Gynecologic Neoplasms Research Articles

HMGA2: A Biomarker in Gynecologic Neoplasia.

High Mobility Group A2 gene (HMGA2), an oncofetal protein, is normally expressed in fetal development and completely shuts down in almost all organs and tissue types during adulthood. It is upregulated or overexpressed again in certain mesenchymal neoplasms due to chromosomal translocations and in malignant epithelial tumors through transcription regulation. HMGA2 overexpression can either drive tumor development or promote the aggressiveness of tumor growth. Many gynecologic neoplasms, including uterine smooth muscle tumors and ovarian cancer, are associated with HMGA2 overexpression. In this article, we review recent developments in the study of HMGA2 and its expression as a potential biomarker for gynecologic neoplasms and clinic application.

The Incidence of Malignant Tumors of the Female Reproductive System in St. Petersburg

Introduction: Malignant neoplasms remain a serious sociomedical problem that requires solutions to health care optimization. In the overall structure of cancer incidence in the female population in 2018, uterine and cervical cancer ranked third (8.0 %) and fifth (5.2 %), respectively. Objective: To determine the main trends in the incidence of gynecologic cancers in Saint Petersburg, Russian Federation, and to monitor achievement of the targets of the Fight against Cancer Program. Materials and methods: To assess the prevalence and the structure of the incidence of malignant neoplasms of the female reproductive system, a comprehensive methodology was developed, which included the analysis of statistical reporting forms officially approved by the Ministry of Health of the Russian Federation for 2010–2020. Results: The prevalence of gynecologic cancers showed a steady rise. In 2011–2019, the incidence rates of cervical, uterine and ovarian cancer in St. Petersburg increased by 6.9 %, 18.2 %, and 18.5 %, respectively. The proportion of cases of the uterine body cancer was the largest (43.6 %), followed by ovarian (28.7 %) and cervical cancer (22.5 %). The shares of malignant neoplasms of other sites, including vulva, vagina and placenta, were much lower and equaled 3.9 %, 1.2 %, and 0.1 %, respectively. At the same time, the percentage of followed-up patients with stages I and II uterine cancer had grown from 74.4 % in 2011 to 79.4 % in 2020 (t = 4.9, p < 0.05) and of those with stages I and II ovarian cancer – from 32.2 % to 35.5 % (t = 3.7, p < 0.05). The one-year gynecologic cancer mortality rate in St. Petersburg decreased significantly, from 25.8 % to 20.1 % (t = 4.0, p < 0.05), while the five-year survival in 2011–2020, on the contrary, increased from 52.3 % to 57.9 %. Conclusions: Malignant tumors of the female reproductive system rank first in the structure of the annual cancer incidence. Every sixth (15.1 %) incident cancer is a gynecologic neoplasm. In 2011–2019, rising incidence rates were observed for the most common female genital tract tumors, including cervical, uterine, and ovarian cancer. It is of great concern that not all monitored indicators approved by the Fight against Cancer Program are being properly implemented in St. Petersburg.

THE USE OF ULTRASOUND GUIDED HIGH INTENSITY FOCUSED ULTRASOUND (HIFU) IN THE TREATMENT OF UTERINE FIBROIDS: AN OVERVIEW

Uterine fibroids are the most common benign gynecological neoplasms, with a higher prevalence in women aged between 30 and 50 years old. Fibroids may be asymptomatic, but in some cases, they can affect seriously the quality of life of the patients. In some cases, we can recommend expectant management for asymptomatic patients. Management depends on the size and location of fibroids, the age of the patient, symptoms, desire for future childbearing and the experience of the gynecologist. Medical therapy includes hormonal contraceptives, tranexamic acid, and nonsteroidal anti-inflammatory drugs (reduce heavy menstrual bleeding). Gonadotropin-releasing hormone agonists or selective progesterone receptor modulators are used mostly preoperatively. Surgical treatment includes hysterectomy, myomectomy – invasive and minimally invasive. Non-surgical management include uterine artery embolization, and focused ultrasound surgery.This review aims to present the role of High-Intensity Focused Ultrasound in the treatment of uterine fibroids.

Immunohistochemical evaluation of forkhead box A1 and EphA5 markers in serous ovarian carcinomas, and their impact on the clinical outcome of patients.

