Impact of molecular genotyping on the diagnosis and treatment of human chorionic gonadotropin-producing tumors.

OBJECTIVES: To assess the use of molecular genotyping to accurately diagnose and treat human chorionic gonadotropin (hCG)-producing tumors and to evaluate the discriminating capacity of molecular testing on prognosis and overall survival. METHODS: We conducted a retrospective descriptive study of patients registered with the French Reference Center for Trophoblastic Disease between 1999 and 2021. We included all patients with hCG-producing tumors for whom results of molecular genotyping were available. RESULTS: Fifty-five patients with molecular genotyping were included: 81.2 % (n = 45) had tumors of gestational origin, 12.7 % (n = 7) of non-gestational origin and 5.5 % (n = 3) of undetermined origin. The results of molecular genotyping influenced the treatment decisions for 17 % of patients in this cohort. Overall survival was 93.3 % for patients with gestational tumors (after a median follow-up of 74 months) compared to 71.4 % for patients with non-gestational tumors (after a median follow-up of 23 months). CONCLUSION: In atypical presentations of hCG-producing tumors, molecular genotyping is a valuable tool to guide diagnosis and tailor treatment recommendations.

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.

Polypoid endometriosis of the Douglas pouch.

Polypoid endometriosis is a rare form of endometriosis that corresponds to a benign variant but which systematically mimics malignant tumors. Magnetic resonance imaging (MRI) is the preferred imaging modality for these lesions. We present herein a case of a 43-year-old female with recent pelvic pain and longstanding dyspareunia related to polypoid endometriosis of the Douglas pouch. MRI found an infiltrative lesion 6 cm in diameter with intermediate signal on T2-weighted imaging, cystic hemorrhagic spots, and fibrous surrounding rim of nodular portion. There was no functional sign of malignancy (no diffusion restriction, pronounced tumor enhancement, or metastasis). The patient underwent total abdominal radical colpohysterectomy with bilateral salpingectomy and ovarian transposition was performed. Histopathological examination found a multinodular endometrial-type polypoid mass arising from the serosa of the cervix, with cystic area and fibrous surrounding tissue. In the case presented, MRI findings were useful for preoperative diagnosis that altered patient management by supporting a complete but reasonable surgical resection that yielded relief of symptoms.

Borderline ovarian tumors: Guidelines from the French national college of obstetricians and gynecologists (CNGOF).

