PTEN hamartoma tumor syndrome: Clinical and genetic characterization in pediatric patients.

OBJECTIVE: The aim of this study was to provide a full characterization of a cohort of 11 pediatric patients diagnosed with PTEN hamartoma tumor syndrome (PHTS). PATIENTS AND METHODS: Eleven patients with genetic diagnostic of PHTS were recruited between February 2019 and April 2023. Clinical, imaging, demographic, and genetic data were retrospectively collected from their hospital medical history. RESULTS: Regarding clinical manifestations, macrocephaly was the leading sign, present in all patients. Frontal bossing was the most frequent dysmorphism. Neurological issues were present in most patients. Dental malformations were described for the first time, being present in 27% of the patients. Brain MRI showed anomalies in 57% of the patients. No tumoral lesions were present at the time of the study. Regarding genetics, 72% of the alterations were in the tensin-type C2 domain of PTEN protein. We identified four PTEN genetic alterations for the first time. CONCLUSIONS: PTEN mutations appear with a wide variety of clinical signs and symptoms, sometimes associated with phenotypes which do not fit classical clinical diagnostic criteria for PHTS. We recommend carrying out a genetic study to establish an early diagnosis in children with significant macrocephaly. This facilitates personalized monitoring and enables anticipation of potential PHTS-related complications.

Imaging findings of children with PTEN-related hamartoma tumor syndrome: a 20-year multicentric pediatric cohort.

BACKGROUND: PTEN-related hamartoma tumor syndrome results from a mutation in the PTEN gene located at 10q23.31. This syndrome represents a spectrum of different phenotypes of variable expressions, now recognized as part of the same condition. Patients with this mutation have an increased risk of developing a wide range of findings, including malignancies. Although widely described in adults, there are no large series describing the imaging findings in patients before adulthood. Knowledge of the findings seen in children and adolescents with PTEN-related hamartoma tumor syndrome can help guide further management and improve surveillance recommendations. OBJECTIVE: To describe the spectrum of imaging abnormalities in pediatric patients with PTEN-related hamartoma tumor syndrome. MATERIALS AND METHODS: We performed a retrospective, cross-sectional, multicenter study conducted between January 2000 and October 2021 in three tertiary pediatric institutions evaluating the imaging findings in children and adolescents (≤ 18 years) with confirmed diagnoses of a PTEN mutation. For each patient, the imaging findings, histopathology reports, and at least a 2-year follow-up of clinical outcomes for non-operative cases were documented. RESULTS: The cohort included 78 children (37 girls), with a mean age at diagnosis of 7.5 years (range 0 days to 18 years). Benign brain findings included enlarged Virchow-Robin perivascular spaces, white matter changes, developmental venous anomalies, and cerebellar hamartomas. Benign thyroid findings were common, but 5/45 (11.1%) with thyroid abnormalities had a malignant nodule. Soft tissue adipocytic tumors, GI/GU polyps, other soft tissue abnormalities, along with vascular anomalies in various anatomic locations were common. CONCLUSION: Brain abnormalities, benign non-vascular soft tissue abnormalities, and vascular anomalies are commonly seen in children and adolescents with PTEN-related hamartoma tumor syndrome. However, malignancies involving the thyroid gland are not uncommon. Familiarity with the phenotype of PTEN-related hamartoma tumor syndrome in the pediatric population can improve diagnosis and prompt appropriate clinical surveillance of abnormal findings that warrant further management.

Diverse imaging findings of Lhermitte-Duclos disease.

AIM: To evaluate the diverse clinical and imaging features of Lhermitte-Duclos disease (LDD) and its subgroup comparison. MATERIALS AND METHODS: Clinical data from 21 patients with LDD were collected, including eight patients with LDD without other tumours and 13 LDD with other tumours. Redefined diagnostic criteria are used to evaluate Cowden Syndrome. Imaging indicators were analysed retrospectively to extract typical and atypical features. Imaging findings and preoperative diagnostic accuracy were compared between the subgroups. RESULTS: None of these patients met the redefined diagnostic criteria. The typical "tiger stripe sign" was seen in most LDD lesions (13/29, 61.9%), with lower density (29.66 ± 2.51 versus 37.81 ± 2.76 HU, p<0.001) and higher apparent diffusion coefficient (ADC) value (1.04 ± 0.05 × 10-3 versus 0.74 ± 0.03 × 10-3 mm2/s, p<0.001) than that of the normal cerebellum. Atypically, some lesions showed abnormal vessels (8/21, 38.1%), intratumoural calcification (3/21, 14.29%), intratumoural haemorrhage (4/21, 19.05%), peritumoural oedema (6/21, 28.57%), and heterogeneous enhancement (5/21, 23.81%). The typical "tiger stripe sign" was more common in LDD with other tumours (84.62% versus 25%, p=0.018). Although LDD without other tumours was more common with abnormal vessels (75% versus 15.38%, p=0.018), intratumoural calcification (37.5% versus 0, p=0.042), intratumoural haemorrhage (50% versus 0, p=0.012), peritumoural oedema (62.5% versus 7.69%, p=0.014) and heterogeneous enhancement (50% versus 7.69%, p=0.047). Preoperative diagnostic accuracy was higher in LDD with other tumours than LDD without other tumours (76.92% versus 25%, p=0.032). CONCLUSION: The "tiger stripe sign" of LDD is characteristic, but not unique. With or without other tumours, it may be associated with the imaging diversity. Combining typical and atypical signs can improve the imaging assessment of LDD.

