During the last 30 years many advances have been made in kidney tumor pathology. In 1981, 9 entities were recognized in the WHO Classification. In the latest classification of 2004, 50 different types have been recognized. Additional tumor entities have been described since and a wide variety of prognostic parameters have been investigated with variable success; however, much attention has centered upon the importance of features relating to both stage and grade. The International Society of Urological Pathology (ISUP) recommends after consensus conferences the development of reporting guidelines, which have been adopted worldwide ISUP undertook to review all aspects of the pathology of adult renal malignancy through an international consensus conference to be held in 2012. As in the past, participation in this consensus conference was restricted to acknowledged experts in the field.

Germline mutations BRCA1&2 are responsible in women for breast and ovarian cancers that commonly occur at a young age: as such, there are strong interactions between the oncological risks and the events of reproductive life, pregnancy, breastfeeding, and management of infertility.

Genetic predisposition is involved in only 10% of patients with breast cancer. This study was to evaluate the impact of prophylactic surgery.

Acantholytic dyskeratosis under BRAF inhibitors are dermatological diseases rarely reported to date.

In patients with melanoma positive for the BRAF V600 mutation, clinical response to specific BRAF inhibitors is usually rapid and striking, with significant benefits in terms of progression-free survival and overall survival. However, resistance to treatment almost invariably arises, typically within a median timeframe of 6 months. Indeed, very few patients exhibit long-lasting response to these targeted therapies.

Poly(ADP-ribosyl)ation is a ubiquitous protein modification involved in the regulation of many cellular processes that is carried out by the poly(ADP-ribose) polymerase (PARP) family. The PARP-1, PARP-2 and PARP-3 are the only PARPs known to be activated by DNA damage. The absence of PARP-1 and PARP-2, that are both activated by DNA damage and participate in DNA damage repair processes, results in hypersensitivity to ionizing radiation and alkylating agents. PARP inhibitors that compete with NAD(+) at the enzyme's activity site can be used in BRCA-deficient cells as single agent therapies acting through the principle of synthetic lethality exploiting these cells deficient DNA double-strand break repair. Preclinical data showing an enhancement of the response of tumors to radiation has been documented for several PARP inhibitors. However, whether this is due exclusively to impaired DNA damage responses or whether tumor re-oxygenation contributes to this radio-sensitization via the vasoactive effects of the PARP inhibitors remains to be fully determined. These promising results have paved the way for the evaluation of PARP inhibitors in combination with radiotherapy in phase I and phase II clinical trials for malignant glioma, head and neck, and breast cancers. A number of challenges remain that are also reviewed in this article, including the optimization of treatment schedules for combined therapies and the validation of biomarkers that will identify which patients will most benefit from either PARP inhibitors in combination with radiotherapy.

Mammary analog secretory carcinoma (MASC) of the parotid gland is a rare and recently described lesion. We report the case of a 46-year-old man with a tumor of the parotid gland which was carried to the diagnosis of MASC. Diagnostic was confirmed by highlighting the ETV6-NTRK3 gene translocation. However, some morphologic and immunohistochemical features are suggestive of this entity. This carcinoma should be distinguished from its main differential diagnoses: acinic cell carcinoma and low grade cribriform cystadenocarcinoma.

Neurofibromatosis type 2 (NF2) is a rare dominantly inherited disease. Its clinical presentation can be completely different in children and adults and early diagnosis is often difficult. The NF2 gene molecular analysis can help for diagnosis, but its result can be negative in case of NF2 mosaicism.

Sezary syndrome (SS) presents clinically as erythroderma, which may be pigmented, and pruritic, associated with peripheral lymphadenopathies. Erythroderma may also occur in a broad range of reactive and malignant conditions including T-cell prolymphocytic leukemia (T-PLL). We report a case initially diagnosed as SS but ultimately diagnosed as T-PLL based upon skin involvement.

Genetic tests in families with a mutation related to breast and ovarian cancers (BRCA1/2) are now offered to the persons before completion of their reproductive project. The aim of this qualitative study was to descriptively explore how the issues of reproduction are faced in women belonging to these families, and how the possible use of prenatal diagnostic (PND) and preimplantation genetic diagnosis (PGD) would be faced in a theoretical context. We conducted in-depth interviews, face to face, according to the so-called Grounded Theory approach. Twenty women with a BRCA genetic mutation participated in the study (age range: 31-57 years); 12 have had a breast and/or ovarian cancer. The knowledge of having the mutation did not modify the parental project; however prophylactic anexectomy was likely to alter it in some women. If the majority of women were in favor of PGD (n = 14), medical termination of pregnancy was a constraint towards the position in relation to PND. Besides ethical and moral arguments, the women's attitudes were constructed differently according to their own personal or familial experience of the disease. The women's perceptions of the cancer severity, risk and cure were organized according to this experience.

