Reproducibility of cytological diagnoses in evaluating liquid cervical smears and immunocytochemical co-expression of p16/Ki-67 using manual and automatic methods

Aim. To assess the reproducibility of cytological diagnoses in evaluating liquid cervical smears and immunocytochemical co-expression of p16/Ki-67 using manual and automatic methods. Materials and methods. Cytological smears prepared using the liquid cytology method on the Becton Dickinson device (SurePath technology) were studied. An immunocytochemical study was carried out using a Ventana BenchMark Ultra automatic immunostainer with a commercial CINtec kit (determination of p16/Ki-67 co-expression). In total, 100 cytological slides (50 pairs of Pap-smears and immunocytochemical slides) were studied. The diagnostic kit was reviewed by five cytologists independently, and the cytologic slides were evaluated using four categories according to the Bethesda system (2014) and according to the categories of normal/abnormal. The co-expression of p16/Ki-67 was assessed per the manufacturer's recommendations (Roche) using the manual method (light microscope) and the automatic Vision Cyto Pap ICC system. Statistical processing of the results was performed using the SPSS software package version 26.0.0.0 with the calculation of the reproducibility indices of Cohen's kappa and Fleiss' kappa. Results. When assessing the reproducibility of four categories of cytological diagnoses according to the Bethesda system (2014), Cohen's kappa was 0.0480.265. The overall Fleiss' kappa between all cytologists was 0.103. When only two categories (normal/abnormal) were used, the reproducibility ranged from 0.058 to 0.377. When assessing the co-expression of p16 and Ki-67, Cohen's kappa reproducibility was from 0.196 to 0.574, while the overall Fleiss' kappa was 0.407. When comparing the evaluation results of each of the cytologists with the neural network, Cohen's kappa reproducibility ranged from 0.103 to 0.436. Conclusion. The reproducibility of cytological diagnoses according to the Bethesda system (2014) and two categories (normal/abnormal) based on the Pap smear study was low. Such results are primarily due to a large number of abnormal smears in the study. The immunocytochemical method has diagnosis reproducibility three times higher, indicating the need to measure the co-expression of p16 and Ki-67 to increase the sensitivity and specificity of the cytological method. Similar reproducibility when comparing the manual and automatic evaluation of the "double label" suggests that the neural network algorithm can currently help in decision support rather than replace the cytologist at the diagnostic stage

Uterine leiomyosarcoma and disseminated peritoneal leiomyomatosis in the surgical treatment of uterine myoma: a retrospective analysis

Aim. To analyze the incidence and types of adverse outcomes and complications of laparoscopic myomectomies. Materials and methods. This work is a retrospective study based on data from the Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology. We analyzed 711 case histories of patients diagnosed with uterine myoma who received surgical treatment in the Department of Innovative Oncology and Gynecology from 2015 to 2019. The frequency of malignant neoplasms, verified by pathomorphological examination, and the characteristics of surgical interventions performed in these patients were comparatively evaluated. Results. Surgical interventions for uterine myoma are leading in gynecology due to the high prevalence of such disorders. Conservative myomectomy remains the "gold standard" in organ-sparing surgery. However, during surgeries for suspected benign neoplasms, there is a risk of morcellation of the malignant tumor, significantly worsening patient survival outcomes. In our study, the incidence of uterine leiomyosarcoma in suspected benign neoplasms was 0.98%. The probability of parasitic myomas or disseminated perineal leiomyomatosis after myomatous nodule morcellation is 0.19%. Conclusion. No reliable information about the malignant potential of the tumor and its proliferative activity can be obtained until a definitive pathomorphological examination. The above considerations warrant the routine use of prophylactic measures to prevent tumor cell dissemination

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Androgen Insensitivity Syndrome with Bilateral Gonadal Sertoli Cell Lesions, Sertoli–Leydig Cell Tumor, and Paratesticular Leiomyoma: A Case Report and First Systematic Literature Review

Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor (AR) gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient’s gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli–Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient’s karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations—a pathogenic frameshift deletion in the AR gene (c.77delT) and a likely pathogenic missense variant in the RAC1 gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads (n = 225; age: 4–84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases (n = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2–49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS