Potential histological discordance revealed by second review in the national rare gynecological cancer network (TMRG).

INTRODUCTION: Since 2010, the network of rare malignant tumors of the ovary (TMRG) was developed to optimize the management of patients, also allowing a histological second opinion of rare ovarian tumors. The aim of this work was to study the contribution of second opinion to improve histological diagnostic accuracy on ovarian rare malignant tumors included in the TMRG database. MATERIAL AND METHODS: Histological data of patients diagnosed with a rare ovarian tumor included in TMRG network over a one-year period (2018) were collected. Initial diagnoses were compared with second opinion from national gynecological pathologist experts. The modalities of histological second opinion requests were studied, as well as the histological characteristics of the tumors. The discordances were classified as minor (if the modification of histological diagnosis did not change patient management) and major (if the patient management can be modified). RESULTS: Of 1185 included patients, 937 matched the inclusion criteria. Full concordance between primary diagnosis and expert second opinion was reached in 611 cases (65,3%), minor discordance was seen in 114 (12,2%) and major discordance in 209 (22,3%) of cases. In systematic review requested by the network, 26% (n = 137) of cases were reported with a change in histological diagnosis, while the change concerned 44% (n = 186) of cases for a second opinion spontaneously requested by the initial pathologist. The discrepancies concerned all categories of ovarian tumors, with a majority of mucinous tumors (43% of major discordances), followed by stromal and sex-cord tumors (13.8% of major discordances) and clear cell tumors (12,4% of major discordances). CONCLUSION: This analysis confirms the diagnostic difficulty of ovarian tumors, due to their rarity and morphological heterogeneity. French pathologists are aware of these difficulties and spontaneously refer ovarian tumors with unusual histology for a second opinion and collaborate with rare tumor networks for systematic review.

Networking for ovarian rare tumors: a significant breakthrough improving disease management.

BACKGROUND: Rare ovarian tumors represent >20% of all ovarian cancers. Given the rarity of these tumors, natural history, prognostic factors are not clearly identified. The extreme variability of patients (age, histological subtypes, stage) induces multiple and complex therapeutic strategies. METHODS: Since 2011, a national network with a dedicated system for referral, up to 22 regional and three national reference centers (RC) has been supported by the French National Cancer Institute (INCa). The network aims to prospectively monitor the management of rare ovarian tumors and provide an equal access to medical expertise and innovative treatments to all French patients through a dedicated website, www.ovaire-rare.org. RESULTS: Over a 5-year activity, 4612 patients have been included. Patients' inclusions increased from 553 in 2011 to 1202 in 2015. Expert pathology review and patients' files discussion in dedicated multidisciplinary tumor boards increased from 166 cases in 2011 (25%) to 538 (45%) in 2015. Pathology review consistently modified the medical strategy in 5-9% every year. The rate of patients' files discussed in RC similarly increased from 294 (53%) to 789 (66%). An increasing number (357 in 5 years) of gynecologic (non-ovarian) rare tumors were also registered by physicians seeking for pathological or medical advice from expert tumor boards. CONCLUSION: Such a nation-wide organization for rare gynecological tumors has invaluable benefits, not only for patients, but also for epidemiological, clinical and biological research.

Prevalence and predictive factors of the need for surgery for advanced colorectal adenoma.

AIM: Endoscopic resection is the primary treatment for colorectal adenoma, but in some cases surgery is necessary. The aim of this retrospective study was to define the prevalence and predictive factors for surgery in patients with advanced colorectal adenoma managed in a referral endoscopy centre. METHOD: Consecutive patients diagnosed with advanced adenoma (Class 4 in the Vienna classification) during a colonoscopy from 2007 to 2009 in the endoscopy centre of the University Hospital of Rennes were included. Predictive factors of surgery were determined by univariate and multivariate analysis. RESULTS: Two-hundred and twelve (135 male) patients with a mean age of 65.8 years were included. The reason for colonoscopy was for diagnosis in 63.2%, surveillance in 25.5% and screening in 11.3%. These referred patients amounted to 20.8% of all patients having colonoscopy. Surgery was performed in 13.7% of the 212 patients and in 16 (8.3%) of the 192 patients in whom endoscopic removal was attempted. In the subgroup of 192 patients, univariate analysis revealed that body mass index (P = 0.04), histology (P = 0.002), size (P = 0.03) and macroscopic appearance (P < 0.001) of the polyp were associated with surgery. Multivariate analysis revealed that the macroscopic appearance and histology only were significantly associated with surgery. CONCLUSION: Surgery was needed in 13.7% of patients with an advanced adenoma, but in only 8.3% of the subgroup of 192 patients in whom endoscopic removal was attempted. Factors associated with surgery included macroscopic appearance and histology.

