Giant cell tumor of the tendon sheath (GCT-TS) is a benign, slow-growing lesion originating from the tendon sheath or adjacent bursal tissue. We present a series of four histologically confirmed cases with atypical presentations in the foot and hand. Clinical features included a slow-growing, painless mass, often associated with prior trauma. All patients underwent surgical excision, with histopathology confirming GCT-TS. This report emphasizes the importance of considering GCT-TS in the differential diagnosis of soft-tissue swellings in tendon-rich areas and highlights the role of surgery as definitive management.

The progression of prostate adenocarcinoma (PCa) toward castration resistance involves complex molecular pathways. This study evaluates the role of NF-κB and EGF receptors (EGFR, HER3) in tumor aggressiveness among Moroccan patients. A retrospective study with immunohistochemical analysis of NF-κB subunits (p65, p50, RelB), EGFR, and HER3 was performed on tissue samples from 88 PCa patients. Results were correlated with castration resistance status and Gleason scores (using Chi-square tests and logistic regression). Strong nuclear localization of NF-κB was detected in castration-resistant cancer cells (p = 0.0005), serving as a predictive marker for progression. Simultaneously, high EGFR expression was identified in hormone-refractory patients (OR = 5.37; p = 0.0010). Nuclear HER3 expression significantly correlated with high Gleason grades (≥ 7) in resistant tumors (p = 0.0064). Nuclear activation of NF-κB and HER3, along with EGFR overexpression, plays a critical role in hormonal escape. These molecules represent promising therapeutic targets and prognostic biomarkers for high-risk PCa management in Morocco.

Recent advances in single-cell transcriptomics have profoundly renewed our understanding of immune cells. They have enabled us to better characterize the heterogeneity of Natural Killer (NK) cells and establish a classification that integrates all their characteristics. These approaches have also shed light on the behavior of NK cells infiltrating the tumor microenvironment, the mechanisms of their dysfunction, and the limits of their antitumor activity. Finally, they are essential for understanding the mechanisms of action of new therapies targeting NK cells.

Clear cell carcinoma (CCC) of the cervix is a rare cancer, particularly in the absence of exposure to diethylstilbestrol (DES). This case is unique because it involves a 40-year-old patient with no history of DES exposure, illustrating the diagnostic and therapeutic challenges in a resource-limited setting such as Mauritania. The patient presented with persistent vaginal bleeding, and a mass was detected during a gynaecological examination. The final diagnosis of CCC was confirmed by histopathological and immunohistochemical examination. Treatment consisted of external radiotherapy and chemotherapy, followed by an extended colpohysterectomy, without the use of brachytherapy because of technical constraints. The patient responded well to treatment, with no clinical or radiological evidence of recurrence. This case underscores the feasibility of effective multidisciplinary management of rare cervical tumors in resource-limited settings.

Cutaneous squamous cell carcinoma (cSCC) is a common cancer with a rising incidence, mainly due to cumulative ultraviolet exposure and immunosuppression. Surgery remains the standard treatment for localized disease, most often providing sustained tumor control. Radiotherapy is an alternative or adjunct option, particularly in cases of surgical contraindications or high-risk features after resection, and can be used as a definitive treatment in some elderly or comorbid patients. Immunotherapy with checkpoint inhibitors has transformed the management of advanced cSCC, inducing high and long-lasting response rates. Promising results in the neoadjuvant and adjuvant settings are paving the way for multimodal strategies and a potential de-escalation of locoregional treatments.

Stereotactic body radiotherapy (SBRT) is a treatment technique for localized non-small cell lung cancer, primarily used in patients who are inoperable or at high surgical risk. It delivers precise ablative doses in a few sessions, ensuring excellent local control (85-98%) and low toxicity. Efficacy relies on a sufficient biological dose that is tailored to the tumor's location. Various techniques allow for the management of respiratory motion, including the placement of fiducials around the lesion. SBRT is suitable for elderly or frail patients, regardless of their initial lung capacity. It is now the standard of care for early-stage, inoperable lung cancer, combining efficacy, safety, and personalized treatment.

