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.

Evaluation and Management of Adnexal Masses in Postmenopausal Women

In the postmenopausal women, adnexal masses can have numerous etiologies. They can range from benign to neoplastic, with origins from a variety of organ systems. The diagnostic work up includes a thorough history, physical exam, as well as potential imaging and laboratory testing. There should be a low threshold for consultations with oncologists when there are cancer concerns. Specifically for gynecologic neoplasms, a referral to a gynecologic oncologist should be strongly considered. In this paper, there is particular attention to ovarian cancer given the gravity of delayed diagnosis.

Could miRNA Signatures be Useful for Predicting Uterine Sarcoma and Carcinosarcoma Prognosis and Treatment?

Changes in microRNA (miRNA) expression may lead to cancer development and/or contribute to its progression; however, their role in uterine sarcomas is poorly understood. Uterine sarcomas (US) belong to a rare class of heterogeneous tumors, representing about 1% of all gynecologic neoplasms. This study aimed to assess the expression profile of 84 cancer-related miRNAs and to evaluate their correlation with clinical pathological features. Eighty-two formalin-fixed paraffin-embedded (FFPE) samples were selected. In leiomyosarcoma (LMS), there was an association of lower cancer-specific survival (CSS) with the downregulation of miR-125a-5p and miR-10a-5p, and the upregulation of miR-196a-5p and miR-34c-5p. In carcinosarcoma (CS), lower CSS was associated with the upregulation of miR-184, and the downregulation of let-7b-5p and miR-124. In endometrial stromal sarcomas (ESS), the upregulation of miR-373-3p, miR-372-3p, and let-7b-5p, and the down-expression of let-7f-5p, miR-23-3p, and let-7b-5p were associated with lower CSS. Only miR-138-5p upregulation was associated with higher survival rates. miR-335-5p, miR-301a-3p, and miR-210-3p were more highly expressed in patients with tumor metastasis and relapse. miR-138-5p, miR-146b-5p, and miR-218-5p expression were associated with higher disease-free survival (DFS) in treated patients. These miRNAs represent potential prediction markers for prognosis and treatment response in these tumors.

Linking type 2 diabetes and gynecological cancer: an introductory overview

Type 2 diabetes (T2D) is a chronic disease with a growing prevalence and a leading cause of death in many countries. Several epidemiological studies observed an association between T2D and increased risk of many types of cancer, such as gynecologic neoplasms (endometrial, cervical, ovarian and vulvar cancer). Insulin resistance, chronic inflammation and high free ovarian steroid hormones are considered the possible mechanisms behind this complex relationship. A higher risk of endometrial cancer was observed in T2D, even though this association largely attenuated after adjusting for obesity. A clear relationship between the incidence of cervical cancer (CC) and T2D has still not be determined; however T2D might have an impact on prognosis in patients with CC. To date, studies on the association between T2D and ovarian cancer (OC) are limited. The effect of pre-existing diabetes on cancer-specific mortality has been evaluated in several studies, with less clear results. Other epidemiological and experimental studies focused on the potential role of diabetes medications, mainly metformin, in cancer development in women. The correct understanding of the link between T2D and gynecologic cancer risk and mortality is currently imperative to possibly modify screening and diagnostic-therapeutic protocols in the future.

An Unusual Coexistence of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma with Endometrioid-Type Endometrial Cancer in a 58-Year-Old Woman: A Case Study with Literature Review

Introduction: The coexistence of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with different gynecologic neoplasms is a rare phenomenon. Here, we report a case of simultaneously developed CLL/SLL with endometrioid-type uterine cancer. Case Report: A 58-year-old woman was admitted to the 2nd Department of Gynecology, Lublin Medical University, Lublin, Poland, in June 2017, where the uterine cancer was diagnosed. After the surgery, pathological examination revealed a uterine moderately differentiated adenocarcinoma of endometrioid subtype (subtype I according to Bokhman) deeply infiltrating the myometrium as well as the uterine cervix. Surprisingly, CLL/SLL was subsequently diagnosed in all removed pelvic as well as para-aortic lymph nodes. Immunohistochemical analysis showed CD45 (++), CD20 (+), CD3 (–/+), CD19 (+), CD23 (+), CD5 (+), and CD34 (+). Proliferative activity, assessed by MIB-1 proliferative index immunostaining, reached 18%. The patient was admitted to radiotherapy and chemotherapy at the Oncology Hospital, Lublin, Poland, and is still on follow-up. Conclusions: The coexistence of CLL/SLL with various gynecological malignancies, especially primary human endometrial cancer, is a rare entity. The detection of both tumors simultaneously, in general, is accidental, and the management should not be different from the situation in which malignancy appears de novo.

Evaluation of the indications for performing magnetic resonance imaging of the female pelvis at a referral center for cancer, according to the American College of Radiology criteria

Objective: To evaluate the indications for performing magnetic resonance imaging of the female pelvis at a referral center for cancer. Materials and Methods: This was a retrospective, single-center study, conducted by reviewing medical records and imaging reports. We included 1060 female patients who underwent magnetic resonance imaging of the pelvis at a cancer center between January 2013 and June 2014. The indications for performing the examination were classified according to the American College of Radiology (ACR) criteria. Results: The mean age of the patients was 52.6 ± 14.8 years, and 49.8% were perimenopausal or postmenopausal. The majority (63.9%) had a history of cancer, which was gynecologic in 29.5% and nongynecologic in 34.4%. Of the patients evaluated, 44.0% had clinical complaints, the most common being pelvic pain (in 11.5%) and bleeding (in 9.8%), and 34.7% of patients had previously had abnormal findings on ultrasound. Most (76.7%) of the patients met the criteria for undergoing magnetic resonance imaging, according to the ACR guidelines. The main indications were evaluation of tumor recurrence after surgical resection (in 25.9%); detection and staging of gynecologic neoplasms (in 23.3%); and evaluation of pelvic pain or of a mass (in 17.1%). Conclusion: In the majority of the cases evaluated, magnetic resonance imaging was clearly indicated according to the ACR criteria. The main indication was local recurrence after surgical treatment of pelvic malignancies, which is consistent with the routine protocols at cancer centers.