DICER1 and FOXL2 mutations in ovarian sex cord-stromal tumours: a GINECO Group study.

AIMS: FOXL2 mutation has been consistently identified in adult granulosa cell tumours (A-GCTs). DICER1 mutations have been described predominantly in Sertoli-Leydig cell tumours (SLCTs). The prognostic implication of these mutations remains uncertain, as moderately sized studies have yielded variable outcomes. Our aim was to determine the implications of DICER1 and FOXL2 mutations in 156 ovarian sex cord-stromal tumours (SCSTs). METHODS AND RESULTS: FOXL2 mutations were found in 94% of pathologically confirmed A-GCTs (95/101), in one of eight juvenile granulosa cell tumours (J-GCTs), and in two of 19 SLCTs. DICER1 mutations in the RNase IIIb domain were found in six of 19 SLCTs, two of eight J-GCTs, and one of 12 undifferentiated SCSTs (Und-SCSTs). Comparison of DICER1-mutated SLCTs with DICER1-non-mutated SLCTs showed that patient age at diagnosis was lower and oestrogen receptor expression was more frequent in DICER1-mutated tumours. With a median follow-up of 22 months, two of five DICER1-mutated SLCTs relapsed, in contrast to none of eight DICER1-non-mutated tumours. CONCLUSIONS: Our results suggest that, in contrast to FOXL2 mutations in A-GCT, DICER1 mutations in SLCT might be more useful for prognosis than for diagnosis. However, study of a larger cohort of patients is necessary to establish this. Identification of genetic alterations in SCST offers promising therapeutic options.

Impact of a second opinion using expression and molecular analysis of FOXL2 for sex cord-stromal tumors. A study of the GINECO group & the TMRO network.

OBJECTIVE: Ovarian sex cord-stromal tumors (SCSTs) are rare and their diagnosis is often difficult to establish. Recently, immunostaining and molecular analysis for Forkhead box L2 (FOXL2) have been developed in this pathology. This study aims to assess the benefit of an algorithm incorporating these new tools for a better diagnosis and classification of SCSTs METHODS: Seventy-two tumors with a potential diagnosis of SCSTs were addressed by 37 different pathologists to one French rare ovarian tumor expert center, member of the Rare Malignant Ovarian Tumor network (TMRO). Then a "second opinion" (SO) through an algorithm incorporating immunostaining (IHC) and molecular analysis of FOXL2 was performed for all these cases. This algorithm was then validated by all pathologists of the TMRO network. RESULTS: After a second opinion including molecular analysis and immunostaining for FOXL2 the initial diagnosis was changed in 15 of 72 samples (21%). FOXL2 mutation was present in 44 out of 47 adult granulosa cell tumors (94%), in 3 out of 8 Thecomas (37%), in 1 out of 10 Sertoli-Leydig cell tumors (SLSTs) (10%) and in 3 out of 5 undifferentiated-SCSTs (Und-SCSTs) (60%). Immunoexpression of FOXL2 was available in 45 cases of SCSTs: FOXL2 was expressed in 44 of them (98%). CONCLUSIONS: A second opinion in an expert center for all cases of SCSTs is fundamental to get an optimal classification of these rare tumors. This second opinion could be performed with an algorithm which integrates FOXL2 mutation and expression status of FOXL2 in order to standardize the practice.

Trichodysplasia spinulosa associated with lupus.

Trichodysplasia spinulosa (TS) is a unique clinical and histological entity described in immunosuppressed patients. The recent discovery of genomic DNA from a new Polyomavirus named trichodysplasia spinulosa-associated Polyomavirus in TS lesions and good clinical response to cidofovir strengthens the hypothesis of a viral etiology for the disease. The authors report a case of TS associated with lupus erythematosus in a 26-year-old woman with no history of transplant, hemopathy, or cyclosporine treatment. The patient developed a progressive worsening eruption composed of confluent papules and spiky filiform excrescences concentrated in the midfacial area. Pathological features were characterized by aberrant distended and abnormally maturated hair follicles with sheets of eosinophilic cells containing large purple granules, and the presence of trichodysplasia spinulosa-associated Polyomavirus DNA was confirmed by polymerase chain reaction. This case is the first description in a nontransplanted lupus patient without underlying hemopathy.