Collagenous gastritis in children: A national cohort.

BACKGROUND: Collagen gastritis is a rare disease that manifests in children mainly as isolated gastric involvement associated with martial deficiency anemia. There are no recommendations for the management and follow-up of these patients. We aimed to describe the clinical data, endoscopic findings, and treatments deployed in France's children with collagenous gastritis. METHODS: All French pediatric gastroenterology centers and pediatric centers for rare digestive diseases (Centres de Maladies Rares Digestives) were contacted to collect cases of collagenous gastritis, defined on gastric biopsies and diagnosed before 18 years of age. RESULTS: A total of 12 cases diagnosed (4 males and 8 females) between 1995 and 2022 could be analyzed. The median age at diagnosis was 12.5 years (7-15.2). The most frequent clinical presentation was abdominal pain (6/11) and/or nonspecific symptomatology attributed to anemia (8/10). Anemia was present in all children (11/11; Hb 2.8-9.1 g/dL). Nodular gastritis was present in 10 patients (antrum: 2; fundus: 4; in antrum and fundus: 4). All patients had a basement membrane thickening (from 19 to 100 µm). The treatments received were PPI (11), oral or intravenous martial supplementation (12), budesonide (1), and prednisone (1). Martial supplementation improved anemia in all cases. At discontinuation, nine of 10 patients had a recurrence of anemia. CONCLUSION: Collagenous gastritis is an exceptional condition, clinically manifested in children as abdominal pain and iron deficiency anemia probably of hemorrhagic origin. Patients require long-term follow-up and monitoring of their disease to describe the risk of progression better.

Paget's disease of the vulva: A challenge for the gynaecologist.

Paget's disease of the vulva is a rare form of extramammary Paget's disease mainly affecting postmenopausal women. Its pathophysiology remains largely unknown. Up to fairly recently, the only treatment for this disease was surgery, often mutilating the vulva, with significant psychosexual repercussions without the assurance of complete therapeutic efficacy. New therapeutic approaches -topical treatments, radiotherapy or chemotherapy- have emerged in recent years but lack consensual guidelines. We present a literature review of the recent results published in this field.

Bicyclist's vulva: Diagnostic and therapeutic aspects.

The authors report a case of a rare vulvar condition in a young cyclist, known as bicyclist's vulva. The diagnosis was based on the clinical context (intensive cycling training with repeated saddle sores, responsible for painless unilateral swelling of the labium majus to a significant size and functional discomfort). Imaging examinations were used to characterize the lesion and its relationship with the pelvic organs. The lesion was composed of connective tissue, poorly demarcated and heavily collagenised without necrotic or hemorrhagic areas. Large cicatricial collagen bundles were observed. The fibroblasts revealed no atypia and just a few scattered undilated vessels ere noted. Special staining did not reveal any amyloid deposits. A complementary immunohistochemical analysis with anti-CD 34 antibody showed vascularization that was homogeneous and morphologically normal. The treatment was surgery, and in our case the cosmetic and functional impact of wide surgical excision of the lesion was improved by in situ injection of autologous fat. The pathology findings enabled us to rule out other perineal tumors such as aggressive angiomyxoma of the vulva and to describe the lesion microscopically.

[Can new molecular profiles in epithelial ovarian cancer modify therapeutics?] / Les nouveaux profils moléculaires dans le cancer de l'ovaire peuvent-ils modifier les stratégies thérapeutiques ?