Ovarian cancer is the most lethal gynaecological neoplasm in females. In ovarian cancer, forkhead box A1 (FOXA1) aids transcription of YAP-associated protein mediated by the cyclic adenosine monophosphate response element-binding protein. As aresult, cellular proliferation and migration increased. The roles of erythropoietin-producing human hepatocellular carcinoma cell (Eph) receptors and ephrin ligands in cell adhesion, migration, cell proliferation regulation in various cancers, and angiogenesis are well characterized. This study included formalin-fixed, paraffin-embedded tissue specimens from 41 patients with ovarian serous cystadenocarcinoma, including both low- and high-grade tumours. For each case, aparaffin block with tumour tissue was chosen for an immunohistochemical procedure using primary antibodies against EphA5 and FOXA1. By the end of 2017, patients finished their chemotherapy and were followed for the next 3 years. Positive FOXA1 and EphA5 results were presented in 68.3% and 39% of patients, respectively. Astatistically significant correlation was detected between FOXA1 expression and each of CA-125 level, tumour stage, tumour grade, and the presence of lymph node metastasis. In our work, the overall survival was positively correlated with EphA5 expression and inversely correlated to FOXA1 immunoreactivity. The estimated disease-free survival (DFS) and EphA5 immunoreactivity had asignificant positive association, whereas DFS and FOXA1 protein expression had asignificant inverse link. FOXA1 and EphA5 expression play arole in ovarian cancer progression and prognosis prediction.

Essentiality of Trace Elements in Pregnancy, Fertility, and Gynecologic Cancers-A State-of-the-Art Review.

Gynecological neoplasms pose a serious threat to women’s health. It is estimated that in 2020, there were nearly 1.3 million new cases worldwide, from which almost 50% ended in death. The most commonly diagnosed are cervical and endometrial cancers; when it comes to infertility, it affects ~48.5 million couples worldwide and the number is continually rising. Ageing of the population, environmental factors such as dietary habits, environmental pollutants and increasing prevalence of risk factors may affect the reproductive potential in women. Therefore, in order to identify potential risk factors for these issues, attention has been drawn to trace elements. Trace mineral imbalances can be caused by a variety of causes, starting with hereditary diseases, finishing with an incorrect diet or exposure to polluted air or water. In this review, we aimed to summarize the current knowledge regarding trace elements imbalances in the case of gynecologic cancers as well as female fertility and during pregnancy.

Role of Mitochondria in Interplay between NGF/TRKA, miR-145 and Possible Therapeutic Strategies for Epithelial Ovarian Cancer.

Ovarian cancer is the most lethal gynecological neoplasm, and epithelial ovarian cancer (EOC) accounts for 90% of ovarian malignancies. The 5-year survival is less than 45%, and, unlike other types of cancer, the proportion of women who die from this disease has not improved in recent decades. Nerve growth factor (NGF) and tropomyosin kinase A (TRKA), its high-affinity receptor, play a crucial role in pathogenesis through cell proliferation, angiogenesis, invasion, and migration. NGF/TRKA increase their expression during the progression of EOC by upregulation of oncogenic proteins as vascular endothelial growth factor (VEGF) and c-Myc. Otherwise, the expression of most oncoproteins is regulated by microRNAs (miRs). Our laboratory group reported that the tumoral effect of NGF/TRKA depends on the regulation of miR-145 levels in EOC. Currently, mitochondria have been proposed as new therapeutic targets to activate the apoptotic pathway in the cancer cell. The mitochondria are involved in a myriad of functions as energy production, redox control, homeostasis of Ca+2, and cell death. We demonstrated that NGF stimulation produces an augment in the Bcl-2/BAX ratio, which supports the anti-apoptotic effects of NGF in EOC cells. The review aimed to discuss the role of mitochondria in the interplay between NGF/TRKA and miR-145 and possible therapeutic strategies that may decrease mortality due to EOC.

