Among the four endometrial cancer (EC) TCGA molecular groups, the MSI/hypermutated group represents an important percentage of tumors (30%), including different histotypes, and generally confers an intermediate prognosis for affected women, also providing new immunotherapeutic strategies. Immunohistochemistry for MMR proteins (MLH1, MSH2, MSH6 and PMS2) has become the optimal diagnostic MSI surrogate worldwide. This review aims to provide state-of-the-art knowledge on MMR deficiency/MSI in EC and to clarify the pathological assessment, interpretation pitfalls and reporting of MMR status.

Folate receptor alpha (FRα), a glycosylphosphatidylinositol-anchored glycoprotein encoded by the FOLR1 gene, plays a crucial role in folate transport during cell growth and development. While minimally expressed in most normal adult tissues, FRα is frequently overexpressed in several epithelial malignancies, particularly in high-grade serous ovarian carcinoma. An immunohistochemical (IHC) evaluation of FRα expression using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay is now approved as a companion diagnostic for selecting patients eligible for mirvetuximab soravtansine, an FRα-targeted antibody–drug conjugate. Clinical trials such as SORAYA and MIRASOL have demonstrated significant clinical benefit in platinum-resistant epithelial ovarian cancer patients with high FRα expression (≥75% of tumor cells with moderate to strong membrane staining). This review summarizes the biological significance of FRα in ovarian cancer progression, its predictive value for targeted therapy, and the technical aspects of IHC assessment, including scoring interpretation and pre-analytical variables. We also discuss heterogeneity in FRα expression across histological subtypes and tumor sites, as well as the impact of archival versus fresh tissue. Understanding FRα expression patterns across histologic subtypes and tissue samples is critical for optimizing clinical decision-making and expanding the role of FRα-targeted therapies in gynecologic oncology.

(1) Background: to evaluate which factors can reduce the upgrade rate of atypical ductal hyperplasia (ADH) to in situ or invasive carcinoma in patients who underwent vacuum-assisted breast biopsy (VABB) and subsequent surgical excision. (2) Methods: 2955 VABBs were reviewed; 141 patients with a diagnosis of ADH were selected for subsequent surgical excision. The association between patients’ characteristics and the upgrade rate to breast cancer was evaluated in both univariate and multivariate analyses. (3) Results: the upgrade rates to ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) were, respectively, 29.1% and 7.8%. The pooled upgrade rate to DCIS or IC was statistically lower at univariate analysis, considering the following parameters: complete removal of the lesion (p-value < 0.001); BIRADS ≤ 4a (p-value < 0.001); size of the lesion ≤15 mm (p-value: 0.002); age of the patients <50 years (p-value: 0.035). (4) Conclusions: the overall upgrade rate of ADH to DCIS or IC is high and, as already known, surgery should be recommended. However, ADH cases should always be discussed in multidisciplinary meetings: some parameters appear to be related to a lower upgrade rate. Patients presenting these parameters could be strictly followed up to avoid overtreatment.

In locally advanced cervical cancer (LACC), definitive chemo-radiotherapy is the standard treatment, but chemo-radiotherapy followed by surgery could be an alternative choice in selected patients. We enrolled 244 patients affected by LACC and treated with CT-RT followed by surgery in order to assess the prognostic role of the histological response using the Mandard scoring system. Results: A complete pathological response (TRG 0) was observed in 118 patients (48.4%), rare residual cancer cells (TRG2) were found in 49 cases (20.1%), increased number of cancer cells but fibrosis still predominating (TRG3) in 35 cases (14.3%), and 42 (17.2%) were classified as non-responders (TRG4–5). TRG was significantly associated with both OS (p < 0.001) and PFS (p < 0.001). The survival curves highlighted two main prognostic groups: TRG1-TRG2 and TRG3-TRG4–5. Main responders (TRG1–2) showed a 92% 5-year overall survival (5y-OS) and a 75% 5-year disease free survival (5y-DFS). Minor or no responders showed a 48% 5y-OS and a 39% 5y-DFS. The two-tiered TRG was independently associated with both DFS and OS in Cox regression analysis. Conclusion. We showed that Mandard TRG is an independent prognostic factor in post-CT/RT LACC, with potential benefits in defining post-treatment adjuvant therapy.

The presence of stromal osteoclast-like giant cells is a distinctive feature of some rare breast tumors, accounting for less than 1% of all breast cancer cases. Although the presence of stromal osteoclast-like giant cells may be encountered in different breast tumors, some authors still describe them as a specific tumor type. Usually, a histological diagnosis of breast carcinoma is made by a pathologist through a biopsy, which is then confirmed through a surgical specimen: it is rare for the two to differ, particularly when there are pathognomonic morphological markers, such as osteoclast-like giant cells. Herein, we report a case of a 45-year-old pre-menopausal woman, who was found to have a single solid mass in her right breast on screening mammogram. She underwent a core biopsy, which showed a malignant epithelial lesion arranged in tubules, glands, and papillae, intermingled with numerous stromal osteoclast-like giant cells. Therefore, a diagnosis of breast cancer with osteoclast-like giant cells was rendered. Curiously, these cells were no longer detectable in the surgical specimen.

Objectives: High-risk human papillomavirus (HPV) has been implicated in breast carcinogenesis, but its role remains controversial. Basal-like breast carcinomas (BLCs) share morphological and immunophenotypic features with HPV-related squamous cell cancers. This study aimed to detect HPV DNA in BLCs, perform genotyping, and evaluate p16 expression as a surrogate marker of HPV infection. Methods: A total of 36 formalin-fixed, paraffin-embedded basal-like breast carcinomas were studied. Additionally, 10 patients with high-grade (G3) invasive ductal carcinoma of no special type (NOS), of a different molecular subtype, were included as a control group. Immunohistochemistry for p16 was performed, followed by DNA PCR using L1-type specific primers for HPV genotyping in all cases, irrespective of p16 status. Ten high-grade invasive ductal carcinomas served as controls. Results: p16 overexpression was observed in 28/36 BLCs (77.8%). Overall, HPV DNA was detected in 11/36 BLCs (30.6%). Among p16-positive BLCs, HPV DNA was detected in 10 cases (35.7%): HPV45 in 4 cases, HPV16 in 4 cases, and HPV18 in 2 cases. One additional BLC that was p16-negative tested positive for HPV16. In the control group, HPV16 DNA was found in 4/5 p16-positive cases. No double infections were identified in the BLC cohort. Conclusions: High-risk HPV DNA (types 16, 18, and 45) is present in a substantial subset of p16-positive basal-like breast carcinomas, suggesting a possible pathogenetic role for the virus in these aggressive tumors, although causality remains to be established. However, p16 is not an absolute surrogate for HPV in breast tissue, and molecular confirmation is required. Further studies with E6/E7 mRNA assays are needed to confirm viral transcriptional activity.