Formation of a de novo intracranial arteriovenous fistula in a child with PTEN hamartoma tumor syndrome.

PURPOSE: Dural arteriovenous fistulae (dAVF) are an uncommon feature of PTEN hamartoma tumor syndrome (PHTS). We report a case of an adolescent male diagnosed with PHTS following the treatment of multiple intracranial dAVF to emphasize the association of vascular anomalies with this disorder and discuss potential implications. CASE REPORT: An adolescent male presented with bilateral proptosis secondary to intracranial venous hypertension. Workup revealed the presence of a complex intracranial dAVF which was treated with several embolization procedures. Following treatment, a de novo dAVF was identified on surveillance imaging. A genetic workup revealed a pathogenic mutation in PTEN consistent with a diagnosis of PHTS. CONCLUSIONS: Recognition that PHTS may be associated with dAVF, and potentially delayed spontaneous formation of dAVF, is critically important due to the potential for devastating yet preventable neurologic sequelae.

Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease) presenting as a prenatally heterotopic hamartoma.

Dysplastic gangliocytoma of the cerebellum (DGC), also called Lhermitte-Duclos disease, is a rare lesion of the posterior fossa consisting of a diffuse hypertrophy of the cerebellar cortex. DGC frequently presents in young adults and rarely in childhood. Only 3 cases have been previously described in newborns. We present an uncommon case of DGC which was diagnosed in utero. The radiological presentation prenatally and at birth was similar to a heterotopic neuroglial brain tissue. MRI aspects evolved from T1/T2 isointense signals to hypoT1 and hyperT2 signals at the age of 1 year. The girl was then operated on total removal of the lesion which was performed with no postoperative complication. Genetics did not demonstrate any germline PTEN mutation or family history suggesting Cowden disease. Two years later, the child was doing well and MRI confirmed complete resection. This case illustrates the difficulties of diagnosing intracranial lesions in foetuses and newborns. Physicians caring for pregnant women and pediatrics should be aware that neoplasm-like lesions such as DGC may present as hamartomas. Surgical resection could then be discussed whenever possible.

Lhermitte-Duclos Disease in Pediatric Population: Report of 2 Cases.

INTRODUCTION: Lhermitte-Duclos disease (LDD), also known as dysplastic cerebellar gangliocytoma, is an uncommon disorder in children, characterized by being a slow-growing lesion of the posterior fossa, which mainly affects the granular cell layer of the cerebellar parenchyma and may be associated with other multiple hereditary hamartomas and neoplasms. CASE PRESENTATION: We report 2 cases of LDD in pediatric patients and describe clinical symptoms and radiological and histopathological characteristics. In addition, we analyzed the relation to Cowden Syndrome based on the International Cowden Syndrome Consortium Operational Criteria and the most updated guidelines by the National Comprehensive Cancer Network (NCCN Guidelines Version 1.2020). CONCLUSION: LDD is a very rare disease in childhood but should be considered in the differential diagnosis of posterior fossa lesions. LDD can mimic low-grade glial tumors or infectious diseases. Patients develop late clinical manifestations due to the slow-growing pattern, and conservative treatment with outpatient follow-up may be an option in asymptomatic children.

[Dysplastic Cerebellar Gangliocytoma(Lhermitte-Duclos Disease)].