Trend of incidence in the last five years of breast, cervical, ovarian and uterine cancer in the main hospital in Romania

In the time of modern medicine, gynecologic cancers kill millions of people annually. Worldwide, breast cancer is the first among cancer types in terms of incidence rate. Cervical cancer continues to be a public health issue, despite all methods of prevention and early detection. Ovarian cancer is considered a "silent killer" and associates high incidence and mortality in women. The incidence of uterine cancer has increased by one percent per year in the last ten years. We analyzed the histopathological results of gynecologic neoplasms during 2016-2021, using the database of the pathological anatomy department within the Bucharest University Emergency Hospital. Breast cancer was the most common type, with an incidence of 34.86%, followed by cervix cancer - 29.44%, uterine cancer - 24.93%, and ovarian cancer - 10.76%. The proportion of each form of cancer respected the reports declared for the worldwide female population. In our opinion, all forces should orient themselves towards campaigns of correct information, promotion of prevention methods, and awareness of unfavorable prognosis.

SMARCA4-Deficient Carcinoma of Uterine Cervix Resembling SCCOHT—Case Report

Small cell carcinoma of hypercalcemic type (SCCOHT) is a rare gynaecological neoplasm, originating mostly in the ovaries. Cervical origin of this very aggressive malignancy with unknown histogenesis is an extremely rare condition, without published management recommendations. Alterations in SMARCA4 gene are supposed to play the major role in SCCOHT oncogenesis and their identification is crucial for the diagnosis. Adequate genetic counselling of the patients and their families seems to be of great importance. Optimal management and treatment approaches are not known yet but may extremely influence the prognosis of young female patients that suffer from this very resistant disease. Nowadays, a translational research seems to be the key for the further diagnostic and treatment strategies of SCCOHT. The purpose of the case report is to provide practical information and useful recommendations on the diagnosis, management, and treatment of SMARCA4-deficient carcinoma of the uterine cervix resembling SCCOHT.

A pedunculated small bowel gastrointestinal stromal tumour (GIST) masquerading as an ovarian tumour.

While gastro-intestinal stromal tumours (GIST) are the most common non-epithelial neoplasms of the gastrointestinal tract, 10% occur externally. Symptomatology is therefore broad, dependent on location. A 42-year-old female presented to the Emergency Department after 12 hours of severe right lower abdominal, preceded by vague pain over two weeks. Imaging revealed a right-sided 7.5 × 5.8 × 5.6 cm ovarian cystic lesion, suspicious for torsion. Laparoscopically, the lesion was densely adherent to small and large bowel, and she was proceeded to resection of an assumed primary ovarian neoplasm. Histopathology revealed an infarcted epithelioid GIST, high-grade with clear margins (stage pT3). There are only 24 cases of GISTs pre-operatively mistaken for gynaecological neoplasms. Additionally, there are reports of GISTs metastasizing to ovaries. Both computed tomography and ultrasound are non-specific, including hypo- and hyperechoic features. In all published cases, imaging was not able to identify presumed gynaecological neoplasms as GISTS. Differential diagnoses for pelvic masses should include non-gynaecological tumours.

Gynecologic organ involvement and incidental gynecologic organ neoplasms in female patients with urothelial carcinoma of the bladder undergoing anterior pelvic exenteration in Rajavithi Hospital

Objective: To evaluate the pathological data of the bladder and gynecologic organs obtained from anterior pelvic exenteration and review the incidence of gynecologic organ involvement and primary gynecologic tumor. Materials and Methods: The clinicopathological data of 70 patients who were diagnosed with bladder transitional cell carcinoma and underwent anterior pelvic exenteration in Rajavithi Hospital between January 2008 and October 2020 were analyzed to examine and determine any correlations. Results: Thirteen (18.5%) patients had gynecologic organ involvement. This consisted of 4 cases (5.7%) involving the uterus, 7 (10%) involving the vagina, 2 (2.8%) involving the ovaries, and 10 (14.2%) involving the cervix. Female patients with gynecologic organ invasion were more likely to have a high pathological T stage (p < 0.001), and have pre-operative hydronephrosis (p = 0.002). From multivariate logistic regression, pre-operative hydronephrosis was associated with increased risk of gynecologic organ invasion (odds ratio 9.57; 95% confidence interval, 1.86 - 49.18; p = 0.007). There were 23 (32%) female patients incidentally diagnosed with benign gynecologic tumors, specifically 16 (22%) cases of myoma uteri, 7 (10%) of adenomyosis and 4 (2.8%) with ovarian cysts. No patient was diagnosed as having primary gynecologic malignancy. Conclusions: The incidence of gynecologic organ involvement in female patients who had undergone anterior pelvic exenteration for urothelial carcinoma of the bladder was 18.5%. Pre-operative hydronephrosis was a risk factor associated with increased risk of gynecologic organ involvement. Information from this study may allow better identification of candidates for gynecologic organ sparing surgery.