[The observatory of rare malignant gynecologic tumors]. / Observatoire des tumeurs malignes rares gynécologiques.

The observatory of gynecological rare tumors (TMRG) has been initially created for ovarian rare neoplasms (TMRO). Because of the similarities between ovarian and other gynecological tumors, this observatory has been then extended to all gynecological rare tumors. The recognition by INCa of three national expert centers (centre Léon-Bérard, hôpitaux de Paris, institut Gustave-Roussy) in rare gynecological cancers and a network of regional expert centers in 2010, expend the experience of the website "Observatoire francophone des tumeurs rares de l'ovaire". The major goals of this gynecology rare tumors experts network, are to promote systematic second opinion for initial diagnostic by experts in gynecopathology, systematic multidisciplinary advice by surgeons and medical oncologist experts, to disseminate clinical guidelines dedicated to rare gynecological tumors, to promote specific fundamental and translational research within clinical trials dedicated to rare tumors. At the end, we would like to improve benefit in term of survival and/or fertility for all these potential young patients.

HIV-1 efficient entry in inner foreskin is mediated by elevated CCL5/RANTES that recruits T cells and fuels conjugate formation with Langerhans cells.

Male circumcision reduces acquisition of HIV-1 by 60%. Hence, the foreskin is an HIV-1 entry portal during sexual transmission. We recently reported that efficient HIV-1 transmission occurs following 1 h of polarized exposure of the inner, but not outer, foreskin to HIV-1-infected cells, but not to cell-free virus. At this early time point, Langerhans cells (LCs) and T-cells within the inner foreskin epidermis are the first cells targeted by the virus. To gain in-depth insight into the molecular mechanisms governing inner foreskin HIV-1 entry, foreskin explants were inoculated with HIV-1-infeceted cells for 4 h. The chemokine/cytokine milieu secreted by the foreskin tissue, and resulting modifications in density and spatial distribution of T-cells and LCs, were then investigated. Our studies show that in the inner foreskin, inoculation with HIV-1-infected cells induces increased CCL5/RANTES (1.63-fold) and decreased CCL20/MIP-3-alpha (0.62-fold) secretion. Elevated CCL5/RANTES mediates recruitment of T-cells from the dermis into the epidermis, which is blocked by a neutralizing CCL5/RANTES Ab. In parallel, HIV-1-infected cells mediate a bi-phasic modification in the spatial distribution of epidermal LCs: attraction to the apical surface at 1 h, followed by migration back towards the basement membrane later on at 4 h, in correlation with reduced CCL20/MIP-3-alpha at this time point. T-cell recruitment fuels the continuous formation of LC-T-cell conjugates, permitting the transfer of HIV-1 captured by LCs. Together, these results reveal that HIV-1 induces a dynamic process of immune cells relocation in the inner foreskin that is associated with specific chemokines secretion, which favors efficient HIV-1 entry at this site.

Chronic meningococcemia cutaneous lesions involve meningococcal perivascular invasion through the remodeling of endothelial barriers.

Chronic meningococcemia is a form of sepsis with frequent polymorphous skin lesions. Both in vivo and in vitro data suggest that, in these lesions, meningococci gain access from the capillary lumen to the peripheral extravascular compartment, in the absence of vascular dislocation, through a paraendothelial route.

From PTEN loss of expression to RICTOR role in smooth muscle differentiation: complex involvement of the mTOR pathway in leiomyosarcomas and pleomorphic sarcomas.

