Russian Journal of Archive of Pathology

Metastatic leiomyoma or synchronous lesion of the uteri corpus and vulva?

To reveal the morphological characteristics of simultaneously diagnosed leiomyoma of the corpus uteri and vulva. The paper describes a case of multiple uterine leiomyomas concurrent with vulvar leiomyoma in a 39-year-old patient with progressive tumor nodule growth over 2 years. Vulvar tumor was biopsied simultaneously with extirpation of the uterus; vulvar leiomyoma was removed six months later. Histological and immunohistochemical studies: such as hematoxylin and eosin staining, the expression of smooth muscle actin, desmin, and progesterone and estrogen receptors, S100, CD10, and determination of Ki-67 proliferation index, were conducted. The largest (14-cm) multiple tumor nodule in the corpus uteri had the structure of leiomyoma of uncertain malignant potential; the large (8-cm) vulvar tumor was a leiomyoma with hyalinosis. The immunohistochemical profile of uterine and vulvar leiomyoma (smooth muscle actin+, desmin+, progesterone+, estrogen+ receptors, CD117-, and Ki-67) was the same (1-3%). The vulvar leiomyoma was assumed to be a tumor of metastatic origin. Vulvar leiomyoma is rare; it can arise from smooth muscle tissue of various anatomical structures of the skin and soft tissues. The pathogenesis of the so-called metastatic leiomyoma is unclear; there are concepts of a metaplastic transformation of subcelomic mesenchyme and multifocal smooth muscle proliferation. The presented case demonstrates the synchronous development of uterine and vulvar leiomyoma.

Molecular genetic profile of seromucinous ovarian tumors

Seromucinous tumors belong to a group of ovarian epithelial tumors. They were originally described as tumors characterized by Müllerian endocervical differentiation. Molecular genetic studies have indicated these tumors as endometriosis-associated tumors due to the presence of

Endometrial vascularisation in hyperplasia without atypia

Various benign processes in the endometrium are the cause of vascular changes. Endometrial cancer is also accompanied by changes in the density of microvessels. The detection of vascularization of the hyperplastic endometrium without signs of atypia, expressed significantly more than described in the literature, served as the basis for this work. Objective. To assess the state of the vascularization of the simple endometrial hyperplasia without atypia and to compare the obtained results with literary data. Material and methods. Vascularization of the endometrium in its simple hyperplasia without atypia was studied in 31 women by light microscopy using an immunohistochemical reaction with antibodies to the CD34 antigen and morphometry. Results. Different patients had different degrees of expression, but always large, vascularization of the endometrium with simple endometrial hyperplasia without atypia. The vessels accounted 5.97±4.18% of the section area, while their number per 1 mm2 was 391±180. These data significantly exceed most of the results of other studies presented in the literature, which differ several times even from each other. Conclusion. Endometrium with simple endometrial hyperplasia without atypia is characterized by different, often very high levels of vascularization, the real average values much exceed most of the literary data, which are also very contradictory. A very critical attention to the results describing the features of angiogenesis and vascularization of hyperplastic endometrium without atypia is necessary.

Comparative analysis of morphometric and histological characteristics of HPV-associated and HPV-independent vulvar squamous cell carcinoma

Squamous cell carcinomas of the vulva are divided into human papillomavirus (HPV)-associated and HPV-independent. There is a need to determine the most effective methods for determining the HPV status of a tumor. Differences in the morphological structure of carcinomas have been shown, but the histological type of tumor does not fully reflect the differences in cell size for understanding the mechanisms of carcinogenesis. Objective. To compare the morphometric and histological characteristics of HPV-associated and HPV-independent vulvar carcinomas and to calculate the specificity of histological, immunohistochemical methods and detection of viral DNA in establishing the HPV status of the tumor. Material and methods. The study retrospectively included 74 patients. HPV typing was performed by real-time PCR, expression of p16 and p53 was determined by immunohistochemical method. The total area of tumor cells, the area of the cytoplasm and the nucleus were measured, and the nuclear-cytoplasmic ratio was calculated. Results. HPV-independent carcinomas are predominantly keratinizing (94.3%). HPV-associated carcinomas are of basaloid histotype in 57.1% of cases and keratinizing in 42.9%. (42.9%). HPV-associated tumor cells are smaller (Me 223.89) compared to HPV-independent carcinoma cells (Me 525.95). The nuclear-cytoplasmic ratio was higher in HPV-associated carcinomas (Me 0.46 vs 0.18). The specificity of determining HPV status using histological characteristics of the tumor was 80.65%, immunohistochemical method — 96.36%, detection of viral DNA in the tumor — 75.47%. Conclusion. A smaller cell area and a nuclear-cytoplasmic ratio shift toward the nucleus characterize HPV-associated carcinomas. With HPV-independent carcinogenesis, tumor cells more often retain the ability to differentiate and mature the epithelium. Immunohistochemical determination of p16 and p53 expression is a more accurate method for determining the HPV status of vulvar carcinoma.