Epithelial ovarian cancer (EOC) affects 4500 women a year in France, with a survival of 30% at 5 years. Treatment is based on extensive surgery and chemotherapy. Around 15% of EOCs are due to genetic mutation predisposition essentially with mutated BRCA1 and BRCA2 genes. Four histological subtypes are described (serous, endometrioid, and mucinous cells to clear), corresponding to different carcinogenesis and distinct molecular mutations. High-grade serous EOCs have a mutation of the BRCA genes in 20-30% of cases. This mutation causes a deficit of repair by homologous recombination of DNA in case of double strand break, allowing greater sensitivity to platinum salts and the use of PARP inhibitors, a protein involved in the repair of single-strand breaks of DNA. PARP inhibitors have shown efficacy in patients mutated BRCA but this effectiveness remains to be demonstrated in patients without congenital mutation, but with acquired BRCAness profile EOC. The BRCAness profile is defined by a tumor having a defect in DNA repair counterpart (not limited to BRCA mutation). Molecular definition of BRCAness is still not consensual but is necessary for the use of PARP inhibitors. Gene expression analyses have identified four subgroups of high-grade serous CEO: mesenchymal, proliferative, differentiated and immunoreactive. These four subtypes, not mutually exclusive, although correlated with prognosis, are not yet used in clinical routine.

[Eosinophilic esophagitis in children: Evaluation of practices through a multicenter study]. / L'œsophagite à éosinophiles chez l'enfant : évaluation des pratiques.

Eosinophilic esophagitis (EE) is a recent pathology defined by abnormal immune response of the esophageal mucosa to exogenous allergens, leading to chronic mucosa infiltration by 15 eosinophils per High-Power-Field (Eos/HPF). The present retrospective study was designed to assess the hospital care for children suffering from EE in several hospitals in western France in order to highlight discrepancies and improve future care. Twenty-eight children ranging from 1.5 months to 17 years old were included in the study. Episodes of food blockage were the most frequently reported symptoms (46 %). A ratio of 29 % of EE patients reported macroscopically normal endoscopy; diagnosis was then established upon histological anomalies found in biopsies. The mean eosinophil count was 72.4 Eos/HPF. Centralized immunohistochemical staining revealed the presence of IgG4-responding plasma cells in 76.5 % of patients, as well as IgG4 intraepithelial degranulation in 14 % of them. The evaluation of the treatment plan showed important inter-center discrepancies with only 43 % of patients receiving endoscopic reevaluation. This study objectively highlights heterogeneities in diagnosis and care provided to children suffering from EE. Therefore, improving the consistency of practices seems to be crucial to optimize the patients' outcome. The role of IgG4 as a new diagnosis marker remains to be clarified.

[Early-stage endometrial cancer: Sentinel node or lymphadenectomy?]. / Cancer de l'endomètre au stade pécoce : ganglion sentinelle ou curage pelvien ?

The endometrial cancers are mainly discovered at an early stage justifying a less aggressive treatment. The therapeutic choices are today based on preoperative classifications themselves based on histo-prognostic factors of the tumor and its extension measured in MRI: consequently, lymph node dissection in case of low and intermediate risk cancer is not systematically achieved. But a number of patients have lymph node involvement finally, probably justifying an adapted surgical and adjuvant treatment. The technique of sentinel node would compensate the weaknesses of preoperative prognostic evaluation. This new operative technique needs to be precised and evaluated: the topics subject to discussion are the technical implementation, the definition of its quality standards and the management of its histological results especially in cases of low volume lymph node metastasis.

[How were used recommendations for endometrial carcinoma? Britain retrospective study]. / Application des recommandations dans la prise en charge du cancer de l'endomètre en pratique clinique. Étude rétrospective bretonne.

