The oligometastatic paradigm refers to an intermediate biologic state of cancer with restricted metastatic capacity. Its phenotype is characterized by a limited number of metastases and a slow tumor growth. Various clinical and pre-clinical studies associated this state to alterations of the biological mechanisms involved in metastatic diffusion. Eventually, this transitional state leads to a wide metastatic dissemination. However, there is a period during which the patient could benefit from local ablative treatment. Depending on several prognostic factors and the treatment provided, long survival or even healing can sometimes be achieved. The selection of patients eligible for such a curative strategy may be adapted following clinical, radiological or biological markers. Recent improvement of therapeutic and imaging are changing the clinical definition of oligometastatic cancer, which should be adapted to evidence from recent clinical and preclinical data.

Lymphoplasmocytic lymphona with monoclonal lgM, rare. Median age at diagnosis 70 years old, frail population. Heterogenous clinic presentation. Molecular diagnosis with MYD88. Treatment required for symptomatic WM patients only. 1st line therapy: DRC. Input of targeted therapies (ibrutinib) for frail patients, maintenance effect.

Diagnosis of mature B cell malignancies is highly multidisciplinary. Biological tools provide diagnostic, prognostic and theranostic information. Biological hematology allows considering mature B cell diseases from two perspectives : cellular and molecular approaches. Cytomorphology and flow cytometry are tools from cell hematology. Conventional cytogenetics, FISH and molecular biology are tools from molecular hematology. NGS is a new technique that could dramatically change diagnostic and therapeutic management of B cell malignancies in the near future. Integration of clinical, pathological and biological data allows for personalized management of these diseases.

In the context of chronic myeloid leukemia (CML) resistant to tyrosine kinase inhibitors (TKIs), BCR-ABL1 tyrosine kinase domain (TKD) mutations still remain the sole biological marker that directly condition therapeutic decision. These recommendations aim at updating the use of BCR-ABL1 mutation testing with respect to new available therapeutic options and at repositioning different testing methods at the era of next generation sequencing (NGS). They have been written by a panel of experts from the French Study Group on CML (Fi-LMC), after a critical review of relevant publications. TKD mutation testing is recommended in case of treatment failure but not in case of optimal response. For patients in warning situation, mutation testing must be discussed depending on the type of TKI used, lasting of the treatment, kinetic evolution of BCR-ABL1 transcripts along time and necessity for switching treatment. The kind and the frequency of TKD mutations occasioning resistance mainly depend on the TKI in use and disease phase. Because of its better sensitivity, NGS methods are recommended for mutation testing rather than Sanger's. Facing a given TKD mutation, therapeutic decision should be taken based on in vitro sensitivity and clinical efficacy data. Identification by sequencing of a TKD mutation known to induce resistance must lead to a therapeutic change. The clinical value of testing methods more sensitive than NGS remains to be assessed.

The human tumor phenotype referred to as MSI (Microsatellite Instability) is associated with inactivating alterations in MMR genes (Mismatch Repair). MSI was first observed in inherited malignancies associated with Lynch syndrome and later in sporadic colon, gastric and endometrial cancers. MSI tumors develop through a distinctive molecular pathway characterized by genetic instability in numerous microsatellite DNA repeat sequences throughout the genome. In this article, french researchers and physicians who have been recently awarded by the Fondation de France (Jean and Madeleine Schaeverbeke prize) make a sum of their activity in the MSI cancer field for more than 20 years. Their findings have greatly contributed to increase our knowledge of this original cancer model, laying the foundation for a personalized medicine of MSI tumors.

Cyclic GMP-AMP synthase (cGAS) is a universal cytosolic DNA sensor that detects nucleic acids of pathogens. Upon DNA sensing, cGAS triggers the formation of the second intracellular messenger, the cyclic GMP-AMP (cGAMP), which activates the adaptor STING. STING engagement induces the secretion of cytokines and type I interferons that contribute to pathogen clearance. However, there is emerging evidence that cGAS is activated by self DNA in cancer cells and in antigen-presenting cells to trigger an antitumoral response. In this review, we will highlight the current understanding of self DNA sensing by cGAS in the context of cancer.

