Lhermitte-Duclos Disease in an Eight-Year-Old Boy: A Case Report.

Lhermitte-Duclos disease (LDD), also known as dysplastic cerebellar gangliocytoma, is a rare, slow-growing, benign lesion that occurs in the cerebellum and is very uncommon in the pediatric population. There is a lack of literature and evidence about LDD management, and only one systematic review is available. Thus, more case reports and studies are warranted. This study reports a pediatric case diagnosed with LDD and describes the patient's clinical presentation, radiological findings, and histopathological criteria. In addition, important aspects of the disease are discussed to help reach the best management options. The main management option is surgical resection, though a "wait and see" approach is also an alternative, especially for asymptomatic patients. More studies are still needed to determine the best management options.

Treatment and Diagnostic Approach for Lhermitte-Duclos Disease and Suspected Cowden Syndrome.

Lhermitte-Duclos disease (LDD) is a rare entity, which may or may not be associated with Cowden syndrome (CS). The authors present a 26-year-old male with a history of emergency treatment due to acute obstructive hydrocephalus and apparent Chiari malformation. In posterior evaluation, mild cerebellar symptoms, mucocutaneous lesions, and a left hemispheric cerebellar lesion were evident. Initially, with the clinical evidence and the radiological study report of a cerebellar tiger-striped lesion, LDD with associated CS was suspected, and a genetic protocol was performed. The protocol included an endoscopy and thyroid ultrasound, and with symptom progression, a new neurosurgical procedure was performed. To complete the approach, we used the clinical criteria for PTEN hamartoma tumor syndrome established in 2013, and CS was diagnosed in the patient. In patients with radiological and clinical suspicion of LDD and CS, it should be mandatory to investigate the presence of other types of tumors due to their association with PTEN hamartomatous tumor syndrome, and in the absence of genetic study, the clinical criteria previously established in the literature should be sufficient to establish the diagnosis.

Lhermitte-Duclos disease in a 51-year old patient.

Lhermitte-Duclos disease (LDD) is a rare, slow-growing neoplasm that develops in the brain's posterior fossa. It can appear as a single lesion or as part of Cowden's syndrome. We report the case of a 51-year-old female with a history of diabetes, hypertension, and a previously treated neuroendocrine tumor, who presented to the hospital after experiencing a generalized tonic-clonic seizure. Except for a tongue laceration, the neurological examination was unremarkable. Brain magnetic resonance imaging (MRI) showed a T2 left cerebellar hemisphere pseudomass lesion with iso-hyperintense signals suggestive of Lhermitte-Duclos disease. This case describes a unique presentation of LDD and its various radiological manifestations, emphasizing the importance of neuroimaging in its diagnosis. Additionally, it contributes to the expanding literature on the varied manifestations of LDD.

Cerebellar phenotypes in germline PTEN mutation carriers.

PTEN hamartoma tumour syndrome (PHTS) comprises different hereditary conditions caused by germline PTEN mutations, predisposing to the development of multiple hamartomas in many body tissues and also increasing the risk of some types of cancer. Cerebellar involvement in PHTS patients has been long known due to the development of a pathognomonic cerebellar hamartoma (known as dysplastic gangliocytoma of the cerebellum or Lhermitte-Duclos disease). Recently, a crucial role of the cerebellum has been highlighted in the pathogenesis of autism spectrum disorders, now recognised as a phenotype expressed in a variable percentage of PHTS children. In addition, rare PTEN variants are indeed identified in medulloblastoma as well, even if they are less frequent than other germline gene mutations. The importance of PTEN and its downstream signalling enzymatic pathways, PI3K/AKT/mTOR, has been studied at different levels in both human clinical settings and animal models, not only leading to a better understanding of the pathogenesis of different disorders but, most importantly, to identify potential targets for specific therapies. In particular, PTEN integrity makes an important contribution to the normal development of tissue architecture in the nervous system, including the cerebellum. Thus, in patients with PTEN germline mutations, the cerebellum is an affected organ that is increasingly recognised in different disorders, whereas, in animal models, cerebellar Pten loss causes a variety of functional and histological alterations. In this review, we summarise the range of cerebellar involvement observed in PHTS and its relationships with germline PTEN mutations, along with the phenotypes expressed by murine models with PTEN deficiency in cerebellar tissue.

Giant cell collagenomas associated with Cowden syndrome: A case report.