OBJECTIVE: To assess the use of French Cancer Institute recommendations for the diagnosis and treatment of endometrial cancer. METHODS: Retrospective observational study involving 137 patients with endometrial cancer between 2011 and 2013. RESULTS: Both MRI and pathological assessment with correct report as recommended were used for 66.4% of patients with endometrial cancer. For patients with correct preoperative assessment, 44.9% of patients were uncorrectly classified and upgraded on final pathological analysis of hysterectomy concerning lymph node involvement risk. These patients did not have confident surgical assessment, according this risk. CONCLUSION: To improve relevance of preoperative assessment in endometrial cancer, radiological and pathological expertise is required. However, even performed optimally, preoperative assessment does not allow correct risk stratification of lymph node involvement in endometrial cancer. This ineffective stratification leads to propose sentinel lymph node biopsy with hysterectomy in case of preoperative low risk endometrial cancer assessment.

Leiomyosarcoma of the inferior vena cava.

BACKGROUND: Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is a rare tumor with poor prognosis. Optimal treatment includes complete resection of the malignant lesion. METHODS: From 1997 to 2013, eight patients underwent surgery in our department for IVC LMS. LMS was considered to arise from the IVC if the tumor presented intraluminal development or if complete resection (R0) required removal of part of the IVC with an extraluminal mass. RESULTS: There were two grade 1 tumors (25%), four grade 2 (50%) and two grade 3 (25%). The median length of stay was 16 days and there were no peri-operative deaths. Median of follow-up was 56 months and mean overall survival was 120 months. Mean 3-year survival rate was 87.5%. Six patients (75%) developed a local recurrence. Four patients died from disease progression. Two patients underwent to surgery for recurrence. CONCLUSION: IVC LMS have a poor prognosis if surgical resection cannot be achieved. Long-term survival is related to an extensive surgery, in the event of recurrence, surgery should again be proposed and may be effective for controlling disease progression, possibly improving survival.

Characterisation and quantification of angiogenesis in beta-tricalcium phosphate implants by immunohistochemistry and transmission electron microscopy.

The aim of this study is the histological characterisation of angiogenesis in a macroporous biomaterial with quantification techniques used in oncology. Porous tricalcium phosphate implants were seated in the tibias of 12 rabbits. This work allows (1) morphological study with photonic microscopy, transmission electron microscopic and immunohistochemistry labelling for (2) quantification of vascularisation using anti-CD31 monoclonal antibody (3) quantification of proliferation using anti-PCNA polyclonal antibody (4) study of two angiogenic growth factors: VEGF and FGF-2. Quantification of angiogenesis revealed an outbreak kinetic with early vascular growth in first several days and a second growth phase after 4 weeks. This study reveals in macropores many isolated cells without adjacent vascular lumen, with endothelial phenotype. Expression of angiogenic growth factors reveals that all endothelial cells were VEGF-negative throughout the test period. FGF-2 expression by endothelial cells began 2 weeks post-implantation. Osteoblasts strongly expressed two markers throughout the test period. Furthermore, the procedure described here can be used to compare angiogenesis in different biomaterials or in the same biomaterial with the influence of macroporosities.

Expression of Po66-CBP, a galectin-8, in different types of primary and secondary broncho-pulmonary tumors.

The monoclonal antibody Po66 is an IgG1 immunoglobulin isolated from a human bronchial squamous carcinoma and directed against a carbohydrate binding protein, Po66-CBP, belonging to the galectin family involved in neoplastic processes. This Po66 antibody has been shown to be useful for immunoscintigraphic detection of squamous cell carcinoma metastasis. We examined the expression of Po66-CBP in a wider range of primary or secondary malignant tumors of the lung of various histological types. We studied 52 specimens of broncho-pulmonary tumors including 41 primary squamous, glandular or neuro-endocrine tumors and 11 secondary tumors of glandular, connective tissue, melanocytic or germinal origin as well as 9 extra-pulmonary primary tumors with histological types similar to lung metastases. An immunohistochemical study was performed using an amplification system on paraffin-embedded sections. All histological types were positive for Po66 antibody, the cell origin giving no influence on the expression of Po66-CBP. There was however a relation between Po66-CBP expression and the degree of differentiation notably for squamous cell cancer and neuro-endocrine tumors. The metastatic character of the tumor tissue did not affect Po66-CBP expression.

