Lung cancer remains the leading cause of cancer death. Understanding lung tumours physiopathology should provide opportunity to prevent tumour development or/and improve their therapeutic management. Cancer stem cell theory refers to a subpopulation of cancer cells also named tumour initiating cells that can drive cancer development. Cells presenting these characteristics have been identified and isolated from lung cancer. Exploring cell markers and signalling pathways specific to lung cancer stem cells may lead to progress in therapy and improve the prognosis of patients with lung cancer. Continuous efforts in developing in vitro and in vivo models may yield reliable tools to better understand cancer stem cell abilities and to test new therapeutic targets. Even if some data are in favour of a higher chemo and radioresistance of cancer stem cells this issue remains disputed. Preclinical data on putative cancer stem cell targets are emerging by now. These preliminary studies are critical for the next generation of lung cancer therapies.

A 51-years-old patient with polyadenopathies presents a non monotypic chronic lymphocytic leukemia (CLL): lymphocytes B CD5+, CD23+, CD22-,CD79b dim, FMC7- express κ (71%) and λ (21%) light chains without coexpression. The caryotype shows two clones with one in evolution. Lymphoid clonality analysis by PCR (polymerase chain reaction) of the heavy and light chains genes of immunoglobulins shows two monoclonal rearrangements for each kind of chains. Lack of lymphoid cells sorting in function of the light chain doesn't allow us to conclude between a biclonal CLL and a biallelic monoclonal CLL. New adenopathies appearance in this patient, one year and a half after the end of his chemotherapy, leads to realisation of a new immunophenotyping: CLL is now monotypic with κ light chains expressed at 95%. In the new caryotype, only one clone is still present: it is the clone in evolution in the first caryotype and which presents additional abnormalities. This evolution allows us to assert the biclonality of the primitive CLL, the two clones evolving differently under treatment. In conclusion, the patient presented a biclonal CLL with one clone responding to treatment and the other one resistant.

Neuroblastoma, the most frequent solid extracranial tumor of childhood, is characterized by a wide variability of its clinical course. The most important clinical prognostic markers are stage and age at diagnosis, but these markers are insufficient to predict outcome reliably and to determine treatment intensity. Recent evidence indicates that neuroblastoma can be considered as a "genetic disease", firstly by the recent observation that certain alleles of specific genes significantly increase the relative risk to develop neuroblastoma, and the discovery of mutations in genes such as ALK or PHOX2B in rare familial cases. On the other hand, a large number of recurrent genetic somatic alterations have been described in neuroblastoma. Recent technological advances, such as array-CGH (comparative genomic hybridisation), now enable the analysis of these markers in a single step and allow the definition of genomic profiles associated with typical clinical features. Numerical chromosome alterations are observed more frequently in tumors of younger children with localised disease and a good prognosis, whereas segmental chromosome alterations are found more frequently in tumors of older children with advanced stages of disease and a poorer outcome. Future therapeutic stratification schemes can make use of the tumor genomic profile by proposing less intense treatment for infants with a neuroblastoma harboring a favorable tumor genomic profile, while intensifying treatment in case of a defavorable tumor genomic profile. Such approaches require standardisation of the molecular techniques and the interpretation of results for application in international trials.

The setting up and the progression of the colorectal cancer (CCR) follow a sequence of events that are spatio-temporally rigorously orchestrated. The failures that specifically target the signaling pathways responsible for the cancerization of the colorectal mucosa have been well described and among these it seems that a dysregulation of the Wnt/β-catenin pathway is involved in the triggering of near 90 % of the cases. It has been also described that several risk factors linked to metabolic disorders (feeding, insulin resistance, metabolic syndrome, etc.) predispose individuals to CCR but no rational explanations were given. We propose that, since it is implicated in the control of the insulin pathway among other actions, the nutritional sensor O-GlcNAcylation may be the element linking these metabolic disorders to CCR.

Adrenocortical carcinomas are rare in children and sometimes occur in patients with predisposing syndrome like Li-Fraumeni or Beckwith-Wiedemann syndromes. The diagnosis is often based on clinical, biological and radiological findings completed by histological examination. The gold standard of treatment remains radical surgery sometimes completed by a cytotoxic chemotherapy based on platinum-derived drugs, etoposide and doxorubicin, in association with mitotane in case of high risk of relapse. The role of radiation therapy is discussed because of the relatively frequent involvement of p53 mutations. The rarity of this type of disease and the poor prognosis of the locally advanced and metastatic forms must lead to the systematic registration of these patients and to the harmonization of the management in a national or even European level.

The molecular classification of Perou and Sørlie breast tumors has to streamline, systematize and make effective use of targeted therapies against specific molecular subtypes, including breast HER2 positive. Trastuzumab and lapatinib are currently the two therapies targeting HER2, which have demonstrated their effectiveness in clinical practice. This literature review aims to make the data points on pertinent and useful data for physicians in daily.

Cancer predisposition syndromes affecting children are rare. One can estimate that only 10% of all childhood cancers are related to predisposition. The identification of these syndromes remains important for the care of an affected child and relatives. If most of the known cancer predisposition syndromes are linked to a dominant inheritance associated with a high risk of cancer, new syndromes associated with complex inheritance are being identified. Diagnosis of a childhood cancer associated with early-onset or multiple lesions, or a malformation syndrome, or a positive family history of cancer should raise an alarm of a cancer predisposition syndrome.