It is recommended to classify Borderline Ovarian Tumors (BOTs) according to the WHO classification. Transvaginal and suprapubic ultrasonography are recommended for the analysis of an ovarian mass (Grade A). In case of an undetermined ovarian lesion on ultrasonography, it is recommended to perform a pelvic MRI (Grade A) with a score for malignancy (ADNEX MR/O-RADS) (Grade C) included in the report and to formulate a histological hypothesis (Grade C). Pelvic MRI is recommended to characterize a tumor suspected of being BOT (Grade C). It is recommended to evaluate serum levels of HE4 and CA125 and to use the ROMA score for the diagnosis of indeterminate ovarian mass on imaging (grade A). If there is a suspicion of a mucinous BOT on imaging, serum levels of CA 19-9 may be proposed (Grade C). For Early Stages (ES) of BOT, if surgery without risk of tumor rupture is possible, laparoscopy with protected extraction is recommended over laparotomy (Grade C). For treatment of a bilateral serous ES BOT with a strategy to preserve fertility and/or endocrine function, bilateral cystectomy is recommended where possible (Grade B). For mucinous BOTs with a treatment strategy of fertility and/or endocrine function preservation, unilateral salpingo-oophorectomy is recommended (grade C). For mucinous BOTs treated by initial cystectomy, unilateral salpingo-oophorectomy is recommended (grade C). For serous or mucinous ES BOTs, routine hysterectomy is not recommended (Grade C). For ES BOTs, lymphadenectomy is not recommended (Grade C). For ES BOTs, appendectomy is recommended only in case of a macroscopically pathological appendix (Grade C). Restaging surgery is recommended in cases of serous BOTs with micropapillary architecture and an incomplete abdominal cavity inspection during initial surgery (Grade C). Restaging surgery is recommended for mucinous BOTs after initial cystectomy or in cases where the appendix was not examined (Grade C). If restaging surgery is decided for ES BOTs, the following procedures should be performed: peritoneal washing (grade C), omentectomy (grade B), complete exploration of the abdominal cavity with peritoneal biopsies (grade C), visualization of the appendix and appendectomy in case of a pathological macroscopic appearance (grade C) as well as unilateral salpingo-oophorectomy in case of a mucinous BOT initially treated by cystectomy (grade C). In advanced stages (AS) of BOT, it is not recommended to perform a lymphadenectomy as a routine procedure (Grade C). For AS BOT in a patient with a desire to fall pregnant, conservative treatment involving preservation of the uterus and all or part of the ovary may be proposed (Grade C). Restaging surgery aimed at removing all lesions, not performed initially, is recommended for AS BOTs (Grade C). After treatment, follow-up for a duration greater than 5 years is recommended due to the median recurrence time of BOTs (Grade B). It is recommended that a systematic clinical examination be carried out during follow-up of a treated BOT (Grade B). If the determination of tumor markers is normal preoperatively, the routine dosage of tumor markers in BOT follow-up is not recommended (Grade C). In case of an initial elevation in serum CA 125 levels, it is recommended to monitor CA 125 during follow up (Grade B). In case of conservative treatment, it is recommended to use transvaginal and transabdominal ultrasound during follow up of a treated BOT (Grade B). In the event of a BOT recurrence in a woman of childbearing age, a second conservative treatment may be proposed (Grade C). A consultation with a physician specialized in Assisted Reproductive Technique (ART) should be offered in the case of BOTs in women of childbearing age (Grade C). When possible, a conservative surgical strategy is recommended to preserve fertility in women of childbearing age (Grade C). In the case of optimally treated BOT, there is no evidence to contraindicate the use of ART. The use of hormonal contraception after serous or mucinous BOT is not contraindicated (Grade C). After management of mucinous BOT, for women under 45 years, given the benefit of Hormonal Replacement Therapy (HRT) on cardiovascular and bone risks, and the lack of hormone sensitivity of mucinous BOTs, it is recommended to offer HRT (Grade C). Over 45 years of age, HRT can be prescribed in case of a climacteric syndrome after individual benefit to risk assessment (Grade C).

[Borderline ovarian tumours: CNGOF Guidelines for clinical practice - Biopathology of ovarian borderline tumors]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Biopathologie des tumeurs frontières de l'ovaire.

OBJECTIVES: Ovarian borderline tumors (OBT) represent a heterogeneous group of lesions with specific management for each histological subtype. Thus, the correct histological diagnosis is mandatory. MATERIAL AND METHODS: References were searched by PubMed from January 2000 to January 2018 and original articles in French and English literature were selected. RESULTS AND CONCLUSIONS: OBT should be classified according to the last WHO classification. Any micro-invasion (foci<5mm) or microcarcinoma (foci<5mm with nuclear atypia and desmoplastic stromal reaction) should be indicated in the pathology report. In case of serous OBT, variants (classical or the micropapillary/cribriform) should be indicated (grade C). The peritoneal implants associated with OBT, should be classified as invasive or noninvasive, according to the extension into the underlying adipous tissue. If no adipous tissue is seen the term undetermined should be used (grade B). In case of mucinous OBT bilateral and/or with peritoneal implants or peritoneal pseudomyxoma a search for primitive gastrointestinal, appendiceal or biliopancreatic tumor should be performed (grade C). In case of OBT, a thorough sampling of the tumor is recommended, with 1 block/cm and 2 blocks/cm in case of mucinous OBT, serous OBT micropapillary variant, OBT with intraepithelial carcinoma or/and micro-invasion. Peritoneal implants should be examined in toto. Omentum without macroscopic lesion should be sampled in 4 to 6 blocks (grade C). In case of ovarian cyst suspicious for OBT, fine needle aspiration is not recommended (grade C). In case of ovarian tumor suspicious for OBT, intraoperative examination should be performed by a gynecological pathologist (grade C).

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Short Text]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Texte court.