Pheochromocytomas and paragangliomas (PHEO/PGL) are neuroendocrine tumors that arise from sympathetic and parasympathetic paraganglia. Although well described in the adult population, diagnosis and treatment of these exceptionally rare neoplasms remains poorly characterized in children. This article reviews recent advances in clinical presentation, genetics, biochemistry, imaging and treatment of children with benign or malignant PHEO/PGL. Compared to adults, pediatric PHEO/PGL are more frequently familial, bilateral, multifocal and malignant. Approximately 50% of pediatric PHEO/PGL are associated with a mutation of one of the 12 known susceptibility genes. Von Hippel-Lindau disease, type 1 neurofibromatosis, type 2 multiple endocrine neoplasia and familial PGL syndrome are hereditary tumor syndromes associated with an increased risk of developing such diseases. Clinical presentation includes symptoms related to catecholamine hypersecretion and/or tumor mass effect. Plasma and/or urine metanephrine dosages are recommended as first-line diagnostic biochemical tests. Magnetic resonance imaging is useful as initial radiological approach. Most pediatric PHEO/PGLs are benign. Surgical resection, with appropriate perioperative management of catecholamine-related symptoms, remains the treatment of choice. In case of metastatic disease, surgical removal of metastases when possible and I-131-MIBG radiotherapy provide limited results whereas chemotherapy is reserved for more advanced stages.

The concept of personalized or stratified medicine in thoracic oncology have led to the development of companion diagnostic testing in the laboratories in order to detect genomic alterations which can be targeted by therapeutic molecules. The use of these companion tests has to be associated with an optimized quality control with the aim of getting solid results before treatment administration to the patients. The great majority of these tests is based on molecular biology approach. However, since the commercial availability of different antibodies targeting genomic alterations which can be used in formalin fixed paraffin sections, an alternative method to the molecular approach is the immunohistochemistry (IHC). Some of these antibodies are or will be probably soon used in a daily routine practice (such as anti-ALK or anti-MET antibodies). Other antibodies have currently a more restricted use in thoracic oncology (such as anti-BRAF V600E, anti-ROS1 and mutation-specific anti-EGFR antibodies). In this review, we aim to detail the advantages and the limits of IHC method in thoracic oncology field for personalized medicine, in particular comparatively to the molecular biology technology. Moreover, we discuss the opportunity to provide accredited IHC tests in the context of stratified medicine for lung cancer patients.

Despite significant progress in the discovery and design of drugs, the interindividual variability to the standard dose of a given drug remains a serious problem in clinical practice. In the future, the aim of pharmacogenetic is to provide new strategies for optimizing drug therapy, both in terms of efficacy and safety. The clinical validation of an increasing number of pharmacogenetic tests, as well as the development of new highly efficient technologies should further promote pharmacogenetics in clinical practice and lead to the optimization and individualization, before treatment, of drug therapy. Therapeutic drug monitoring is a valid tool to determine the pharmacokinetic of a drug and individualized drug therapy, adjusting patient's dose requirement through the measurement and interpretation of drug concentrations. Thus, phenotyping and genotyping tests are now available that determine or predict the metabolic status of an individual and enable the evaluation of risk of drug failure or toxicity. Based on clinical applications, this review focuses on interest of pharmacogenetics, in combination with anticancer agents TDM, on the individualization of treatments used in oncology.

Crizotinib (XALKORI(™), Pfizer) is a tyrosine kinase inhibitor of ALK, MET, and ROS1, which is currently approved for the second line treatment for ALK-rearranged lung cancer. This work from an expert group, based on the review of the data from the Profile studies, aims to provide practical elements in order to optimize the tolerability of crizotinib. Specific major or frequent side effects of crizotinib are discussed: visual disturbances, cardiac effects, elevated transaminases, and hypogonadism. In the routine practice, patients should be advised about visual disturbances, especially with regard to driving in low brightness. Digestive disorders related to crizotinib are exceptionally persistent or severe. Dietary measures and symptomatic treatments usually control these disorders. It is recommended to perform an electrocardiogram before introduction of crizotinib, to identify prolonged QT interval. Torsades de pointes may produce dizziness or syncope. Hypogonadism should be considered in case of fatigue, decreased libido, and even depression, taking into account that these symptoms may be related to cancer; testosterone serum level should be measured to identify patients that may be eligible to receive a supplementation. Monitoring of liver function tests, including transaminases and bilirubin, is necessary. To conclude, these practical elements are helpful to optimize treatment with crizotinib in patients with ALK-rearranged lung cancer; in the future, academic initiatives should be taken to study these aspects, based on the monitoring of large cohorts of patients treated with crizotinib.

Allogeneic stem cell transplantation (SCT) is an increasingly important therapeutic option for the treatment of adult patients with acute myeloid leukemia. Here we review the current indications of SCT in this disease. While patients with favorable cytogenetics should receive consolidation chemotherapy, patients with unfavorable karyotype are prime candidates for SCT or new approaches to SCT (which should be done in first complete remission). Patients with intermediate prognoses should also receive SCT in first complete remission. In the absence of a suitable matched related donor, most patients will be able to find an alternative donor to proceed to a potentially curative allogeneic transplantation. The use of reduced-intensity conditioning regimens before SCT has allowed patients in the sixth or seventh decades of life to be routinely transplanted. Despite major differences among transplant centers in the intensity and composition of the conditioning regimen and immunosuppression, choice of graft source, postgraft immune-modulation, and supportive care, there has been a dramatic improvement in terms of tolerance. Although it is presumed to be a curative strategy, major complications of SCT remain graft-versus-host disease, delayed immune recovery, multiple comorbidities, and relapse after transplant.