CASE REPORTA 29-year-old man presented with a 2-month history of

neurological symptoms suggestive of raised intracranial

pressure and with a swelling in the right neck. He was entirely

well previously, only suffering occasional non-specific head-

aches in his teenage years. There was no history in his nuclear

family of any cancer or neurocutaneous condition but, anec-

dotally, his grandfather was said to have died of a brain tumour

in his late 20s.

A cranial CT revealed a large, non-enhancing mass in the

left cerebellar hemisphere (Fig. 1).An MR scan provided further

information (Figs 2–4).

A confident diagnosis of Lhermitte–Duclos disease (LDD)

was made on the basis of the imaging findings. The patient

underwent a subocccipital craniectomy and the left cerebellar

hemisphere was debulked.The excised tissue comprised small

pieces of cerebellar cortical tissue in which the normal laminar

architecture of the granular layer was disturbed. Histologically, a

disorganized population of large, haphazardly arranged

neuronal cells was evident, with areas of dystrophic calcification

in the surrounding neuropil (Fig. 5). The neuronal nature of the

cells was confirmed by immunohistochemical positivity for

synaptophysin and neurone-specific enolase.

During the course of his postoperative recovery, the patient

was noted to have an incidental lump in the right axilla and a

thyroid mass. An ultrasound of the thyroid gland revealed

two nodules within the right lower pole. An excisional biopsy

of the right axillary lesion and a right hemithyroidectomy

were performed. The axillary lesion was a lipoma. The thyroid

pathology revealed multiple adenomas with features of chronic

follicular thyroiditis. In addition, two occult well-differentiated

papillary carcinomas of the thyroid, which measured 5 mm and

2 mm in diameter, were present.

The patient received genetic counselling and underwent

DNA analysis of a blood specimen. He was found to have a

mutation in a tumour suppressor gene on chromosome 10

consistent with Cowden’s syndrome.

DISCUSSIONCowden’s syndrome (CS) is a rare autosomal-dominant

disorder characterized by multiple hamartomas of ectodermal,

endodermal and mesodermal origin. Specifically, the syndrome

features facial tricholemmomas, acral keratosis, oral

papillomatosis, intestinal polyposis and fibrocystic disease of

the breast. In addition, there is a high incidence of malignant

tumours, most notably of the breast.1–3 Central nervous system

Case Report

Lhermitte–Duclos disease associated with Cowden’ssyndrome: Case report and literature reviewConor Murray,1 Peter Shipman,1 Mark Khangure,1 Turab Chakera,1 Peter Robbins,2

William McAuliffe1 and Stephen Davis3

1Department of Diagnostic Imaging, Royal Perth Hospital and Departments of 2Neuropathology and 3Radiology, QE2 Medical Centre,

Perth, Western Australia, Australia

SUMMARY

Lhermitte–Duclos disease (LDD) is a rare entity that may occur in the setting of Cowden’s syndrome (CS). Accuratepreoperative diagnosis can be made on the characteristic CT and MR appearances, thereby obviating the need forbiopsy. It is important to be aware of the link between LDD and CS so that appropriate genetic counselling and tumoursurveillance can be undertaken.

Key words: Cowden’s syndrome; dysplastic gangliocytoma; Lhermitte–Duclos disease.

C Murray MBBS; P Shipman FRANZCR; M Khangure MD, FRANZCR; T Chakera MD, FRANZCR; P Robbins FRANZCR; W McAuliffe FRANZCR;

S Davis FRANZCR.

Correspondence: Dr Conor P Murray, c/o Department of Diagnostic Imaging Hospital for Sick Children Toronto, Ontario, Canada M5G 1X8.

Email: conormurray33@hotmail.com

Submitted 13 April 2000; resubmitted 11 April 2001; accepted 26 April 2001.

Australasian Radiology (2001) 45, 343–346

344 C MURRAY ET AL.

Fig. 1. Non-contrast head CT demonstrates a mass within the left

cerebellar hemisphere. There is considerable mass effect with

obstructive hydrocephalus at the level of the aqueduct. A small focus of

calcification is present near the centre of the lesion (arrow).

Fig. 4. T1-weighted gadolinium-diethylenetriamine penta-acetic acid-

enhanced images were performed in the axial plane and did not

demonstrate any abnormal enhancement.

Fig. 3. Axial T2-weighted images demonstrate a striking laminar

pattern to the lesion – the so-called ‘tiger stripe’appearance.

Fig. 2. Sagittal T1-weighted images demonstrate the left cerebellar

hemisphere lesion displacing the tentorium superiorly and causing

anterior compression of the aqueduct of Sylvius. Non-communicating

hydrocephalus is present.

