Organ-sparing strategies in the management of local or locally advanced cancers meet a dual objective: tumor control and preservation of the function of the involved organ. Given the morbidity and mortality of cystectomy and its impact on quality of life and bladder function, bladder-sparing strategies have emerged for the management of urothelial muscle invasive bladder cancer, mostly through trimodal treatment, which consists in maximal trans-urethral resection of bladder tumor, followed by chemo-radiotherapy. This review presents the modalities of trimodal treatment, before exposing the advantages and limitations of this strategy compared to cystectomy among operable patients. Despite the absence of comparative data from randomized trials, the two approaches seem to provide similar oncological results among appropriately selected patients. In modern series, the rate of salvage cystectomy is approximately 15% at 5 years; this delayed cystectomy does not seem to be associated with greater morbidity and mortality as compared to upfront cystectomy. Emphasis is placed in the review on quality of life data of these two approaches. In order to optimize the selection of patients eligible to trimodal therapy, the classical predictive factors of response to radio(chemo)therapy are critically analyzed, with the perspective of innovative molecular biomarkers. Finally, a close multidisciplinary collaboration is needed for the choice and the execution of the therapeutic strategy, and the patient should be fully involved in the decision-making process.

The proportion of patients irradiated in the context of malignant hematological pathologies decreased over the last decades. The main causes are the late side effects of the historical series and the new therapeutic strategies aiming to relay radiotherapy to the rank of option. At the same time, radiotherapy has been modernised, target volumes and total doses have been drastically reduced. Hodgkin's lymphomas, indolent follicular lymphomas and primary cerebral lymphomas are the main witnesses of this therapeutic deflation.

About 5% of gastric cancers are associated with hereditary cancer syndromes. Histology is paramount in this context, as major susceptibility genes are associated with specific subtypes. Germline pathogenic variants in CDH1 and CTNNA1 cause Hereditary Diffuse Gastric Cancer (HDGC). Major advances have been made in the past ten years regarding HDGC. Penetrance estimates for diffuse cancer are now lower than previously thought, at 30-40%. Surveillance upper gastrointestinal endoscopy is now an acceptable alternative to prophylactic total gastrectomy. Indeed, its sensitivity in detecting advanced disease is satisfactory assuming it is performed by an expert and according to a specific protocol. The risk of intestinal-type gastric cancer is increased in patients with Lynch syndrome, although it is much lower than the risk of colorectal and endometrial cancer. Intestinal-type gastric cancers are also observed in excess in patients with hereditary polyposis, the main one being APC-associated familial adenomatous polyposis. The main and most clinically relevant manifestations in patients with polyposes remain colorectal and duodenal polyps and carcinomas, well ahead of gastric cancer. Finally, recent data point towards increased gastric cancer risk in hereditary breast and ovarian cancer.

Gastrointestinal stromal tumors (GIST) are rare digestive tumors. Activating KIT mutations are the most common molecular alteration in these patients, identified in approximately 70 % of cases, followed by PDGFRA mutations (10-15 %), of which the D842V mutation accounts for most cases. Succinate dehydrogenase (SDH) deficiency and alterations involving NF1, BRAFV600E, RAS or NTRK genes are rare molecular subgroups. In advanced GIST, treatment is based on tyrosine kinase inhibitors, including imatinib, which has been the standard first-line treatment since the early 2000s, with sunitinib and regorafenib as second- and third-line standards, respectively. Two new compounds have recently been evaluated in patients with advanced GIST. Ripretinib has become the validated fourth-line therapy for patients with KIT or PDGFRA non-D842V mutations, and avapritinib has been shown to be effective in patients with D842V mutations who were previously resistant to validated treatments. Avapritinib is now the recommended first-line treatment in this subgroup and may represent an additional option, whose place remains to be clarified, in pre-treated patients without D842V mutations. Specific treatments are available or under evaluation for some rare subgroups, and new therapeutic strategies are likely to further improve the management of advanced GIST in the coming years. This overview summarizes the results of recent trials and the place of these new molecules, as well as the main strategies under development for advanced GIST.

Fatty liver disease is a common condition that rarely occurs on a multifocal mode. In this form, the differential diagnosis with hepatic carcinomatosis is not obvious, especially when a neoplastic condition coexists. Radiologically, MRI can almost systematically differentiate these two entities. However, concerning metabolic imaging with [18F]FDG PET/CT it is important to keep in mind that a multifocal hepatic steatosis may appear hypermetabolic in rare cases. By mimicking a typical presentation of metastatic carcinomatosis, it may lead to a false positive result. Here we report the case of a 73-year-old woman with a recent diagnosis of colorectal cancer. As part of the initial assessment, a MRI of the liver is performed and shows multiple lesions described as multifocal steatosis. A [18F]FDG PET/CT subsequently describes the same liver lesions but assimilates them to colorectal metastatic carcinomatosis. Due to this mismatch between the two different imaging modalities, several biopsies of the liver lesions are performed, first echoguided (two different lesions) then surgically (removal of a third lesion). The pathological analysis of the specimens fails to highlight any malignant lesion and the diagnosis of multifocal steatohepatitis is made.

