Juvenile myelomonocytic leukemias (JMML) are rare but severe myelodysplastic and myeloproliferative neoplasms of infancy. They represent about 10 new cases per year in France and preferentially affect males. JMML are all stem cell diseases the common denominator of which is RAS pathway dysregulation, due to mutations in RAS (NRAS, KRAS) or RAS regulatory components (PTPN11, NF1 or CBL). This leads to an hypersensivity of myeloid progenitors to GM-CSF (granulo-macrophagic colony stimulating factor) which induces in turn excessive monocytic and macrophagic proliferation in blood and bone marrow. All organs can be infiltrated by this monocytic proliferation leading to multisystemic failure. Blast crisis with transformation into acute myeloid leukemia occurs in one third of patients. A salient feature of JMML is their frequent association with predisposition syndromes such as Noonan syndrome, neurofibromatosis and CBL syndrome, which are developmental diseases associated with a constitutional RAS pathway deregulation, now grouped under the name RASopathies. Clinical heterogeneity makes JMML diagnosis difficult. Splenomagaly is the most constant sign. Palor, adenopathy, respiratory or cutaneous symptoms can also be present. Blood smear shows monocytosis (>1×10(9)/L) presence of myeloid progenitors and abnormal basophils. The demonstration of an endogeneous in vitro growth of myeloid progenitors although not very specific can help JMML diagnosis. Nowadays, genetic typing has to be included in the workup of JMML diagnosis and allows to evidence a mutation in more than 90% of cases. JMML have a poor prognosis. The only curative treatment is bone marrow transplantation but approximately 35% of patients relapse. JMML clinical course is highly heterogeneous and unpredictable. Some rare patients have an indolent evolution or even spontaneous remission. Age over two years, thrombopenia below 33×10(9)/L and high foetal hemoglobin (HbF) level for age are poor prognosis criteria but hardly predict individual outcome. Several research directions are currently being explored to improve prognosis prediction and provide more effective targeted treatments.

Small nucleolar RNAs or snoRNAs, principally implicated in post-transcriptional chemical modification of other RNAs, were among the first non-coding RNA identified, together with ribosomal and transfer RNA. Lately, snoRNA have been involved in various unexpected functions, which renewed researcher's interest for these molecules. SnoRNA processing into smaller functional RNA species (sdRNA for snoRNA-derived RNA) or into miRNA (sno-miR), snoRNA mediated regulation of messenger RNA alternative splicing or snoRNA links to human disorders, including cancers, are some of the topics developed in this review.

The recent discovery of a new kind of massive chromosomal rearrangement in different cancers, named "chromothripsis" (chromo for chromosome, thripsis for shattering) has questioned the established models for a progressive development of tumors. Indeed, this phenomenon, which is characterized by the shattering of one (or a few) chromosome segments followed by a random reassembly of the fragments generated, occurs during one unique cellular event. The same phenomenon was identified in constitutional genetics in patients with various developmental pathologies, indicating that chromothripsis also occurs at the germ cell level. Diverse situations can cause chromothripsis (radiations, telomere erosion, abortive apoptosis, etc.), and two express "repair routes" are used by the cell to chaotically reorganise the chromosomal regions concerned: non-homologous end-joining and repair by replicative stress. The in-depth analysis of the DNA sequences involved in the regions of chromothripsis leads to a better understanding of the molecular basis of chromothripsis and also helps to better apprehend its unexpected role in the development of constitutional pathologies and the progression of cancers.

Renal carcinomas are histologically and prognostically heterogeneous. Genomic as well as chromosomal studies of these tumors have permitted a better comprehension of molecular mechanisms implicated in their development and progression. The most frequent histological subtypes are characterized by recurrent cytogenetic abnormalities, such as the loss of the chromosome 3 short arm involving a VHL gene copy in clear cell renal carcinomas, or trisomies 7 and 17 in papillary renal cell carcinomas. New histological subtypes like renal carcinomas associated with Xp11.2 translocations have also been individualized. Besides diagnosis, some chromosomal aberrations like the loss of a short arm of chromosome 9 in different renal carcinoma histological subtypes have a worse prognostic impact. The identification of chromosomal shuffles contributes in backing histological diagnosis and in precising the individual prognosis of patients. This review describes chromosomal abnormalities associated to renal carcinomas and their impact for an accurate classification of these tumors and the evaluation of their prognosis.

Melanoma is a rare cancer but it is the cancer with the biggest increase of incidence, especially in caucasian populations. UV exposure and genetic predisposition are the two main risk factors. The diagnosis is often clinically suspected with the "ABCDE" rule. However, there are some diagnostic traps. Histological exam of the whole lesion will confirm diagnosis and guide the management. In case of localised melanoma, Breslow index is the best prognostic index. In case of metastatic melanoma, prognostic is dark. The AJCC classification stages patients in 4 groups according to their global survival.

Herein we report the first case of toxic epidermal necrolysis (TEN) occurring with use of vemurafenib.