Over the past decade, comprehensive genomic studies demonstrated that leiomyosarcomas and most of the tumors previously labeled as 'malignant fibrous histiocytomas' share complex karyotypes and genomic profiles, and can be referred to as 'sarcomas with complex genomics'. We recently reported a series of 160 sarcomas with complex genomics such as leiomyosarcomas, myxofibrosarcomas, pleomorphic liposarcomas/rhabdomyosarcomas and undifferentiated pleomorphic sarcomas. These tumors present with a frequent loss of chromosome 10 region encompassing the tumor suppressor gene PTEN. In the present study, we assessed PTEN genomic level and protein expression in this large series of sarcomas with complex genomics, as well as activation of downstream pathways. PTEN partial genomic loss was observed in only 46% of tumors, especially in well-differentiated leiomyosarcomas, whereas up to 68% of these tumors demonstrate a loss of protein expression on western blot analysis. Specific discrepancies in PTEN immunohistochemical results suggested bias in this latter technique. PTEN mutations were rare, with only 4 point mutations in the 65 samples studied. Subsequent activation of AKT and mTOR pathways was only observed in 2 out of 3 of PTEN-deleted tumors. On the other hand, RICTOR, a major component of the mTOR complex 2, was significantly overexpressed in well-differentiated leiomyosarcomas. These results, confirmed on tissue micro-array immunohistochemical analysis of 459 sarcomas, could suggest a link between RICTOR overexpression and leiomyosarcomas oncogenesis. As therapeutics directed against the mTOR pathway are assessed in sarcomas, RICTOR overexpression in sarcomas and its links to therapeutic response need to be assessed.

Enhanced expression of ephrins and thrombospondins in the dermis of patients with early diffuse systemic sclerosis: potential contribution to perturbed angiogenesis and fibrosis.

OBJECTIVE: To determine the skin and fibroblast expression of ephrins (EphB4 and EphrinB2) and thrombospondins (TSPs: TSP1 and TSP2) in patients with SSc. METHODS: All experiments were performed in skin sections and dermal fibroblasts issued from control and clinically involved/non-involved SSc skin biopsies. Dermal fibroblasts were stimulated with hypoxia or TGF-ß, or treated with TGF-ß-neutralizing antibodies. Ephrin and TSP mRNA levels were assessed in skin tissue and dermal fibroblasts by in situ hybridization and quantitative RT-PCR, respectively, and protein levels were assessed by immunohistochemistry and western blots, respectively. RESULTS: Enhanced ephrin and TSP mRNA and protein levels were observed in clinically involved SSc skin. EphrinB2, TSP1 and TSP2 mRNA and protein levels were also up-regulated in non-involved SSc skin. Similar mRNA and protein levels of ephrinB2 and EphB4 were detected in unstimulated and stimulated control and SSc dermal fibroblasts. TSP1 and TSP2 mRNA and protein levels were significantly increased in fibroblasts issued from involved and non-involved SSc skin. This up-regulation was not modified by hypoxic exposure, but was markedly reduced by the addition of TGF-ß-neutralizing antibodies. Stimulation of healthy fibroblasts with TGF-ß significantly increased TSP1 and TSP2 mRNA and protein levels. CONCLUSION: EphB4 and EphrinB2 are up-regulated in clinically involved skin of SSc patients, suggesting their participation in SSc-perturbed angiogenesis. TSP1 and TSP2 are up-regulated in both clinically involved and non-involved SSc skin and are constitutively overexpressed in a TGF-ß-dependent and hypoxia-independent manner in SSc dermal fibroblasts, suggesting their potential early contribution in SSc pathogenesis.

Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo.

Endometriosis affects 6-10% of women in their reproductive years, causing chronic pelvic pain and infertility. Its pathogenesis remains poorly understood and current treatments, based on hormonal therapy or surgery, are often insufficient. The purpose of our study was to investigate the role of the ERK pathway in the development of endometriosis and to test the effects of protein kinase inhibitors on the proliferation of endometriotic cells in vitro and in vivo. We studied ex vivo human endometrial and endometriotic cells in culture. Stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from patients with endometriosis and from patients without endometriosis. The ERK pathway was explored by western blot on cell lysates and by ELISA on total crushed specimens of endometrium. Cells in culture were treated with A771726, PD98059, and U0126. Human endometriotic lesions were implanted in nude mice. Mice were treated with A771726, leflunomide, PD98059, U0126 or PBS during 2 weeks before sacrifice and extraction of the endometriotic implants for histological examination. We found that the ERK pathway was significantly activated in endometriotic cells and in endometrial cells from patients with endometriosis compared to endometrial cells of control patients, both by ELISA and by western blot. This phenomenon was associated with an increased proliferation of endometriotic cells compared to endometrial cells. Treating endometriotic cells with A771726, PD98059 or U0126 abrogated the phosphorylation of ERK and significantly decreased the cellular proliferation in vitro. In vivo, A771726, leflunomide, PD98059, and U0126 controlled the growth of endometriotic implants in the mouse model of endometriosis. Our study shows that protein kinase inhibitors could be new candidates to treat endometriosis. However, further studies are needed to evaluate their effects and tolerability in humans.