Lenalidomide is an immunomodulatory drug widely used in the treatment of multiple myeloma. Several cases of nephrotoxicity have been reported, but few have been documented histologically.

Triple-negative breast cancer (TNBC) is a very heterogeneous disease and refers to a subgroup of breast cancer. The purpose of this study was to describe the clinical, pathological and molecular features of TNBC. We conducted a retrospective analysis of 56 cases of TNBC diagnosed in the Department of Pathology at the Farhat Hached University Hospital over a period of three years (2018-2020). The incidence of TNBC was 5.62% and the mean age of the patients was 50.36 years. The most frequent reason for consultation was the discovery of breast nodules (98.21%). The diagnosis of TNBC was confirmed in 24 cases (42.86%) based on the analysis of mastectomy specimens. Invasive carcinoma of no special type (NST) was the most common histological type (47 cases; 82.5%). Mean tumor size was 35.5 mm. SBR grading was only specified in 42 cases (73.68%). Grade III was the most predominant type (78.6%, n = 33). The notion of lymph node metastasis was found in 44 reports and lymph node invasion was reported in 19 patients (43.2%). Immunohistochemical study showed that all patients were hormone receptor-negative (RO and RP) with no Her2 overexpression (n = 56; 100). This study results are generally in agreement with literature data. Despite recent molecular classifications, there is no clinically verified diagnostic test allowing for clear therapeutic standardization.

Chemotherapy-induced neutropenia (FN) is the most common infectious complication in pediatric oncology. To our knowledge, no pediatric research has been published in Tunisia. The purpose of our study was to describe the features of FN among Tunisian children and to investigate factors correlated with FN. We conducted a prospective study of children with chemotherapy-induced FN at the Department of Pediatric Medicine A of the Tunis Children´s Hospital from July 2019 to December 2019. We recorded 50 episodes of FN in 32 patients whose mean age was 5.3 years (3 months-16 years). We included 26 patients with solid tumors (81%) and six patients with hemopathies (18.7%). The mean time between last treatment and fever onset was 10.67 days. Bacteriological investigation was contributory in 18% of cases and mainly showed gram positive cocci. Therapeutic protocol including 1st line empirical antibiotic therapy (3rd generation cephalosporin with aminoglycoside) was effective in 62% of cases. Mortality rate of patients with FN was 2%. The statistical study did not reveal any factor of correlation with late-onset neutropenia. In conclusion, our results are consistent with literature data on bacteriological documentation and mortality. Our 1st line treatment option based on 3rd generation cephalosporin associated with aminoglycoside was effective in 2/3 of the cases. In the future, oral antibiotics may be considered in patients at low risk for infection.

OVARIAN CANCER SURGERY Surgery has a central role in the management of patients with epithelial ovarian cancer, and the quality of its implementation is a factor influencing the prognosis. For advanced stages, it is schematically based on two main steps: peritoneal cytoreductive surgery, and pelvic and para-aortic lymph node dissections. While the prognostic impact of reducing the peritoneal tumor burden has been well demonstrated (with the objective of no macroscopic residue at the end of the procedure), the prognostic impact of lymph node surgery is still debated in certain indications. Other questions are discussed, such as the place of surgery in the first-line therapeutic sequence (primary/upfront surgery or after neoadjuvant chemotherapy), the indication of intraperitoneal hyperthermic chemotherapy, or the role of surgery in recurrence situations.

FERTILITY PRESERVATION BEFORE OVARIAN MALIGNANCY TREATMENT While most ovarian epithelial malignancies affect postmenopausal women, 12% occur in reproductive age patients. In addition, borderline ovarian tumors and rare non epithelial ovarian tumors are diagnosed in young patients as well. The prognosis of early-stage epithelial tumors, non-epithelial and frontier tumors is good. Increased knowledge in this specific field now allows the development of fertility preservation strategies. They include conservative surgery when applicable, associated with oocyte and / or ovarian tissue cryopreservation. Indications remain limited, and any decision must be validated by a multidisciplinary expert committee. The different strategies depend on specific tumoral or genetic context.

IMAGING OF OVARIAN CANCERS Imaging of ovarian lesions is based on the triptych: pelvic ultrasound with Doppler, magnetic resonance imaging (MRI) and computed tomography (CT). Endovaginal pelvic ultrasound is the first-line examination; tools are available to help with its interpretation (IOTA group rules, O-RADS US classification). When an ovarian mass is detected on ultrasound and if its characterization is «undetermined» or complex, MRI with perfusion sequences is used to clarify the criteria. Finally, a thoraco- abdominopelvic CT scan is necessary for extension assessment in the case of ovarian cancer, in particular to look for peritoneal carcinosis and to anticipate surgical difficulties.

