Long considered mere degradative compartments, lysosomes are now recognized as key regulators of metabolism, signaling, and tumor invasion. Here, we discuss how their intracellular localization controls their function, signaling, and secretion. In melanoma, the peripheral distribution of lysosomes promotes aggressiveness and metastasis. Similar changes exist in other types of cancer, highlighting the role of lysosomal trafficking as a factor in malignancy and as a promising biomarker for diagnosis and treatment.

During decades, first-line treatment of advanced cervical cancer solely consisted of platinum-based chemotherapy, associated with bevacizumab whenever possible. Since 2022, immunotherapy is part of standard therapeutic strategy with pembrolizumab on the one hand, associated with chemotherapy and bevacizumab in patients with PD-L1 positive tumors (CPS≥1), and cemiplimab on the other hand, in patients who did not receive prior immunotherapy and progress after first line regardless of PD-L1 expression. Pretherapeutic work-up includes CT of the chest, abdomen and pelvis potentially associated with 18F-FDG PET-CT and MRI in case of relapse, as well as evaluation of PD-L1 status on tumor and immune cells to define the CPS score that will determine eligibility to pembrolizumab treatment (CPS≥1). Whenever possible, molecular screening and determination of HER2 status may allow orienting patients to clinical trials. Indeed, inclusion in investigational studies must be systematically considered and early supportive care is always recommended.

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.

Histomolecular diagnosis of endometrial cancer systematically includes the evaluation of hormonal receptors, P53 and MMR statutes (determination of PD-L1 and HRD statutes is not required). Therapeutic progress in advanced endometrial cancer is mainly related to the first-line utilization of immunotherapy associated with chemotherapy, a strategy assessed in five randomized controlled trials, although at the moment, only dostarlimab is available in France. Immunotherapy administration requires specific pretherapeutic workup and monitoring. Hormone therapy remains an option in non-aggressive, low grade endometrioid cancer, expressing hormone receptors. Treatment choice is based on clinical situation (upfront metastatic disease or relapse after adjuvant therapy, and duration of platinum-free interval in case of adjuvant therapy), disease aggressivity, molecular status (in particular, MMR status) and patients' comorbidities. PARP inhibitors are not recommended as maintenance therapy. In second line, the combination of pembrolizumab and lenvatinib is the standard treatment if chemoimmunotherapy has not been used previously. If it has been, therapeutic strategy depends on the duration of platinum-free interval. Inclusion in a clinical trial should always be considered when the patient's performance status makes it possible. The choice of the trial is guided by HER2 status in immunohistochemistry and results of new generation sequencing when available. The current trend towards the development of personalized medicine highlights the importance of pathological and molecular characterization of the tumor.

Localized or locally advanced cervical cancer is treated with a curative intent. Its management requires multidisciplinary expertise and a rigorously structured approach to optimize the probability of success. Initial workup (clinical examination, imaging, pathology) allows precise characterization of the tumour and staging according to TNM and FIGO classifications. Surgical management of early stage cancers, ranging from conization for small tumour to hysterectomy, sometimes including sentinel lymph node biopsy, is based on therapeutic algorithms that take into account stage, pathological criteria (invasion, margins, node involvement) and risk category. Postoperative treatment, when required, includes radiochemotherapy, that can be followed by brachytherapy. In locally advanced cancers, treatment consists of radiochemotherapy followed by uterovaginal brachytherapy and immunotherapy that has recently demonstrated its benefits. Since cervical cancer often develops in young women, its management raises important questions related to fertility and sometimes, to the management of cancer during pregnancy. Finally, although it is not the topic of these recommendations, it is important to highlight the major role of vaccination to avoid the vast majority of these cancers.

Metastatic castration-sensitive prostate cancer (mCSPC) has undergone major therapeutic advances with the introduction of next-generation androgen receptor pathway inhibitors (ARPI). Two treatment strategies have demonstrated clinical benefit at this stage: doublet therapy, combining androgen deprivation therapy (ADT) with one of the four currently available ARPI, and triplet therapy, integrating abiraterone or darolutamide with docetaxel. The choice of therapeutic strategy is based on a personalized assessment that considers both tumor aggressiveness and the patient's overall profile, particularly cardiovascular and cognitive comorbidities, regardless of age, frailty, or level of activity. Optimal management of mCSPC requires a multidisciplinary approach, including a baseline cardiovascular workup, systematic geriatric assessment, non-pharmacological interventions (such as tailored physical activity and cognitive stimulation programs), calcium and vitamin D supplementation, structured sexual health support, and a comprehensive medication review conducted in collaboration with a pharmacist. Ongoing trials are exploring treatment de-escalation strategies, notably intermittent ADT, to preserve antitumor efficacy while improving quality of life. This review highlights the importance of a personalized, multidisciplinary approach, integrating therapeutic innovations with individualized supportive care, in a context marked by emerging differentiations of therapeutic options for mCSPC.

