Combining high-dose stereotactic body radiation therapy (SBRT) with FOLFIRINOX (FFX) is promising as neoadjuvant strategy for pancreatic ductal adenocarcinoma (PDAC). This study provides an in-depth histo-molecular characterisation of resected PDAC samples from patients treated with FFX ± SBRT. Residual tumour tissues from 56 non-metastatic PDAC patients were analysed: seventeen underwent upfront surgery, seventeen received neoadjuvant FFX alone and twenty-two FFX followed by radiotherapy (sixteen SBRT, six radiochemotherapy [RT-CT]). Samples were assessed using RNAseq and immunohistochemistry/fluorescence, including multiplex. Addition of SBRT to FFX favourably remodelled PDAC, influencing stromal, immune, metabolic and molecular features. Unlike RT-CT, SBRT counteracted several detrimental effects induced by FFX alone. Notably, FFX + SBRT enriched tumours with ‘Classical’ and ‘Inactive stroma’ signatures—linked to better prognosis - while reducing ‘Basal-like’ cell enrichment. SBRT promoted COL1A1-driven stromal remodelling while globally preserving T-lymphocyte infiltration, including cytotoxic T cells, which maintained close proximity to tumour cells despite increased desmoplasia. Key transcriptional alterations induced by SBRT were identified, offering targets for future combination therapies. Highlighting a more favourable stromal and molecular profile after integration of high-dose SBRT to FFX, this study supports the development, rationale and validation in prospective trials of using this treatment combination in non-metastatic PDAC.

We report a case of GALT-associated carcinoma, a rare morphological variant of colorectal adenocarcinoma characterised by cystic glands containing eosinophilic material, set within dense lymphoid stroma with germinal centres. Since its first description in 1999, only 26 cases have been documented. Its association with lymphoid tissue, the presence of intraepithelial lymphocytes, and the absence of goblet cells led to the hypothesis that it may originate from M-cells located in the dome epithelium of gut-associated lymphoid tissue, hence the alternative term “dome-type carcinoma”. Through detailed histological, immunohistochemical, ultrastructural and molecular analyses of our case, supported by a comprehensive literature review, we found no evidence supporting M-cell differentiation: intraepithelial B lymphocytes were absent, GP2 immunostaining was negative and ultrastructural features were inconsistent with M-cell morphology. Nevertheless, the lesion’s pushing growth pattern, lack of high-risk histopathological features and indolent behaviour justify its recognition as a distinct morphological subtype of colorectal cancer.

Endometrial carcinoma is the most frequent of gynecological cancers, and its treatment is primarily dictated by the identification of molecular alterations, which distinguish four subgroups, each one associated with a specific prognosis. In this article, we report, to our knowledge for the first time, 2 cases of endometrial endometrioid carcinoma exhibiting particular eosinophilic cells and associated with a BRAF mutation. Both patients, women with post-menopausal bleeding, underwent endometrial resection. For the first patient, the examination of the specimen demonstrated a low-grade endometrioid endometrial carcinoma with an associated component of micropapillary structures composed of atypical eosinophilic cells. The resection of the second patient revealed endometrial intraepithelial neoplasia, which was also associated with atypical eosinophilic cells. Molecular analysis of both samples revealed BRAF mutations, specifically p.G469A and p.D594N. The link between the presence of eosinophilic cells and BRAF mutation was previously reported in cases of ovarian serous borderline tumors, which are at a lower risk of progressing toward low-grade serous ovarian carcinoma. The presence of this eosinophilic cell population may help identify endometrial carcinomas harbouring BRAF mutations. Still, this association remains preliminary and merits confirmation in larger cohorts, ideally coupled with functional models.

Primary neuroendocrine carcinomas of the vulva are rare and poorly characterised. We report a case of small cell neuroendocrine carcinoma in a 90-year-old woman, associated with differentiated vulvar intraepithelial neoplasia and superficially invasive squamous cell carcinoma. Immunohistochemistry confirmed neuroendocrine differentiation and excluded Merkel cell carcinoma. Next-generation sequencing performed on both the intraepithelial and neuroendocrine components identified identical pathogenic mutations in TP53 and CDKN2A, supporting a clonal relationship. Loss of RB1 expression was observed across all tumor components. HPV testing was negative. These findings support the hypothesis of stepwise tumor progression from a squamous precursor with RB1 and TP53 alterations, suggesting a mechanism for neuroendocrine transdifferentiation.