Hymenialdisine is Cytotoxic Against Cisplatin-Sensitive but Not Against Cisplatin-Resistant Cell Lines.

ObjectivesNew compounds are needed to overcome the resistance to commonly used cytotoxic chemotherapy for epithelial ovarian cancer. Marine sponges are a rich source of diverse chemical compounds and hymenialdisine has been found to have antiproliferative effects. This study aimed to investigate the cytotoxic effect of hymenialdisine in cisplatin-sensitive and cisplatin resistant ovarian cancer cell lines.MethodsThis study took place at Sultan Qaboos University, Muscat, Oman between August and November, 2019. The anti-cancer effects of hymenialdisine or cisplatin were assessed using treating cells with different concentrations of hymenialdisine and cisplatin. Cell viability was determined using the AlamarBlue® Assay.ResultsThe half-maximal inhibitory concentration (IC50) of cisplatin was estimated at 31.4 μM for A2780S and 76.9 μM for A2780CP, whereas the IC50 of hymenialdisine was evaluated at 146.8 μM for A2780S cells. Despite the higher concentrations of hymenialdisine (up to 300 μM), IC50 could not be determined for the A2780CP cell line.ConclusionWhen compared to cisplatin, hymenialdisine was less toxic against both A2780S and A2780CP ovarian cancer cell lines.

Descriptive characteristics of gynecological malignant neoplasms

Background. Gynecological malignant neoplasms (GMN) are the leading disease group among female cancers.Objective: to characterize GMN in females occupationally exposed to ionizing radiation over prolonged periods.Materials and methods. The cohort considered in the study included females (n = 5689) who had been hired at the Mayak Production Association in the period between 1948 and 1982. All these females were exposed to ionizing radiation over prolonged periods during their employment. They were followed up until 31.12.2018. Two groups of females were identified in the study cohort: the one with a verified GMN (the main group) and another one free of GMN (the control group). The occupational and reproductive characteristics were analyzed for the identified groups of females, and associations of GMN with various risk factors were assessed.Results. Among GMN the uterine corpus cancer had the top position. In 70 % of the females GMN were diagnosed during a menopausal period. The females of the main group demonstrated significantly higher frequency of underlying pre-malignant conditions (endometriosis, uterine myoma, endometrial hyperplastic processes, ovarian epidermoids, menopausal bleedings) compared to the control group.Conclusion. Studies of GMN in females occupationally exposed to ionizing radiation over prolonged periods for sure are of a certain scientific and practical interest. The findings can provide the basis for specialized cancer care for employees of the nuclear industry.

Robotic surgery - prevention of the risk of cytokine storm in women with endometrial cancer

Abstract Background Endometrial carcinoma is frequently diagnosed gynecologic neoplasm all over the world. Most often, women aged between 50 and 70 are affected by it. One third of the diagnosed patients pertain to a younger age group. The data of Bulgarian National Cancer Registry show that uterine body cancer accounts for 8,3% of all oncologic diseases of women. Methods 97 women with endometrial carcinoma, Ist stage, with clarified diagnosis for one year (2020) and already operated in UMHAT “Dr.G.Stranski”- Pleven, have been tested. 62 of these patients had undergone robotic surgery and 35 - conventional surgery. The immunologic parameters were tested before the surgical intervention, at the 3rd hour and on the 3rd day via Human ELISA-Diaclone. Statistic processing is with STATGRAF. Results The comparative survey between the robotic surgery patients and open surgery patients demonstrated that in the early post-operation period the open surgery patients had considerably increased serum cytokine level compared to the robotic surgery patients. The minimal invasive surgery demonstrates a reduced acute-phase response and a better preservation of cellular immune mechanisms compared to the open surgery. Conclusions The acceptance and implementation of mini-invasive surgical system Da Vinci in Bulgaria for treatment of endometrial carcinoma (Ist stage) reduces the cytokine explosion, decreases the post-surgical risk as well as the reanimation care days and hospital stay. Psychological stress and hospitalization time are reduced, quality of life is improved. Key messages Surveying the robotic surgery role in the treatment of women with endometrial carcinoma, Its stage via cytokine profile determination. Through Da Vinci, the hemorrhage and post-surgical complications are minimal, the psychological stress and hospital stay are reduced, the treatment cost is diminished and life quality is improved.