Castration resistant prostate cancers are highly heterogenous at the molecular level. With the use of new generation sequencing technologies, a series of alterations were identified, opening the way for potential alternative treatments that could be more efficient for specific molecular subtypes. In this brief update, we summarize the new targetable pathways that are currently investigated. In this era of liquid biopsy and of precision medicine, it seems pertinent to be able to screen for these alterations on a more systematic basis before initiating any treatment.

Lung cancer remains the leading cause of cancer mortality in France. Research has shown that immune cells play a major role in tumor growth, angiogenesis and promotion of metastasis. While the density of intra-tumoral adaptive immune cell infiltrate is associated with a favorable prognosis, the presence of polynuclear neutrophils (innate immune cells) is associated in different types of cancer with a poor prognosis. The reviewed studies underline the abundance of intra-tumoral neutrophils involved in tumor progression by their immunosuppressive activity. More specifically, it has been shown that the neutrophil/lymphocyte (N/L) ratio is a prognostic marker. Different mechanisms promoting tumor progression have been identified, particularly the pro-angiogenic and immunosuppressive activities of neutrophils. However, under certain conditions, they can also exert effective anti-tumor activity through their interactions with the adaptive immune system. The complexity of the role of neutrophils in oncology resides in the diversity of subpopulations and their plasticity under the influence of the tumor environment. In this review, we will discuss the different properties of neutrophils not only as pro- and anti-tumor effector cells, but also as immunomodulatory cells, and we will conclude by considering therapeutic perspectives in lung cancer.

Osteoid osteoma is a benign but painful bone tumor whose treatment is based on complete surgical resection. We here report the case of a young patient with osteoid osteoma of the upper extremity of the radius through a literature review.

Adnexal carcinomas are rare, accounting for less than 1% of skin carcinomas. Sclerosus carcinoma of the sweat glands was first described by Goldstein et al. in 1982. We here report the case of a 33-year-old female patient with a retracted perianal skin lesion. Histological examination of perilesional skin biopsy, immunohistochemistry, and negative results of laboratory tests, radiological and endoscopic investigations allowed for the diagnosis of eccrine sclerosus carcinoma. This is a rare tumor, usually characterized by facial localization and slow but aggressive progression. It poses problems in differential diagnosis with benign and malignant tumors; hence the challenge encountered by pathologist of suspecting this carcinoma in patients with any sclerotic and infiltrating skin lesion characterized by slow progression, in a context of preservation of the general state and in the absence of neoplastic history as well as of feeling free to ask for new deep biopsies when in doubt.

Acromegaly is a rare endocrine disorder leading to an acquired physical disfigurement and multisystem damage. It is caused in over 95% of cases by a secreting pituitary adenoma. Latency period between disease onset and diagnosis is mainly 10 years due to progressive chronic evolution and exposure to high levels of GH and IGF-1. Here we present a case of acromegaly with over 25 years of diagnostic delay in 69-years-old male with typical features and recurrent urolithiasis. Biochemical diagnosis was confirmed by high levels of IGF-1and lack of suppression of GH during an oral glucose load. Imaging and histological study revealed a co-secreting GH/ prolactine macroadenoma. After three months of complete transphenoidal surgical resection, biochemical remission was not obtained and the patient was treated by a somatostatin receptor ligand. Based on this severe case with atypical manifestations, the diagnosis of acromegaly should be always considered.

New combinations of antiangiogenic tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) or dual ICI have been shown to be effective in phase III trials compared to sunitinib in the first-line treatment of metastatic renal cell cancer. While ICI doublet is already used in other indications, TKI/ICI combinations are more recent and the management of their adverse effects (AEs) are less well known, particularly with regard to the accountability of each therapeutic class. The objective of this article is to analyze the safety data from the main phase III studies to provide clinicians with practical advice for managing the AEs from these combinations. Their management depends largely on the type of combination and their grade. In the case of a TKI/ICI combination, discontinuation of the 2 molecules is considered from grade 2. Rapid improvement in symptoms suggests that the AE is related to the TKI. It is then possible, after resolution, to reintroduce the TKI, if needed by reducing the dose, and to continue the ICI. Otherwise, the blame falls on the ICI and treatment usually involves corticosteroids. Management also depends on the type of AE and its severity. In some cases (dysthyroidism), treatment with TKI/ICI may be continued. In other situations (cardiac or neurological toxicity), it should be discontinued from grade 1 and hospitalization and corticosteroid therapy should be considered immediately. In all cases, information and education are integral parts of the prevention and proper management of potential AEs.

Dermatofibrosarcoma is a rare cancer, accounting for 0.01% of all cancers. We here report the case of a 44-year-old female patient presenting with the 5th recurrence of locally advanced Darier-Ferrand dermatofibrosarcoma, that progressed on many cycles of neoadjuvant therapy and required emergency radiotherapy with good response. This allowed to perform wide excision of the tumor with healthy limits. The patient had remission after 1 year of follow-up. Prognosis for patients with Darier-Ferrand dermatofibrosarcoma is generally excellent. Wide surgery and the advent of Mohs surgery have improved local control. The role of radiotherapy is limited for non-resectable tumors or positive margins.