The implementation of biomarker testing for targeted therapies and immune checkpoint inhibitors is a cornerstone in the management of metastatic and locally advanced non-small cell lung cancer (NSCLC), playing a pivotal role in guiding treatment decisions and patient care. The emergence of precision medicine in the realm of operable NSCLC has been marked by the recent approvals of osimertinib, atezolizumab, nivolumab, pembrolizumab and alectinib for early-stage disease, signifying a shift towards more tailored therapeutic strategies. Concurrently, the landscape of this disease is rapidly evolving, with several further pending approvals and numerous clinical trials in progress.To harness the benefits of these innovative neo-adjuvant and adjuvant therapies, the integration of predictive biomarker testing into standard clinical protocols is imperative for patients with operable NSCLC. A multidisciplinary international consortium has identified three primary obstacles impeding the effective testing of patients with operable NSCLC. These challenges encompass the limited number of test requests by physicians, the inadequacy of tissue samples for comprehensive testing, and the prevalence of cost-reduction measures leading to suboptimal testing practices.This review delineates the aforementioned challenges and proposed solutions, and strategic recommendations aimed at enhancing the testing process. By addressing these issues, we strive to optimize patient outcomes in operable NSCLC, ensuring that individuals receive the most appropriate and effective care based on their unique disease profile.

Over the past decade, neuropathological diagnosis has undergone significant changes, integrating morphological features with molecular biomarkers. The molecular era has successfully refined neuropathological diagnostic accuracy; however, a substantial number of CNS tumor diagnoses remain challenging, particularly in children. DNA methylation classification has emerged as a powerful machine learning approach for clinical decision-making in CNS tumors. The aim of this study is to share our experience using DNA methylation classification in daily routine practice, illustrated through clinical cases. We employed a classification system to evaluate discrepancies between histo-molecular and DNA methylation diagnoses, with a specific focus on adult versus pediatric CNS tumors. In our study, we observed that 40% of cases fell into Class I, 47% into Class II, and 13% into Class III among the "matched cases" (>= 0.84). In other words, DNA methylation classification confirmed morphological diagnoses in 63% of adult and 23% of pediatric cases. Refinement of diagnosis was particularly evident in the pediatric population (65% vs. 21% for the adult population, p = 0.006). Additionally, we discussed cases classified with low calibrated scores. In conclusion, our study confirms that DNA methylation classification provides significant added-value for CNS tumors diagnosis, particularly in pediatric cases.

Primary retroperitoneal mucinous carcinomas (PRMCa) are exceedingly rare and poorly understood neoplasms, with <80 cases documented in the medical literature and molecular profiling hardly ever performed. Recent theories suggest that PRMCa might develop from mature cystic teratomas or Brenner tumors, mirroring their ovarian counterparts. However, only 2 cases of primary retroperitoneal mucinous tumors associated with teratoma have been reported in the literature to support this idea. In this paper, we detail an exceptional case: a 66-yr-old woman with ovarian metastases stemming from a PRMCa that originated in a mature cystic teratoma. The patient initially presented with a long-standing cystic mass in the retroperitoneum, diagnosed as a mucinous carcinoma after surgical removal. Following initial resection, the patient experienced rapid metastatic progression requiring aggressive treatment. Interestingly, the later ovarian metastases exhibited the full spectrum of architectural complexity observed in the initial lesion. This "maturation phenomenon," frequently observed in ovarian metastases of mucinous tumors, remains enigmatic. Molecular analysis revealed a KRAS mutation along with an ERBB3 mutation, making it the first instance of ERBB3 mutation being documented in this specific entity. This case underscores the importance of thorough data collection and continued research to improve our understanding of these rare tumors.

