Diagnosis of haematological malignancies is based on multiparametric analysis such as morphology, phenotype and genotype studies. Some entities are only defined by one of these approach. Flow-cytometry (FCM) is useful to determined the normal counterpart of the tumoral process and its differentiation status within the involved lineage. Furthermore, FCM is able to detect clonality in B or T proliferations and criteria for malignancies such as abnormal phenotype. Finally it also specifies prognosis criterias. Among the different haematological malignancies, acute lymphoblastic leukaemia (ALL) can be diagnosed using FCM, whereas acute myeloblastic leukaemia diagnosis is only confirmed by this methodology, which could moreover determine prognosis factors. A scoring system (EGIL) determine the normal counterpart of tumoral cells using a panel of different markers. Immunophenotyping is also useful in chronic lymphoproliferative disorders, such as chronic lymphocytic leukaemia (CLL) by using a similar scoring system (so-called Matutes scoring). Since FCM is able to detect simultaneously numerous cell markers it could be more accurate than immunohistochemistry for the diagnosis of follicular lymphoma, mantle cell lymphoma or hairy cell leukaemia. Finally, during treatment follow-up, minimal residual disease characterised by the detection of rare specific events, may be examined using FCM, in some situations.

The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French cancer centers (FNCLCC), the 20 French cancer centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery.

The authors report a case of familial pyoderma gangrenosum following a mammoplasty reduction. This disease should be known by all surgeons, because its occurrence may follow all surgical procedure. The only efficient treatment is based on steroids and large surgical excisions must be contraindicated.

Through a national retrospective study, the authors report the clinical and hematological characteristics of 124 acute lymphoblastic leukemia of the adult diagnosed during 5 years (1993-1997). The national prevalence is of 0.28/100.000 inhabitants/year. The sex-ratio is of 1.3. Sixty six per cent of patients were 16-35 years of age, and only 10% of them were more than 60 years of age. A tumoral syndrome was present at 71% of the cases with peripheral adenopathies in 55%, splenomegaly in 40%, hepatomegaly in 19% and a mediastinal tumor in 18% of the cases. The bone pain were rarely signaled (10%) and neuro-meningeal affection was found in only 3% of cases. There was no testicular lesions. The white blood cells count was less than 30.000/mm3 in 60% whereas an important hyperleucocytosis superior than 100.103/mm3 was observed in 20% of the cases. Anemia and thrombopenia were noted in 94% and 90% of the cases respectively. Acute lymphoblastic leukemia typing by cytological study of Bone marrow according to the Fransh-American-Britain criteria (FAB) had found 43%, 48% and 4% for type 1,2 and 3 respectively. In 5% of the cases the type of the acute lymphoblastic leukemia was not precised (diagnosis based on the Bone biopsy).

Prostate cancer (CaP) is the most frequent cancer among men over 50 and its frequency increases with age. It has become a significant public health problem due to the ageing population. Epidemiologists report familial aggregation in 15 to 25% of cases and inherited susceptibility with autosomal dominant or X-linked model in 5 to 10% of cases. Clinical and biological features of familial CaP remain controversial.

Our team was at the origin of the discovery of the relationship between rearrangements in genes encoding the retinoic acid receptors and tumorigenesis in human. Studying the molecular basis for hepatitis B virus (HBV)-associated liver cancer, we demonstrated that the viral DNA can behave as an insertional mutagen. This work also led to the identification of the first gene (RAR beta) encoding a receptor for the active derivative of vitamin A, retinoid acid. In collaboration with L. Degos, we then demonstrated the existence a systematic alteration of another retinoic acid receptor, RAR alpha, in acute promyelocytic leukemia (APL). Most recent work allowed us to involve a novel subnuclear organelle, the so-called PML Nuclear Bodies, in APL pathogenesis, underlying the major role played by the functional organization of the nucleus both in the normal and the pathological cell.

Molecular biology studies have led to the identification of two different types of colorectal carcinomas. The first group, called LOH (for loss of heterozygosity), represents 80% of colorectal cancers and is characterised by aneuploidy, allelic losses and a location in the distal colon. The second group displays phenotypic microsatellite instability (MSI-positive tumours), has a near-diploid karyotype and a relatively low frequency of allelic losses. It accounts for 15% of all colorectal cancers and for about 30% of right-sided cancers. Four different pathways have been identified as responsible for tumour progression: the WNT/Wingless, the K-ras, the Transforming growth factor (TGF) and the P53 pathways. The involvement of these pathways depends on the tumour type. In LOH-positive tumours, the WNT/Wingless pathway is activated through an APC mutation, whereas MSI+ tumours do so through a catenin stabilising mutation. The TGFb growth inhibitory pathway is altered either by mutations in the signal transduction molecules SMAD2 and SMAD4 in LOH positive tumours or by mutations of TGFbRII in MSI+ tumours. In the p53 pathway, mutations in BAX may contribute to the adenoma-carcinoma transition just as p53 mutations may do in LOH positive tumours. Until now, cancer phenotype determination has had no clinical implications. However, the predictive value of the MSI status was recently stressed as a predictive factor for response to chemotherapy. Immunohistochemistry could represent a complementary strategy to molecular biology in assessing MSI status. This simple test would allow to screen all colorectal carcinomas for MSI status, which would provide valuable management information in addition to the histological assessment for tumour stage and grade.

