Cytopathological analysis of salivary gland cancer: REFCOR recommendations by the formal consensus method.

OBJECTIVE: To determine the indications for fine-needle cytology and the modalities of frozen section pathological analysis in the management of salivary gland cancer. MATERIAL AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group who drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group according to the formal consensus method. RESULTS: Fine-needle cytology is recommended as part of the diagnostic work-up for a major salivary gland tumor suspicious for malignancy. Fine-needle cytology should be performed after MRI to avoid artifacts. Frozen section analysis is recommended to confirm the malignant nature of the tumor, to adapt the extent of resection and to indicate neck dissection. Whenever possible, the entire tumor and adjacent salivary or periglandular tissue should be sent for frozen section analysis. CONCLUSION: Fine-needle cytology and frozen section analysis play an essential role in the management of salivary gland cancers.

Molecular and clinical diversity in primary central nervous system lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity. PATIENTS AND METHODS: To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data. RESULTS: Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue. CONCLUSIONS: The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions.

Antenatal screening of small for gestational age: Impact on obstetrical management and neonatal outcomes in case of trial of labor after 37 weeks.

OBJECTIVE: Antenatal screening of small fetuses for gestational age (SGA) is a public health challenge. The aim of this study is to assess the obstetrical management and the immediate neonatal outcomes, according to the antenatal screening of the SGA fetuses. METHODS: We performed a retrospective study in a French tertiary care hospital between January 1, 2016 and December 31, 2018. Women were eligible if they had a monofetal pregnancy with a fetus in head presentation and a trial of labor after 37 weeks. A fetus was considered SGA when the estimated fetal weight was less than the 10th percentile at the third trimester ultrasound. A newborn was considered hypotrophic when the birthweight was less than the 10th percentile. RESULTS: 8 153 newborns were included and 948 of the newborns were hypotrophic (308 were suspected for SGA, 640 were not suspected for SGA) and 7205 were eutrophic. Among the hypotrophic neonates, we observed no significant difference regarding the immediate neonatal outcomes between the two groups of fetuses suspected and not suspected for SGA. Among the fetuses not suspected for SGA, the rate of arterial umbilical cord pH below 7.10 was significantly higher in the hypotrophic newborns compared to the non hypotrophic newborns (4.7% vs 3.1%, p = 0.041). CONCLUSION: In our population, unsuspected fetal hypotrophy may be associated with an increased risk of neonatal acidosis. These results emphasize the benefit of improving prenatal screening to identify the SGA fetuses.

Guidelines of the French Society of Otorhinolaryngology-Head and Neck Surgery (SFORL), part I: Primary treatment of pleomorphic adenoma.

INTRODUCTION: The authors present the guidelines of the French Society of Otorhinolaryngology-Head and Neck Surgery (SFORL) for the diagnosis and treatment of pleomorphic adenoma (PA) of the salivary glands. METHOD: A review of the literature was performed by a multidisciplinary task force. Guidelines were drafted based on the articles retrieved and the workgroup members' individual experience. Guidelines were graded A, B, C or expert opinion by decreasing level of evidence. RESULTS: In clinically suspected salivary gland PA, MRI should be performed, including head and neck lymph node levels. Fine needle aspiration cytology is particularly recommended for tumours difficult to characterise by MRI. Frozen section biopsy should be performed to confirm diagnosis and adapt the surgical procedure in case of intraoperative findings of malignancy. Complete resection of the parotid PA should be performed en bloc, including margins, when feasible according to tumour location, while respecting the facial nerve. Enucleation (resection only in contact with the tumour) is not recommended. For the accessory salivary and submandibular glands, complete en bloc resection should be performed.

Guidelines of the French Society of Otorhinolaryngology-Head and Neck Surgery (SFORL), part II: Management of recurrent pleomorphic adenoma of the parotid gland.