Background and Objectives: Central Nervous System (CNS) pediatric tumors represent the most common solid tumors in children with a wide variability in terms of survival and therapeutic response. By contrast to their adult counterpart, the mutational landscape of pediatric CNS tumors is characterized by oncogenic fusions rather than multiple mutated genes. CNS pediatric tumors associated with oncogenic fusions represent a complex landscape of tumors with wide radiological, morphological and clinical heterogeneity. In the fifth CNS WHO classification, there are few pediatric CNS tumors for which diagnosis is based on a single oncogenic fusion. This work aims to provide an overview of the impact of rare oncogenic fusions (NTRK, ROS, ALK, MET, FGFR, RAF, MN1, BCOR and CIC genes) on pathogenesis, histological phenotype, diagnostics and theranostics in pediatric CNS tumors. We report four cases of pediatric CNS tumors associated with NTRK (n = 2), ROS (n = 1) and FGFR3 (n = 1) oncogenic fusion genes as a proof of concept. Cases presentation and literature review: The literature review and the cohort that we described here underline that most of these rare oncogenic fusions are not specific to a single morpho-molecular entity. Even within tumors harboring the same oncogenic fusions, a wide range of morphological, molecular and epigenetic entities can be observed. Conclusions: These findings highlight the need for caution when applying the fifth CNS WHO classification, as the vast majority of these fusions are not yet incorporated in the diagnosis, including grade evaluation and DNA methylation classification.

Background: The most frequently invaded margins on pancreatoduodenectomy specimens for pancreatic ductal adenocarcinoma are vascular margins, particularly the superior mesenteric artery (or mesopancreatic) margin. Due to limited exploration of the radiological aspect of the mesopancreas, the aim of this study was to evaluate mesopancreatic infiltration through imaging of patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy, to correlate these findings with histopathology and evaluate their impact on survival. Methods: Data for all patients who underwent pancreatoduodenectomy for pancreatic ductal adenocarcinoma from 2015 to 2021 were reviewed, including review of surgical margin histopathology and blinded review of preoperative diagnostic imaging. According to qualitative radiological assessment, the mesopancreas was characterized as having normal fat, fat stranding, or solid infiltration. Survival data were analysed using Cox regression. Results: A total of 149 patients were included. At baseline imaging, mesopancreatic fat stranding or solid infiltration was present in 47 patients (31.5%) and 20 patients (13.4%) respectively. Median overall survival and disease-free survival were significantly lower with mesopancreatic solid infiltration (17 and 8 months) compared with normal fat (30 and 14 months) and fat stranding (29 and 16 months) (P = 0.017 and 0.028 respectively). In multivariable analysis, pathological tumour size was an independent prognostic factor for overall survival, and tumour location in the uncinate process and pathological tumour size were independent prognostic factors for disease-free survival. Conclusion: At diagnostic imaging, solid infiltration (but not fat stranding) of the mesopancreas is associated with a poor prognosis for pancreatic ductal adenocarcinoma patients who undergo pancreatoduodenectomy. Pathological tumour size significantly influences the prediction of overall survival, and tumour location in the uncinate process and pathological tumour size significantly influence the prediction of disease-free survival, suggesting further exploration of underlying mechanisms related to retroperitoneal tumoral invasion of vascular margins and the mesopancreas.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest tumors with slow progress in systemic therapies due to its peculiar and resistant tumor microenvironment. Inclusion of isotoxic high-dose stereotactic body radiation therapy (iHD-SBRT) into a total neoadjuvant strategy (TNT) is promising for the treatment of localized PDAC. However, the histo-molecular effects of iHD-SBRT are still poorly explored. In this study, we have shown that TNT, associating FOLFIRINOX [FFX] followed by iHD-SBRT, leads to significant and long-lasting remodeling of PDAC, affecting its stromal, metabolic, and molecular features. Contrary to FFX alone, TNT is able to enrich tumors with Classical and Inactive stromal signatures associated with better prognosis. Furthermore, iHD-SBRT seems capable to counteract several of the detrimental modulatory effects induced by FFX such as Epithelial-to-Mesenchymal Transition or angiogenesis. Additionally, we identified inflammatory cancer-associated fibroblasts signatures as an important prognostic factor. This work provides new rationale to sequentially combine FFX with iHD-SBRT and suggests new pathways that can be targeted in combination with a TNT. ![Figure][1] ### Competing Interest Statement The authors have declared no competing interest. [1]: pending:yes