Stereotactic radiosurgery is now a reference treatment for small-to-medium-sized vestibular schwannomas. It provides excellent tumor control with low associated morbidity. The preservation of auditory and vestibular function remains a major concern and largely depends on dosimetric optimization, particularly the reduction of the dose delivered to the cochlea and vestibular system. Recent advances in understanding the radiobiological tolerance of these structures, coupled with technological innovations (high-resolution imaging, modern radiosurgery platforms, and artificial intelligence tools), allow for more precise and personalized treatment planning. Together, these innovations enhance therapeutic efficacy while minimizing toxicity.

Historically, prostate cancer radiotherapy relied on conventional fractionation of 2 Gy per session over several weeks to limit toxicity to healthy tissues. Technological advances in imaging and treatment precision have enabled the development of hypofractionated schedules, involving fewer sessions, while maintaining similar efficacy. Combining radiotherapy with hormone therapy improves outcomes by increasing tumor cell sensitivity to radiation. The addition of abiraterone or enzalutamide to the treatment plan for some very high-risk patients further improves survival rates. However, these treatments may cause bone, metabolic, cardiovascular, and sexual side effects, requiring multidisciplinary management.

Immunotherapy has revolutionized the management of metastatic non-small cell lung cancer (NSCLC) without targetable alterations. Its use depends on histology, tumor PD-L1 expression, Performance Status (PS) score and patient age. The objective is to describe real-life therapeutic attitudes in France in 2020 and to analyze the adequacy with the professional standards applicable. The KBP-2020 study is a prospective observational study, including patients diagnosed de novo with primary lung cancer in 2020, followed in France in the participating non-university hospitals. Retrospective data analysis provides information on the first-line distribution of systemic treatments (immunotherapy, chemotherapy or the combination of both) in patients with stage IV NSCLC (542 squamous and 2082 non-squamous) without ALK rearrangement/alteration or EGFR mutations and PS score≤2. Immunotherapy alone or combined with chemotherapy is prescribed according to tumor PD-L1 expression: in case of PD-L1≥50%, in 85.2% of non-squamous and 86.6% of squamous patients, in case of PD-L1 [1-49%], in 61.7% of non-squamous and 45% of squamous patients and in case of PD-L1<1%, immunotherapy alone or combined with chemotherapy is prescribed in 56.48% of non-squamous and 30.86% of squamous patients. The use of immunotherapy in real life in 2020 in France shows an apparent gap with national guidelines that is more marked in cases of squamous cell NSCLC or with PD-L1 expression<50% with less exposure of patients to the immunotherapy-chemotherapy combination compared to current recommendations. This gap could be partly explained by the progressive reimbursement schedule of pembrolizumab and by other factors not documented in KBP-2020-CPHG.

The management of locally advanced head and neck tumors is complex due to the multimodal nature of the treatment and the frequent presence of comorbidities in this patient population. International guidelines recommend the use of cisplatin concomitantly with radiotherapy; however, its administration is often limited by contraindications and potential toxicities. The management of treatment-related adverse effects, as well as the use of induction chemotherapy, remains heterogeneous. Therefore, we aimed to assess the current practices of French oncologists in order to identify potential needs and evaluate the relevance of issuing national recommendations to harmonize clinical practice.

Paraneoplastic dermatoses are rare cutaneous manifestations that are secondary to an underlying neoplasm. They may precede the diagnosis of cancer by months or even years. Some clinical presentations are relatively specific, which allows for an early diagnosis and treatment of certain cancers. In this context, their recognition by both specialists and non-specialists is essential. The aim of this article is to highlight some of these clinical presentations.