INTRODUCTION: The authors present the guidelines of the French Society of Otorhinolaryngology-Head and Neck Surgery (SFORL) for the management of recurrent pleomorphic adenoma (RPA) of the parotid gland. METHOD: A review of the literature was performed by a multidisciplinary task force. Guidelines were drafted, based on the articles retrieved and the work group members' individual experience. There were then read and re-edited by an independent reading group. The proposed recommendations were graded A, B or C on decreasing levels of evidence. RESULTS: Complete resection under neuromonitoring is recommended in case of RPA. The risks of progression and malignant transformation, which are higher the younger the patient, have to be taken into consideration. The risk of functional sequelae must be explained to the patient. MRI is recommended ahead of any surgery for parotid RPA, to determine extension and detect subclinical lesions. Radiotherapy should be considered in case of multi-recurrent pleomorphic adenoma after macroscopically complete revision surgery at high risk of new recurrence (microscopic residual disease), in case of RPA after incomplete resection, and in non-operable RPA.

The crucial choice of reference genes: identification of miR-191-5p for normalization of miRNAs expression in bone marrow mesenchymal stromal cell and HS27a/HS5 cell lines.

Bone marrow mesenchymal stromal cells (BM-MSCs) have a critical role in tissue regeneration and in the hematopoietic niche due to their differentiation and self-renewal capacities. These mechanisms are finely tuned partly by small non-coding microRNA implicated in post-transcriptional regulation. The easiest way to quantify them is RT-qPCR followed by normalization on validated reference genes (RGs). This study identified appropriate RG for normalization of miRNA expression in BM-MSCs and HS27a and HS5 cell lines in various conditions including normoxia, hypoxia, co-culture, as model for the hematopoietic niche and after induced differentiation as model for regenerative medicine. Six candidates, namely miR-16-5p, miR-34b-3p, miR-103a-3p, miR-191-5p, let-7a-5p and RNU6A were selected and their expression verified by RT-qPCR. Next, a ranking on stability of the RG candidates were performed with two algorithms geNorm and RefFinder and the optimal number of RGs needed to normalize was determined. Our results indicate miR-191-5p as the most stable miRNA in all conditions but also that RNU6a, usually used as RG is the less stable gene. This study demonstrates the interest of rigorously evaluating candidate miRNAs as reference genes and the importance of the normalization process to study the expression of miRNAs in BM-MSCs or derived cell lines.

Cyclin D1 targets hexokinase 2 to control aerobic glycolysis in myeloma cells.

Cancer cells are characterized by the Warburg effect, a shift from mitochondrial respiration to oxidative glycolysis. We report here the crucial role of cyclin D1 in promoting this effect in a cyclin-dependent kinase (CDK)4/6-independent manner in multiple myeloma (MM) cells. We show that the cyclin D1 oncoprotein targets hexokinase 2 (HK2), a major glycolysis regulator, through two original molecular mechanisms in the cytoplasmic and nuclear compartments. In the cytoplasm, cyclin D1 binds HK2 at the outer mitochondrial membrane, and in the nucleus, it binds hypoxia-inducible factor-1α (HIF1α), which regulates HK2 gene transcription. We also show that high levels of HK2 expression are correlated with shorter event-free survival (EFS) and overall survival (OS) in MM patients. HK2 may therefore be considered as a possible target for antimyeloma therapy.

Vocal-fold leukoplakia and dysplasia. Mini-review by the French Society of Phoniatrics and Laryngology (SFPL).

Vocal-fold leukoplakia and dysplasia are together designated "epithelial hyperplastic laryngeal lesions" (EHLL). Work-up and follow-up are founded on optical examination with high-definition imaging, stroboscopy and narrow-band imaging. Diagnosis is based on pathology, using the new 2017 WHO classification, dichotomizing "low grade" and "high grade". Statistically, the risk of cancerous progression is 20% within 5 to 10 years of diagnosis, or more in over-65 year-old males; risk for any given patient, however, is unpredictable. Research focuses on the genetic criteria of the lesion and characterization of the tumoral microenvironment. Treatment is exclusively microsurgical. Resection depth is adjusted according to infiltration. EHLL is a chronic disease, necessitating long-term follow-up, which may be hampered by residual dysphonia and surgical sequelae in the vocal folds. Sequelae need to be minimized by good mastery of microsurgical technique and indications. When they occur, biomaterials such as autologous fat and hyaluronic acid can be useful. Tissue bio-engineering is a promising field.

