Ewing sarcoma (ES) is an aggressive sarcoma with a peak incidence in adolescents and young adults. Current therapy involves multiagent chemotherapy and local therapy but despite intensification of treatment patients with metastases at diagnosis and recurrent disease have poor prognosis. Improved understanding of ES biology has identified novel targets with promising activity in ES patients. Tyrosine kinase inhibitors are currently being evaluated as combination and maintenance therapy. Other emerging therapies include those that target the EWSR1:FLI1 fusion oncoprotein, cell cycle, apoptotic and DNA-repair pathways. Immunotherapeutic approaches are also being investigated, particularly CAR-T and CAR-NK cell therapy. Close collaboration between clinicians and biologists has also highlighted the importance of biomarkers that are still being validated prospectively and might be incorporated into standard of care in the future.

Pediatric-type follicular lymphoma is a rare entity, predominantly involving lymph nodes in the head and neck of children and young adults. Ocular adnexal involvement, particularly of the conjunctiva, is exceptionally uncommon in this age group.

Histopathological examination is a cornerstone in the diagnosis, prognostic stratification, and therapeutic planning of breast cancer. It combines morphological, immunophenotypic, and molecular data to guide clinical decision-making. This article provides a comprehensive overview of the main histological types, technical modalities, and conventional and emerging biomarkers in breast cancer pathology. Breast carcinomas are categorized into in situ (DCIS, LCIS) and invasive forms. The most frequent invasive types are invasive carcinoma of no special type (NST) and invasive lobular carcinoma (ILC). Rare histologic variants (e.g., mucinous, micropapillary, metaplastic) exhibit distinct biological and prognostic features. The diagnostic workflow includes standardized steps: sampling, formalin fixation, paraffin embedding, H&E staining, immunohistochemistry (ER, PR, HER2, Ki-67), and molecular testing when needed (FISH, PCR, NGS). Routine biomarkers help define surrogate molecular subtypes (luminal A/B, HER2-positive, triple-negative) and guide systemic therapies. The emergence of the HER2-low category exemplifies how biomarker refinement impacts clinical practice. Additional markers such as PIK3CA and ESR1 mutations, BRCA/HRD status, PD-L1 expression, and tumor-infiltrating lymphocytes (TILs), along with multigene signatures (e.g., Oncotype DX, MammaPrint), further individualize prognostic assessment and treatment selection. Innovative approaches such as liquid biopsy and next-generation sequencing (NGS) enable minimally invasive monitoring and personalized care, especially in advanced disease. Breast cancer pathology is thus a dynamic, integrative discipline central to precision oncology, driven by ongoing technological and molecular advances, and essential to multidisciplinary cancer care.

Uveal melanomas (UM) are rare intraocular tumours. A third of these patients develop metastases, mostly hepatic ones. Patients can be given prognosis estimations thanks to clinical and genomic criteria. Nonetheless, in the context of UM, the transmission of information pinpoints numerous ethical concerns for physicians, due to the complex nature of its therapeutic care.

The rising incidence of cancer and the frequent resistance to treatments are driving the scientific community to explore new biological frontiers in search of concrete solutions for personalized patient care. These initiatives are made possible by the ongoing development of innovative technologies, which are shedding new light on our understanding of biological mechanisms. One such area is ribonucleic acid (RNA) chemical modifications-known as the epitranscriptome-which play a key role in all post-transcriptional stages of gene expression. An increasing number of studies are linking these modifications to tumor progression and treatment resistance. Functionally, epitranscriptomic modifications are orchestrated by a set of proteins known as "writers", "erasers" and "readers" which respectively add, remove, or read these chemical marks on RNA. The expression of these regulatory proteins is often dysregulated in cancer, thereby contributing to carcinogenesis. Clinically, these modifications are relevant across the entire patient care continuum, including diagnostic, prognostic, predictive, and therapeutic aspects. Many epitranscriptomic marks are associated with overall survival, tumor stage, the presence of metastases, or the detection of specific cancer types. They can enhance treatment efficacy or help anticipate resistance by modulating gene expression in target cells and revealing molecular signatures associated with therapeutic escape mechanisms. Moreover, inhibitors targeting epitranscriptomic regulatory proteins are currently under development and being evaluated in clinical trials, paving the way for novel therapeutic strategies in oncology.