Dysplastic cerebellar gangliocytoma or Lhermitte-Duclos disease(LDD)is a rare benign cerebellar lesion composed of dysplastic ganglion cells that conform to the existing cortical architecture. In this disease, the enlarged ganglion cells are predominantly located within the internal granular layer, and they thicken the cerebellar folia. The architecture of the affected cerebellar hemisphere with the enlarged cerebellar folia and the cystic changes, in some cases, present as "tiger-striped striations," a characteristic imaging finding that is not specific to LDD. This imaging feature may be observed in medulloblastoma and isolated cerebellar Rosai-Dorfman disease. This cerebellar lesion is a major central nervous system manifestation of Cowden syndrome, an autosomal dominant condition that causes various hamartomas and neoplasms. A molecular-based study estimated the prevalence of Cowden syndrome to be 1 case per 200,000. In a study involving 211 patients with Cowden syndrome, 32% developed LDD. LDD can be diagnosed in young children and older adults within the eighth decades of life. PTEN mutations have been identified in virtually all adult-onset LDDs, but not in childhood-onset cases.

Lhermitte-Duclos disease: A case report and literature review. / 小脑发育不良性神经节细胞瘤1ä¾‹åŠæ–‡çŒ®å¤ä¹ .

Lhermitte-Duclos disease (LDD) is a type of rare brain tumor located in posterior fossa. A patient with LDD located in the left cerebellum and vermis was admitted by the Department of Neurosurgery, Xiangya Hospital, Central South University. MRI scan showed slightly heterogeneous enhancement at the region close to vermis. The patient underwent partial resection on August 11, 2016 without postoperative chemoradiotherapy. The progress free survival was 11 months and the overall survival was 17 months. What the case reveals is that the partial resection is not beneficial to these patients with LDD as the residual lesion probably recurs in a short term after operation. The pathogenesis, diagnosis and treatment of LDD are explored and summarized in combination with relevant literature.

Brain morphological analysis in PTEN hamartoma tumor syndrome.

PTEN hamartoma tumor syndrome (PHTS) is a spectrum of hereditary cancer syndromes caused by germline mutations in PTEN. PHTS is of high interest, because of its high rate of neurological comorbidities including macrocephaly, autism spectrum disorder, and intellectual dysfunction. Since detailed brain morphology and connectivity of PHTS remain unclear, we quantitatively evaluated brain magnetic resonance imaging (MRI) in PHTS. Sixteen structural T1-weighted and 9 diffusion-weighted MR images from 12 PHTS patients and neurotypical controls were used for structural and high-angular resolution diffusion MRI (HARDI) tractography analyses. Mega-corpus callosum was observed in 75%, polymicrogyria in 33%, periventricular white matter lesions in 83%, and heterotopia in 17% of the PHTS participants. While gyrification index and hemispheric cortical thickness showed no significant differences between the two groups, significantly increased global and regional brain volumes, and regionally thicker cortices in PHTS participants were observed. HARDI tractography showed increased volume and length of callosal pathways, increased volume of the arcuate fasciculi (AF), and increased length of the bilateral inferior longitudinal fasciculi (ILF), bilateral inferior fronto-occipital fasciculi (IFOF), and bilateral uncinate fasciculus. A decrease in fractional anisotropy and an increased in apparent diffusion coefficient values of the AF, left ILF, and left IFOF in PHTS.

Imaging of Neuronal and Mixed Glioneuronal Tumors.

Neuronal and mixed glioneuronal tumors represent a group of neoplasms with varying degrees of neural and glial elements. Their age of presentation varies, but they are most commonly seen in children and young adults. With the exception of anaplastic ganglioglioma and other atypical variants, most lesions are low grade; however, they can have significant morbidity because of seizures, mass effect, or difficult to treat hydrocephalus. Although many tumors show overlapping clinical and imaging features, some have relatively distinctive imaging characteristics that may aid in narrowing the differential diagnosis. In this review, we discuss relevant clinical and pathologic characteristics of these tumors and provide an overview of conventional and advanced imaging features that provide clues as to the diagnosis.

Updated Imaging Features of Dysplastic Cerebellar Gangliocytoma.

OBJECTIVE: The aim of this study was to perform an updated review of the imaging features of dysplastic cerebellar gangliocytoma (DCG). METHODS: Imaging findings were retrospectively reviewed in 14 patients with DCG. The analysis included size, location, cyst formation, calcification, intralesional hemorrhage, enhancement pattern, and apparent diffusion coefficient (ADC). RESULTS: In addition to revisiting many well-established imaging features of DCG, enhancement was much more common (64.3%) than previously reported, and small enhancing veins were also frequently encountered within or along the periphery of the lesions (50%). Dysplastic cerebellar gangliocytomas had an elevated ADC compared with normal cerebellum (967.8 ± 115.7 vs 770.4 ± 47.3 × 10 mm/s; P < 0.0001). CONCLUSIONS: Enhancement on magnetic resonance imaging within DCG should be an accepted imaging finding rather than being viewed as uncommon or atypical. Dysplastic cerebellar gangliocytomas typically have an elevated ADC compared with normal cerebellum, which may assist in differentiation from other posterior fossa neoplasms.