Germline mutation p.N363K in POLE is associated with an increased risk of colorectal cancer and giant cell glioblastoma.

Germline mutations of the POLE gene are responsible for polymerase proofreading-associated polyposis syndrome (PPAP). These mutations were hypothesised to predispose to extra-gastrointestinal tumours (ovary, endometrium, brain), but this association has not been confirmed so far. We report a family with an autosomal dominant inheritance of PPAP due to a c.1089C>A; p.Asn363Lys mutation in the proofreading exonuclease domain of POLE. Ten patients presenting a history of colorectal tumours and three patients with polyposis are indexed in this family. Three carriers (including siblings and a distant cousin at 30, 45 and 52 respectively) and another member (at 37 not tested) presented glioblastoma. This is the second family reported to carry this mutation. Among the four glioblastomas in the family that we report, both show similar pathology: giant cell glioblastoma. These cases suggest that the c.1089C>A germline POLE mutation may confer an increased risk of brain cancer [incidence 17.4% (4/23) in mutation carriers combining the two families]. More observations are needed to support this hypothesis. It seems that not all mutations of POLE are equally associated with extra-gastrointestinal tumours. Although carriers of a mutation responsible for PPAP should benefit from screening for colorectal and uterine cancer, due to the rapid evolution of glioblastoma the value of neurological follow-up and brain imaging screening remains questionable. Nevertheless, considering the limitations of standard therapy for glioblastoma, mutation status could be useful for targeting therapy. The biological mechanism linking POLE mutation to glioblastoma remains to be determined.

A French retrospective study on clinical outcome in 102 choroid plexus tumors in children.

The aim of this study was to review and describe therapeutic approaches in children with choroid plexus tumor (CPT) based on a nationwide series. The World Health Organization classification subdivides these rare tumors into three histological subtypes corresponding to three grades of malignancy: low grade (grade I) choroid plexus papilloma (CPP), intermediate grade (grade II) atypical choroid plexus papilloma (aCPP) and high grade (grade III) choroid plexus carcinoma (CPC). This retrospective study included 102 French children younger than 18 years, treated from 2000 to 2012: 54 CPP, 26 aCPP and 22 CPC. The 5 year overall survival was 100% in CPP, 96.2% in aCPP and 64.7% in CPC. In patients with localized disease, complete surgical resection was achieved in 48/52 CPP, 20/26 aCPP and 7/14 CPC. In this group, patients with complete surgical resection had better event free survival than patients with partial resection (88.9 vs. 41.6%). 28 patients (1 CPP, 6 aCPP and 22 CPC) had adjuvant chemotherapy. 2 aCPP and 9 CPC had radiotherapy. We underlined the need for a central histological review to accurately analyze clinical data; we reported a much higher overall survival for CPC than in most previous CPT series probably including atypical teratoid rhabdoid tumors. In our series, the 5 years overall survival in CPC (64.7%) was higher than event free survival (25.2%) and could be interpreted as a clue for the efficiency of adjuvant/salvage therapy even if the heterogeneity of applied treatments in this retrospective series does not allow for meaningful statistical comparisons.

Use of fluorescent in-situ hybridisation in salivary gland cytology: A powerful diagnostic tool.