Ewing's sarcoma (or peripheral neuroectodermal tumour) is generally found in bone tissue, and a primary dermal site is extremely rare. We report a case of primary cutaneous Ewing's sarcoma in a 21-year-old woman.

Epidermal growth factor receptor (EGFR) is a cell membrane tyrosine kinase receptor. Activating mutations at exon 19 and 21 of the EGFR gene are associated with the occurrence and development of lung adenocarcinoma. These gain of function mutations predict responsiveness to EGFR tyrosine kinase inhibitors (TKis), erlotinib or gefitinib and are also a favorable prognostic factor in lung cancer. Sequencing is the recommended technique to detect the mutations, but other more sensitive technics are under evaluation. Treatment as first line therapy by gefitinib is limited to lung cancer patients harboring an EGFR mutation. Erlotinib can be given regardless of the EGFR status as second or third line therapy, as well as maintenance therapy in patients with a stable disease after platinum based chemotherapy. In EGFR mutated tumors, most patients present a recurrence of the disease, despite an initial response on EGFR TKis. Two mechanisms of secondary resistance have been identified, the selection of the T790M mutation in EGFR exon 20 and the MET amplification. Other molecular anomalies as the ras mutations or the EMLA-ALK protein fusion are mutually exclusive with the EGFR mutations and are associated with primary resistance to EGFR TKis.

Cystic kidney diseases often are discovered at the time of initial work-up of renal failure through ultrasound or family history, or incidentally at the time of an imaging test. Hereditary diseases include autosomal dominant or recessive polycystic kidney disease (PKD), tuberous sclerosis (TS) and medullary cystic kidney disease (MCKD). Autosomal dominant PKD is characterized by large renal cysts developing in young adults. Renal failure is progressive and becomes severe around 50-60 years of age. Atypical cysts (hemorrhagic or hyperdense) are frequent on CT and MRI examinations. Imaging plays a valuable role in the management of acute complications such as cyst hemorrhage or infection. Autosomal recessive PKD is often detected in neonates, infants or young adults. It is characterized by renal enlargement due to the presence of small cysts and liver disease (fibrosis and biliary ductal dilatation). Late manifestation or slow progression of autosomal recessive PKD may be more difficult to distinguish from autosomal dominant PKD. These cystic kidney diseases should not be confused with non-hereditary incidental multiple renal cysts. In tuberous sclerosis, renal cysts are associated with angiomyolipomas and sometimes pulmonary lymphangioleiomyomatosis. Renal failure is inconstant. Other hereditary cystic kidney diseases, including MCKD and nephronophtisis, are usually associated with renal failure. Non-hereditary cystic kidney diseases include multicystic renal dysplasia (due to complete pelvi-ureteric atresia or hydronephrosis), acquired multicystic kidney disease (chronic renal failure, chronic hemodialysis) and varied cystic kidney diseases (multicystic renal disease, glomerulocystic kidney disease, microcystic kidney disease).

Cancer is a genetic disease of cells linked to the accumulation of mutations in genes mainly involved in cell cycle, apoptosis, and in DNA damage repair. In most patients, these mutations are acquired (somatic) during life; in some others, some mutations may be germline, inherited from one parent and transmissible to the offspring. The latter are more prone to cancer. Family cancer genetic clinics, developed since the early nineties, aim to understand the origin of a family history through the first analysis of an index case and to provide adapted counselling regarding the management of index cases and his relatives (genetic test targeted on a mutation identified in the index case). The two most frequent cancer predispositions are presented: breast-ovary syndrome linked to BRCA1 and BRCA2 mutations and Lynch syndrome linked to mutations in the DNA mismatch repair genes and associated with high risks of colorectal and endometrial cancers.

During the last two decades, the understanding of molecular biology of thyroid cancers has greatly improved, and this has permitted the development of novel therapeutic tools in patients with refractory disease. Kinase inhibitors inhibit kinases of the VEGF receptors, and by doing this inhibit angiogenesis, and some of these agents also inhibit other kinases of the Mitogen-Activated Protein kinases (MAPkinase) pathway. These inhibitors are effective in differentiated and medullary thyroid cancers, and induce a partial response or a long-term stabilisation in more than half of patients.

The Birt-Hogg-Dubé (BHD) syndrome is associated with cutaneous disorders including fibrofolliculomas and trichodiscomas, and also lung pneumatocysts and kidney tumours. The BHD syndrome occurs as a consequence of an autosomal dominantly inherited genodermatosis, linked to multiple germline mutations in the 14 exons of the BHD gene, mapped on 17p11.2 and encoding for folliculin (FLCN). The size and number of lung pneumatocysts are extremely variable and the cysts are surrounded by normal pulmonary tissue. In the absence of smoking lung function is usually unimpaired. The lung cysts are frequently complicated by the development of recurrent pneumothoraces. Treatment of pneumothorax in patients with the BHD syndrome is similar to the approach taken for patients with spontaneous pneumothorax. Lung cysts in the BHD syndrome are a rare cause of cystic pulmonary lesions. However, they must be systematically evaluated since kidney tumours occur in one third of patients. We report a case of classical BHD syndrome with specific cutaneous involvement, recurrent pneumothoraces complicating lung cysts, an exon 12 germline mutation on BHD gene and a familial history suggesting other related cases. This observation allows us to update this orphan disease, to consider BHD in the differential diagnosis of lung cysts and, above all, to highlight the high frequency and the prognostic significance of associated kidney tumours.