Abstract INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest tumors. Unlike other tumors, the progress of systemic therapies has been very slow, mainly due to the peculiar and resistant tumor microenvironment (TME) of PDAC. The addition of ablative stereotactic body radiation therapy (SBRT) in a total neoadjuvant strategy is promising for the treatment of localized PDAC and is currently being explored in several clinical trials. However, if radiation therapy possesses the ability to modulate the TME, the impact of high-dose SBRT is still poorly known in PDAC. Here, we aim to characterize by immunohistochemistry (IHC) and RNA sequencing (RNAseq) analysis the immuno-modulations of the TME following isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT). MATERIAL: Paraffin-embedded residual tumoral tissues of 50 localized PDAC resected between 2011 and 2020 were used: seventeen patients had surgery first, seventeen received an induction chemotherapy with FOLFIRINOX (FFX) only and sixteen with FFX followed by an iHD-SBRT designed to individually maximize the dose prescribed to the tumor and vessels interfaces up to Dmax(0.5cc)<53Gy in 5 fractions. RESULTS: We found that although collagen deposition increases significantly after iHD-SBRT (COL1: 83.27 vs 78.60 vs 68.04%, p<0.001 for iHD-SBRT, FFX and treatment naïve cohort respectively), the intra-tumoral lymphocyte infiltration is globally not altered, including for cytotoxic CD8+ lymphocytes. Only the IHC expression of CD4+ T helper population is significantly decreased after iHD-SBRT. Using gene set enrichment analysis (GSEA) of the KEGG pathway, the IL-17 signaling pathway related to the T17 cells is particularly significantly increased after iHD-SBRT compared to FFX only. After iHD-SBRT, the IHC expression levels of FOXP3+ cells and PD-L1 are significantly increased. No difference is observed for CD68+ expression however, cell type enrichment analysis from our RNA-seq data using xCell algorithm shows that the M2-polarized CD68+ cells are increased after iHD-SBRT compared to FFX alone. PD-1 expression is significantly decreased after iHD-SBRT. Furthermore, RNAseq data revealed that iHD-SBRT is associated with significant enrichment in basaloid cells (p<0.0024), a subtype of basal–like cells associated with immunomodulatory stroma and better clinical outcomes. GSEA canonical pathway analysis further revealed metabolism-related pathways such as oxidative phosphorylation and gluthathione metabolism significantly enriched in iHD-SBRT treated group, suggesting the potential of mitochondrial inhibitors as candidates for combination therapy. CONCLUSIONS: iHD-SBRT is able to durably immuno-modulate the TME of PDAC. If the overall T-cell infiltration is preserved, we have identified some increased pro-tumoral cells and pathways after iHD-SBRT that could improve the development of better-oriented combination trials involving high-dose SBRT. Citation Format: Christelle Bouchart, Oier Azurmendi Senar, Julie Navez, Laurine Verset, Anaïs Boisson, Matthieu Hein, Nicky D’Haene, Dirk Van Gestel, Luigi Moretti, Pieter Demetter, Jean-Baptiste Bachet, Karen Willard-Gallo, Rémy Nicolle, Tatjana Arsenijevic, Jean-Luc Van Laethem. Immuno-modulation of the tumor microenvironment of pancreatic adenocarcinoma following isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B014.

The rectovaginal septum is an unusual location for neoplastic processes. The majority of these are extensions of tumors of the rectum or vagina. Masses arising primarily from the rectovaginal fascia are rare. Most primary rectovaginal malignant neoplasms are carcinomas that arise in the setting of endometriosis. Sarcomas in this location are exceedingly rare, with only few cases reported in the literature. We report a case of a 44-year-old lady who developed a high-grade sarcoma in the rectovaginal septum in the setting of endometriosis. We also discussed the differential diagnosis of this lady’s challenging and unique lesion, which is most probably an extra-uterine “uterine-type” high-grade sarcoma that shows overlapping features of several entities. Moreover, we performed a literature review of sarcomas in this rare location. Given the fact that the rectovaginal septum is a common location for endometriosis, in the case of a rectovaginal neoplasm, a thorough sampling and a careful search for endometriotic lesions are important, as they may be a clue for the diagnosis. Although rare, sarcomas should always be considered in the differential diagnosis of rectovaginal neoplasms.