Placenta increta into the scar in combination with high-grade squamous intraepithelial lesion of the cervix

Placenta increta is a pathological condition characterized by an invasion of placental tissue into the myometrium. The placenta doesn’t detach naturally after delivery and cannot be separated without pathological hemorrhage. Previous cesarean section represents the main risk factor for the occurrence of placenta accreta. Pregnancy-related tissue changes complicate the identification of co-existing diseases of the cervix and uterine body. This case report discusses the characteristics and diagnostic methods of placenta increta in combination with cervical high-grade intraepithelial neoplasia in a 35-year-old female patient.

Clinical morphology of cervical conization variants for high-grade squamous intraepithelial lesions

Surgical options for organ-preserving operations on the cervix (conization and contour-loop excision (C-LETZ)) regarding squamous intraepithelial lesions, morphological features of the cervix after surgery are determined, which are significant for HPV persistence and reproductive function. Objective. To evaluate the results of a lifetime pathoanatomic examination of the surgical material of cervical conization with diathermy loops of various shapes and sizes — a triangular loop and a wavy C-LETZ loop. Material and methods. The study included 49 patients with a clinical diagnosis of high-severity squamous intraepithelial lesion (HSIL), established by the results of a cytological smear examination or a previous histological examination of a cervical biopsy at the Moscow Regional Research Institute of Obstetrics and Gynecology named after Academician V.I. Krasnopolsky from 2016 to 2023. Histological examination of resected cervical cones (n=32) and wavy C-LETZ cones (n=17) was performed. Results. At a cone height of less than 1.5 cm, both edges of the resection enter the section. With a higher cone height — 1.5—2cm — the endocervical edge of the resection can be examined by cutting and labeling it in a separate cassette. Undulating C-LETZ conization ensures excision of the crypts of the endocervix to a depth of 0.5 cm not only throughout, but also in the endocervical edge of the excision. Conclusion. The analysis of the results of a lifetime pathoanatomic examination of the surgical material of conization with a triangular loop and a wavy C-LETZ loop showed the advantages and disadvantages of each of the studied variants of organ-preserving surgery. The advantage of wavy C-LETZ conization is the deep excision of the crypts of the endocervix throughout the cone, including the endocervical edge of conization.

Endometrial adenocarcinoma with mutations in POLE, TP53 genes and microsatellite instability

The molecular classification of endometrial cancer developed by The Cancer Genome Atlas project (TCGA, 2013) is currently actively used in gynecological oncology. According to it, endometrial carcinoma is divided into four molecular subtypes: POLE-mutated, MMR deficient (dMMR), TP53-aberrant and unspecified. Endometrial cancer samples belonging to the dMMR and POLE-mutant types are characterized by specific genetic profiles reflecting the hyper- and ultramutant phenotypes of the tumor. At the same time POLE-mutated endometrial carcinomas recur rarely and exhibit the excellent prognosis. Here we report the rare case of 65 y.o. female patient with endometrioid carcinoma sharing immunohistochemical and molecular features of TP53-aberrant, MMR deficient and POLE-mutated subtypes.