Extra-uterine leiomyomatosis is a rare pathology defined by the presence of benign smooth uterine muscle cells in unusual localizations, including different entities. It mainly affects premenopausal women with a medical history of uterine myoma with or without surgical treatment. Three main types are discribed: intraveinous leiomyomatosis, benign metastatisizing leiomyoma and leiomyomatosis peritonealis disseminata. The diagnosis may be complex with many differential diagnosis, and relies on histology. The treatment depends on multiple factors such as age, localization, size, symptoms and associated comorbidities. It is based on surgical resection and hormonal privation, surgical (adnexectomy) or medical (hormonotherapy). There is a high risk of recurrence. Some malignant evolutions have been reported, mostly leiomyosarcoma following peritoneal disseminated leiomyomatosis. Long term follow-up of these patients is mandatory. A particular manifestation of extra-uterine leiomyomatosis is the hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. It is an autosomal dominant disorder which confers an increased risk of cutaneous and uterine leiomyomas and renal cell cancer, with a poor prognosis due to the urologic tumor.

BAF complexes are chromatin remodelling complexes made up of 15 subunits which overview transcription regulation. A subset of their subunits are notoriously linked to cancer, with the examples of SMARCB1, SMARCA4, ARID1A/1B and PBRM1. The complexes act as tumor suppressor genes, commonly mutated in a wide array of malignancies with an overrepresentation of sarcomas and tumors of the central nervous system. The recurrent inactivation of their genes points towards their driving role in the tumorigenesis of SMARCB1 in malignant rhabdoid tumors and SMARCA4 in small cell carcinoma of the ovary, hypercalcemic type. These tumors are morphologically similar composed of solid sheets of cells displaying vesicular nuclei dotted with clear chromatin and conspicuous nucleoli. Genomically, they share simple diploid profiles with no other alterations than in the culprit gene. Other mesenchymal tumors, distinct from malignant rhabdoid tumors are associated with BAF alterations, namely epithelioid sarcomas, SMARCA4-deficient thoracic sarcomas. BAF subunits are mostly inactivated through mutations or deletions but also occur through translocations in medullary carcinoma of the kidney and synovial sarcomas. Apart from tumors displaying recurrent alterations of the complexes, some variants or tumor variants display BAF alterations, including epithelioid malignant peripheral nerve sheet tumors and poorly differentiated chordomas. Lastly, some malignancies display low frequency of BAF alterations, in keeping with their passenger role in tumorigenesis with the example of dedifferentiated carcinomas, especially in colon, lung and uterus. BAF complexes alterations correlate with morphological features recognizable by microscopy, paving the way for their routine diagnosis and potential therapeutic prospects.

The benefit of tyrosine kinase inhibitors for patients with an EGFR wild-type non-small cell lung cancer (NSCLC) remains controversial.

The central nervous system (CNS), through carcinomatous meningitis or solid brain metastases, is the most common site of recurrence in non-small cell lung cancers (NSCLC) with activating mutations. Our retrospective study describes the population of patients with CNS metastases of NSCLC harboring activating mutation with targeted therapy (EGFR, ALK, BRAF, HER2) in 4 French regional reference hospitals. 60 patients were analyzed. The proposed treatments were heterogeneous and included combinations of chemotherapy, targeted therapy and radiotherapy±associated with topical treatments. Median overall survival following CNS metastasis in these patients was 15.8 months for meningitis carcinoma and 26 months for brain metastases. In patients with brain metastases, the addition of targeted therapy treatment allows a significant improvement in median progression free survival from 5.9 months to 10.6 months (HR 0.48 CI95 [0.24 to 0.97] P=0.035). These patients seem therefore benefit from systemic therapy and particularly targeted therapy with better survival than usual.

To describe didactically the local, regional and systemic spread of choroidal melanoma.

Clonal hematopoiesis of undetermined significance or CHIP describes the identification, in individuals without hematologic disease, of one or more somatic mutations in hematopoietic cells. These mutations, detected by high-throughput genes sequencing (Next-Generation Sequencing or NGS), affect genes first identified in acute myeloid leukemia or myelodysplastic syndrome, such as DNMT3A, TET2 and ASXL1. CHIP is associated with an increased risk of malignant hemopathy, both myeloid and lymphoid, evaluated from 0.5 to 1% per year. CHIP is also associated with an increased risk of overall mortality and cardiovascular diseases. CHIP detection using NGS is currently limited to basic science field, but recent studies suggest that it may be of clinical interest.

New targeted therapies modify therapeutic strategies for advanced stage breast and tubo-ovarian cancers. Chemotherapy and endocrine therapy remain the cornerstones of breast cancer treatment. Inhibitors of CDK4/6, mTOR and PI3K are associated with endocrine therapy to increase its effectiveness. PARP inhibitors outperform chemotherapy in BRCA1/2 mutation carriers. Immunotherapy integrates into the treatment of triple-negative cancers with very promising results. For tubo-ovarian cancers, the concept of « platinum-sensitive » has been tempered since the arrival of antiangiogenic treatment and PARP inhibitors that prolong the disease control not only in patients with BRCA1/2 mutation, but also in others.