Storiform collagenoma, also known as sclerotic fibroma, is a relatively rare benign cutaneous tumor consisting of a proliferation of fibroblasts that shows increased production of type I collagen. It may appear as a solitary, sporadic lesion, or, especially when multiple, associated with Cowden syndrome. Giant cell collagenoma has a histopathologic appearance similar to that of storiform collagenoma with the addition of floret-type giant cells. Herein, we report the finding of multiple giant cell collagenomas arising in an individual with Cowden syndrome. In a review of the published literature, this histopathologic variant appears to be rarely observed in association with Cowden syndrome.

Enfermedad de Lhermitte-Duclos y síndrome de Cowden. Reporte de un caso / Lhermitte-Duclos Disease and Cowden Syndrome. A Case Report

Presentación del caso. Se trata de una paciente femenina de 45 años con antecedentes de hipertensión arterial y múltiples cirugías por cáncer, entre ellas, cáncer de tiroides, carcinoma de parótida, cáncer de mama y cáncer endometrial. De manera incidental se identificó una lesión en el hemisferio cerebeloso derecho en una tomografía de senos paranasales, que fue confirmada a través de una resonancia magnética cerebral. La lesión presentaba una apariencia estriada, característica de gangliocitoma displásico del cerebelo o enfermedad de Lhermitte-Duclos. Considerando los antecedentes de diversos tipos de cáncer y los criterios de diagnóstico propuestos por el Consorcio Internacional Cowden y la Red Nacional Integral del Cáncer, se estableció el diagnóstico de síndrome de Cowden que había pasado desapercibido hasta el momento. Intervención terapéutica. Posteriormente, la paciente fue hospitalizada debido al crecimiento de una masa metastásica en el hemicuello derecho con afectación del plexo braquial, adenopatías cervicales, infraclaviculares y axilares derechas. Evolución clínica. En la actualidad, se encuentra recibiendo tratamiento paliativo con el objetivo de controlar los síntomas y mejorar su calidad de vida, ya que expresó su negativa a someterse a una intervención quirúrgica de resección tumoral

Case presentation. The report is of a 45-year-old female patient with a history of high blood pressure and multiple surgeries for cancer, including thyroid cancer, parotid carcinoma, breast cancer, and endometrial cancer. Incidentally, a lesion in the right cerebellar hemisphere was identified in a tomography of the paranasal sinuses, which was later confirmed in a brain magnetic resonance. The lesion had a striated appearance, characteristic of dysplastic gangliocytoma of the cerebellum or Lhermitte-Duclos disease. Considering the history of various types of cancer and the diagnostic criteria proposed by the International Cowden Consortium and the National Comprehensive Cancer Network, the diagnosis of Cowden syndrome, which had gone unnoticed until now, was established. Treatment. Subsequently, the patient was hospitalized due to the growth of a metastatic mass in the right hemicollar with involvement of the brachial plexus, cervical, infraclavicular, and right axillary lymph nodes. Outcome. She is receiving palliative treatment to control the symptoms and improve her quality of life, since she expressed her refusal to undergo tumor resection surgery

Lhermitte-Duclos Disease: A Case Series.

Lhermitte-Duclos disease (LDD), or dysplastic cerebellar gangliocytoma, is a rare benign tumor characterized by unilateral hemispheric cerebellar expansion. It is linked to mutations in the phosphatase and tensin homolog (PTEN) gene, which inhibit the phosphatidylinositol-3'-kinase pathway, leading to increased cell division and defective neuronal migration. This study aims to compare the clinical, radiological, histopathological, surgical resolution, and follow-up characteristics of reported cases of this rare condition. An in-depth search of LDD patients' clinical records at our institute between 2003 and 2023 was conducted, in addition to a systematic literature review on PubMed. Three patients with a diagnosis of LDD were found. Cerebellar abnormalities, varying headaches, and visual impairment were all present clinically. On T2 in the posterior fossa, all three MRI scans displayed the typical hyperintense parallel streak appearance. The histopathological report showed that large ganglion cells had replaced the granular layer, Purkinje cells had degenerated, the molecular layer had become hyper-myelinated, and synaptophysin and chromogranin were positive. Partial tumor resection and avoiding intracranial hypertension were the main goals of treatment. Genetic follow-up was conducted for all three patients. Neurosurgeons must be aware of LDD to provide close genetic monitoring despite the benign nature of the tumor because of its link to Cowden syndrome and elevated risk of cancer in other organs.

Anesthetic Management for a Patient with Rosai-Dorfman Disease, Cowden Syndrome, and Lhermitte-Duclos Disease: An Extremely Rare Disease Combination.