Hepatoblastoma is a rare tumor, accounting for less than 1% of childhood cancers. Its incidence is increasing, at approximately 2.16 cases per million per year. Between 80-90% of hepatoblastomas occur in children aged 6 months to 5 years, with a median age of 18 months. The 5-year survival rate is 90% for standard-risk patients and 65 % for high-risk patients. Thanks to broad international collaboration, increasingly precise morphologic and molecular characterization of these tumors has led to a better understanding of tumorigenesis mechanisms and the emergence of new biomarkers. Morphologically, hepatoblastomas are characterized by great heterogeneity, combining epithelial and mesenchymal components with or without teratoid features. While the most common subtypes (fetal epithelial, embryonal epithelial, and osteoid mesenchymal) are well defined morphologically, certain diagnostic challenges remain for pathologists-specifically, the definition of hepatocellular neoplasms not otherwise specified (HCN-NOS), which lie at the interface between hepatoblastoma and hepatocellular carcinoma, and the characterization of undifferentiated small cell components. Pathologists play an essential role in the clinical management of children with hepatoblastoma, and the most precise possible morphological characterization is crucial to advance research on this pediatric tumor.

In 85% of cases, kidney tumours in children are represented by nephroblastoma or Wilms' tumour. Children are treated according to protocols developed by SIOP-RTSG in Europe and several other continents and by NWTSG-COG in North America. The SIOP-RTSG protocol includes upfront chemotherapy, usually without biopsy, followed by nephrectomy, which must be performed rigorously, precisely and according to a protocol by the pathologist in order to classify the tumour into its appropriate risk group (low risk, intermediate risk or high risk) and to assess its local stage of extension (stage 1, 2 or 3). These criteria will determine the choice and duration of post-operative chemotherapy, with or without radiotherapy. The molecular abnormalities of nephroblastoma are heterogeneous, involving several chromosomal regions such as 1p, 16q, 1q, 11p15 and several genes such as WT1, CTNNB1, WTX, SIX1/2, DROSHA/DGCR8, TP53, MYCN, FBXW7 and TRIM28. Analyses are underway to determine whether these molecular abnormalities associated with the absolute volume of chemoresistant blastema could help divide children into different groups. In 15% of cases, these are tumours other than nephroblastoma, very different from one another, with a highly variable prognosis ranging from benign tumours such as nephrogenic rest, paediatric cystic nephroma and metanephric tumour to very aggressive tumours such as rhabdoid tumour of the kidney or medullary carcinoma of the kidney. In this group, each tumour has its own genetics, whose molecular mechanisms are increasingly well understood, with fusions, tandem duplications or gene mutations which can help the pathologist to achieve to an accurate diagnosis in each morphological context. In some situations, the identification of these molecular alterations may lead to a targeted treatment.

High-grade B-cell lymphoma with 11q aberration (HGBL-11q) is a recently recognized entity according to the 2022 WHO classification that often morphologically and immunohistochemically resembles Burkitt lymphoma but has distinct molecular characteristics. In HGBCL-11q, the defining abnormality is a characteristic gain/loss pattern of chromosome 11q without MYC rearrangement, whereas Burkitt lymphoma is characterized by a classical MYC rearrangement with one of the three immunoglobulin genes. HGBL-11q is a rare lymphoma that predominantly affects children and adolescents. Clinically, patients typically present without B symptoms. The disease most commonly involves lymph nodes in the head and neck region (approximately 60-70% of cases), while gastrointestinal involvement is observed in about 30-40% of patients.

PD-L1 immunohistochemical assessment has become an essential biomarker in the management of squamous cell carcinomas of the upper aerodigestive tract (UADT). The Combined Positive Score (CPS) is currently the gold standard method for quantifying PD-L1 expression. This article provides an update on the technical and interpretative aspects of the CPS, practical recommendations for pathologists, and associated therapeutic implications. Particular attention is paid to challenges such as reproducibility of scoring, antibody selection, and the integration of PD-L1 expression data in therapeutic decisions, especially in the context of immunotherapy. The objective is to provide pathologists with an up-to-date synthesis of best practices and to give clinicians a better understanding of the role of PD-L1 in the personalized management strategy for patients with UADT squamous cell carcinoma.