A pictorial review of ultrasonography of the FIGO classification for uterine leiomyomas.

Uterine leiomyomas are the most common gynecological and pelvic neoplasm, reported in up to 80 percent of women by age 50. While the majority are asymptomatic, uterine leiomyomas, depending on size, number, and location can result in bulk symptoms, abnormal uterine bleeding (AUB), infertility or recurrent pregnancy loss. Ultrasonography (USG) remains first-line for the diagnosis of leiomyomas and is the most appropriate imaging modality for the initial assessment of abnormal uterine bleeding. In an effort to standardize nomenclature and identify causes of AUB, the International Federation of Gynecology and Obstetrics (FIGO) developed a classification system based on the acronym PALM-COEIN (polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic; and not yet classified). For the L category of leiomyoma, when present, a secondary and tertiary subclassification system is described distinguishing submucosal masses from others and categorizing the relationship of the mass to the endometrium and serosa. With advancements in newer minimally to non-invasive techniques developed for the management of leiomyomas, uniform characterization, mapping, and classification of leiomyomas is necessary to decide the optimal therapeutic approach. While this classification system has recently been reviewed on MR, to our knowledge, it has not been reviewed on ultrasound in the radiology literature. We hereby present a pictorial review of USG images of all the FIGO categories of leiomyomas to provide a standard guide for radiology reporting.

Purified Vitexin Compound 1 Serves as a Promising Antineoplastic Agent in Ovarian Cancer.

Ovarian cancer is a common gynecologic aggressive neoplasm. The mortality of ovarian cancer is top among gynecologic malignancies due to the insidious onset, atypical early symptoms, and chemoresistance. Therefore, it is urgent to seek another promising treatment for ovarian cancer. Purified vitexin compound 1 (VB1) is a kind of neolignan from the seed of traditional Chinese herb vitex negundo that possessed diverse pharmacological effects. VB1 can exhibit anti-neoplastic activities against various cancers. However, the role of VB1 in ovarian cancer treatment has not been elaborated, and the mechanism is unknown. The aim of this study was to investigate the therapeutic effects of VB1 in ovarian cancer cells both in vitro and in vivo, along with the molecular mechanism of action. In vitro, VB-1 can effectively suppress the proliferation, induce apoptosis, and block cell cycle at G2/M phase with a concentration dependent manner in ovarian cancer cells. Western blot assay showed that VB1 induce apoptosis via upregulating expression of cleaved-caspase3 and block cell cycle at G2/M phase through upregulating expression of P21. Meanwhile, VB1 can effectively inhibit tumor growth in xenograft mouse model. Our research indicated that VB1 can significantly exert its anti-neoplastic effects and may represent a new class of agents in ovarian cancer therapy.

Incidental Gonadal Vein Thrombosis Diagnosed Using Computed Tomography Imaging: A Single-Center, Retrospective, Cohort Study.

ObjectivesGonadal vein thrombosis is an uncommon but serious condition that can be fatal if it goes unnoticed. Up to 80% of cases occur in patients after delivery, hysterectomy, or lymphadenectomy for gynecological neoplasms. The objective of this study was to determine the incidence of gonadal vein thrombosis using computed tomography (CT) imaging at our center and to describe associated risk factors.MethodsA retrospective, single-center, observational study was conducted at King Abdulaziz Medical City in Jeddah, Saudi Arabia. Data were collected for all patients diagnosed with incidental gonadal-vein-thrombosis using contrast-enhanced computed tomography imaging of the abdomen and pelvis between January 2005 and December 2017. We included all patients with incidental findings of gonadal vein thrombosis and excluded those with incomplete data.ResultsIn total, 58/68,268 (0.08%) patients were included. Fifty-seven patients were females, and only one was male. The mean age (years) of the patients was 50.0±15.0 (range 4-87). Thirty-four patients (59%) had right gonadal vein thrombosis, 20 (34%) had thrombosis on the left side, and four (7%) had bilateral thrombosis. Nineteen patients (33%) had undergone pelvic surgery previously. Forty-four patients (76%) had a malignancy at the time of diagnosis. Forty-two patients (72%) were treated with anticoagulants after the diagnosis.ConclusionGonadal vein thrombosis is a rare clinical entity with vague clinical presentation. The incidence in the oncology population is similar to the reported incidence in the obstetric population. Initiation of anticoagulation therapy is important to treat this condition and limit complications.