Gastrointestinal stromal tumors (GISTs) are non differentiated sarcoma of the gastrointestinal tract and have for a long time been confused with well differentiated tumors and classified as leiomyosarcoma. These tumors are characterized immunohistochemically by CD 117 staining. This marker represents the expression of c-kit which is a receptor for growth factor with enzymatic activity (tyrosine kinase). Recent studies have found that an inhibitor of specific tyrosine kinase is effective in the treatment of GIST with an estimated response rate of more than 60%. This new drug could significantly improve the prognosis of these aggressive chemoresistant tumors.

Familial Multiple Polyposis Coli is an autosomal dominant hereditary illness characterized by the appearance in childhood of hundreds of colorectal polyps which inexorably undergo malignant transformation. It is accompanied by extracolonic manifestations some of which may also be life-threatening. Total colectomy should not be postponed beyond age 20 except in rare cases of an attenuated form of the disease (AAPC). Subtotal Colectomy with ileorectal anastomosis is a well-tolerated procedure with quite acceptable functional results, but the need for eventual proctectomy is about 30% at 20 years and the risk of rectal cancer is about 10% at 20 years even with close endoscopic surveillance. Total colectomy with ileal pouch-anal anastomosis is therefore the intervention of choice since it eliminates the risk of late rectal carcinoma albeit with more serious morbidity and less good functional results. Desmoid tumors are the leading cause of death in patients who have undergone total colectomy. NSAID's, tamoxifen, and chemotherapy are used preventively and therapeutically; surgical excision is sometimes required. Duodenal adenomas are present in almost 100% of these patients post-colectomy and the risk of duodenal cancer is 200 times higher than in the general population. Endoscopic surveillance of the duodenum is essential and prophylactic duodenal resection should be considered when duodenal polyposis is extensive.

Bourneville's disease, first described in 1862, is a phacomatosis that is either autosomal dominant or sporadic. Its typical clinical signs include mental retardation, epilepsy and cutaneous adenomas. The pulmonary form is rare, less than 1%, and is secondary to occlusion of the bronchus, vascular and lymphatics by immature smooth muscle cells. Chylothorax may appear in more than 50% of all cases. No guidelines currently exist for treatment of recurrent chylothorax. However, several possibilities are described in the literature.

Retrocervical cystic hygroma is a congenital defect associated to chromosomic anomalies. We report a retrospective study about 35 cystic hygroma autopsies colliged in C.M.N.T in 10 years. Antenatal sonography has a sensibility 94.5%. Genetic abnormalities dominated by trisomie 13 Turner syndrome dad found in 11.5%. Medical abortion has done in 48.5%. A multidisciplinary management autorized to understand etiopathogeny of this defect.

A better knowledge of fundamental mechanisms of carcinogenesis allows the development of novel therapeutic tools specifically targeting the cancer cell. Our understanding of cellular and molecular mechanisms controlling cellular cycle and cell survival is an important step for new anti-cancer treatments. This review will focus on new therapeutic's strategies in advanced pancreatic cancer.

FROM A CLINICAL POINT OF VIEW: Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant, inherited multiglandular disease with familial and individual age-related penetration and variable expression. A medullary thyroid carcinoma (MTC) is always concomitant to MEN2 and associated in varying proportion with pheochromocytoma (50%) and hyperparathyroidism (5 to 20%). PROGNOSTIC DATA: The prognosis of MEN2 is related to the carcinological evolution of MTC, which depends mainly on the stage of discovery and the quality of the first surgical treatment, emphasizing the need for early diagnosis. THE IMPORTANCE OF THE ERT GENE: The identification of mutations in proto-oncogene RET, responsible for the various forms of the disease allows subjects at risk in a family circle to be identified and early screening of various endocrine damage, notably MTC, should be performed. Biological explorations in all persons carrying this mutation would permit diagnosis and surgical treatment of the endocrine lesions, before their clinical manifestation.

Benign lipomatous tumors are characterized at the genetic level by different types of chromosomal abnormalities. A rearrangement of the HMGIC (HMGA2) gene, localized in 12q15 and coding for an architectural non-histone DNA protein, is observed in a majority of solitary superficial lipomas. Alterations of HMGIC are often resulting from reciprocal translocations, such as t(3;12)(q27-28;q15) that fuses LPP with HMGIC, but a variety of chromosomal anomalies, such as deletions, inversions or insertions are also observed. Rearrangements of chromosomal regions 6p21-22, 13q, 11q13, 12q13 or others are described in approximately one third of superficial lipoma cases with abnormal karyotypes. The genes involved in these alterations remain to be determined. Lipoblastomas are pediatric neoplasms that are characterized by rearrangements of PLAG1, located in 8q11-12 whereas hibernomas, that resemble brown fat, are associated with 11q13 rearrangements together with often complex chromosomal alterations. Deletions of 13q and 16q have been identified in spindle cell lipomas. A t(11;16)(q13;p12-13) have been described in the two published karyotypes of chondroid lipomas. The chromosomal features of other rare benign lipomatous tumors, the differential diagnosis of which is occasionally difficult, such as infiltrating intra-muscular lipomas, organic deep-seated lipomas, or angiomyolipomas, myolipomas, myxolipomas are still poorly defined. Although the genetic characterization of benign lipomatous tumors has been dramatically in progress over the last ten years, many aspects remain obscure and warrant future investigations for a better comprehension of underlying molecular mechanisms.

Lymphomas are the most frequent haematological malignancies in France. Their histoclinical heterogeneity reflects their complex and combinatorial nature which remains poorly elucidated at the molecular level. Today, DNA arrays allow to tackle this diversity by measuring the mRNA expression level of thousands of genes simultaneously in one sample. Recent publications show the potential of DNA arrays to improve the prognostic classification of diffuse large B cell lymphomas and of Hodgkin's lymphoma, by identifying new tumour classes unrecognised by classical factors.