We report the case of a 45-year-old woman in whom a solitary 5.5cm hepatic tumor was discovered during oncologic surveillance for a papillary thyroid carcinoma diagnosed ten years earlier. Biopsy revealed a tumor cell proliferation with "endocrinoid" morphology and convincing immunohistochemical expression of neuroendocrine markers, initially suggesting a well-differentiated grade 3 neuroendocrine tumor. FDG-PET/CT demonstrated isolated hypermetabolic activity in the liver lesion, with no corresponding uptake on DOTATOC-PET. Following neoadjuvant chemotherapy, the patient underwent segmental liver resection. Histopathological examination of the resected specimen showed a proliferation of monomorphic cells with ovoid nuclei, arranged in a tubulo-solid architecture, with focal areas reminiscent of a "thyroid-like" pattern. Tumor cells exhibited heterogeneous expression of neuroendocrine markers and strong, diffuse positivity for alpha-inhibin. RNA sequencing identified a NIPBL::NACC1 fusion transcript, leading to a revised diagnosis of hepatic carcinoma with NIPBL::NACC1 fusion. This recently described and rare hepatic tumor is challenging to diagnose on biopsy. Histologically, it is characterized by a monomorphic ovoid cell proliferation with a tubulo-solid growth pattern and focal thyroid-like morphology. Neuroendocrine marker expression is variable, but strong and diffuse alpha-inhibin staining is a consistent feature.

This review aims to describe the role of poly-ADP-ribose polymerase inhibitors (PARPi) in the treatment of metastatic castration-resistant prostate cancer (mCRPC), an aggressive and lethal form of the disease. The introduction of PARPi has led to improved prognosis, particularly in patients with at least one somatic or germline mutation in DNA damage repair genes such as BRCA1 or BRCA2. Several recent studies have shown that PARPi, used alone or in combination with abiraterone or enzalutamide, improve progression-free survival and overall survival in patients with mCRPC. However, whether the three PARPi evaluated in phase 3 trials are therapeutically equivalent, and whether combination therapies should be recommended as first-line treatment for all mCRPC patients or reserved for those carrying mutations, particularly BRCA1/2, remain to be determined.

Molecular biologists play an important role in therapeutic decisions in the context of Chronic Myelogenous Leukemia (CML). Before treatment, it is mandatory to identify the BCR::ABL1 fusion and any prognostic cytogenetic abnormalities that may be present. During treatment, regular assessment of measurable residual disease (MRD) is essential to objectively evaluate the optimal response and identify situations of resistance to treatment. Monitoring of MRD is also required when considering treatment discontinuations. In cases of resistance, identifying mutations that confer resistance to tyrosine kinase inhibitors is essential for adapting the treatment. The Group of Molecular Biologists of Hematologic Malignancies (GBMHM) and the France Intergroup of Chronic Myeloid Leukemia (Fi-LMC) convened a panel of experts to critically review methods used for molecular diagnostics and follow-up of patients with CML, define best practices applicable in this context and formulate recommendations.

The national investigators group for ovarian and breast cancer studies (GINECO) is an academic clinical research group specialized in gynecological oncology. Within the translational research group, the pathologists have several roles, including qualifying samples from patients included in clinical trials (tumor surface and cellularity). Since 2015, several clinical trials have required the qualification of tissue material, leading to a substantial database gathering tumor surface and cellularity associated with the concentration and quantity of DNA/RNA extracted. The main objective of this study was to investigate variations in nucleic acid concentration and quantity depending on the tumor cellularity and surface, using 1734 formalin-fixed, paraffin-embedded (FFPE) specimens from several GINECO clinical trials. The quantities of DNA and RNA extracted appeared to correlate well with tumor surface. The amount of RNA extracted also appeared to correlate with tumor cellularity. An optimal DNA concentration (>50ng/μL) was achieved with a tumor surface of at least 51-100mm2 and a tumor cellularity of at least 20%. An optimal RNA concentration (>100ng/μL) was obtained with a tumor surface of at least 26-50mm2 and a tumor cellularity of at least 51%. These data underline the importance of sending FFPE material with the highest tumor surface and cellularity when including patients in clinical trials. Inclusion in clinical trials enables patients to benefit from innovative therapeutic management.

