Paradoxical oncogenesis and benign paradoxical proliferations occur in off-target rapidly regenerating labile tissues of patients treated for malignancies with small-molecule inhibitors of cell-signaling such as kinase inhibitors. These paradoxical proliferations, particularly well listed in patients treated with selective BRAF inhibitors carrying BRAF-mutated solid malignancies, have had their incidence reduced upon the advent of BRAF/MEK double blockade therapies. Mechanistically, the underlying molecular events involved in paradoxical proliferations in off-target tissues could prove to be as complex as those involved in the adaptive resistance of malignant cells to targeted therapies.

The two main subtypes of primary cutaneous T-cell lymphomas include the most frequent, mycosis fungoides (MF), and the rare leukemic variant, Sézary syndrome (SS). MF presents as cutaneous patches and can progress to plaques, tumors and erythroderma. SS is characterized by the presence of erythroderma, generalized lymphadenopathy and clonal T cells in the peripheral blood, consistent with a poorer prognosis. Histologically, early CTCL lesions are sometimes indistinguishable from more common inflammatory skin diseases and a clinico-pathological correlation is essential for an accurate diagnosis. Except for allogenic stem-cell transplantation, therapy is generally palliative and aims to improve patient quality of life.

Succinate dehydrogenase (SDH) is a mitochondrial enzyme that participates in both the tricarboxylic acid cycle and the electron transport chain. Mutations in genes encoding SDH are responsible for a predisposition to pheochromocytomas and paragangliomas, and more rarely, to gastrointestinal stromal tumors or renal cell carcinomas. A decrease in SDH activity, not explained by genetics, has also been observed in more common cancers. One of the consequences of the inactivation of SDH is the excessive production of its substrate, succinate, which acts as an oncometabolite by promoting a pseudohypoxic status and an extensive epigenetic rearrangement. Understanding SDH-related oncogenesis now makes it possible to develop innovative diagnostic methods and to consider targeted therapies for the management of affected patients.

Mullerian cysts are mostly described in women, near the genitourinary organs. Exceptional cases of retroperitoneal and posterior mediastinal located Mullerian cysts have been reported. When located in the retroperitoneum, those cysts are often confused with other retroperitoneal cysts such as cystic lymphangioma and cystic mesothelioma of peritoneum because of the poor clinical picture and a nonspecific radiologic presentation. The histopathological analysis is essential to make the diagnosis, and the positive staining of a Müllerian marker is a decisive argument in favor of a Müllerian cyst. Here, we report a case of an incidental finding of a retroperitoneal Müllerian cyst in a 68-years-old woman.

Medulloblastoma is a cerebellar grade IV tumour according to the WHO classification, mainly seen in children under the age of 15. This cancer can nevertheless occur in adults. We report the case of a 22-year-old patient with a medulloblastoma disseminated in the spine. The patient had a type 1 Arnold-Chiari malformation causing hydrocephalus treated by ventriculoperitoneal shunt. The current condition began with perineal and lower limb hypoesthesia, ataxic gait, erectile dysfunction and urinary incontinence. Subsequently, a predominant paraparesis of the right lower limb appeared. The patient was treated according to the PNET HR+5 protocol combining two courses of conventional chemotherapy followed by two courses of high-dose chemotherapy with autograft recovery. Given the excellent response, a proton therapy was then delivered to the whole cerebrospinal axis with boosts to the primary tumour sites. The case of this young adult patient shows on the one hand an atypical presentation, and on the other hand underlines, in the absence of a specific therapeutic strategy established for adults, the importance of collaboration between the adult and pediatric oncology departments, with management integrating innovations such as proton therapy and molecular typing.

Sinonasal cancers. Sinonasal cancers (SNC) belong to the spectrum of rare tumors, with respect to other tumors of the head and neck and intrinsically by the multiple histological entities that they cover. It is important to raise awareness among physicians about the diagnostic and therapeutic elements of SNC, as well as their functional consequences, so that these patients are better diagnosed and monitored during and following specific oncological treatment. We also shed light on the various histological entities and new therapeutic options, in particular endoscopic surgery, conformational radiotherapy and systemic treatments. Finally, we underline the importance of the REFCOR network of expertise, which makes it possible to offer optimal management of these rare tumors, and of the CORASSO association, which provides patients a major additional extra-medical support.

Rectal cancer: is the era for de-escalation arrived? The reference treatment of rectal cancer relies on carcinologic resection including total mesorectal excision. In patients with locally advanced rectal cancer (cT3T4 and/or cN+), preoperative treatment is used to improve outcome and includes radiochemotherapy to optimize local control and systemic chemotherapy to decrease metastatic recurrence. The combination of these treatments with rectal cancer surgery induces short term and long-term toxicities potentially leading to treatment related sequelae on digestive and genitourinary function. Lastly, time is coming for de-escalation for the treatment to rectal cancer. For patients with small tumors (cT2T3 inférieur 4 cm) who respond to radiochemotherapy, organ preservation avoiding rectal resection can be discussed. In patients with locally advanced resectable rectal cancer, preoperative chemotherapy without pelvic irradiation could be used before total mesorectal excision to decrease the risk of long-term side effects. In patients with more advanced, primarily non resectable rectal cancer, a tailored strategy based on tumor response to chemotherapy could be used to rationalize the use of preoperative irradiation. New treatment strategies are constantly proposed and the optimal treatment option should be decided on a per patient basis during multidisciplinary discussion.