This work was carried out under the aegis of the CNGOF (Collège national des gynécologues et obstétriciens français) and proposes guidelines based on the evidence available in the literature. The objective was to define the diagnostic and surgical management strategy, the fertility preservation and surveillance strategy in Borderline Ovarian Tumor (BOT). No screening modality can be proposed in the general population. An expert pathological review is recommended in case of doubt concerning the borderline nature, the histological subtype, the invasive nature of the implant, for all micropapillary/cribriform serous BOT or in the presence of peritoneal implants, and for all mucinous or clear cell tumors (grade C). Macroscopic MRI analysis should be performed to differentiate the different subtypes of BOT: serous, seromucinous and mucinous (intestinal type) (grade C). If preoperative biomarkers are normal, follow up of biomarkers is not recommended (grade C). In cases of bilateral early serous BOT with a desire to preserve fertility and/or endocrine function, it is recommended to perform a bilateral cystectomy if possible (grade B). In case of early mucinous BOT, with a desire to preserve fertility and/or endocrine function, it is recommended to perform a unilateral adnexectomy (grade C). Secondary surgical staging is recommended in case of serous BOT with micropapillary appearance and uncomplete inspection of the abdominal cavity during initial surgery (grade C). For early-stage serous or mucinous BOT, it is not recommended to perform a systematic hysterectomy (grade C). Follow up after BOT must be pursued for more than 5 years (grade B). Conservative treatment involving at least the conservation of the uterus and a fragment of the ovary in a patient wishing to conceive may be proposed in advanced stages of BOT (grade C). A new surgical treatment that preserves fertility after a first non-invasive recurrence may be proposed in women of childbearing age (grade C). It is recommended to offer a specialized consultation for Reproductive Medicine when diagnosing BOT in a woman of childbearing age. Hormonal contraceptive use after serous or mucinous BOT is not contraindicated (grade C).

Management of epithelial cancer of the ovary, fallopian tube, primary peritoneum. Long text of the joint French clinical practice guidelines issued by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY, endorsed by INCa. (Part 2: systemic, intraperitoneal treatment, elderly patients, fertility preservation, follow-up).

Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum. Long text of the Joint French Clinical Practice Guidelines issued by FRANCOGYN, CNGOF, SFOG, and GINECO-ARCAGY, and endorsed by INCa. Part 1: Diagnostic exploration and staging, surgery, perioperative care, and pathology.

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). For FIGO stages III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancer (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B).

Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum. Short text of the French Clinical Practice Guidelines issued by FRANCOGYN, CNGOF, SFOG, and GINECO-ARCAGY, and endorsed by INCa.

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (Grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (Grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). For FIGO stage III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (Grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancers (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III disease, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

[Part II drafted from the short text of the French guidelines entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Systemic and intraperitoneal treatment, elderly, fertility preservation, follow-up)]. / Partie 2 rédigée à partir de la synthèse de la recommandation nationale de bonnes pratiques cliniques intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa. (Traitement systémique et intrapéritonéal, personnes âgées, préservation de la fertilité et suivi).

Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A). For BRCA mutated patient, Olaparib is recommended (grade B).

[Focus on mucinous adenocarcinoma of the uterine cervix]. / Les adénocarcinomes mucineux du col utérin.

Cancer of the uterine cervix is the fourth most common cancer in women worldwide, and the fourth leading cause of cancer death in women. Squamous cell carcinoma is the first type of cervical cancer (about 75% of cases), and adenocarcinoma the second. Adenocarcinoma of the uterine cervix were redefined in the 2014 WHO classification. Endocervical adenocarcinoma, usual type, is the mose common. Mucinous adenocarcinoma were classified by this classification into different subtypes: gatric type, intestinal type and signet-ring cell type. This literature review shows the caracteristics of these various subtypes of cervical cancer, little known. These are physiopathological, clinical, cytological histological, pronostic caracteristics, and their treatments.

[Part I drafted from the short text of the French Guidelines entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Diagnosis management, surgery, perioperative care, and pathological analysis)]. / Partie 1 rédigée sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa. (Explorations diagnostiques et bilan d'extension, chirurgie, soins périopératoires et anatomopathologie).

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B).

[Biopathology of ovarian carcinomas early and advanced-stages: Article drafted from the French guidelines in oncology entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY under the aegis of CNGOF and endorsed by INCa]. / Biopathologie des carcinomes ovariens des stades précoces et avancés. Article rédigé sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY sous l'égide du CNGOF et labellisée par l'INCa.