Predictive markers of immunotherapy in cervical cancer

Objective. Study of PD-L1 expression in squamous and adenosquamous cell cervical cancer (CC) by immunohistochemical (IHC) method, assessment of the relationship between PD-L1 tumor status and its clinical and morphological characteristics, TILs, MSI/dMMR, and HPV tumor status. Material and methods. Surgical material was obtained from 41 patients with CC, on which the expression of PD-L1, proteins of the MMR system and p16 was studied by the IHC method, the TILs index was determined. Results. Positive PD-L1 status was found in 51.2% of the studied CC samples. In the study sample, the level of PD-L1 expression depended on the severity of lymphoid infiltration of the tumor (p=0.038), it was shown that a positive PD-L1 status of CC can be expected with a TILs value greater than or equal to 50%. The age of the patients, the histological variant of the tumor, the pT and pN stage, the presence of lymphovascular invasion, and the HPV status did not statistically significantly affect the level of PD-L1 expression, however, there was an association between the PD-L1 status and the grade of CC malignancy (p=0.027). The presence of the MSI/dMMR phenomenon was detected in a small percentage of carcinomas (4.9%), the PD-L1 status of these tumors was determined as positive. Conclusion. A positive PD-L1 status is determined in a significant number of cases of CC, regardless of most of the studied clinical and morphological characteristics; there is a statistically significant relationship between PD-L1 expression and the degree of tumor differentiation and TILs. It has been shown that CC with the MSI/dMMR phenomenon is characterized by a positive PD-L1 status. The authors consider it necessary to study the expression of PD-L1 in patients with cervical carcinomas in order to determine the possibility of prescribing personalized therapy with immune checkpoint inhibitors.

Vaginal leiomyosarcoma in pregnancy

The article presents a rare clinical observation of a vaginal tumor detected during pregnancy, which prevented delivery through the natural birth canal and caused a cesarean section at full term. According to the primary biopsy at 34 weeks, neurofibroma was diagnosed. In the postpartum period, due to profuse bloody discharge, the patient was admitted to the Moscow Regional Research Institute of Obstetrics and Gynecology for surgical treatment, where, according to the results of a morphological study of the removed tumor, vaginal leiomyosarcoma was diagnosed.

Eosinophilic cells associated with BRAF mutation in borderline serous ovarian tumors

Objective. To define the diagnostic value of eosinophilic cells for the detection of BRAF-mutated serous borderline ovarian tumors. Material and methods. The study included 42 cases of serous borderline ovarian tumor, each of which was analyzed by 3 pathologists for the presence of eosinophilic cells. Genetic profiling using Sanger sequencing was performed to identify the BRAFV600E mutation. Comparisons between two groups were performed using the Mann-Whitney test, Fisher’s exact test. Fleiss’s kappa was used to assess the interobserver agreement. To assess the diagnostic value of eosinophilic cells, sensitivity and specificity were assessed. Results. According to the results of a genetic study, the BRAFV600Emutation was found in 19 of 42 tumors. When analyzing interobserver agreement, the Fleiss’s kappa values allowed us to determine the reliability of the test as sufficient (ϰ=0.7). The sensitivity and specificity for predicting BRAFV600Emutation for eosinophilic cells were 78.9% and 91.3%, respectively. Patients with the BRAFV600E mutation were significantly younger than patients without it. Thus, the average age of patients in the group with the BRAFV600E mutation was 33.6±15.6 years, while in the group of tumors without the mutation the average age of patients was 43.9±12.7 years (p=0.002). Non-invasive implants were less frequently found in tumors with the BRAFV600E mutation compared to tumors without the mutation: 11.76% (2/17) versus 33.3% (6/18), respectively, but these differences were not statistically significant (p=0.228). Conclusion. Eosinophilic cells in ovarian serous borderline tumors may sufficiently reflect the BRAFV600E mutation, thereby correlating with disease prognosis (low risk of progression to low-grade serous carcinoma).

Sex cord tumor with annular tubules

Sex cord tumor with annular tubules is a rare type of ovarian tumor, which seems to arise from Sertoli cells. Most tumors are associated with Peutz—Jeghers syndrome and have a benign course and favorable prognosis; however, about 20% of sporadic sex cord tumors with annular tubules have a high risk of developing metastases. We present a case report about 18-year-old patient who presented with irregular menstruation and abdominal pain. Based on the histological features and immunohistochemical results, the diagnosis of a sex cord tumor with annular tubules was confirmed. The above-described ovarian tumor is rare in childhood and adolescence compared to the general population, which, combined with nonspecific clinical manifestations, can result certain diagnostic difficulties in this age group of patients.