[An uncommon tumor of the urinary bladder: the small cell carcinoma]. / Une tumeur vésicale rare: le carcinome à petites cellules.

Primary small cell carcinoma of the urinary bladder is an uncommon tumor, compared to the frequency of urothelial tumors. Fifty percent of cases are combined with a non endocrine carcinomatous component. We report six new cases of this tumor, three of pure, and three associated with an urothelial carcinoma. Diagnosis is easy established by the immunohistochemical study which show the neuro-endocrine differentiation of these aggressive tumors. Pathologist needs to look for a neuro-endocrine part in all bladder cancer, as its presence modify the treatment. Chemotherapy is used in these cancers, due to their high metastatic power. Places of radical surgery and radiotherapy need to be specified.

[Hibernoma of the axilla]. / Hibernome de la région axillaire.

Hibernomas are benign tumors derived from brown fat that most often present as painless, slowly enlarging masses in the interscapular region, the neck, the inguinal region and the mediastinum. We report one case of hibernoma of the axillary region and we review the clinical presentation, diagnostic and therapeutic of this kind of soft tissue neoplasm.

[Ultrasonographic evaluation of the uterine cervix length remaining after LOOP-excision]. / Évaluation échographique de la longueur de col utérin restant après conisation par électrorésection.

OBJECTIVES: To assess whether there is a correlation between the length of a conization specimen and the length of the cervix measured by vaginal ultrasonography after the operation PATIENTS AND METHODS: Prospective observational study including patients less than 45 years with measurement of cervical length before and the day of the conization, and measuring the histological length of the specimen. RESULTS: Among the 40 patients enrolled, the average ultrasound measurements before conization was 26.9 mm (± 4.9 mm) against 18.1mm (± 4.4mm) after conization with a mean difference of 8.8mm (± 2.4mm) (difference statistically significant P<.0001). The extent of histological specimen was 9 mm (± 2.2mm) on average. A correlation between ultrasound and histological measurements with a correlation coefficient R=0.85 was found statistically significant (P<0.0001). Moreover, the rate of cervix length remove by loop-excision in our series is 33% (± 8.5%). DISCUSSION: A good correlation between the measurements of the specimen and the cervical ultrasound length before and after conization was found, as a significant reduction in cervical length after conization. The precise length of the specimen should be known in case of pregnancy and the prevention of prematurity due to conization rests on selected indications and efficient surgical technique.

[Cervical Pap smear in an epidemiologically exposed population: ideas, facts and arguments]. / Pratique du frottis cervico-utérin dans une population épidémiologiquement exposée : idées reçues, faits et arguments.

OBJECTIVES: To analyse the prevalence of abnormal papsmears in a primary care center and the screening practices. MATERIALS AND METHODS: Single-center retrospective study on 1,430 FCU performed in 1,251 patients between January 2009 and December 2011 with analysis of demographic, clinical and epidemiological chararacteristics of the women, and the monitoring of the patients with pathological papsmears. RESULTS: The study population was predominantly young (under 25), unmarried, nulliparous, and using contraception. Among the 1,244 FCU, nearly 90% of them were interpretable with the junction area interested. Nine percent were pathological with mainly ASC-US and L-SIL (3.5% and 4.5%) with no difference between more and less than 25years. Two factors were significantly associated with the presence of pathological papsmear: first intercourse before age 14 and smoking more than 10 cigarettes per day. Monitoring of patients with a pathological papsmear showed that 33% of patients had not an appropriate follow-up especially younger patients. DISCUSSION: To perform papsmear before 25 years because the patient has associated high risk HPV co-factors does not appear justified by the severity or frequency of cytological lesions, especially as it increases the financial cost and is responsible of potential deleterious actions such as conizations probably excessive among the youngest patients. Personalized monitoring of these patients with a pathological papsmear is required. The French practice recommendations on cervical cancer screening (first screening at age 25, 26 years cytological control then every 3 years up to 65 years in patients who have or have had sex) deserve to be applied in young and disadvantaged patients.