The most common cancer in women is breast cancer (BC). MicroRNA-21 was one of the first oncomiRs to be found at elevated levels in a number of malignancies, including gliomas, BC, and colorectal cancer (miR-21). MiRNA is associated with processes such as apoptosis, invasion, metastasis, and proliferation, which are known features of cancer. This study aimed to investigate the molecular basis and clinical significance of miR-21 in BC, as microRNAs play a critical role in this disease.

In France breast cancer is the most common cancer among women and the leading cause of cancer deaths. Identifying women with a "high" or "very high" breast cancer risk, according to the terminology of the Haute Autorité de santé 2014 guidelines, is essential to offer them special cares in term of screening and prevention. Women genetically predisposed have a very high risk of breast cancer. During the oncogenetic specialist consultation, familial and personal history of cancer is considered to evaluate the risk of hereditary Breast/Ovarian syndrome and thus the need of a genetic screening. In 2017 a list of 13 genes involved in hereditary ovarian or breast cancer has been established in France (Genetic and Cancer Group - Unicancer). Women carrying a BRCA1, BRCA2, PALB2, TP53, CDH1, PTEN mutation have a higher risk of breast cancer and are considered as "high risk". Therefore medical breast surveillance similar to carriers of BRCA1/BRCA2 mutation is recommended for these patients (INCa guidelines 2017). However a mutation in one of those genes is only identified in approximatively 10% of the screened families. The oncogenetic specialist's assessment distinguishes families in which women remain at a "high" risk of breast cancer (HAS 2014 for screening) from those where women have a "very high" risk (INCa guidelines 2017 for screening and prevention).

Breast cancer affects 5% of women of childbearing age, accounting for 30% of cancer cases in this population. These cancers are often more aggressive with a less favorable prognosis in younger women. Hormonal exposure plays a key role in the development of this cancer, although the specific impact of certain exposures, such as hormonal contraception or ovarian stimulation treatments, remains debated. Studies on the link between hormonal contraception and breast cancer risk present contradictory results. Some suggest a slight increase in risk, particularly after prolonged use, while others find no significant association. Regarding assisted reproductive technology, data show no increased risk of breast cancer after ovarian stimulation. For women with breast cancer, fertility preservation is possible before the implementation of gonadotoxic treatments without significantly impacting the risk of recurrence. Pregnancy after breast cancer, including hormone-dependent cancer, is not associated with a higher risk of recurrence. Lastly, women with BRCA mutations would face an increased risk of reduced ovarian reserve, but fertility preservation, as well as the use of contraception or hormone replacement therapy, can be considered in this high-risk population.

Breast cancer in adolescents and young adults (AYAs) is a rare event but requires a well-structured and tailored approach for this specific population. Oncogenetic and oncofertility consultations are essential at the time of breast cancer diagnosis in an AYA. Therapeutic management follows breast cancer guidelines, with particular attention to the risks of long-term side effects, potential constitutional genetic mutations, and specific considerations regarding hormone therapy. The number of adults who have survived cancer during childhood or adolescence/young adulthood increases each year. The morbidity associated with prior treatments and the risk of secondary cancers create needs for care and follow-up, which must be organized, anticipated, and adapted.

Isocitrate dehydrogenase IDH1 and IDH2, key enzymes in central and energy metabolism, are frequently mutated in acute myeloid leukemia (AML). They catalyze the production of the oncometabolite R-2-hydroxyglurate, which plays a key role in leukemogenesis and relapse of patients after standard AML treatments. Although the recent introduction of selective inhibitors of IDH1 (ivosidenib) and IDH2 (enasidenib) has improved the prognosis of patients with IDH1- and IDH2-mutant AML, several mechanisms of resistance to these treatments have already been identified, including metabolic reprogramming. The study of these mechanisms has opened up new therapeutic opportunities for the monitoring and treatment of patients with this subtype of AML.

Currently, the main means of diagnosing ovarian cancer at an early stage involve risk prediction, prevention and screening in patients identified as being at genetic risk. Our aim is to identify patients who may benefit from bilateral salpingo-oophorectomy for risk reduction purposes, as well as the modalities for its realization. We list the genes associated with ovarian cancer predisposition, their frequency in the general population, the risk of patients carrying these genes developing ovarian cancer, and the risk-reducing surgical procedures associated with each gene.