Characteristics of the immune microenvironment of endometrial cancer depending on the MMR status of the tumor

Objective. To study the microenvironment features of MMR-proficient (pMMR) and MMR-deficient (dMMR) endometrial cancer. Material and methods. The study included 34 patients with pMMR endometrial cancer and 10 patients with dMMR endometrial cancer. Using the method of multiplex TSA-associated (tyramide signal amplification) immunofluorescence, phenotyping of the tumor microenvironment was performed with an assessment of stromal and intratumor cell localization and PD-1 expression. Results. In pMMR endometrial tumors, the predominant cell population was CD163+ macrophages, and in tumors with dMMR, CD163+ macrophages were found equally with CD8+ T lymphocytes and CD20+ B lymphocytes. In dMMR tumors, the number of CD8+ T lymphocytes and CD20+ B lymphocytes (as well as CD20+ B lymphocytes expressing PD-1) is higher compared to pMMR tumors, while the number of FoxP3+ T lymphocytes was significantly lower. The number of CD163+ macrophages did not differ depending on the MMR status, while the number of CD163+ macrophages was higher in the stroma compared to the number of these cells located intraepithelially. In patients with dMMR tumors, the number of CD8+ T lymphocytes was higher in the stroma, and did not differ in pMMR tumors. Conclusion. In this study, it was found that dMMR endometrial tumors are characterized by an increase in the proportion of CD8+ T lymphocytes and CD20+ B lymphocytes, which may be associated with a better response to immunotherapy. The differences in spatial distribution of CD8+ T lymphocytes and CD163+ macrophages confirmed the importance of immune cell localization for prognosis and treatment efficacy. These results highlight the need for further study of the endometrial cancer microenvironment in order to personalize therapy.

Predictive immunotherapeutic markers of adenocarcinomas and adenosquamous carcinoma of the cervix

Adenocarcinoma and adenosquamous carcinoma of the cervix together account for up to 20% of all cervical cancers. These histologic subtypes are characterized by a worse prognosis compared with squamous cell cancer of the same grade and have specific epidemiologic, morphologic and molecular features. Despite fundamental differences, therapeutic approaches for cervical cancer are similar regardless of tumor histology. This article discusses promising companion diagnostic markers for cervical cancer treatment, including MSI, PD-L1 and TIL’s, that may find application in the therapy of prognostically unfavorable subtypes of cervical cancer. The literature review revealed that despite the low frequency of immunotherapy markers among adenocarcinomas and adenosquamous carcinomas of the cervix, analyzing them will allow us to identify a group of patients who will benefit most from immunotherapy, a key step towards improving treatment outcomes.

Morpho-functional features of the endometrium in uterine leiomyoma before and after embolization of the uterine arteries

The question of the degree of influence of uterine artery embolization (UAE) on fertility is open. It is important to evaluate the pathomorphological structure and functional activity of the endometrium, the disruption of which can lead to infertility. Objective. To study morpho-functional changes in the endometrium of patients with uterine fibroids before and after UAE. Material and methods. 116 patients were divided into 2 groups depending on the type of the leading fibroid node: 1st — 54 patients examined with uterine fibroid (UF) types 2, 2—5, 3, 2nd — 62 patients observed with UM types 4, 5, 6. The comparison group — 30 healthy women. Aspiration biopsy of the endometrium was performed in the middle stage of the secretory phase before and 6—12 months after UAE. The percentage and maturity of pinopodes, the expression level of estrogen (ER), progesterone (PR) receptors in the glands, endometrial stroma, inflammatory markers (CD56+, CD138+) were determined. Results. The negative impact of UF on the morpho-functional state of the endometrium was determined. Changes were more pronounced in patients of 1st group. Stroma indices before and after UAE corresponded to comparison group in most patients. After UAE, the number of mature pinopodes decreased in 1st group, but not in 2nd group. ER and PR expression levels in the glandular component decreased in all patients, being consistently higher in 1st group. An increase in proinflammatory markers was observed only in 1st group. Conclusion. UF and UAE can disturb morpho-functional state of the endometrium. The impact assessment should be made taking into account the topographic and anatomical location of the myomatous node.

Morphological precursors of high-grade serous ovarian cancer

At the beginning of this century, there was a paradigm shift in understanding the histogenesis of high-grade serous carcinomas. The theory of the origin of these tumors from the ovarian surface epithelium was replaced by the concept of their origin from the secretory epithelium of the fallopian tubes. In recent years, researchers have put forward the hypothesis of the “escape” of the precursor of high-grade serous carcinomas. It allows looking at the carcinogenesis of these neoplasms as a natural history of tumor transformation of the serous epithelium without reference to a specific localization.