Fallopian tube cytology as a diagnostic tool for adnexal malignancy: the CytoSaLPs score.

INTRODUCTION: During the past decade, the theory that high-grade extrauterine pelvic tumors originate from the fallopian tube has been strongly suggested. Our study aims to illuminate the possible role of tubal cytology as an accessory identification tool for gynecologic extrauterine malignancies, allowing in the long term the implementation of population-level cytologic tube evaluation during all benign gynecologic surgeries that do not result in salpingectomy. MATERIALS AND METHODS: We ex vivo collect salpingeal epithelial cells from the fibria directly from fresh fallopian tube specimens from women undergoing salpingectomy for any indication. The cytomorphologic characteristics of the salpingeal cells are subsequently evaluated and categorized into malignant and non-malignant. Finally, the ipsilateral adnexa are examined with the SEE-FIM (Sectioning and Extensively Examining the FIMbriated End) protocol and the pathology reports are corelated with the cytologic findings. Our research protocol is ongoing and is designed to include a total of 300 patients in order to confirm the sensitivity and specificity of salpingeal cytology as a method in the early diagnosis of extrauterine gynecologic malignancies. RESULTS: So far, we have obtained 343 salpingeal brushings from a total of 214 patients. The sensitivity of cytology regarding distinguishing malignant from non-malignant tumors is 69.64% (95% CI: 55.90%-81.22%), and its specificity 75.96% (95% CI: 70.59%-80.79%). Cytology's positive predictive value (PPV) is 16.33% (95% CI: 12.57%-20.67%), while the negative predictive value (NPP) reached 92.77% (95% CI: 89.56%-95.04%). In general, the diagnostic accuracy of the cytologic evaluation reaches 74.93% (95% CI: 66.99%-79.43%). CONCLUSIONS: Salpingeal cytomorphologic evaluation appears to be a promising method for early detection of adnexal cancer.

The Utility of Fallopian Tube Cytology in the Early Detection of Extrauterine Serous Gynecological Malignancies: A Narrative Literature Review.

INTRODUCTION: The aim of the study was to analyze the published evidence for the use of fallopian tube brush cytology for the early detection of extrauterine serous gynecological cancer. METHODS: We systematically searched the literature and, additionally, cross-checked on the bibliographies of selected articles. The inclusion criteria involved studies assessing the utility of fallopian tube brush cytology and its applications in the diagnosis, screening, or follow-up of extrauterine serous gynecological cancer. RESULTS: The search strategy resulted in 21 abstracts or full-text articles, 5 of which met the inclusion criteria. The year of publication ranged from 2016 to 2022, and a total of 193 fallopian tube samples were investigated. Cytobrush, Tubebrush©, and Cytuity™ were used to obtain salpingeal samples for liquid-based cytology evaluation. CONCLUSIONS: Our findings indicate that, at present, there is a lack of satisfying evidence-based data in the literature which would support the implementation of fallopian tube brush cytology as an adjunctive tool for early detection of extrauterine serous gynecological cancer. Thus, we believe that there is need for well-designed clinical studies to assess the effectiveness and diagnostic accuracy of the method as well as to validate the cytological criteria for the diagnosis and prediction of gynecological malignancies.

CytoSaLPs score: a promising new tool for the detection and screening of extrauterine high grade serous carcinoma.

BACKGROUND: A recent theory supports that high-grade serous epithelial ovarian cancer derives from the fimbrial end of the fallopian tube and during the last decade, a few studies have examined the fallopian tube cytology. Our study aims to determine the cytomorphological characteristics of both benign and non-benign salpingeal samples, in order to establish fallopian cytology as a valuable diagnostic test for women with high risk for development of ovarian/fallopian/peritoneal cancer. METHODS: Our study included patients undergoing salpingoophorectomy or total hysterectomy and salpingoophorectomy for any gynecological pathology. Using a soft brush, fallopian tube smears from the fimbrial end were collected ex vivo. The Cytologists of our Institution described the morphological characteristics of the fallopian cells by adopting a proposed Table, which had a calibration system ranging from 3 to 29. This Table is referred to as the CytoSaLPs Score. Our study compared the two diagnostic cytological methods, the one of the conventional cytology and the other using the CytoSaLPs Score, having as gold standard the tubal's pathological findings. RESULTS: A total of 230 tubal specimens from 144 patients were included in this study. The Score's mean for the benign and non-benign arm was 12.8 and 18.7 respectively. The cut-off point for both arms was 16.5. The CytoSaLPs Score tool showed significantly higher specificity (87.50% vs. 75.96, p-value < 0.001) and positive predictive value PPV (40.91% vs. 26.47%, p-value < 0.001) compared to conventional cytology. Regarding the accuracy, the Score's superiority is highlighted (86.96% vs. 76.52%, p-value < 0.001). CONCLUTIONS: The evaluation of tubal cytology using the CytoSaLPs Score could be used as a reliable diagnostic method. Further evaluation with larger studies is warranted.

Identification of amino acid residues critical for the anti-interferon activity of the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus.

Lymphocytic choriomeningitis virus (LCVM) nucleoprotein (NP) counteracts the host type I interferon (IFN) response by inhibiting activation of the IFN regulatory factor 3 (IRF3). In this study, we have mapped the regions and specific amino acid residues within NP involved in its anti-IFN activity. We identified a region spanning residues 382 to 386 as playing a critical role in the IFN-counteracting activity of NP. Alanine substitutions at several positions within this region resulted in NP mutants that lacked the IFN-counteracting activity but retained their functions in virus RNA synthesis and assembly of infectious particles. We used reverse genetics to rescue a recombinant LCMV strain carrying mutation D382A in its NP [rLCMV/NP*(D382A)]. Compared to wild-type (WT) LCMV, rLCMV/NP*(D382A) exhibited a higher level of attenuation in IFN-competent than IFN-deficient cells. In addition, A549 cells infected with rLCMV/NP*(D382A), but not with WT LCMV, produced IFN and failed to rescue replication of the IFN-sensitive Newcastle disease virus.

Differential inhibition of type I interferon induction by arenavirus nucleoproteins.

We have documented that the nucleoprotein (NP) of the prototypic arenavirus lymphocytic choriomeningitis virus is an antagonist of the type I interferon response. In this study we tested the ability of NPs encoded by representative arenavirus species from both Old World and New World antigenic groups to inhibit production of interferon. We found that, with the exception of Tacaribe virus (TCRV), all NPs tested inhibited activation of beta interferon and interferon regulatory factor 3 (IRF-3)-dependent promoters, as well as the nuclear translocation of IRF-3. Consistent with this observation, TCRV-infected cells also failed to inhibit interferon production.