Antiproliferative and antimetastatic characterization of an exo-heterocyclic androstane derivative against human breast cancer cell lines

Cancer in general, and specifically gynaecological neoplasms, represents a major public health issue worldwide. Based on the effect of sex hormones on breast tumorigenesis and prognosis, as well as on the development of breast cancer metastases, modification of the steroid skeleton is a hotspot of research for novel anticancer agents. Numerous recent studies support that minor modifications of the androstane skeleton yield potent antiproliferative and antimetastatic drug candidates. The aim of the present study was to assess the antitumor and antimetastatic properties, as well as the mechanism of action of a D-ring-modified exo-heterocyclic androstadiene derivative named 17APAD. The test compound was found to be highly selective towards human breast cancer-derived cell lines (MCF-7, T47D, MDA-MB-361, MDA-MB-231) compared to non-cancerous fibroblast cells (NIH/3T3), and exerted superior effect compared to the clinically applied reference drug cisplatin. Changes in MCF-7- and MDA-MB-231 cell morphology and membrane integrity induced by the test substance were assessed by fluorescent double staining. Cell cycle disturbances were analyzed by flow cytometry, and concentration-dependent alterations were detected on breast cancer cell lines. Mitochondrial apoptosis induced by the test compound was demonstrated by JC-1 staining. Inhibitory effects on metastasis formation, including the inhibition of migration, invasion and intravasation were investigated in 2D and 3D models. Significant anti-migratory and anti-invasive effects on MCF-7 and MDA-MB-231 cells were detected after 24 h exposure in 2D wound healing and Boyden-chamber assays. The anti-intravasative properties of 17APAD were evident after 4 h of incubation in a co-culture 3D circular chemorepellent-induced defects (CCID) assay, and the level of inhibition at concentrations ≥2 µM was comparable to that exerted by the focal adhesion kinase inhibitor defactinib. Single cell mass cytometry revealed that chemosensitive subpopulations of MDA-MB-231 cells engaged to apoptosis were less positive for EGFR, CD274, and CD326, while the percentage of cells positive for GLUT1, MCT4, Pan-Keratin, CD66(a,c,e), Galectin-3 and TMEM45A increased in response to 17APAD treatment. Finally, the novel androstane analogue 17APAD had an outstanding inhibitory effect on tumour growth in the 4T1 orthotopic murine breast cancer model in vivo after 2 weeks of intraperitoneal administration. These findings support that substitution of the androsta-5,16-diene framework with a N-containing heterocyclic moiety at C17 position yields a molecular entity rational to be considered for design and synthesis of novel, effective antitumor agents, and 17APAD is worth further investigation as a promising anticancer drug candidate.

Clinicopathologic characteristics of appendiceal mucinous tumor misdiagnosed as gynecological neoplasms

