Keywords
gangliocitoma - Lhermitte-Duclos - cerebellar tumor - benign tumor
Palavras-chave
gangliocitoma - Lhermitte-Duclos - tumor cerebelar - tumor benigno
Introduction
Lhermitte-Duclos disease (LDD), or cerebellar dysplastic gangliocytoma, is a rare
type of cerebellar tumor of unknown origin.[1]
[2] The first report was documented in 1920.[2]
[3]
[4] Patients can be asymptomatic for several years, but there are usually imprecise
neurological signs for long periods.[1]
[5] Diagnosis is made through magnetic resonance imaging (MRI) and confirmed by histopathological
exam.[1]
[2]
[3] We report the case of a 74-year-old patient, with sudden onset of symptoms, presenting
this uncommon cerebellar lesion.
Case Report
A 74-year-old female patient sought medical attention due to a sudden onset of gait
disturbance associated with headache and vomiting 20 days earlier. The patient had
a history of tobacco use, systemic arterial hypertension, type-2 diabetes mellitus,
cardiac insufficiency, schizophrenia, and a sigmoid adenocarcinoma, treated several
years earlier. On neurological examination, the patient presented mild consciousness
disturbance (Glasgow 14), dysmetria, and dysdiadochokinesia. An MRI was performed,
which evidenced a mass lesion in the right cerebellar hemisphere, hyperintense on
T2-weighted imaging and hypo intense on gadolinium-enhanced T1-weighted imaging. The
lesion measured 5.8 × 3.6 cm and was associated with peripheral vasogenic edema ([Fig. 1]), which caused mass effect, sulci blurring among the cerebellar folia as well as
compression of the cerebellar-pontine cistern and fourth ventricle.
Microsurgical treatment was performed through a suboccipital craniotomy, with a near
total resection of the lesion. Control computed tomography (CT) scan confirmed the
extent of the resection. In the postoperative period, the patient sustained the previous
deficits. Anatomo-pathological examination evidenced proliferation of round cells
in the cerebellum ([Fig. 2]), and immunohistochemistry was suggestive of cerebellar dysplastic gangliocytoma
(World Health Organization [WHO] grade I— Lhermitte-Duclos disease), positive for
Neu-N, glial fibrillary acidic protein (GFAP), synaptophysin and phosphatase and tensin
(PTEN) antibodies.
The patient presented increase in the clinical status, with improvement in the gait,
and was able to walk without assistance. The patient also present transient neuropathy
of the accessory nerve. She remains in rehabilitation program to this day.
Discussion
Lhermitte-Duclos disease (LDD) is an extremely rare type of benign cerebellar tumor
of unknown ethiology.[1] It was initially documented in 1920.[3]
[4] It usually presents in young adults, with no predilection for gender or race,[2]
[4]
[6]
[7] with a prevalence of < 1 for 1,000,000 patients.[1] It is a lesion of the cerebellar cortex,[3] characterized by loss of the normal cortex architecture and focal widening of the
cerebellar folia. It is still not clear if the cerebellar dysplastic gangliocytoma
is a neoplastic or hamartomatous lesion of the cortex; if neoplastic, it corresponds
to a grade I lesion of the WHO classification.[5]
Generally, it has an indolent and chronic course, with the possibility of acute onset
of symptoms.[3] It manifests with headache, visual disturbance, cerebellar dysfunction, ataxia,
cranial nerve palsies, and obstructive hydrocephalus,[2]
[6]
[7] mainly in the 3rd or 4th decade of life.[6]
[7] Acute onset of neurological deficits, as in the case presented, is rarely reported.[5]
Lhermitte-Duclos disease can be familiar or sporadic.[8] The occurrence of associated hereditary syndromes, such as Cowden disease, has been
reported.[2]
[5]
[6]
[7] Cowden disease is an autosomal dominant disturbance characterized by multiple hamartomas
and associated with a wide range of malignancies of the thyroid, skin, breast, intestine,
and kidney. The exact correlation, nevertheless, is still uncertain.[3] Molecular studies suggest a high frequency of abnormalities in the PTEN/AKT path,
an important regulator of cellular growth.[6]
[8] It is recommended that every patient diagnosed with LDD should be investigated regarding
Cowden disease and mutations in PTEN. Furthermore, individuals with LDD and Cowden
disease or PTEN mutation should receive continuous attention in order to prevent the
associated malignancies.[3]
[4]
[8]
Although the confirmatory diagnosis is made through histopathological findings, the
MRI can give good markers of the usual characteristics of this specific condition.
Lesions are usually hypointense on T1-weighted sequence and hyperintense in T2-weighted
and fluid-attenuated inversion recovery (FLAIR) sequences.[1]
[2]
[3]
[6]
[8] Thus, widening of the cerebellar folia appears as parallel linear stria in the lesion
surface. This pattern is called “tiger's stripe” or “striated cerebellum”, which is
characteristic of LDD.[5]
[6] The mass lesion is circumscribed, usually restricted to one cerebellar hemisphere
and has different appearance compared to the adjacent tissue. In rare cases, there
is contrast enhancement, which is a finding that can represent venous proliferation
of the external layers of the cerebellar cortex and prominent venous drainage.[8] The computed tomography (CT) scan image characteristics consisting of hypodense
areas and calcifications are unspecific to the diagnosis of LDD.[5]
[7]
The disease has classic histopathological characteristics[3]; the internal granular and molecular layer have diffuse enlargement, with dysplastic
cells, replacing the internal molecular layer with hypermyelinization of the molecular
layer.[1]
[2]
[6] There are no mitotic figures, nor necrosis.[3] The Purkinje cells, as well as the white matter, are reduced or absent.[2]
[5]
[6] In the immunohistochemistry studies, these cells are positive for synaptophysin.[3]
[6]
The definitive treatment for this condition involves microsurgical resection of the
lesion.[1]
[6]
[7]
[8] Nevertheless, in asymptomatic patients, diagnosed incidentally through MRI, conservative
management can be justified.[1] Patients that present acute onset of symptoms, or with significant cerebellar mass
effect on CT scan should be submitted to microsurgical resection of the lesion, even
when the diagnosis is unclear.[5] In elderly patients, partial resection can be recommended in order to reduce the
mass effect and avoid surgical complications.[2]
[7]
Recurrence of the disease in the postoperative period is considered rare.[1]
[6] Due to its association with the Cowden disease in adults, one should always rule
out concomitant malignancies (particularly breast and genitourinary cancers) and perform
genetic tests to diagnose Cowden disease.[3]
[8]
Conclusion
Lhermitte-Duclos disease is an extremely rare lesion of unknown etiology that can
be associated with Cowden disease and mutations in the PTEN path. For this reason,
if the MRI is compatible, histopathological analysis should be performed. The definitive
treatment is surgical, with resection of the lesion.
Fig. 1 (a,b) T1-weighed axial magnetic resonance imagining (MRI) with gadolinium, evidencing
extensive lesion in the right cerebellar hemisphere, with imprecise limits, moderate
enhancement by the contrast and mass effect, distorting the fourth ventricle. (c)
T1-weighed coronal MRI. (d) T2-weighed axial MRI. (e) fluid-attenuated inversion recovery
(FLAIR) axial MRI confirming the infiltrative pattern of the lesion. (f) Post-operative
axial CT scan, evidencing extensive resection of the lesion.
Fig. 2 Ganglionic cells with smooth atypia and single calcification focus. Hematoxylin &
Eosin stain, 50x.
