Renal tumors associated with hereditary diseases are a rare entity characterized by many renal tumors and other manifestations such as pulmonary, neurological and dermatological expressions. The management requires a close collaboration between surgical specialties and geneticists. Precocious, bilateral and/or multifocal tumors call to mind a hereditary disease. Early diagnosis and screening are essential to optimize a strict observation and a most conservative treatment.

microRNA are small non coding RNA, which negatively regulate the expression of their targets. Due to their various targets, miRNAs play a key role in number of physiological processes and in oncogenesis. The identification of specific miRNA signatures in various types of tumours, including hepatocellular carcinoma (HCC), highlights the dual role of miRNA, both oncogenes and tumour suppressors. Here, we review the current knowledge concerning the deregulation of miRNA expression in liver disease. All studies focusing on miRNAs argue for their possible use as diagnostic, prognostic and therapeutic markers. Here, we preferentially discuss the promising therapeutic strategies based on miRNAs that have been tested in HCC.

The Smoothened (Smo) receptor is a major component involved in signal transduction of the Hedgehog (Hh) morphogens both during embryogenesis and in the adult. Smo antagonists represent a promi-sing alternative for the treatment of cancers linked to abnormal Hh signalling. The crystal structure of the human Smo receptor bound to an antitumour agent demonstrates that this receptor belongs to the superfamily of G-protein coupled receptors. The antagonist binds to a pocket localized at the extracellular side formed by the seven transmembrane domains and the complex arrangement of the unusually long extracellular loops. The structure of the Smo receptor will promote the development of small molecules interacting with a key therapeutic target with interests in regenerative medicine and cancer.

Endometrial cancer is the most common gynecologic cancer in France with an incidence in France in 2010, of 6560 new cases and 1900 deaths secondary to endometrial cancer. The main risk factors are age, hyperoestrogenic factors and hereditary syndroms. Prophylactic hysterectomy could prevent endometrial cancer in case of risk factors such as genetic syndroms. Actually, only Lynch syndrome is a validate indication and should be discussed in patients older than 40-45 years. Prophylactic hysterectomy does not seem a reasonable option to patients carrying BRCA 1 or 2 mutation.

Since January 16(th) 2010, the French legislation requires that the medical laboratories must be accredited according to ISO 15189 standards. Thus, all medical laboratories in France must be accredited for at least part of their biological tests before the end of October 2013. Molecular biology tests are also concerned by the accreditation. Validation of molecular biology methods is made difficult, for reasons related to the methods, but also by the type of analytes that are basically rare. This article describes the validation of the qualitative detection of KRAS mutations in metastatic colorectal cancer using TaqMan PCR according to ISO 15189 and to the technical guide for accreditation in Human Health, SH-GTA-04, edited by the COFRAC.

We report a rare case of association of two distinct hematologic malignancies: refractory cytopenia with multilineage dysplasia associated with del(5q) and symptomatic multiple myeloma associated with del(17p) and del(13q). After 16 months, the patient presented an acute leukemic transformation of the myelodysplasic syndrome.

Hairy cell leukemia is a rare chronic lymphoproliferative disorder. Its diagnosis remains difficult due to different variant forms and differential diagnosis that are splenic marginal zone lymphoma and b-prolymphocytic leukemia. The prognosis of this malignancy has been transformed by purine nucleoside analogs, interferon, monoclonal antibodies and recombinant immunotoxins usually used in refractory or relapsed disease. The discovery of BRAF V600E mutation has become the milestone in the disease's history since it was uniformly identified in a HCL series in 2011. This mutation, commonly identified in melanoma, involves the protooncogene BRAF, a MAP3Kinase belonging to the RAF-MEK-ERK signaling pathway, which is the central key in several oncogenic processes. This mutation suggests disease-specific oncogene dependence. The detection of this mutation provides an additional diagnosis marker (because not found in variant forms), a best for monitoring minimal residual disease and a therapeutic target with the BRAF inhibitors in specific subgroups of patients, already tested in melanoma. This review aims to summarize the clinical and biological aspects and treatment of hairy cell leukemia and discusses the perspectives provided by the discovery of BRAF mutation in this disease.