345LHERMITTE–DUCLOS DISEASE

manifestations of the disease have been emphasized only

recently and include megalencephaly, epilepsy and dysplastic

gangliocytoma of the cerebellum – so-called LDD.

The gene for CS has been localized to chromosome

l0q22-23.1,2,4 Recently, a series of germline mutations have

been identified from CS families in a gene known as PTEN.1–5

The PTEN gene encodes a phosphatase mutated in a variety of

human cancers, and is recognized as a powerful tumour

suppressor gene. Both somatic and germline mutations have

been detected in association with the PTEN gene. PTEN

germline mutations are found in three related disorders

characterized by tumour susceptibility: CS, LDD and

Bannayan–Zonana syndrome.

Lhermitte–Duclos disease cosegregates with a subset of

CS families and the coexistence of these two entities has been

described in 22 cases.5–14 The majority of patients with LDD

have a germline mutation of the CS gene.15 The relationship

between LDD and CS is similar to that between a neoplasm

and a genetic disease predisposing to the formation of that

neoplasm; for example, meningioma and neurofibromatosis

type 2. In fact, CS shares many of the features of the

phakomatoses, including an autosomal-dominant inheritance

and tumour suppressor gene inactivation.5 Although CS is

uncommon, making the diagnosis is important as genetic coun-

selling and vigilant cancer screening for affected individuals

and family members is warranted.

Dysplastic gangliocytoma of the cerebellum typically

presents in young adults with symptoms of raised intracranial

pressure due to obstructive hydrocephalus.16 It has been

reported incidentally at autopsy and has been associated with

sudden death.17 The pathogenesis remains unknown, and

considerable debate exists in the literature as to whether it

represents a neoplastic, malformative or hamartomatous

lesion. Recent studies have demonstrated that the dysplastic

neurones in LDD are not mitotically active and contain no

abnormalities of tumour suppressor or oncogenes.18

Macroscopically, LDD represents a focally indolent growth

of the cerebellar cortex resulting in gross thickening of the

cerebellar folia.The enlarged folia lose their secondary foldings

and asymmetrically expand the cerebellar hemisphere. The

disease is typically unilateral with a predilection for the left

cerebellar hemisphere.15 Histologically, LDD is characterized

by a thickening of the outermost ‘molecular’ layer and replace-

ment of the innermost Purkinje and granular cell layer with

a profusion of dysplastic ganglion cells.7,17 Mitoses, neo-

vascularity and necrosis are not observed, emphasizing the

presumed hamartomatous nature of the lesion.

The diagnosis of LDD was, until recently, made post-

operatively or on autopsy. Morphological changes produce a

unique pattern on some CT and all MRI, allowing a preoperative

diagnosis by the radiologist.16,19,20 On CT, alternating isodense

and hypodense layers may be discernible. The first diagnostic

MR images of this condition were reported in the literature in

1988.21 On MR, the hypodense layers on CT are hypointense

(with respect to grey matter) on T1-weighted (T1W) images and

hyperintense on T2-weighted (T2W) images. The isodense

layers on CT are isointense on both T1W and T2W MR images.

It has been proposed that the bands of T1 and T2 prolongation

correspond to the inner layer and subcortical white matter, and

the isointense bands represent the outer molecular layer.17 This

pattern reflects the abnormally thickened folia and has been

likened to a ‘tiger-stripe’appearance.

Magnetic resonance is the imaging modality of choice

because of inherent Hounsfield artefact in the posterior fossa

with CT. Gadolinium enhancement is unusual and has been

reported in only two cases in the literature.7,16 The finding

of intralesional calcification in the present case is interesting

as, to the authors’ knowledge, this has not been reported

previously. Preservation of the normal cerebellar lamellar

pattern and a lack of contrast enhancement helps to dif-

ferentiate LDD from other cerebellar pathologies, including

infarction, medulloblastoma, astrocytoma, ependymoma, hae-

mangioblastoma and metastases. The characteristic imaging

findings obviate the need for biopsy and permit accurate

surgical planning.

The only effective treatment for LDD is surgical

decompression or excision. The postoperative prognosis is

usually favourable, although a few cases have recurred after

apparent gross total resection.6,17,19

CONCLUSIONLhermitte–Duclos disease is a rare entity that may occur in the

setting of Cowden’s syndrome. The CS–LDD complex may be

considered a phakomatosis with a molecular basis in the

alteration of the PTEN tumour suppressor gene. Accurate

preoperative diagnosis can be made on the characteristic CT

Fig. 5. Histology of the cerebellar tissue. Large, haphazardly arranged

neuronal cells characterized the abnormal excised cerebellar tissue

(H&E).

346 C MURRAY ET AL.

and MR appearances, thereby obviating the need for biopsy. It

is important to be aware of the link between LDD and CS so that

appropriate genetic counselling and tumour surveillance can be

undertaken.

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