TENpath is a network for the expert pathological diagnosis of malignant neuroendocrine tumors of the adult, both familial and sporadic, created by the French National Institute of Cancer in 2010. After 3years of activity, a first evaluation can be made. The perimeter of the network includes all neuroendocrine tumors (except small cell carcinomas of the lung), medullary carcinomas of the thyroid and extra-adrenal paragangliomas. The objectives of the network are not only the pathological review of all newly diagnosed cases of neuroendocrine tumors, but also the epidemiological surveillance, the training of pathologists, the production of recommendations and the initiation of research projects. The organisation of the network includes a database in which all referred cases are declared and a virtual expert system making it possible collegial expertises in line. Twenty-two expert centers are currently participating to TENpath. A total of 1350 cases have been referred in 2011 and 1518 in 2012. Major discrepancies amounted up to 5.9% in 2011 and to 2.9% in 2012. They mainly involved problems of differential diagnosis and wrong evaluations of the differentiation status of the tumor. The lessons to draw from the first years of TENpath are: (a) the long-standing underestimation of the actual number of patients with neuroendocrine tumors in France, (b) a better delineation, based on objective data, of the cases raising actual problems of diagnosis, (c) the existence of cases raising problems of classification even to experts and justifying a particular effort of research. These informations will be important to discuss the future evolution of TENpath.

All adrenal masses with atypical characteristics at conventional imaging must be explored as potential adrenocortical cancer. CT scan with delayed contrast media wash-out and/or abdominal MRI including chemical shift and/or wash-out analysis and 18F-FDG PET help to characterize the adrenal mass. Open adrenalectomy is the first step in the treatment of resectables adrenocortical cancer, as potentially curative. It must be complete (R0), without tumoral dissemination. The management of the adrenocortical cancer requires a multidisciplinary approach, including the endocrinologist, oncologist, surgeons, radiologist, nuclear medicine, pathologist, and geneticians in order to guarantee to the patient the best care. At the national level, the French network COMETE (supported by the Institut National du Cancer) and the international level, the European Network for the Study of Adrenal tumors -ENS@T- (supported by ESF and FP7) contribute to improve the clinical management and the understanding of the pathogenesis of the adrenocortical cancers. Recently, a new insight on molecular markers has been done. These approaches will be soon used "in routine".

Up to 30% of phaeochromocytomas and paragangliomas occur in the context of inherited tumor syndromes. Familial history and clinical presentation have to be strongly detailed to guide genetic testing. The identification of a genetic predisposition in a patient with phaeochromocytoma or paraganglioma has a positive impact in terms of medical care and follow-up for the proband and allows genetic testing in apparently asymptomatic family members. Two clusters of genes are described depending on their implication in the pathogenesis of inherited tumors. An algorithm for the genetic diagnosis of phaeochromocytomas and paragangliomas is proposed by The French network of oncogenetic laboratories. These recommendations will probably change with the identification of new predisposition genes and the development of new sequencing technologies.Genetic testing is prescribed by a specialist, as part of a cancer genetics specialist consultation in endocrine tumors. The psychological support is essential throughout the family survey.

To investigate the frequency of family history of breast cancer in male patients with breast cancer and the association with other cancers.

The management of locally advanced and metastatic non-small cell lung cancer has been revolutionized thanks to recent progress in pathology and molecular biology. The first molecular subgroup is defined by activating mutations of the epidermal growth factor receptor (EGFR), and a dramatic response to specific tyrosine kinase inhibitors. Since then, multiple genetic alterations (KRAS, HER2, BRAF, PIK3CA, ALK, ROS, RET…) have been identified as potential target of novel therapies, and molecular profiling has become common practice. This review focus on the molecular alterations associated with non-small cell lung cancer, including molecular profiling and response to targeted therapies.

The data describing the urologic extracolonic cancers associated with Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]) are variable. The aim of our study was to establish the frequency of mutations in mismatch repair (MMR) genes in patients with upper urinary tract transitional cell carcinoma (UUT-TCC) and to evaluate the clinical benefits of a systematic screening.

Hereditary ovarian cancers account for 10% of all cases. Two major syndromes with dominant autosomal transmission are identified. The most common one is breast-ovarian cancer syndrome due to BRCA1 and BRCA2 genes mutations, and the Lynch syndrome with mutated MMR genes is the other. Alterations in homologous recombination specifically observed in ovarian cancer with BRCA defects associated to Parp inhibition create a synthetic lethality of special interest. Numerous studies are in progress to explore this promising new approach. Furthermore, it seems that carcinogenesis of these two syndromes are different, suggesting alternative therapeutic options in the near future in order to improve prognosis of ovarian carcinomas.

This review will describe the current knowledge in the pathophysiology, diagnosis, prognosis and treatment of pulmonary MALT (Mucosa Associated Lymphoid Tissue) lymphoma. Pulmonary MALT lymphomas are low-grade B cell lymphoma and are the most frequent lymphomas arising from the lung. Tumour cells arise from mucosa associated lymphoid tissue. Unlike other sites, no pathogen has been associated with pulmonary location of MALT lymphoma. However addictive translocations involving the MALT1 gene are frequently evidenced Patients are frequently asymptomatic and present with a chronic alveolar opacity. Diagnosis requires histology that may be retrieved by minimally invasive procedures during bronchial endoscopy or by CT scan guided percutaneous biopsies. Prognosis is good and treatment may vary with abstention, surgery, radiotherapy, immunotherapy or chemotherapy.