Cervical cancer is caused by persistent infection with high-risk human papillomaviruses (HR-HPV). Current screening programs rely on cytology and HR-HPV molecular detection. However, as most infections are transient, effective triage for HR-HPV positive women is crucial to identify those at high risk of progression to cancer. DNA methylation analysis, an epigenetic modification involved in HPV-induced oncogenesis, is emerging as a promising triage tool. This marker could stratify risk, thereby reducing invasive examinations (colposcopies) and unnecessary overtreatment (conizations), which may impact future pregnancies. Methylation tests, applicable to both cervical smears and self-collected vaginal samples, target viral genes (e.g., L1, L2) or host cell genes (e.g., FAM19A4, CADM1, MAL). While many markers show good performance, their optimal place in screening strategies and the choice of the most relevant test are still under investigation and require further comparative studies.

Enthusiasm for multi cancer early detection tests remains high, with many companies involved and, notably, significant sales of a non-FDA-approved, non-reimbursed test. This contrasts with the still incomplete clinical validation of these tests. Such unjustified hype is not unheard of in the biotech world….

The evolution of serous high grade ovarian cancer management is characterized by a more regulated patients' journey on the one hand and the development of new therapeutic options on the other hand, the selection of which is guided by tumor molecular characteristics. Surgery remains the cornerstone of treatment. It can be performed only in authorized expert sites that can demonstrate sufficient experience from highly skilled surgical teams, and quality criteria including prehabilitation and rehabilitation programs. The diagnostic step is crucial; it comprises multiple biopsies that allow reliable pathological and molecular analyses, and a comprehensive surgical staging. Determination of BRCA1/2 mutation and homologous recombination deficiency statuses by validated methods guide maintenance therapy at advanced stages and referring to oncogenetic consultation if appropriate. For these advanced diseases, the two main questions for surgical strategy are the feasibility of complete resection (without residual disease, CC-0), assessed during surgical exploration of pelvis and abdomen, and the optimal timing of this surgery (upfront or after neoadjuvant chemotherapy). In recurrent diseases, surgery remains a main piece of treatment in case of late relapse and medical treatment depends on drugs used in the first line; in early platinum resistant relapse, a new therapeutic option is available with mirvétuximab soravtansine.

This article reviews a selection of recent developments in various fields of endocrinology. Advances in the diagnosis and management of endocrine disorders of general interest are highlighted, focusing on the following areas: a) new recommendations for the diagnosis and management of primary hyperaldosteronism; b) confirmation of the validity of therapeutic deescalation in low-risk differentiated thyroid cancer and c) the expansion of indications for genetic testing in multiple endocrine neoplasia syndromes.

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.

Over the past 30 years, since the identification of the BRCA1 and BRCA2 genes, the panorama of breast cancer predisposition tests has continued to evolve: today, ultra-high-throughput sequencing enables the study of eight predisposition genes, and indications are constantly expanding, with the new entry point being the identification of BRCA1/2 alterations in tumors, 75% of which are of constitutional origin. While these tests can be used to provide appropriate preventive treatment in cases where risk factors have been identified, many challenges remain to be met: identification of new predisposition genes, or rather validation of candidate genes such as ATM, detection of new modes of inactivation of genes already included in the diagnosis (remote deletions, epigenetic modifications), classification of variants of unknown significance as pathogenic or benign, and identification and inclusion of modifying factors, whether genetic or not, in multifactorial risk models. Patients and their relatives have played, and continue to play, a major role in the development of oncogenetics. We owe them quality tests, information, support and protection.

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.

The 2021 World Health Organisation (WHO) classification of tumours of the central nervous system introduced molecular biomarkers (homozygous deletion of CDKN2A/B and TERT promoter mutation) in the grading of meningiomas. Since, the cIMPACT-NOW consortium has proposed a new prognostic algorithm (published in the update 8), integrating epigenetic and genetic data. The aim of the study was to report on the experience of the neuropathology department of Sainte-Anne Hospital in integrating this algorithm into the gradingof meningiomas.

Predictive oncogenetics offers individual risk estimates aimed at improving diagnostic, preventive and potentially therapeutic measures for people defined as being at risk due to their genetic heritage. Alongside the benefits of predictive medicine, critical voices are also being raised, as the use of personal genetic data raises a range of social and ethical questions, surrounding the motivations and consequences of acquiring this information, as well as its implications for individuals' lives and for society as a whole.

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.

Molecular analyses performed on cell and tissue samples play a major diagnostic, prognostic, and theragnostic role. Their complexity and diversity, as well as that of the biological matrix involved (formalin-fixed paraffin-embedded tissue, frozen tissue, cytological sample, liquid biopsy), are increasing. The tumor cell content of the sample is an important limiting factor as well as the quality and quantity of nucleic acids extracted from the initial matrix. Therefore, it is crucial to understand and manage the conditions of sample preparation and storage, as those will directly impact the quality of the extracted material and constrain the types of analyses that will be performed. This article highlights the key pre-analytical steps as well as the limitations and interpretative biases that may result from mishandling of the samples.

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.

Granulosa cell tumors (GCTs) are rare ovarian neoplasms, accounting for 2-5% of all ovarian cancers. Two histological types have been described: juvenile (JGCT) and adult (AGCT), the latter accounting for around 95% of the GCTs. AGCTs are mostly diagnosed at an early stage and commonly have a good prognosis. However, GCTs tend to be associated with late recurrence in about a third of cases which are a major concern. These recurrences often require repeated surgical interventions. Systemic treatments, for their part, show limited effectiveness in this context, highlighting the need to identify new therapeutic targets. Thus, better biological characterization of these tumors would enable us to propose more targeted treatments. To achieve this, the molecular characteristics of GCTs have been explored. Most AGCTs harbor a mutation in the FOXL2 transcription factor sequence, therefore allowing to investigate therapeutic perspectives targeting its signalling, as well as setting the first steps towards immunotherapy in these tumors. Knowledge of JGCTs is more limited due to their rarity. However, molecular analysis revealed that ∼60% of the JGCTs bore a genetic mutation in the AKT1 oncogene. However, its clinical significance has still to be explored. For both GCTs subtypes, the CDK4/6-Rb1 axis is promising. Consequently, exploring the molecular features and their role in the biology of these tumors could open up new avenues for targeted and personalized therapies, thereby improving patient care.

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.