Stage IV non-small cell lung cancer (NSCLC) without actionable mutations remains a major therapeutic challenge, especially following immunotherapy failure. The introduction of immune checkpoint inhibitors (anti-PD-1/PD-L1) has revolutionized first-line treatment, but second-line options remain largely dependent on older chemotherapies such as docetaxel or pemetrexed. A significant number of patients experience disease progression despite immunotherapy, highlighting tumor resistance mechanisms, whether primary (rapid failure) or acquired (after initial response). Resistance mechanisms include low CD8+ T-cell infiltration, genetic mutations (PTEN, JAK), loss of neoantigens, and tumor-induced immunosuppression. Innovative strategies are under investigation: antibody-drug conjugates (anti-TROP-2, anti-CEACAM-5), cancer vaccines (TEDOPI), external electric fields (TTFields), oncolytic viruses, and PROTACs. While some of these show promise in progression-free survival, global survival benefit remains modest. The identification of robust predictive biomarkers is essential for tailoring future therapies.

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.

Oral squamous cell carcinoma (OSCC) is a genetically driven malignancy characterized by a high burden of oncogenic mutations that contribute to aggressive tumor behavior, therapeutic resistance, and poor survival outcomes. Conventional treatment modalities largely target downstream molecular pathways without correcting the underlying genetic aberrations, underscoring the need for precision-based therapeutic strategies. This study aimed to assess the feasibility and functional impact of CRISPR-Cas9-mediated gene editing in reversing oncogenic mutations associated with OSCC using an in vitro experimental model.

Pancreatic Acinar Cell Carcinoma (PACC) are a uncommon histological subtype (around 1-2%) of pancreatic adenocarcinoma. These tumors derive from acinar cells and may be associated with mixed histologies such as neuro-endocrine or ductal excreto-pancreatic contingents. The histological diagnosis of acinar differentiation relies on morphology and immunohistochemistry using anti-BCL10 immunohistochemical staining. Due to the low prevalence of PACC, dedicated studies are difficult to conduct and PACC management is similar to that of ductal adenocarcinoma (PDAC) in international guidelines. Retrospective studies appear to show larger but less aggressive tumors, with fewer lymph node involvement and a more favorable prognosis than PDAC. Recent research also highlighted a different carcinogenesis. Unlike PDAC, KRAS mutations are unfrequent, but Homologous Recombination Deficiencies (HRD) are commonly found (30% of cases). In most cases, they are associated with germline mutations, notably BRCA2, which may offer an opportunity for genetic counselling. Other molecular alterations, such as BRAF (approximately 3%) or MMR deficiency (2-4%), have also been reported. Thus, the identification of pancreatic acinar cell carcinoma should trigger theranostic molecular analyses for treatment personalization.

The therapeutic management of metastatic breast cancers has benefited in the past few years from important progress linked to the development of new molecules, inhibiting poly adenosine diphosphate ribose polymerase (PARP), cyclin-dependent kinases (CDK4/6) or immune checkpoints. More recently, the development of antibody-drug conjugates (ADC) targeting tumor cells, allows for the delivery of cytotoxic agents, at low doses, while increasing their concentration in the tumoral microenvironment. Currently, two ADC are available for the management of HER2-negative metastatic breast cancers, sacituzumab govitecan and trastuzumab deruxtecan. However, these ADC still induce significant grade 3/4 adverse events in more than 40% of the cases. Here, a practical review of the characteristics of these 2 ADC is proposed, with their mode of action and formulation, posology and place in the treatment schedules of HER2-negative metastatic breast cancers. The major results of phase III clinical trials are summarized, and a special focus is made on the management of toxicities.