OBJECTIVES: Ovarian carcinomas represent a heterogeneous group of lesions with specific therapeutic management for each histological subtype. Thus, the correct histological diagnosis is mandatory. MATERIAL AND METHODS: References were searched by PubMed from January 2000 to January 2018 and original articles in French and English literature were selected. RESULTS AND CONCLUSIONS: In case of ovarian mass suspicious for cancer, a frozen section analysis may be proposed, if it could impact the surgical management. A positive histological diagnosis of ovarian carcinoma (type and grade) has to be rendered on histological (and not cytological) material before any chemotherapy with multiples and large sized biopsies. In case of needle biopsy, at least three fragments with needles>16G are needed. Histological biopsies need to be formalin-fixed (4% formaldehyde) less than 1h after resection and at least 6hours fixation is mandatory for small size biopsies. Tissue transfer to pathological labs up to 48hours under vacuum and at +4°C (in case of large surgical specimens) may be an alternative. Gross examination should include the description of all specimens and their integrity, the site of the tumor and the dimension of all specimens and nodules. Multiples sampling is needed, including the capsule, the solid areas, at least 1 to 2 blocks per cm of tumor for mucinous lesions, the Fallopian tube in toto, at least 3 blocks on grossly normal omentum and one block on the largest omental nodule. WHO classification should be used to classify the carcinoma (type and grade), with the use of a panel of immunohistochemical markers. High-grade ovarian carcinomas (serous and endometrioid) should be tested for BRCA mutation and in case of a detectable tumor mutation, the patient should be referred to an oncogenetic consultation.

The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade.

BACKGROUND: Never-smokers and never-drinkers patients (NSND) suffering from oral squamous cell carcinoma (OSCC) are epidemiologically different from smokers drinkers (SD). We therefore hypothesized that they harbored distinct targetable molecular alterations. PATIENTS AND METHODS: Data from The Cancer Genome Atlas (TCGA) (discovery set), Gene Expression Omnibus and Centre Léon Bérard (CLB) (three validation sets) with available gene expression profiles of HPV-negative OSCC from NSND and SD were mined. Protein expression profiles and genomic alterations were also analyzed from TCGA, and a functional pathway enrichment analysis was carried out. Formalin-fixed paraffin-embedded samples from 44 OSCC including 20 NSND and 24 SD treated at CLB were retrospectively collected to perform targeted-sequencing of 2559 transcripts (HTG EdgeSeq system), and CD3, CD4, CD8, IDO1, and PD-L1 expression analyses by immunohistochemistry (IHC). Enrichment of a six-gene interferon-γ signature of clinical response to pembrozulimab (PD-1 inhibitor) was evaluated in each sample from all cohorts, using the single sample gene set enrichment analysis method. RESULTS: A total of 854 genes and 29 proteins were found to be differentially expressed between NSND and SD in TCGA. Functional pathway analysis highlighted an overall enrichment for immune-related pathways in OSCC from NSND, especially involving T-cell activation. Interferon-γ response and PD1 signaling were strongly enriched in NSND. IDO1 and PD-L1 were overexpressed and the score of response to pembrolizumab was higher in NSND than in SD, although the mutational load was lower in NSND. IHC analyses in the CLB cohort evidenced IDO1 and PD-L1 overexpression in tumor cells that was associated with a higher rate of tumor-infiltrating T-cells in NSND compared with SD. CONCLUSION: The main biological and actionable difference between OSCC from NSND and SD lies in the immune microenvironment, suggesting a higher clinical benefit of PD-L1 and IDO1 inhibition in OSCC from NSND.

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.

Multidisciplinary management of advanced ovarian cancer for an optimal therapeutic strategy.

The management of advanced ovarian cancer generally requires specialist multidisciplinary teamwork to achieve optimum outcomes. Preoperative computed tomography scans are the imaging modality of choice in determining the extent of disease and aiding in surgical planning. Histological classification is crucial to define various subtypes with their different behaviour and prognosis and to plan the best therapeutic strategy. Pathological prognostic factors, such as histological type, degree of differentiation, and FIGO stage must be described. To determine the ability to optimally cytoreduce advanced ovarian cancer, an experienced gynaecological oncologist needs to explore the entire upper abdomen and the pelvic and para-aortic lymph node regions to define the peritoneal cancer index (PCI). The final assessment is the completeness of cytoreduction (CC) score which is important in predicting prognosis and decision of post-surgical surgery. Ovarian cancer is the leading cause of death from gynaecologic cancers. Initial management is best provided by a specialist multidisciplinary team, including a radiologist, a pathologist, a gynaecologic oncologist, and a medical oncologist.