Purpose: To identify clinical, biological and pathological risk factors for the incidental discovery of papillary thyroid microcarcinomas (PTMCs) in patients undergoing thyroidectomy for presumed benign conditions. Methods: Cross sectional, single center study, involving all consecutive patients (N=3015) who were submitted to thyroid surgery between 2001-2019. All medical files were retrospectively reviewed. A total of 1961 patients in the benign group and 145 patients in PTMC group were analyzed. Results: No significant differences in age, sex, body mass index, smoking status, thyroid volume or weight and preoperative thyroxine treatment between benign and PTMC groups were observed. Circulating anti- thyroid antibodies, histological thyroiditis and serum thyrotropin (TSH) were significantly associated with PTMC in univariable analysis. Independent risk factors for incidental PTMC by multivariable analysis where possible (OR: 1.51, 95% CI: 0.99 - 2.28) and certain (OR: 1.74, 95% CI: 1.09 - 2.78) thyroid autoimmunity (p= 0.002) and higher serum TSH (OR: 1.25, 95% CI: 1.08 -1.45, p= 0.03), whereas thyroid lobectomy was associated with a lower risk of PTMC (OR: 0.40, 95% CI: 0.24 - 0.67, p< 0.001). The most frequent genetic alteration was BRAFV600E mutation, found in 56.3 % of PTMC submitted to DNA sequencing. No association between clinical, biological or histological characteristics of PTMC and BRAFV600E mutation was observed. Conclusions: Thyroid autoimmunity and higher preoperative serum TSH level were independent predictors of PTMC incidentally discovered during thyroid surgery. Larger prospective studies are needed to better identify possible risk factors for papillary thyroid carcinoma initiation and progression.

A close relationship has been demonstrated between genomic complexity and clinical outcome in uterine smooth muscle tumors. We studied the genomic profiles by array-CGH of 28 fumarate hydratase deficient leiomyomas and 37 leiomyomas with bizarre nuclei (LMBN) from 64 patients. Follow-up was available for 46 patients (from three to 249 months, mean 87.3 months). All patients were alive without evidence of disease. For 51 array-CGH interpretable tumors the mean Genomic Index (GI) was 16.4 (median: 9.8; from 1 to 57.8), significantly lower than the mean GI in LMS (mean GI 51.8, p < 0.001). We described three groups: (1) a group with FH deletion (24/58) with low GI (mean GI: 11 vs. 22,4, p = 0.02), (2) a group with TP53 deletion (17/58) with higher GI (22.4 vs. 11 p = 0.02), and (3) a group without genomic events on FH or TP53 genes (17/58) (mean GI:18.3; from 1 to 57.8). Because none of these tumors recurred and none showed morphological features of LMS we concluded that GI at the cut-off of 10 was not applicable in these subtypes of LM. By integration of all those findings, a GI <10 in LMBN remains a valuable argument for benignity. Conversely, in LMBN a GI >10 or alteration in tumor suppressor genes, should not alone warrant a diagnosis of malignancy. Nine tumors were tested with Nanocind CINSARC® signature and all were classified in low risk of recurrence. We propose, based on our observations, a diagnostic approach of these challenging lesions.

Pancreatic ductal adenocarcinoma (PDAC) is reported to be amongst the cancers with the lowest survival rate at 5 years. In the present study we aimed to validate a targeted next-generation sequencing (tNGS) panel to use in clinical routine, investigating genes important for PDAC diagnostic, prognostic and potential theragnostic aspect. In this NGS panel we also designed target regions to inquire about loss of heterozygosity (LOH) of chromosome 18 that has been described to be possibly linked to a worse disease progression. Copy number alteration has also been explored for a subset of genes. The last two methods are not commonly used for routine diagnostic with tNGS panels and we investigated their possible contribution to better characterize PDAC. A series of 140 formalin-fixed paraffin-embedded (FFPE) PDAC samples from 140 patients was characterized using this panel. Ninety-two % of patients showed alterations in at least one of the investigated genes (most frequent KRAS, TP53, SMAD4, CDKN2A and RNF43). Regarding LOH evaluation, we were able to detect chr18 LOH starting at 20% cell tumor percentage. The presence of LOH on chr18 is associated with a worse disease- and metastasis-free survival, in uni- and multivariate analyses. The present study validates the use of a tNGS panel for PDAC characterization, also evaluating chr18 LOH status for prognostic stratification.

Introduction and importance: The presence of eosinophilic inclusion bodies in the breast is very rare and fewer than 20 cases were described in the literature. Herein we report the first case of borderline phyllodes tumour associated with this kind of cells. To the best of our knowledge, this is also the first time that a molecular sequencing is made targeting the stroma cells with inclusion bodies. Case presentation: A 33-yr-old woman presented a large mass in the right breast. Imaging techniques by mammogram and ultrasonographic examination were performed. After multidisciplinary approach, a breast conserving surgery has been decided. Microscopic analysis, immunohistochemical stains and molecular tests were performed on the lesion. The proposed diagnosis is borderline phyllodes tumour with eosinophilic inclusion bodies.Clinical discussion: Inclusion bodies are typically found in the infantile digital fibromatosis. Finding them in extradigital fibromatosis is rare. Their signification is still unclear. Some studies suggest a disturbance in the metabolism of proliferating myofibroblasts.Conclusion: The presence of inclusion bodies in breast tumour do not seem to have a prognosis impact. It might be interesting to perform others molecular tests on lesions with eosinophilic inclusion bodies to discover potential mutations.

