Cancer is a multi-etiologic, multistage disease with a prevalent genetic component, which happens when a large number of genes, critical for cell growth, death, differentiation, migration, and metabolic plasticity are altered irreversibly, so as to either "gain" (oncogenes) or "lose" (tumour suppressors) their function. Recent discoveries have revealed the previously underestimated etiologic importance of multiple epigenetic, that is to say, reversible factors (histone modifications, DNA methylation, non-coding RNA) involved in the transcriptional and post-transcriptional regulation of proteins, indispensable for the control of cancerous phenotype. Stable alterations of epigenetic machinery ("epimutations") turn out to play a critical role at different steps of carcinogenesis. In addition, due to substantial recent progress in stem cell biology, the new concept of cancer stem cells has emerged. This, along with newly discovered epigenetic cancer mechanisms, gives rise to a hope to overcome radio- and chemo-resistance and to eradicate otherwise incurable neoplasms.

Refractory thyroid cancers include medullary and differentiated cancers with locally advanced disease that is not amenable to surgery or with distant metastases, differentiated thyroid carcinomas being refractory to radio-iodine treatment and all anaplastic carcinomas. These carcinomas are rare, with an estimated incidence in France of 350 new cases per year. Their management may benefit from the TUTHYREF network. Kinase inhibitors inhibit kinases of the VEGF receptors, and this inhibits angiogenesis, and some of these agents also inhibit other kinases of the 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. Their toxicity is significant and these treatments should be given only to selected patients with locally advanced or metastatic disease, with progression or with clinical symptoms.

The objective of this study was to describe morphologic and immunohistochemical features of precursor tubal lesions in prophylactically removed Fallopian tubes.

We report the case of a patient carrying a right breast carcinoma whose imaging exams showed lung and bone metastasic release, and incidentally synchronous right renal tumor. Histologic examination of the renal tumor found a mammary carcinoma metastasis into a clear renal cell carcinoma. This is the second case report of breast cancer with metastasis in a resected renal clear cell carcinoma.

Ovarian carcinomas are a heterogeneous group of lesions, among which serous histologic subtype is the most frequent. Ovarian and peritoneal serous carcinomas are subdivided into low- and high-grade tumors. Low-grade carcinomas derive from serous tumors of low malignant potentiel, while high-grade carcinomas were thought to derive de novo from ovarian surface epithelium. Studies from prophylactic salpingo-oophorectomy in women with BRCA mutations revealed a precursor to pelvic serous carcinomas that originates in the distal fallopian tube, called STIC (serous tubal intraepithelial carcinoma). This review reports new findings on serous carcinogenesis in the tube (SCAT). It brings an explanation in French on different terminologies used in the English literature these last years such as SCOUT (secretory cell outgrowth), p53 signature, TILT (tubal intraepithelial lesion in transition), STIC and SCAT and on the macroscopic protocol of Brigham and Women's Hospital of annexectomies specially in the setting of BRCA mutation, the SEE-FIM (sectioning and extensively examining the fimbriated end of the fallopian tube).

Lynch syndrome is an autosomal dominant disease associated with an important risk of cancer, mainly endometrial and colorectal-cancer. This risk can be efficiently lessen by an appropriate screening as far as the mutations carriers are identified. As current clinicopathological recommendations lack sensitivity, a systematic pre-screening of every patient with a colorectal or endometrial cancer can be proposed. Oncogenetic units of the HUG in Geneva and ICHV in Valais have set up a population-based study to evaluate the efficacy of such a strategy. Whatever the approach, the pathologist is directly implicated as Lynch syndrome harbors specific histological aspects that can help to its identification, but also as pre-screening tests are directly realized on tumor-tissue.

Important advances in lung cancer treatment have been made over the last decade. Several drugs designed to target molecular pathways involved in cancer-cell growth and survival have been shown to be effective in a selected fraction (<20%) of non-small cell lung cancer patients. Somatic mutations in several genes (i.e.: EGFR and KRAS) can predict patient's response to targeted therapies. Those mutations are commonly detected on histopathological samples (core-needle biopsy/ surgical resection). However, when tissue biopsies are not available, molecular testing has to be performed on cytological specimens. Issues raised by molecular testing on cytological specimen are discussed in this article.

Acute lymphoblastic leukemia Type T PH1 positive (with t (9.22)) are exceptional. These effects can occur immediately or in the evolution of chronic myeloid leukemia known. We report the case of a patient aged 31 years with acute lymphoblastic leukemia T PH1 + cyologiques with cytological atypia. The overall appearance of blood and marrow: the signs of dysplasia the presence of a monocytic contingent, with blood monocytes evoked a myeloid acute leukemia AL. But the immunophenotype was unequivocally in favor of T- acute lymphoblastic leukemia with one aspect of lymphoid blasts in morphology and myeloperoxidase negative. The karyotype showed the presence of Philadelphia chromosome in all mitoses with additional abnormalities (chromosomes 2, 11.16…).

Aleukaemic leukaemia--without blasts in the blood or the bone marrow--with isolated cutaneous manifestations has been very rarely reported since only seven patients have been described to date. The prognosis is variable, and the indications for an aggressive treatment such as polychemotherapy are currently unclear. We report a case of spontaneously remitting aleukaemic leukaemia in a newborn child and compare it with other cases in the literature.

OMICS is the term used to designate new biological sciences investigating a large group of molecules in biological samples. For instance, genomics and transcriptomics study changes in genome and transcription expression respectively. Numerous others OMICS are emerging (e.g. epigen-, prote-, metabol-, lipid-, glucid-OMICS). Support from bioinformatics and biostatistics, together with new molecular biology technologies for screening these large molecular groups (i.e. high-throughput biological arrays), has led to the development of these scientific fields. They help to draw relevant molecular identity cards of tumors.

Nck is an adaptor protein composed of three N-terminal Src Homology (SH) 3 domains followed by a unique C‑terminal SH2 domain. Like other SH2/SH3 domains-containing adaptor proteins, Nck mediates signal transduction from activated cell surface receptors by directing the flow of information to elicit properly orchestrated cell responses. In this way, Nck appears to be unique in its contribution to a wide variety of cellular processes. Moreover, in addition to the typical signal/pY-SH2/SH3-effectors mode of signaling, Nck also transduces signals through an inverse mode of -signaling (signal-SH3/SH2-pY/effectors) and from various cell compartments. Since Nck contributes to important morphogenic and mitogenic processes, deregulated expression of Nck could be detrimental to cellular homeostasis. In agreement, Nck expression has been found upregulated in numerous types of cancer. In this paper we delineate the main molecular -signaling -complexes associated with Nck, focusing on those involved in cancer progression.