CYSTIC LESIONS OF THE PANCREAS. The practice of every gastroenterologist is daily punctuated by the management of patients with pancreatic cystic lesions (PCL). The discovery is usually fortuitous and the lesions in majority are small (less than 10mm). The prevalence of PCL in the general population of adults is very high and probably greater than 40% if we consider lesions of 2 mm. Some PCL are precancerous lesions, (as intraductal papillary mucinous neoplasm [IPMN]) with a real risk of pancreatic adenocarcinoma and others cystic lesions have a risk of metastases such as pseudopapillary and solid tumors or cystic neuroendocrine tumors. The follow-up protocol, recommended by international experts, is highly debated because it is expensive, potentially invasive (in case of repeated use of endoscopic ultrasound) and not perfect. Only a few patients will develop aggressive and potentially invasive lesions. However, the lack of specific diagnostic tools for the grade of dysplasia and the mortality rate of pancreatic cancer leads European experts to recommend regular monitoring.

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.

Medical treatment of breast cancer today depends on the tumor profile. For triple-negative breast cancer, the standard treatment before surgery now combines chemotherapy and immunotherapy, significantly improving the chances of cure. In the metastatic stage, new therapies such as the antibody conjugate (ADC) sacituzumab-govitécan have substantially prolonged survival. For HER2-positive tumours, the strategy is also to treat before surgery. For metastatic forms, a new-generation ADC, trastuzumab deruxtecan, has proved its immense efficacy, becoming a benchmark. Finally, for hormone-dependent (HR+) cancers at high risk, the addition of CDK4/6 inhibitors to hormone therapy after surgery reduces the risk of recurrence. In addition, ADCs are also of interest in advanced forms, particularly for tumours known as "HER2-low".

Breast cancer accounts for approximately 24% of all new cancer cases in women worldwide and remains a major challenge for the medical community despite advances in screening and treatment. The management of axillary lymph nodes is crucial for local-regional control and tumor staging. Historically, radical mastectomy was introduced by William Halsted in the late 19th century; however, this method resulted in significant morbidity. Over time, less invasive techniques have been developed, notably sentinel lymph node biopsy (SLNB) in the 1990s, which assesses the status of axillary lymph nodes based on the sentinel node. If this node is disease-free, a complete axillary dissection can often be avoided, thereby reducing complications. SLNB is now recognized as the standard of care for patients with early-stage breast cancer without clinical nodal involvement, supported by studies such as ACOSOG Z0011 and AMAROS. However, questions remain regarding the best surgical approach for patients with specific tumor subtypes or extensive nodal involvement. This article offers an analysis of the scientific foundations of lymph node surgery, technical advancements, clinical trial outcomes, and the future prospects of increasingly personalized medicine.

Immediate breast reconstruction (IBR) following total mastectomy is now an established surgical approach that combines oncological safety with aesthetic benefits. This review discusses indications, techniques, and surgical adaptations of IBR based on breast morphology and adjuvant therapy planning. At Institut Curie, experience with over 600 reconstructions has led to refined patient selection, with an overall implant removal rate of 5.8%, dropping to 4% in "low risk" patients. Prepectoral implant placement, with or without acellular dermal matrices (ADM), has emerged as a reliable alternative to subpectoral techniques. It offers less postoperative pain, eliminates animation deformity, and significantly reduces capsular contracture. For large or ptotic breasts, skin-reducing mastectomy or two-stage reconstruction enhances outcomes.

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.

Merkel's carcinoma is a rare but highly aggressive cutaneous neuroendocrine tumor whose incidence has increased due to an aging population and increased UV exposure. It is characterized by rapid growth, high risk of recurrence and early metastatic spread. Two subtypes have been identified: Merkel polyomavirus-related (MCPyV), present in 80% of cases in Europe, and UV-related. The main risk factors are advanced age, male gender, light phototypes and immunosuppression. Clinically, it appears as a painless, red or purplish nodule, often on photo-exposed areas. Diagnosis is based on histopathology and immunohistochemistry (CK20+ and synaptophysin+). Extension assessment is essential, and relies on PET-CT, brain MRI and lymph node ultrasound. Staging follows the AJCC 8th edition, distinguishing between localized (I/II), lymph node involved (III) and metastatic (IV) stages. Treatment is based on surgery (excision with 1cm margins) and adjuvant radiotherapy. In the case of lymph node involvement, lymph node dissection and radiotherapy are recommended. Metastatic forms now benefit from immunotherapy (anti-PD-1/PD-L1), which has improved prognosis. Merkel carcinoma has a high recurrence rate (25-50%). Monitoring is based on regular clinical and radiological follow-up over several years. Biomarkers such as NSE and anti-MCPyV serology are currently being evaluated.

Since the 2010s, the management of locally advanced and metastatic melanoma has been completely transformed by the use of immune checkpoint inhibitors and anti-BRAF/anti-MEK targeted therapies. These therapies have also recently been used as neoadjuvant and adjuvant treatments in certain high-risk melanoma indications (stage IIB to stage IIID).