Objective: To explore the clinicopathologic features and prognosis of female appendiceal mucinous tumor misdiagnosed as gynecological neoplasm. Methods: The clinical data of 12 cases of suspected gynecological neoplasm but confirmed as appendiceal mucinous tumor by operation and pathology in Beijing Obstetrics and Gynecology Hospital hospital from 2010 to 2019 were collected. The clinicopathologic features, treatment and prognosis of these patients were analyzed. Results: The median age of 12 patients was 58 years old and the clinical manifestations were atypical, including 5 cases with gastrointestinal symptoms, 6 cases with touched lesion in the right adnexal area, 3 cases with pseudomyxoma of peritonei, and 4 cases with increased serological tumor markers and ascites. Before operation, ultrasonic diagnosis showed cystic or cystic-solid mass in the right adnexal region in all cases. Pelvic and abdominal enhanced CT and/or enhanced MRI were performed in 5 cases. Two cases indicated possible origin of appendix and 1 case indicated lymphatic cystic tumor. Laparoscopic or laparotomy exploration was performed in all patients, during the operation 7 cases were performed appendectomy, 4 cases were performed tumor cell reduction and 1 case was treated in another hospital after laparotomy exploration. Eleven cases were diagnosed as low-grade appendiceal mucinous tumor and 1 case as appendiceal mucinous adenocarcinoma by postoperative pathology. Among the 11 patients with low-grade appendiceal mucinous tumor, 9 cases had no recurrence, 1 case lost follow-up, 1 case died of breast cancer and 1 case died 18 months after the operation. Conclusions: Gynecologists should improve their ability to differentiate appendiceal mucinous tumor from gynecological neoplasm. They can include ultrasonic diagnosis and CT scanning into their preoperative physical examination to improve their examination ability, and strive for specialist or surgical treatment to achieve the best result.

Neuroendocrine tumor (NET) of the vagina in the light of WHO 2020 2-tiered grading system: clinicopathological report of the first described case.

Up to now, a vaginal well-differentiated neuroendocrine tumor (NET) has never been well described in the literature. A 2-cm vaginal nodule morphologically revealed a proliferation of mild to moderately atypical eosinophilic epithelioid cells, without tumor cell necrosis. Immunohistochemistry (IHC) showed positivity for CK (AE1/AE3), chromogranin A, and synaptophysin, focal positivity for CDX2, and negativity for PAX8 and TTF1. Metastatic origin was excluded by imaging and the morphological context with benign mucinous glands as present in the surgical resection specimen. Considering mitotic index and Mib1/Ki67 (8 mitoses/2 mm2; >20%), the case was diagnosed as vaginal NET G2 in the light of the WHO 2020 grading system for the gynecologic neuroendocrine neoplasms (NENs). Ranges of Mib1-Ki67 are not yet standardized. Currently, mitotic index and tumor cell necrosis were taken into consideration for the grading system. Gynecologic NENs still represent a diagnostic challenge. A clinico-radiologic workup and an appropriate diagnostic path ruling out the metastatic nature are mandatory to achieve the diagnosis.

An Emerging Anti-p16 Antibody-BC42 Clone as an Alternative to the Current E6H4 for Use in the Female Genital Tract Pathological Diagnosis: Our Experience and a Review on p16ink4a Functional Significance, Role in Daily-Practice Diagnosis, Prognostic Potential, and Technical Pitfalls.

Background: To date, useful diagnostic applications of p16 IHC have been documented in gynecological pathology both for HPV-related and non-HPV-related lesions. In the present article, we reported our experience with the novel anti-p16 INK4a antibody (clone BC42), whose expression was tested across all different gynecologic neoplasms; we also compared it to the traditional E6H4 clone. Moreover, we discussed and explored all the diagnostic applications of p16 IHC in gynecologic pathology. Methods: Consultation cases covering a 5-year period (2016–2020) regarding gynecological neoplastic and non-neoplastic lesions in which immunohistochemistry for p16, clone E6H4 was originally performed, were retrospectively retrieved from the files of our institution. Immunohistochemical staining for p16ink4a (BC42) [Biocare Medical group-Paceco USA; Bioptica Milan] and p16ink4a (E6H4) [Ventana Medical Systems-Arizona USA; Roche] was performed by using the Ventana automated immunostainer (Ventana Medical Systems, Tucson, AZ, USA). The immunostaining pattern was defined as negative, focal/patchy, or diffuse. Results: A total of 196 cases, represented by 36 high-grade SIL/CIN3 of the uterine cervix, 30 cervical adenocarcinomas, 22 cervical squamous cell carcinoma, 70 endometrial carcinomas, 25 high grade serous ovarian carcinomas, 6 uterine adenomatoid tumors, and 10 uterine leiomyosarcomas were included in this study. Results showed concordant staining quality of both clones on all tested neoplastic tissues. Conclusions: The novel anti-p16 antibody (BC42 clone) appeared as an alternative to the current E6H4 for use in gynecological neoplasms, offering similar levels of positivity and equally reliable staining results.