[Microscopic extensions of head and neck squamous cell carcinomas: impact for clinical target volume definition]. / Approche anatomopathologique de l'extension microscopique des carcinomes épidermoïdes ORL : implications pour la définition du volume cible anatomoclinique.

PURPOSE: To assess microscopic extensions of head and neck squamous cell carcinomas aiming at a proposal for target volumes of radiation therapy. MATERIALS AND METHODS: Surgical specimens were prospectively analysed macroscopically and microscopically. Tumour borders were identified per macroscopic visual examination and inked on stained slides. Then microscopic implants (perineural or lymphatic involvement, or in situ carcinomas) were looked for with an optic microscope in the macroscopic healthy tissue surrounding the tumour. The maximal length from tumour border was correlated with the maximal length of macroscopically healthy tissues assessable. RESULTS: Twenty-one specimens were analysed and 12 were locally advanced tumours. Mean and median maximal microscopic extensions were 2.9 and 1.0mm (0-15mm), respectively. The 90th and 95th percentiles were 5 and 11mm, respectively. The ratio between healthy tissue length and maximal microscopic tumour extension was 10%. No correlation was found with tumour grade or volume. CONCLUSION: The presence of microscopic tumour was unlikely after 5mm from macroscopic tumour (≤5% of patients in this series) but should be assessed along with other histoclinical factors and particularities of tumour behaviour by anatomic site. A rigorous terminology should authorize a relevant appreciation of local risk of recurrence, particularly in adjuvant setting or for clinical target volume definition. Larger and more homogenous confirmatory series are needed.

Fetal thrombotic vasculopathy is associated with thromboembolic events and adverse perinatal outcome but not with neurologic complications: a retrospective cohort study of 54 cases with a 3-year follow-up of children.

OBJECTIVE: to test the hypothesis that placental fetal thrombotic vasculopathy (FTV) is associated with obstetric complications and predisposes the child to unfavorable outcomes. METHODS: 54 placentas with FTV lesions and 100 placentas without FTV lesions were collected over a 5-year period at the Croix-Rousse Pathology Department. Clinical findings including maternal, fetal, neonatal condition and pediatric outcome up to three years were collected for each case and control observation. The statistical analyses were assessed with Wald's chi-square derived from conditional logistic regression modeling. RESULTS: FTV was associated with a significantly higher frequency of obstetric complications: (pregnancy-induced hypertension (OR 3.620, CI 1.563-8.385), preeclampsia (OR 3.674, CI 1.500-8.998), emergency delivery procedures (OR 3.727, CI 1.477-9.403), cesarean sections (OR 2.684, CI 1.016-7.088)), poor fetal condition (intrauterine growth restriction (IUGR) (OR 5.440, CI 2.007-14.748), nonreassuring fetal heart tracing (OR 6.062, CI 2.280-16.115), difficulties in immediate ex utero adaptation (OR 3.416, CI 1.087-10.732)) and perinatal or early childhood demise (OR 3.043, CI 1.327-6.978). On pathological examination, FTV was associated with marginal cord insertion (OR 3.492, CI 1.350-9.035), cord stricture and hypercoiled cord (OR 3.936, CI 1.209-12.813). Thromboembolic events were significantly more frequent in cases with FTV (OR 2.154, CI 1.032-5.622). Neurological complications within the first 3 years of life were also more frequent in the FTV group compared to the control group, but this association was not statistically significant. CONCLUSIONS: FTV is associated with maternal complications, pathological findings in the placenta, especially gross cord abnormalities, IUGR, and poor perinatal or early childhood outcome. It may also predispose children to somatic thromboembolic events.

[An ovarian mucinous borderline tumour with mixed mural nodules]. / Une tumeur ovarienne mucineuse borderline avec des nodules muraux mixtes.

The occurrence of mural nodules in serous or mucinous ovarian tumours is not frequent. Mural nodule can be developed in benign, borderline or malignant tumours. They can be benign, malignant or mixed type. Thus the prognosis of the ovarian tumour can be dramatically modified by the presence if these nodules. Eighty-two cases of mural nodules were reported in the literature, among which we account four cases of mixed nodules type. We report an additional case of mixed type mural nodules of anaplastic carcinoma and sarcoma-like developed in an ovarian mucinous borderline tumour at a 60-year-old woman.We give details about the classification, the differential diagnosis and prognosis of theses nodules.