OBJECTIVE: Salivary gland cytology is challenging because it includes a diversity of lesions and a wide spectra of tumours. Recently, it has been reported that many types of salivary gland tumours have specific molecular diagnostic signatures that could be identified by fluorescent in-situ hybridisation (FISH). The aim of the present study was to demonstrate the feasibility and efficiency of FISH on routine cytological salivary gland smears. METHODS: FISH was conducted on 37 cytological salivary gland smears from 34 patients. According to the cytological diagnosis suspected, MECT1/MAML2 gene fusion and rearrangements of PLAG1, MYB, or ETV6 were analysed. The presence and percentages of cells that had gene rearrangements were evaluated. Results were compared with the histological surgical samples, available from 26 patients. RESULTS: The PLAG1 rearrangement was observed in 12/20 (60%) cases of pleomorphic adenoma. MECT1/MAML2 gene fusion was observed in 1:2 mucoepidermoid carcinomas but was not observed in five other tumours (two pleomorphic adenomas, one Warthin's tumour, one mammary analogue secretory carcinoma [MASC] and one cystic tumour). MYB rearrangement was observed in 4/4 adenoid cystic carcinomas. ETV6-gene splitting identified one MASC. CONCLUSION: Overall, FISH had a specificity of 100% and a sensitivity of 66.7%. When FISH and cytological analyses were combined, the overall sensitivity was increased to 93.3%. It can thus be concluded that when the FISH analysis is positive, the extent of surgery could be determined with confidence pre-operatively without needing a diagnosis from a frozen section.

Subventricular zones: new key targets for glioblastoma treatment.

BACKGROUND: We aimed to identify subventricular zone (SVZ)-related prognostic factors of survival and patterns of recurrence among patients with glioblastoma. METHODS: Forty-three patients with primary diagnosed glioblastoma treated in our Cancer Center between 2006 and 2010 were identified. All patients received surgical resection, followed by temozolomide-based chemoradiation. Ipsilateral (iSVZ), contralateral (cSVZ) and bilateral (bSVZ) SVZs were retrospectively segmented and radiation dose-volume histograms were generated. Multivariate analysis using the Cox proportional hazards model was assessed to examine the relationship between prognostic factors and time to progression (TTP) or overall survival (OS). RESULTS: Median age was 59 years (range: 25-85). Median follow-up, OS and TTP were 22.7 months (range 7.5-69.7 months), 22.7 months (95% CI 14.5-26.2 months) and 6.4 months (95% CI 4.4-9.3 months), respectively. On univariate analysis, initial contact to SVZ was a poor prognostic factor for OS (18.7 vs 41.7 months, p = 0.014) and TTP (4.6 vs 12.9 months, p = 0.002). Patients whose bSVZ volume receiving at least 20 Gy (V20Gy) was greater than 84% had a significantly improved TTP (17.7 months vs 5.2 months, p = 0.017). This radiation dose coverage was compatible with an hippocampal sparing. On multivariate analysis, initial contact to SVZ and V20 Gy to bSVZ lesser than 84% remained poor prognostic factors for TTP (HR = 3.07, p = 0.012 and HR = 2.67, p = 0.047, respectively). CONCLUSION: Our results suggest that contact to SVZ, as well as insufficient bSVZ radiation dose coverage (V20Gy <84%), might be independent poor prognostic factors for TTP. Therefore, targeting SVZ could be of crucial interest for optimizing glioblastoma treatment.

[Congenital neuromuscular diseases with neonatal respiratory failure excluding myotonic dystrophy type 1 and infantile spinal muscular atrophy. Diagnosis strategy according to a 19-child series]. / Maladies neuromusculaires congénitales à expression respiratoire néonatale à l'exclusion de la dystrophie myotonique de type 1 et de l'amyotrophie spinale infantile. Stratégie d'exploration d'après une série de 19 enfants.