Rosai-Dorfman disease (RDD) is a rare condition that causes massive lymphadenopathy, most commonly in the cervical area. Cowden syndrome (CS) causes hamartomas in the skin and mucosa and predisposes individuals to various malignancies. Lhermitte-Duclos disease (LDD), or dysplastic cerebellar gangliocytoma, is often associated with CS. A 41-year-old female with all three conditions presented with abnormal uterine bleeding and endometrial intraepithelial neoplasia (EIN). Precautions should be considered when evaluating patients with RDD and CS preoperatively and during airway management owing to the potential for multisystem involvement, anatomical distortion, and difficult airways. The likelihood of having all three conditions is extremely rare.

Lhermitte-Duclos disease: A systematic review.

Background: Lhermitte-Duclos disease (LDD) is a rare tumor, with only about 300 reported cases. It often shows comorbidity with Cowden syndrome (CS); however, it can occur by itself. Radiologically, the "tiger-stripe" appearance is considered pathognomonic. Surgical resection remains the mainstay of treatment. This report aims to describe the clinical and radiological characteristics of LDD and its relationship with CS according to age group. Methods: PubMed electronic databases were searched in August 2022. The search terms included "Lhermitte- Duclos disease" and "dysplastic gangliocytoma," which yielded 297 and 103 research articles, respectively. The articles were collected and reviewed by three researchers. Results: Out of 400 identified articles, we analyzed 302 reported cases. The mean age at presentation was 33.6 ± 16 years; 171 patients (56.6%) were female, and 123 (40.7%) were male. The most commonly reported symptom was headache (174 patients, 57.6%), followed by ataxia (109, 36.1%). In addition, 99 cases (32.8%) were associated with CS, and 60 (19.9%) had a confirmed phosphatase and tensin homolog (PTEN) mutation. A tiger-stripe appearance was observed in 208 cases (58.7%); surgical resection was performed in 64.2% of the cases. Mortality and recurrence rates were 4.3% and 8.6%, respectively. No statistically significant difference was found between adult- and pediatric-onset LDD for the association with CS (P = 0.128). Conclusion: Our findings suggest that adult and pediatric LDD have major commonalities; however, further prospective studies are warranted.

A young female of Cowden syndrome presenting with Lhermitte-Duclos disease: An illustrative case.

Background: Lhermitte-Duclos Disease (LDD), or dysplastic gangliocytoma, which is a benign hamartomatous condition involving the cerebellum, has a possible association with Cowden syndrome (CS), a rare autosomal dominant disorder due to germline mutations in the phosphatase and tensin homolog (PTEN) tumor-suppressor gene in chromosome 10. Combined CS and LDD cases are rarely reported in the literature. Case Description: We present here a case of a young female patient presented at the emergency department with a severe headache associated with vertigo, vomiting, and cerebellar ataxia. A magnetic resonance imaging scan revealed mixed intensity posterior fossa lesion with almost preserved cerebellar cortical striations. Her facial skin had extensive trichilemmoma. Her symptoms improved after the excision of the posterior fossa lesion through suboccipital craniotomy and histopathology revealed LDD. Conclusion: In a low-resource country where genetic testing for neurosurgical condition is still inadequate, we used the validated Cleveland Clinic Adult Clinical Scoring for PTEN Testing and the patient had an 82-98% chance for a PTEN gene mutation. Finally, she along with her family was adequately counseled and was advised for regular screening and monitoring since it is a premalignant condition where early detection is imperative if any cancer arises in the near future and is now under our follow-up.

Lhermitte-Duclos disease with concomitant KCNT2 gene mutation: report of an extremely rare combination.

Lhermitte-Duclos disease (LDD) refers to cerebellar dysplastic gangliocytoma, a slow-growing tumor. Pathogenic variants of voltage-gated potassium channels have been associated with epilepsy of variable severity. These include the sodium-activated potassium channel subfamily T member 2 (KCNT2) gene, which encodes for pore-forming alpha subunits. KCNT2 gene mutations have been recently described to cause developmental and epileptic encephalopathies (DEEs). The purpose of the present article is to describe an extremely rare case of a young child who has both LDD and KCNT2 mutation. Our patient is an 11-year-old boy who presented with an absence episode, and his investigations revealed electroencephalography (EEG) abnormalities, LDD, and a heterozygous KCNT2 mutation. Regarding LDD patients, epileptic seizures have been reported in very few cases. Reports of patients with mutated KCNT2 variants are also extremely rare. It is for sure that LDD and KCNT2 mutation is an extremely rare combination. Although further follow-up is mandatory in order to draw safe conclusions for our case, the available data support that our patient is either the first reported case of a subclinical KCNT2 mutation or the first case of its clinical expression in late childhood so far.

Association between Cowden syndrome and Lhermitte-Duclos disease: A case report of an uncommon Genetic Hamartomatous Disorder.