[An unusual adrenal tumor: Ewing tumor]. / Une tumeur surrénalienne inhabituelle : tumeur d'Ewing.

We report the case of a voluminous tumor of the adrenal diagnosed in a young pregnant woman at 26(th) week of amenorrhea. Morphologically, a soft white tumor with haemorragic areas was observed, made of sheets of monomorphous, medium sized, spindle-shaped to polygonal, with high mitotic activity. Tumorous cells expressed cytokeratins AE1/AE3, EMA, and CD99 (expression of vimentin is not relevant). Contemplated diagnoses included poorly differentiated synovialosarcoma, sarcomatoid carcinoma and Ewing tumor. Thanks to molecular biology, showing the specific transcript of Ewing/peripheral primitive neuroectodermal tumor (pPNET) EWS/FLI1, the diagnosis of this atypical tumor in an unusual location was performed. Indeed, 75% of Ewing tumors involve bones (especially, the diaphysis of long bones) and 20 to 25% soft tissues. Primitive visceral involvement is rare; less than 10 cases of adrenal involvement have been reported. The hypothesis that Ewing cell's origin is a mesenchymal stem cell, which may derive from neural crest cell, could explain the uncommon adrenal involvement. Diagnosis of Ewing tumor is based on pathologic and molecular findings, especially in atypical cases.

Dermal tissue and cellular expression of fibrillin-1 in diffuse cutaneous systemic sclerosis.

OBJECTIVE: To assess dermal expression and fibroblast production of fibrillin-1 (FBN-1) in SSc. METHODS: In vivo analysis of microfibrillar network was performed using EM from affected and unaffected skin biopsy specimens of dcSSc patients (n = 5) compared with healthy controls (n = 2). FBN-1 matrix deposition and organization by dermal fibroblast cultures from dcSSc (n = 6), healthy (n = 5) and Marfan (n = 4) controls was analysed in vitro by IF with or without TGF-beta activation. Finally, production of FBN-1 by cultured dermal fibroblasts was evaluated by western blot (WB) and real-time PCR. RESULTS: We observed a striking decrease of tissue microfibrillar network in the dermis of SSc patients compared with healthy controls affecting both clinically involved and uninvolved skin. In cultures, SSc dermal fibroblasts displayed no apparent in vitro alteration of synthesis, secretion and organization of microfibril network. The WB and real-time PCR analyses showed similar FBN-1 amounts in matrix and FBN1 gene expression in SSc and healthy controls. CONCLUSIONS: We observed a striking decrease of in vivo microfibrillar network in clinically affected and unaffected skin in early dcSSc patients. This does not relate to an inability of SSc dermal fibroblasts to produce, secrete and organize microfibrils in vitro. Therefore, the disturbances of microfibrils in SSc may be a secondary event to matrix remodelling that occurs in this disease.

Gene expression profiling provides insights into the pathways involved in solid pseudopapillary neoplasm of the pancreas.

Solid-pseudopapillary neoplasms (SPNs) are rare human pancreatic neoplasms usually associated with a good prognosis. In contrast to other pancreatic tumours, aberrant activation of the Wnt-beta-catenin pathway appears to be a constant feature in SPN. Aside from activation of the Wnt-beta-catenin pathway, little is known about biological pathways deregulated in SPN. We carried out transcriptome profiling of SPN to gain insights into the pathogenesis of these tumours. As expected, the over-expression of AXIN2, TBX3, SP5 and NOTUM demonstrated activation of the beta-catenin pathway. Members of the Notch pathway (HEY1, HEY2, NOTCH2) were also up-regulated, relative to their expression in ductal adenocarcinomas (DAC) or pancreatic endocrine tumours (PET). Other genes, such as EDN3, HAND2, netrin-G2 and the receptor netrin-G1 ligand, involved in neural crest differentiation, were also identified as altered. Increased levels of SOX10 and TuJ-1 proteins were also indicative of neural-like differentiation. In conclusion, SPN display a complex expression profile, distinct from that observed in PET and DAC and involving both the beta-catenin and Notch pathways, together with expression of neural differentiation markers.