Objectives The acceptance of conventional autopsy (CA), the gold standard method for investigating fetal death, often remains problematic. Post-mortem magnetic resonance imaging (PMMRI) is increasingly advocated, particularly for neurologic malformations. However, PMMRI performances to diagnose non-neurologic malformations remain unclear. We aim to clarify whether a full body CA remains needed after prenatal ultrasound (US) and PMMRI in assessing non-neurologic fetal malformations. Methods In this retrospective IRB-approved study, during a 6-year period, all fetuses who underwent PMMRI, prenatal US, and full body CA were included. Body abnormalities were identified in US, PMMRI, and CA reports. US and PMMRI images were all reviewed. All abnormalities were graded as major (2 points) or minor (1 point). Each technique (US, PMMRI, CA) was given a score by adding all grading points. In each fetus, results were compared for both separate and combined US and PMMRI to CA. Sensitivity and specificity were calculated for detecting major abnormalities. Results Fifty fetuses were included. The score of CA, US, and PMMRI was respectively 53, 37, and 46. Compared with US-PMMRI, CA added information in 2 cases (4%) with major abnormalities and 7 cases (14%) with minor abnormalities. PMMRI and US were concordant in 36/50 (72%) fetuses. Separate US/PMMRI sensitivities and specificities for detecting major body malformations respectively were 80%/80% and 100%/94%. Combined US-PMMRI had a sensitivity of 90% and a specificity of 94%. Two cardiac malformations (2/6) were only described by CA. Conclusions After prenatal US and PMMRI, few additional fetal body malformations are discovered with CA. Nevertheless, fetal heart autopsy remains mandatory. Clinical relevance statement A cardiac conventional autopsy complemented by prenatal ultrasound and post-mortem MRI allows to detect all major fetal body abnormalities. With this efficient and much less invasive approach, a higher acceptance rate of fetal autopsy can be expected. Key Points • Excepting cardiac malformations, most major fetal body malformations can reliably be identified by prenatal US combined with post-mortem MRI. • In the post-mortem diagnosis of fetal body malformations, a conventional autopsy limited to the fetal heart might replace a full body autopsy after a well-conducted prenatal US and post-mortem MRI.

Le neuroblastome du système nerveux central, auparavant classé parmi les tumeurs neuroectodermiques primitives, est une tumeur de grade 4 extrêmement rare. La présence d'un profil de méthylation d'ADN spécifique associé à l'activation du gène FOXR2 a permis d'en définir une entité tumorale à part entière dans la classification de l'Organisation mondiale de la Santé de 2021. Néanmoins, les caractéristiques épidémiologiques, cliniques, histologiques et moléculaires restent mal définies. Nous rapportons le cas d'une patiente de 4 ans présentant des céphalées, phono-photophobies, nausées, vomissements et boiterie du membre inférieur droit depuis 3 mois. A l'examen neurologique, on met en évidence un signe de Romberg latéralisé à droite, une marche avec steppage et une latéropulsion du tronc vers la droite. L'IRM cérébrale montre une lésion expansive de 87 x 81 x 78 mm, intraparenchymeuse, fronto pariétale gauche avec une extension vers le carrefour ventriculaire et la région intraventriculaire, entrainant une déviation des structures médianes vers la droite et un engagement sous-falcoriel. L'examen microscopique montre une prolifération de cellules tumorales, richement cellularisée, constituée de petites cellules bleues, discohésives, mitotiquement actives, exprimant les protéines Synaptophysine, OLIG2 et NeuN. L'analyse du profil moléculaire par « Next Generation Sequencing » et du profil de méthylation de l'ADN tumoral ont révélé un gain du chromosome 1q36 et l'activation du facteur de transcription FOXR2. Ce cas supporte que le profil de méthylation d'ADN permet le diagnostic de tumeurs pédiatriques qui auraient été auparavant inclassées ou mal classées, permettant une prise en charge optimale du patient.