The dysplastic gangliocytoma of the cerebellum, also known as Lhermitte-Duclos disease, is an uncommon hamartomatous lesion in the posterior fossa with some distinctive neuroradiological characteristics. It can happen in combination with Cowden syndrome or sporadically. Cowden disease, or multiple hamartoma-neoplasia syndrome, is a rare autosomal dominant condition which is characterized by mucocutaneous lesions and systemic malignancies. We present a case of Lhermitte-Duclos disease and Cowden disease occurring in adult patients. The clinical and radiological features as well as the management approaches of this unusual disease complex are addressed.

Lhermitte-Duclos disease: A rare case of cerebellar tumor with successful surgical treatment.

Background: Lhermitte-Duclos disease (LDD) or dysplastic gangliocytoma of the posterior fossa is a slow-growing and extremely rare mass lesion that involves the Purkinje neurons and the granular layer of the cerebellum. It is characterized by specific neuroradiological features and secondary hydrocephalus. However, documentation of surgical experience is scarce. Case Description: A 54-year-old man with LDD manifesting as progressive headache is presented with vertigo and cerebellar ataxia. Magnetic resonance imaging demonstrated a right cerebellar mass lesion with the characteristic "tiger-striped appearance." We decided to perform partial resection with reduction of tumor volume improving symptomatology as a result of the mass effect in the posterior fossa. Conclusion: Surgical resection is a good alternative for the management of LDD, especially when neurological compromise exists due to mass effect.

Lhermitte-Duclos disease: A series of six cases.

The Lhermitte-Duclos disease (LDD), also known as dysplastic cerebellar gangliocytoma, is a rare lesion characterized by variable enlargement of cerebellar folia. The pathological basis of LDD has long been debated, as it has overlapping features of both, a neoplasm and hamartoma. Association between LDD and Cowden syndrome (CS) has been established based on the presence of phosphatase and tensin homologue germline mutation in both. We present a series of six cases of LDD: Four females and two males, aged between 16 and 38 years, presenting with headache and imbalance on walking of 1-7 months duration. Histomorphology showed thickening and vacuolation of the molecular layer, loss of Purkinje cells, and replacement of granular cell layer by large dysplastic ganglion cells. Awareness of histological features of this rare entity and a higher level of suspicion is required for the correct diagnosis, which, in turn, should prompt thorough investigations to exclude features of associated CS. LDD is a rare entity, awareness of its histological features and correlating them with radiology is essential, especially in tiny biopsies; to render the correct diagnosis. Diagnosis of LDD warrants further clinical workup and close follow-up for the associated features of CS.

Subacute Posterior Inferior Cerebellar Artery Stroke Radiographically Mimicking Lhermitte-Duclos Disease.

Lhermitte-Duclos disease (LDD) is a rare cerebellar lesion characterized by a hamartomatous lesion of the cerebellum. Mainly diagnosed by MRI, the clinical presentation is usually made of neurological symptoms. Modern neuroimaging techniques such as MRI have led to accurate diagnosis of this disease in both its pre- and post-operative periods. We present the case of a 68-year-old male with a past medical history of cardiac stenting and coronary artery disease who originally presented to the emergency department as a transfer for evaluation of possible obstructing hydrocephalus and left posterior inferior cerebellar artery (PICA) infarct. Based on the clinical presentation and imaging, the favored diagnosis of his left cerebellar abnormality was LDD rather than an unusual acute/subacute infarct or a metastatic lesion. The rapid progression of symptoms with rapidly progressive cytotoxic edema on serial CTs helped exclude LDD, which is nearly always more of a chronic process. The classic neuroimaging findings and clinical presentation of LDD are also discussed.

Posterior Fossa Intra-Axial Lesion: There Are Pathologies Beyond Metastases.

Cerebellar metastases represent the most common lesion requiring surgical treatment in the daily neurosurgical praxis. We report a rare case with Lhermitte-Duclos disease presenting to the neurosurgical outpatient department and describe our diagnostic and treatment challenges. A 57-year-old man presented with transient cerebellar manifestations, including walking difficulties, dizziness, and a persistent occipital headache. The magnetic resonance imaging demonstrated a high-intensity lesion in the right cerebellar hemisphere on T2-weighted images. We initially considered surgery to establish a histopathological diagnosis. However, the magnetic resonance spectroscopy was compatible with a dysplastic gangliocytoma of the cerebellum. Therefore, we preferred a more conservative approach. Posterior fossa contrast-enhancing lesions are much more than metastases. The role of advanced magnetic resonance in avoiding unnecessary surgical interventions is priceless.