Sarcomas represent a complex and heterogeneous group of rare malignant tumors and their correct diagnosis is often difficult. Recent molecular biological techniques have been of great diagnostic use and there is a need to assess the cost of these procedures in routine clinical practice. Using prospective and observational data from eight molecular biology laboratories in France, we used "microcosting" method to assess the cost of molecular biological techniques in the diagnosis of five types of sarcoma. The mean cost of fluorescence in situ hybridization (FISH) was 318 € (273-393) per sample; mean reverse transcription polymerase chain reaction (RT-PCR) cost ranged from 300 € (229-481) per formalin-fixed, paraffin-embedded specimen to 258 € (213-339) per frozen specimen; mean quantitative polymerase chain reaction (Q-PCR) cost was 184 € (112-229) and mean CGH-array cost was 332 € (329-335). The cost of these recently implemented techniques varied according to the type of sarcoma; the method of tissue collection and local organizational factors including the level of local expertise and investment. The cost of molecular diagnostic techniques needs to be balanced against their respective performance.

Anaphylaxis is a severe, generalized, life-threatening reaction of rapid onset. We report the case of a patient presenting several systemic anaphylactic reactions over many years, initially ascribed to a cereals allergy but which finally proved to be due to systemic mastocytosis hidden for a long time.

Breast cancer is the most common cancer among women with more than 53,000 new cases every year in France. The PI3K/AKT pathway is one of the major pathways involved in mammary tumorigenesis. The first effector of this pathway downstream Human Epidermal growth factor Receptor (HER receptors) is the enzyme phosphatidyl-inositol-3-kinase (PI3K). Some mutations in the gene encoding for the catalytic subunit of this enzyme, the PIK3CA gene, plays an important role, especially in the resistance to targeted therapies used clinically during the last decade. Indeed, the presence of alterations, an overexpression of the PI3K/AKT pathway, or the presence of PIK3CA mutation could explain some resistance to targeted therapies. PIK3CA mutations also appear to have a significant interest in the prediction of response to targeted therapies. Finally, many drugs in development, specifically targeting PI3K or other effectors of the PI3K/AKT pathway are intended to be administered only to patients with tumor bearing a mutation of PIK3CA, which makes the somatic mutations detection more and more important. The aim of this article is to consider biological aspects, clinical significance, diagnostic and theranostic interest of PIK3CA mutations in breast cancer.

The characterization of genetic abnormalities in non-small cell lung cancer (NSCLC) constitutes a theranostic revolution which is leading to rapid progress in the personalized management of this condition.

Uterine leiomyosarcoma is a rare disease with a poor prognosis. The rarity of this tumor needs a specialized management in tertiary reference centers in order to provide patients with optimal diagnostic, prognostic and therapeutic care. The pathological diagnosis relies on the presence of three characteristics in proliferating smooth muscle cells: necrosis, cytologic atypia and mitosis. Despite progress in the knowledge of the biology of these tumors, no oncogenic driver has been found. Prognosis depends mainly on the age of the patient, race, FIGO stage, mitotic index and hormonal receptor expression in the tumor. Surgery is one of the cornerstones of management and cytotoxic chemotherapy is the mainstay of treatment in metastatic disease with a potential role in the adjuvant setting. In locally advanced or metastatic disease, prognosis is poor with a median overall survival of about 12 to 14 months despite a 30% response rate to polychemotherapy regimens. Anti-angiogenics and hormonal therapy have a role to play in the setting of metastatic disease. It is mandatory to include such patients in clinical trials aiming to improve the therapeutic management of these patients. Multimodal therapy can improve the prognosis of selected patients too.

Currently, the increasing number of ancillary methods to be performed from tumoral tissues in a pathology laboratory determines the necessity to have an optimal strategy for tissue management. The size of tissue samples dedicated for a pathological examination becomes smaller and smaller, as the diagnosis can be made with non or less invasive methods. However, the samples should also allow to provide the prognosis as well as to realise biological molecular testing in order to found a genomic alteration. Thus, it is critical to think about how to share and to pool the different expertises and abilities in a pathology laboratory in order to optimize the achievement of the different ancillary methods. Thus, following the morphological study made in hematoxylin-eosin staining, it is necessary to preempt the number of immunohistochemical and in situ hybridization studies, which will be potentially done from the tissue samples. Moreover, since the genomic alteration detection in tumours is mainly performed from DNA extracted from tissues, it is necessary to take in account some numerous parameters, in particular the nature and the time of fixation, the percentage of tumour cells, the presence of necrotic area, the percentage of inflammatory cells and the sample size. The strategy for an optimal tissue management in an oncology-pathology laboratory is critical and takes part of the different steps allowing to get an accreditation according the ISO15189 norm.

We report the case of a 16-year-old girl with an anaplastic large cell lymphoma of lymphohistiocytic pattern revealed by a hemophagocytic syndrome. Histologically, the lymphomatous population was concealed by clusters of histiocytes. Immunohistochemical study allowed the diagnosis. The combination of these two entities is rarely described and may be a source of delay in diagnosis of a life-threatening condition.