Unexpected diagnosis for an adrenal tumor: synovial sarcoma.

A 39-year-old woman presented with an incidentally discovered mass of the left adrenal fossa. Computed tomography and magnetic resonance imaging did not show any other lesion. Histologically, this mass was composed of a dense proliferation of spindle cells with a fibrosarcomatous-like pattern. Immunohistochemistry using anticytokeratin showed some epithelial cells within the tumor. The diagnosis of primitive synovial sarcoma of the left adrenal fossa was confirmed by the presence of the characteristic t(X;18) translocation. Despite radiotherapy, several chemotherapies, and 2 other surgical resections, the patient died 30 months after the initial diagnosis. To our knowledge, this report constitutes the first described case of synovial sarcoma arising in the adrenal gland.

[Bilateral lymphoepithelial cysts of the thyroid]. / Kystes lymphoépithéliaux bilatéraux de la thyroïde.

Lymphoepithelial cysts are rare lesions of the thyroid, with exceptional bilateral presentation. We report the case of a 62-year-old woman presenting with a multinodular goiter, without associated clinical or biological abnormality. Histological examination demonstrated multiple cysts lined by squamous or respiratory-type epithelium, associated with a dense lymphoid infiltrate. Chronic thyroiditis and numerous solid cell nests were also observed in the adjacent parenchyma. We briefly discuss differential diagnosis and current hypothesis concerning the pathogenesis of these peculiar lesions.

Fertility preservation, contraception and menopause hormone therapy in women treated for rare ovarian tumours: guidelines from the French national network dedicated to rare gynaecological cancers.

INTRODUCTION: Rare ovarian tumours include complex borderline ovarian tumours, sex-cord tumours, germ cell tumours and rare epithelial tumours. Indications and modalities of fertility preservation (FP), infertility management, contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and experts in reproductive medicine and gynaecology have built guidelines on FP, contraception and menopause hormone therapy in women treated for ovarian rare tumours. MATERIAL AND METHODS: A panel of 35 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review and then rated through two successive rounds. RESULTS: Thirty-five recommendations were identified, concerning indications for FP, contraindications for ovarian stimulation, contraceptive options and menopause hormone therapy for each tumour type. DISCUSSION: Overall, caution has been recommended in the case of potentially hormone-sensitive tumours such as sex-cord tumours, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumours. CONCLUSION: In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients.

[Fertility preservation, contraception and menopause hormone therapy in women treated for rare ovarian tumors: Guidelines from the French national network dedicated to rare gynaecological cancer]. / Préservation de la fertilité, contraception et traitement hormonal de la ménopause chez les femmes traitées pour tumeurs malignes rares de l'ovaire : recommandations du réseau national dédié aux cancers gynécologiques rares (TMRG/GINECO).

INTRODUCTION: Rare ovarian tumors include complex borderline ovarian tumors, sex-cord tumors, germ cell tumors, and rare epithelial tumors. Indications and modalities of fertility preservation, infertility management and contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and of experts in reproductive medicine and gynaecology have worked on guidelines about fertility preservation, contraception and menopause hormone therapy in women treated for ovarian rare tumors. METHODS: A panel of 39 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review, and then rated through two successive rounds. RESULTS: Thirty-five recommendations were selected, and concerned indications for fertility preservation, contraindications for ovarian stimulation (in the context of fertility preservation or for infertility management), contraceptive options (especially hormonal ones), and menopause hormone therapy for each tumor type. Overall, prudence has been recommended in the case of potentially hormone-sensitive tumors such as sex cord tumors, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumors. DISCUSSION: In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients.

Mutations of beta-catenin in adrenocortical tumors: activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors.