[Immunotherapy in epithelial ovarian carcinoma: hope and reality]. / L'immunothérapie dans le cancer épithélial de l'ovaire : entre espoir et réalité

INTRODUCTION: Epithelial ovarian carcinoma (EOC) has a worst prognosis with little progress in terms of survival for the last two decades. Immunology received little interest in EOC in the past, but now appears very important in the natural history of this cancer. This review is an EOC immunology state of art and focuses on the place of immunotherapy in future. MATERIAL AND METHODS: A systematic review of published studies was performed. Medline baseline interrogation was performed with the following keywords: "Ovarian carinoma, immunotherapy, T-lymphocyte, regulator T-lymphocyte, dendritic cells, macrophage, antigen, chemotherapy, surgery, clinical trials". Identified publications (English or French) were assessed for the understanding of EOC immunology and the place of conventional treatment and immunotherapy strategy. RESULTS: Intratumoral infiltration by immune cells is a strong prognotic factor in EOC. Surgery and chemotherapy in EOC decrease imunosuppression in patients. The antitumoral immunity is a part of the therapeutic action of surgery and chemotherapy. Until now, immunotherapy gave some disappointing results, but the new drugs that target the tolerogenic tumoral microenvironnement rise and give a new hope in the treatment of cancer. CONCLUSION: Immunology controls the EOC natural history. The modulation of immunosuppressive microenvironment associated with the stimulation of antitumoral immunity could be the next revolution in the treatment of cancer.

[Are vaginal pap smear necessary after total hysterectomy for CIN3?]. / Faut-il pratiquer des frottis vaginaux après hystérectomie totale pour CIN3 ?

The practice of vaginal smears after total hysterectomy should be discussed according to the indication for hysterectomy. We have thus performed a literature review using PubMed medical database with selection of articles presenting a practical interest for clinicians. The practice of vaginal smears after endometrial cancer can be abandoned, but in case of cervical cancer it improves the performance of clinical examination in the early follow-up (in the first 5 years of follow-up) especially in early diagnosis of subclinical recurrence. After this period, the interest of vaginal smears drop drastically and the follow-up is mainly clinical. When hysterectomy is proposed as part of cervical intraepithelial neoplasia (particularly when associated uterine lesions and cervical conization not accessible), the risk of vaginal recurrence of HPV-induced pathology fully justifies an annual monitoring (recurrences or virus-induced lesions are seen up to 25 years after surgery). Finally, after hysterectomy for benign uterine non-HPV-induced, there is no need to propose a systematic follow-up cytology.

[Adenocarcinoma of the uterine cervix: particularities in diagnosis and treatment]. / L'adénocarcinome du col utérin : particularités diagnostiques et thérapeutiques.

INTRODUCTION: The adenocarcinoma of the uterine cervix accounts for 10 to 20% of the premalignant and malignant lesions and is different from the cervical intraepithelial neoplasia and invasive squamous cell carcinoma. MATERIALS AND METHODS: Recent literature review (from 1985 to 2012) based on the literature available. RESULTS AND DISCUSSION: Adenocarcinoma in situ is an induced HPV lesion (role of HPV 18) of the glandular epithelium: its preferential endocervical situation explains the difficulties in the diagnosis and follow-up after conservative treatment. If the hysterectomy remains the gold standard for treatment, the conservative treatments (resection in sano of the lesions with margins of more than 1cm, meticulous study of the operative specimen, compliance with the follow-up) are possible in the young patients who desire to preserve their fertility. The invasive adenocarcinoma is characterized by a more difficult diagnosis because of its endocervical development, and a prognosis less favorable when compared to squamous cell carcinoma with a greater frequency of the lymphatic node involvement and metastatic diffusion. Its treatment must take into account the particular gravity of the factors of worse prognosis (FIGO stage, tumor size, lymphatic node spreading, adenosquamous histological subtype) in particular in the advanced stages and includes beside the surgery, radiotherapy and chemotherapy.