Contribution of neoadjuvant chemotherapy. IN RECTAL CANCER In patients with locally advanced rectal cancer, preoperative radiotherapy and complete mesorectal excision have reduced the risk of locoregional recurrence. However, these treatments have not reduced the risk of metastatic recurrence and the benefit of adjuvant chemotherapy has never been formally demonstrated. The chemotherapy efficacy on the rectal tumor as well as the difficulties to administer adjuvant chemotherapy after proctectomy has led to the development of treatment regimens with neoadjuvant chemotherapy. Two phase III studies evaluating induction chemotherapy with FOLFIRINOX followed by chemoradiotherapy for one and short radiotherapy followed by consolidation chemotherapy for the other are positive for their main objective and constitute new therapeutic standards.

Hypofractionated stereotactic radiotherapy and stereotactic radiosurgery are major therapeutic weapons in the brain, whether for tumor, vascular or functional treatments. They tend increasingly to democratize and to become standard treatments. However, human brain anatomy is very complex and not limited to the currently described organs at risk. Diffusion tensor imaging (DTI) tractography is a simple tool that enables to identify reproducibly big white matter fiber tracts. Not only does tractography allow a redefinition of organs at risk in the brain, but it would also allow the identification of new targets, such as the ventral intermediate nucleus (Vim) within the thalamus for treatment of movement disorders. We present here a review of the role of tractography and the anatomy, function and currently described dose-effect relationships of white matter fiber tracts with a major functional impact: the pyramidal tract for motor ability, the optic radiation for vision and the arcuate fasciculus for language.

Nasopharyngeal carcinoma diagnosis is often made at a locally advanced stage (75 to 90% of cases) due to its deep localization. Concomitant radio-chemotherapy is the cornerstone of the treatment of locally advanced forms. The advent of intensity-modulated radiotherapy has improved oncological outcomes and reduced toxicity and is currently the gold standard for irradiation technique. For the locally advanced stage, the addition of induction chemotherapy has become the new standard care according to the latest international recommendations to reduce tumor volumes and act early on micro-metastases. Despite these therapeutic advances, the local and especially distant failure rate remains high. This article reviews current treatment strategies and discuss new approaches and perspectives of locoregional and systemic treatment to reduce treatment failures.

Few data are available regarding positive surgical margins (PSM) in patients who underwent surgery for localized prostate cancer (PC). Our objective was to evaluate the impact of PSM on biochemical recurrence-free survival (BRFS) for patients who underwent PC for pT2 tumor without adjuvant treatment.

Round cell sarcomas represent a diagnostic challenge for pathologists due to the poorly differentiated pattern of these high-grade tumors. Their diagnosis often requires large immunohistochemical panels and the use of molecular pathology. These tumors are largely dominated by Ewing sarcomas, but new families are now well characterized, including in decreasing frequency order in bone, BCOR-altered sarcomas, NFATc2-rearranged sarcomas, mesenchymal chondrosarcomas and more rarely CIC-rearranged sarcomas and myoepithelial tumors. This progress report presents microscopic, immunohistochemical and molecular features of these tumors previously named by the inappropriate term "Ewing-like" sarcomas, in order to enable any pathologist to perceive the morphological features of these sarcomas, to select the immunohistochemical panel that will lead to the diagnosis and to better guide the molecular approach needed to establish the final diagnosis.

Translocations involving FN1 gene have been described in several tumours, which share the presence of a cartilaginous matrix with or without calcifications and a good prognosis. They encompass: soft tissue chondroma, synovial chondromatosis, calcifying aponeurotic fibroma, phosphaturic mesenchymal tumour and a new spectrum of tumours: "the calcified chondroid mesenchymal neoplasms". We review all the clinical, histopathological and molecular data of these tumours and discuss the differential diagnoses.

Mitomycin C is the gold standard intravesical adjuvant therapy for intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Tensions in the supply of mitomycin have emerged in France since late 2019. The ANSM in agreement with the AFU proposed to use epirubicin, already available in other European countries in this indication. The objective of our study was to report the initial French experience with the use of epirubicin in adjuvant treatment of NMIBC.

Overall, 2021 was marked by the confirmation of the major interest of cell cycle inhibitors for hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative advanced breast cancers with very high overall survival data exceeding five years for hormone-sensitive disease. Studies have also confirmed the efficacy and safety of this therapeutic class in the elderly population. New cell cycle inhibitors are under development (SHR6390). New combinations are also being evaluated, notably palbociclib with SAR439859 (a new selective estrogen receptor degrader: SERD). Targeting of the Phosphoinositide 3-kinases (PI3K) pathway by taselisib, in hormone-resistant disease with a Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) mutation, modestly improves progression-free survival but with a non-negligible toxicity of the treatment.