UNLABELLED: Apart from spinal muscular atrophy (SMA) and myotonic dystrophy type 1 (DM1), congenital neuromuscular diseases with early neonatal symptoms mean diagnostic and prognostic challenges mainly when infants require ventilatory support. OBJECTIVES: Consider a standardized strategy for infants suspected of congenital neuromuscular disease from analysis of the literature and retrospective experience with floppy and ventilatory support-dependent infants, after exclusion of well-known diseases (DM1, SMA). PATIENTS AND METHODS: Floppy infants requiring ventilatory support in their 1st month of life, but showing no evidence of DM1, SMA, Prader-Willi syndrome, or encephalopathy. The retrospective multicenter study was based on the response of regional referent neuropediatricians in the Reference Centre for Neuromuscular Diseases of Greater Southwest France to an inquiry about prenatal and perinatal history, investigations, diagnosis, and outcome of the child and family. It was conducted between 2007 and 2012. RESULTS: Among the 19 newborns studied, all had severe hypotonia. Prenatal and perinatal features were similar. Their outcome was generally severe: the median survival as measured by the Kaplan-Meier method was 6.9 months. Thirteen children died at a median age of 61 days; ten of them were treated with a palliative procedure. Five children had achieved respiratory independence but suffered from a small delay in motor development. Among the three children who continuously required ventilatory support, only one survived (follow-up period: 23 months); he was the only one undergoing tracheostomy in the cohort. Diagnostic processes were different, leading to pathological and genetic diagnosis for only six infants. There was only histological orientation for seven and no specific diagnostic orientation for the last six. These difficulties have led us to propose an exploration process based on the literature. CONCLUSION: This study highlights difficulties in obtaining a diagnosis and a precise prognosis for floppy ventilated infants. An exploration-standardized process for infants suspected of congenital neuromuscular diseases was made in order to standardize procedures. It could be used as a tool for all professionals involved.

[Value of neck dissection before definitive radiation therapy for locoregionally advanced squamous cell carcinoma of the head and neck]. / Place du curage ganglionnaire avant radiothérapie exclusive dans la prise en charge des carcinomes épidermoïdes localement évolués des voies aérodigestives supérieures.

PURPOSE: Optimal timing of neck dissection remains debated in the conservative management of patients with locoregionally advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: The files of 63 patients with radiographic evidence of bulky or necrotic nodal metastases treated by up-front neck dissection and definitive radiotherapy between 2000 and 2012 at two institutions were retrospectively reviewed. RESULTS: The primary site was oropharyngeal, hypopharyngeal or laryngeal in 63%, 21% and 13% cases, respectively. Overall, 83% of the tumours were staged pN2b or more. Extracapsular spread was found in 48 cases (77%). After a 48-month median follow-up, the 3-year locoregional control and overall survival were 88% and 68%, respectively. Only one isolated failure occurred in the dissected neck. CONCLUSION: This combination therapy provides a good locoregional tumour control. It should be considered as an option in laryngeal, hypopharyngeal or oropharyngeal squamous cell carcinomas with bulky or necrotic nodal metastases at presentation.

A case of laryngeal sialolipoma: pathology in focus.

We are reporting a rare case of laryngeal sialolipoma in a 66-year-old male affected by Parkinson's disease. He was evaluated for dysarthria and swallowing disorders during which a swelling of the left ventricular fold, was always present and enlarged over a span of six months. Surgical removal of the left ventricular fold was performed. Microscopic examination, showed a circumscribed mass with organoid seromucous glands surrounded by numerous mature adipocytes, separated from the parenchyma and fatty tissue by dense fibrous tissue. This mass fulfilled the diagnostic criteria of sialolipoma. Sialolipomas can develop in a variety of sites in which there is both adipose and salivary gland tissue. To our knowledge, this is the first case of sialolipoma arising in the larynx.

Cerebral amyloid angiopathy and microhemorrhages after amyloid beta vaccination: case report and brief review.

After the interruption of the international multicenter Phase 2 clinical trial with active immunotherapy based on synthetic Abeta42 (AN1792), few reports about the neuropathological findings in those patients and those from the Phase 1 clinical trial were published. These reports described some pathological similarities among the patients such as a reduction in the burden of amyloid plaques, the reactions of microglia/macrophages and the persistence of neurofibrillary tangles and neuropil threads. In addition, a lymphocytic inflammatory infiltrate as well as white matter lesions were present in some cases with meningoencephalitis. In both animal models of vaccination, as well as some vaccinated patient samples, there appears to be a correlation between vaccination and hemorrhages. Subsequently, two series reports concerning 8 patients from the Phase 1 initial trial showed that immunization with Abeta42 seemed to result in clearance of amyloid plaques, but did not prevent progressive neurodegeneration and that it increased vessel wall amyloid angiopathy as well as cortical microhemorrhages. Recent clinical data gave further encouraging results regarding vaccination in humans demonstrating that long term follow-up of patients from the second clinical trial revealed reduced functional decline, at least, in antibody responders. Here we describe a patient diagnosed with Alzheimer's disease who also participated in the Phase 2 clinical trial. A neuropathological examination confirmed Alzheimer's disease without meningoencephalitis and revealed a severe amyloid angiopathy with frequent microhemorrhages, the decrease of amyloid load being difficult to ascertain. Our results are in agreement with previous studies and confirm the presence of severe amyloid angiopathy after vaccination. The latter may be a transient phenomenon depending on the degree of immune response and the pathological stage of the disease when the patient underwent treatment. In addition, our vaccinated case also demonstrated microhemorrhages and microinfarcts which were already noticed to occur with a higher density in immunized Alzheimer's disease patients.