Lhermitte-Duclos Disease in a Six-Year Old Child: A Rare Presentation.

Lhermitte-Duclos disease (LDD) is a rare, slow-growing, benign lesion of the cerebellum. It is often seen in the second and fourth decades. This disease is extremely rare in childhood. A 6-year-old girl presented with loss of balance. A mass lesion in the right cerebellum was detected by magnetic resonance imaging. The patient underwent surgical removal of the lesion, and the histological diagnosis was dysplastic gangliocytoma (LDD). The patient was discharged without complication, and her balance improved in the follow-up period. In this report, we present this rare occurrence in childhood and discuss the clinical course and management. LDD is very rare in early childhood and should be considered in the differential diagnosis of posterior fossa lesions.

PTEN hamartoma of the soft tissue: the initial manifestation of an underlying PTEN hamartoma tumor syndrome in a 4-year-old female.

A 4-year-old female was referred to pediatric orthopedic surgery for left leg pain and limping for 3 months following a motor vehicle collision. Recently, the patient's mother had noted left knee swelling and dragging of the left leg when walking. Past medical history was significant for hip dysplasia with slight leg length discrepancy. The patient was otherwise healthy. Physical examination was remarkable for left pre-patellar soft tissue fullness with normal range of motion. There was no warmth or tenderness. Subsequent ultrasound revealed a heterogeneous soft tissue mass superior and medial to the patella with a moderate degree of internal vascularity. MR exhibited a heterogeneous soft tissue mass with heterogeneous signal on both T1- and T2-weighted images centered within the vastus medialis obliquus muscle infiltrating the quadriceps tendon. Excisional biopsy was performed with a histopathologic diagnosis of fibroadipose tissue with anomalous vessels, suggestive of phosphatase and tensin homolog (PTEN) hamartoma of the soft tissue (PHOST). The patient was found to be positive for the PTEN gene mutation on genetic testing. The child was also determined to be macrocephalic, a major criterion for PTEN hamartoma tumor syndrome (PHTS). The geneticist advised the patient to undergo yearly physical examinations and early, routine surveillance for several malignancies occurring with PHTS. This case report presents the ultrasound and MRI appearance of a rare benign tumor typically appearing in pediatric patients. The strong association between PHOST and other soft tissue malignancies and the resulting need for life-long surveillance make PHOST an important pathology to recognize.

Pseudotumoral hemicerebellitis as a mimicker of Lhermitte-Duclos disease in children: does neuroimaging help to differentiate them?

The clinical presentation and neuroimaging findings of children with pseudotumoral hemicerebellitis (PTHC) and Lhermitte-Duclos disease (LDD) may be very similar. The differentiation between these entities, however, is important because their management and prognosis are different. We report on three children with PTHC. For all three children, in the acute situation, the differentiation between PTHC and LDD was challenging. A review of the literature shows that a detailed evaluation of conventional and neuroimaging data may help to differentiate between these two entities. A striated folial pattern, brainstem involvement, and prominent veins surrounding the thickened cerebellar foliae on susceptibility weighted imaging favor LDD, while post-contrast enhancement and an increased choline peak on (1)H-Magnetic resonance spectroscopy suggest PTHC.

Torsion of a giant mesocolic lipoma in a child with Bannayan-Riley-Ruvalcaba syndrome.

A 6-year-old boy with Bannayan-Riley-Ruvalcaba syndrome (BRRS) presented to the emergency department with periumbilical abdominal pain for 12 h. A contrast-enhanced abdominal and pelvis CT examination revealed significant interval change in the size and appearance of a previously seen hypoattenuating right mesocolic fatty mass suggestive for lipoma, first observed 5 months prior. This lesion demonstrated new enhancing internal septations, a thickened capsule, interval development of adjacent mesenteric fat stranding and engorgement of the mesenteric vessels. Given the short follow-up interval and acute clinical presentation, imaging findings were suggestive for torsion. We present this case for the unusual imaging findings as well as to highlight the differential diagnosis for abdominal fat containing lesions by imaging in patients with BRRS and other hamartomatous syndromes.