Adrenocortical cancer is a rare cancer with a very poor prognosis. The genetic alterations identified to date in adrenocortical tumors are limited. Activating mutations of the Wnt signaling pathway have been observed in more frequent cancers, particularly digestive tract tumors. We investigated whether Wnt pathway activation is involved in adrenocortical tumorigenesis. In a series of 39 adrenocortical tumors, immunohistochemistry revealed abnormal cytoplasmic and/or nuclear accumulation of beta-catenin in 10 of 26 adrenocortical adenomas and in 11 of 13 adrenocortical carcinomas. An activating somatic mutation of the beta-catenin gene was shown in 7 of 26 adrenocortical adenomas and in 4 of 13 adrenocortical carcinomas; these mutations were observed only in adrenocortical tumors with abnormal beta-catenin accumulation and most were point mutations altering the Ser45 of exon 3 (in the consensus GSK3-beta/CK1 phosphorylation site). Functional studies showed that the activating Ser45 beta-catenin mutation found in the adrenocortical cancer H295R cell line leads to constitutive activation of T-cell factor-dependent transcription. This is the first molecular defect to be reported with the same prevalence in both benign (27%) and malignant (31%) adrenocortical tumors. beta-Catenin mutations are also the most frequent genetic defect currently known in adrenocortical adenomas. In adrenocortical adenomas, beta-catenin alterations are more frequent in nonfunctioning tumors, suggesting that beta-catenin pathway activation might be mostly involved in the development of nonsecreting adrenocortical adenomas and adrenocortical carcinomas. The very frequent and substantial accumulation of beta-catenin in adrenocortical carcinomas suggests that other alterations might also be involved. This finding may contribute to new therapeutic approaches targeting the Wnt pathway in malignant adrenocortical tumors, for which limited medical therapy is available.

Frontline Science: Human bone cells as a source of IL-27 under inflammatory conditions: role of TLRs and cytokines.

IL-27 regulates immune responses as well as hematopoiesis and bone remodeling, but its cellular sources in the bone remain unknown. In this study, we investigated whether osteoclasts and osteoblasts-the 2 cell types orchestrating bone homeostasis-could be a source of IL-27 and identified stimuli that induce its expression in vitro. We observed that human monocyte-derived osteoclasts expressed a broader range of TLRs than did human primary osteoblasts and that both cell types exhibited a differential induction of IL-27 expression in response to TLR or cytokine stimulation. Whereas several TLR agonists, notably TLR4 and TLR7/8 agonists, induced substantial expression of IL-27 by osteoclasts, stimulation of osteoblasts with agonists of TLR3 and/or TLR4-the 2 TLRs selectively expressed by these cells-resulted in no or low IL-27 expression. In addition, IL-27 increased TLR3 expression in osteoclasts and enhanced poly(I:C)-mediated induction of IL-27 in these cells. IFN-γ, when combined with either IL-1ß plus TNF-α, IL-11, or CNTF, induced significant levels of IL-27 in osteoclasts but not in osteoblasts. In the latter cells, the addition of type I IFN, together with proinflammatory cytokines, was necessary to induce substantial levels of IL-27. Immunohistochemical studies of inflamed and remodeling bone tissue, including cases of infectious osteomyelitis and bone metastases, provided evidence that osteoclasts, osteoblasts, and occasionally osteocytes or chondrocytes, could express IL-27 in situ. This autocrine production of IL-27 by TLR- or cytokine-activated bone cells might constitute a negative-feedback mechanism to limit bone erosion and to dampen T cell-mediated immune pathology during bone inflammation.

[French pathologist' implication in cervical cancer screening]. / Implication des pathologistes français dans le dépistage du cancer du col utérin.

The cytological test issue mostly from individual opportunistic or for some department from organized screening programme, must benefit of the same quality in all the procedures. Pathologists are very implicated in. The purpose of this document is to summarize cytopathologists' initiatives and to present their specific tools for that. The French association for quality assurance in pathology (AFAQAP) has been validated by HAS in March 2006 for EPP. Commission 1 of AFAQAP organized an annual voluntary test for diagnostic evaluation since 2000 with the adoption of new technologies (CD-rom, virtual digital slides), and in 2005 a test of Pap Smear reporting quality concerning TBS 2001 use. A referring evaluation on this theme is in press. Furthermore pathologists made tools are available to codify lesions they diagnose (ADICAP), to collect and to study data (FCRISAP), to standardize the histological and cytological reports (CRFS), to evaluate the procedures and structural requirements and techniques. Pathologists participate in the elaboration of national guidelines (ANAES 1998 et 2002, DGS 2006) and performance indicators with InVS. The cervix cancer screening programme must take in account and valorises the role of pathologists according to assessment of efficacy and evaluation of the screening.