Cutaneous squamous cell carcinoma (CSC), formerly known as squamous cell carcinoma, is the most common skin cancer after basal cell carcinoma, accounting for 20% of all skin cancers. It is a malignant epithelial tumor of keratinocytic origin. Its incidence has risen sharply in recent decades. CEC is characterized by a more rapid evolution than basal cell carcinoma, with a risk of local recurrence and distant lymphatic and hematogenous metastatic dissemination. Early surgical management usually leads to a cure; adjuvant radiotherapy should be considered in cases of poor prognosis. Finally, immunotherapy has supplanted conventional chemotherapy in the management of advanced forms of the disease, thanks to its superior efficacy (40-50% response rate) and much better tolerability.

Cancer is a multigenic pathology whose dynamic, evolving and heterogeneous nature has led to the development of a variety of models to study it. Traditionally, two-dimensional (2D) cell culture has been used in vitro. However, an accumulated body of data demonstrates the relevance of three-dimensional (3D) cultures for modeling and studying the mechanisms involved in the initiation, progression, and resistance to treatments of tumors, particularly solid tumors. By better reproducing the spatial architecture, cell-cell and cell-matrix interactions, and phenotypic heterogeneity of tumors, these 3D models help bridge the gap between in vitro studies and in vivo conditions. This review describes the main 3D culture models - spheroids, organoids, tumoroids, tumor explants and cancers-on-a-chip - highlighting their principles, advantages and limitations. The techniques used to generate these 3D culture models, such as liquid-based or scaffold-based 3D culture, microfluidics, and 3D bioprinting, are also presented. Finally, examples of applications of these models are discussed, including the study of vascularization and its role in immune system recruitment, the modeling of the metastatic process, the screening of drug candidates and the elucidation of treatment resistance. The potential of 3D models is also addressed in the context of personalized medicine.

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.

Fine needle aspiration is a well-known procedure for the diagnosis and management of solid lesions. The approach to cystic lesions on fine needle-aspiration is becoming a popular diagnostic tool due to the increased availability of high-quality cross-sectional imaging such as computed tomography and ultrasound guided procedures like endoscopic ultrasound. Cystic lesions are closed cavities containing liquid, sometimes partially solid with various internal neoplastic and non-neoplastic components. The most frequently punctured cysts are in the neck (thyroid and salivary glands), mediastinum, breast and abdomen (pancreas and liver). The diagnostic accuracy of cytological cyst sampling is highly dependent on laboratory material management. This review highlights how to approach the main features of superficial and deep organ cysts using basic cytological techniques (direct smears, cytocentrifugation), liquid-based cytology and cell block. We show the role of a multimodal approach that can lead to a wider implementation of ancillary tests (biochemical, immunocytochemical and molecular) to improve diagnostic accuracy and clinical management of patients with cystic lesions. In the near future, artificial intelligence models will offer detection, classification and prediction capabilities for various cystic lesions. Two examples in pancreatic and thyroid cytopathology are particularly developed.

Monocytes, circulating mononuclear phagocytes, play a fundamental role in innate immunity and the maintenance of tissue homeostasis. Using advanced technologies like flow cytometry, the characterization of monocytes has evolved from a simplistic view of a homogeneous population to a more complex understanding of a heterogeneous system comprising three main subtypes: classical monocytes (CD14++CD16-), intermediate monocytes (CD14++CD16+), and non-classical monocytes (CD14+CD16++). The identification of these subpopulations has enabled precise characterization of their functional profiles, enhancing the understanding of their roles in various pathological contexts, particularly in oncology. While anti-tumoral functions of monocytes have been clearly established in certain categories of cancers through tumor antigen presentation, induction of cytotoxic responses, and inhibition of metastatic progression, their role in promoting the development and progression of other cancers has also been highlighted during recent years. The utilization of monocytes in cancer immunotherapy presents promising opportunities, particularly by reprogramming their activity to enhance anti-tumoral responses or suppress their pro-tumoral functions. This review provides a comprehensive analysis of recent advances in the phenotypic and functional diversity of monocytes and their role in tumor progression, while highlighting emerging therapeutic strategies targeting these cells to optimize cancer treatment.

The prognosis for patients with high-risk neuroblastoma in the event of disease relapse/progression after first line therapy remains poor. However, over the past decade, new therapies have emerged that offer physicians, families and patients the hope of tumor control and, in some cases, a cure. Given the rapid evolution of new therapies in this field, it is strongly recommended that such cases be discussed at a multidisciplinary level and with patients/families regarding treatment options based on existing data. We summarize here the recommendations of the Neuroblastoma Committee of the Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'adolescent (SFCE) for the treatment of patients with high-risk neuroblastoma in relapse/progression in France. These recommendations concern chemoimmunotherapy, the combination of ALK inhibitors with chemotherapy, and consolidation treatment options in the absence of tumor progression, as well as the place for early clinical trials.