic gangliocytoma of the cerebellum) is a rare hamartoma of the cerebellum with a unique “tiger-stripe” appearance on magnetic resonance imaging (MRI).1, 2 Cowden syndrome (CS) is an autosomal dominant, hereditary, multisystem disease involving hamartomatous overgrowth of tissues of all embryonic layers. It mainly affects the breast, thyroid, uterus, and skin. Since 1991, LDD has been considered part of CS.3 PTEN is known as a tumor suppressor gene, and the mutation of this gene has been shown in multiple cancer types. Almost all adult-onset LDD cases were associated with PTEN gene mutations.4, 5 Nowadays, LDD and CS are included in PTEN hamartoma tumor syndrome (PHTS).4, 5, 6, 7, 8, 9

Since its first description by Lhermitte and Duclos in 1920,10 more than 200 cases have been reported in the literature.11, 12 Because of the rarity of this disease, there is currently controversy regarding LDD and CS diagnosis and management. Therefore, in this study, we discuss the relationship between these two diseases and provide a summary of the patient diagnosis and management.

Section snippets

Materials and Methods

This study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University. Informed consent was obtained from all participants or their parent or legal guardian. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. Between January 2001 and January 2017, 18 patients with LDD were admitted to Beijing Tiantan Hospital. Seventeen patients underwent surgery to remove the cerebellar tumor, with the exception of 1 patient who

Results

Results are summarized in Table 1. In our study, 6 patients were male, and 12 were female. The median patient age was 45 years (range, 2–56 years). Only 2 patients were younger than 18 years (2 and 11 years old). The range of follow-up time was 6–180 months (mean, 52 months). Sixteen of 18 tumors were located primarily in the unilateral cerebellar hemisphere (6 left side, 10 right side), and cerebellar vermis was present in 2 patients. One patient received gamma knife treatment in other

Discussion

LDD was first recognized as being related to CS by Padberg et al. in 1991.3 Adult-onset LDD is thought to be nearly pathognomonic with CS now, but the association of child-onset LDD with CS is still unclear.14 It has been suggested that CS is frequently overlooked in patients who are treated for LDD.15 LDD patients should be evaluated carefully to rule out CS, because CS patients have a high incidence of multisystemic cancers and other diseases. The commonly reported rates of cancer in patients

Conclusion

LDD has a unique appearance on T2-weighted MRI. The most difficult aspect of surgery is determining the actual margins of the tumor. Total resection is difficult in some patients. There was no tumor recurrence after long-term follow-up in our case series. For pediatric patients with LDD, DNA analysis should be performed to rule out CS.

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      It is a rare, slow-growing cerebellar tumor, containing dysplastic and hypertrophic cells, currently classified with neuronal and mixed neuronal-glial tumors in the most recent “WHO Classification of Tumours of the Central Nervous System” [7]. LDD can present as a cerebellar mass of varying size with larger series suggesting a slight predilection for right-sided involvement [8–13], and the vermis can also be affected [9,10,13,14]. The imaging features of LDD (Fig. 1), which are best depicted using magnetic resonance imaging (MRI), have been well-correlated with the underlying histopathology [8,11,13,14].

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      CS is a phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome, a part of a collection of syndromes that are all associated with mutations in the PTEN gene. In the adult form of LDD, germline PTEN mutations have accounted for 75%–83% of cases,24 and LDD will develop in ∼40% of patients with CS.25-31 Adult LDD is considered a major criterion in the clinical diagnosis of CS as reported by Pilarski et al.32 (Table 1).

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      It is reported that approximately 80% of patients with CS have germline mutation of phosphatase and tensin homolog, which is known as a tumor suppressor gene that maps to chromosome 10q23.12,13 As phosphatase and tensin homolog mutations are often found in adult-onset LDD,5,14,15 it is recommended that these patients be investigated for concomitant neoplasms to exclude CS.5,16 In the present case, we excluded CS after systemic screening.

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    Chunde Li, Ying Wang, and Jian Xie contributed equally to this work.

    Conflict of interest statement: This work was supported by National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2013BAI09B03) and a cooperation program between Capital Medical University and Beijing Tiantan Hospital (17JL50, 16JL[TTZX]05). The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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