Hepatitis E virus-induced neurological symptoms in a kidney-transplant patient with chronic hepatitis.

It has been shown that hepatitis E virus (HEV) may be responsible for chronic hepatitis in solid-organ transplant patients. It has also been suggested that HEV may be responsible for atypical neurological symptoms during the acute phase. However, the relationship between the neurological symptoms and HEV infection was based on the detection of anti-HEV IgM in the sera. Herein, we report a case where neurological symptoms, that is peripheral nerve involvement with proximal muscular weakness that affected the four limbs joints with central nervous-system involvement and bilateral pyramidal syndrome, occurred in a kidney-transplant patient who was chronically infected by HEV. For the first time, HEV RNA was detected in the serum and cerebrospinal fluid. In addition, clonal HEV sequences were analyzed in both compartments, that is serum and cerebrospinal fluid. The discovery of quasispecies compartmentalization and its temporal association suggests that neurological symptoms could be linked to the emergence of neurotropic variants.

Hemangioblastoma of the corpus callosum: A case report and review of the literature on its origin.

A third case of corpus callosum hemangioblastoma (HB) is presented. With no preoperative embolization, surgery was uneventful and the postoperative course was excellent. Based on the literature, we attempted to clarify the histogenesis of HB and to explain why they are exceptional in the supratentorial region in contrast to the posterior cranial fossa. The VHL gene is expressed particularly in Purkinje cells of the cerebellum, but this expression is also possible in supratentorial structures. Its mutation leads to developmental arrest of angioblasts that become potentially neoplastic cells. These CD133-positive pluripotent neoplastic angioblasts, similar to stem cells, may be immature HB in the brain. They also express VEGF, coexpress Epo/EpoR, and are capable of differentiation into primitive vascular structures. This coexpression may not only mediate developmental stagnation, but may also induce HB proliferation. Therefore, HB tumorigenesis may be initiated during embryogenesis and may originate from angiomesenchyma because of the expression of three cell types (stromal cells, pericytes, and endothelial cells) in vimentin. Their capacity for proliferation and differentiation in HB depends on the microenvironment.

Desmoplastic infantile astrocytoma with benign histological phenotype and multiple intracranial localizations at presentation.

Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are rare intracranial tumors that mostly occur in the first 2 years of life and involve superficial cerebral cortex. Despite the large size of these lesions and some worrisome histological and radiological features, prognosis is generally favorable after gross total resection. We report an original observation of a desmoplastic infantile astrocytoma in a 5-year-old boy with multiple localizations on initial presentation, including the unusual subtentorial region. Magnetic resonance imaging showed a temporal tumor with prepontine and interpeduncular extension, and two other distinct localizations in cisterna magna and left cerebellar hemisphere. Leptomeningeal enhancements were present around the basal cistern. The surgical samples, corresponding exclusively to subtentorial lesions, were devoid of anaplastic features; the temporal lesion was untouched because of the interpeduncular extension. Adjuvant chemotherapy was applied, with shrinkage of lesions. DIA and DIG are more generally unifocal at initial presentation. When the tumor is large, multilobular involvement is common, but multiple location of DIG is, on the contrary, very rare. Previously, only five cases of DIG/DIA located in two or more separate locations have been published. We report the sixth, and first noninfantile, case of DIA/DIG with multifocal initial presentation.