The management of melanoma has evolved significantly over the past decade with the advent of immunotherapies and BRAF/MEK inhibitors, which have changed the prognosis for patients with advanced disease. Having demonstrated their efficacy in advanced disease, these treatments have been evaluated and shown to be effective in adjuvant treatment at earlier stages, first in stage III and then in stage IIB-IIC. Alongside the development of these adjuvant treatments, which have become the standard of care, new therapeutic strategies have emerged. Neoadjuvant treatments have been shown to be superior to adjuvant treatments in phase II and III trials. These neoadjuvant strategies will undoubtedly become the new standard for patients with macroscopic lymph node disease. However, there are still many unanswered questions regarding the optimal treatment regimen. Should mono- or bi-immunotherapy be used? Can surgery be de-escalated? Is additional adjuvant treatment essential or can it be withheld in the event of a major pathological response? Should patients with BRAFV600 mutations switch to targeted therapies in the event of pathological non-response? Should we switch to targeted therapies in the event of pathological non-response in BRAFV600 mutant patients? Therapeutic strategies, which are becoming increasingly personalised, are evolving very rapidly, with a trend towards de-escalation. We still lack robust biomarkers for patient selection.

The detection of circulating tumor DNA (ctDNA) has made significant advances in oncology in recent years. ctDNA offers a range of applications, including the identification of theranostic mutations, monitoring of tumor recurrence, and assessing treatment efficacy. In breast cancer, several ctDNA-based tests for detecting relapse during follow-up are currently under validation, with some already available in countries like the United States. In metastatic breast cancer, ctDNA levels and their dynamics during treatment have prognostic value. The PADA-1 trial demonstrated that a therapeutic adaptation based on the detection of a circulating subclone via circulating tumor DNA (ctDNA) was feasible and potentially beneficial for patients. This review will explore the methods for ctDNA detection and discuss the potential benefits of incorporating this technology into breast cancer monitoring and management across various clinical scenarios.

Breast cancer associated with pathogenic variants of BRCA1 and BRCA2 genes requires specific management. This review examines the prognostic benefits, prophylactic surgical strategies, and impact on quality of life of patients at very high risk of breast cancer. Breast surgical prophylaxis concerns women at high risk of breast cancer with a risk assessment based on their personal and family history, or by diagnosis of pathogenic variants in high-risk genes. Personalized management is based on enhanced clinical and radiological monitoring, the use of predictive tools such as BOADICEA, and surgical options such as prophylactic bilateral mastectomy, which can reduce the risk of cancer by over 90 %. Although its impact on overall survival is still debated, advances in surgical techniques have significantly improved aesthetic results and patient satisfaction, thanks to modern reconstruction methods. The surgical strategy, whether primary or secondary, must be individualized, considering the patient's history, therapeutic needs, and preferences. Mastectomy with preservation of the skin envelope, often performed in one or two stages, offers significant psychosocial benefits, although radiotherapy may increase the risk of complications. Options include immediate reconstruction, by implant or autologous technique, adapted to the patient's morphology and any adjuvant treatments.

Breast cancer is a complex disease influenced by genetic and environmental factors. Molecular profiling research has revealed significant diversity within the disease, including among tumours with similar morphological features. This diversity can lead to significant differences in tumour behaviour. Scientists have turned their attention to molecular biomarkers to predict cancer behaviour and/or response to treatment, and to ensure personalised, optimal management of breast cancer patients. This article presents four examples of molecular biomarkers and genetic tests used in the field of breast cancer, highlighting their latest advances and their clinical use as predictive and/or prognostic markers.

Alterations in DNA methylation profiles are typically found in cancer cells, combining genome-wide hypomethylation with hypermethylation of specific regions, such as CpG islands, which are normally unmethylated. Driving effects in cancer development have been associated with alteration of DNA methylation in certain regions, inducing, for example, the repression of tumor suppressor genes or the activation of oncogenes and retrotransposons. These alterations represent prime candidates for the development of specific markers for the detection, diagnosis and prognosis of cancer. In particular, these markers, distributed along the genome, provide a wealth of information that offers potential for innovation in the field of liquid biopsy, in particular thanks to the emergence of artificial intelligence for diagnostic purposes. This could overcome the limitations related to sensitivities and specificities, which remain too low for the most difficult applications in oncology: the detection of cancers at an early stage, the monitoring of residual disease and the analysis of brain tumors. In addition, targeting the enzymatic processes that control the epigenome offers new therapeutic strategies that could reverse the regulatory anomalies of these altered epigenomes.