Çiğdem Özdemir

This report describes the exceedingly rare and undocumented coexistence of minute pulmonary meningothelial-like nodules (MPMNs) with metastatic endometrioid carcinoma in the lung. A 60-year-old female with a history of endometrioid carcinoma presented with an ill-defined soft tissue density lesion measuring 38 × 42 mm in the right upper lobe. Computed tomography showed mild narrowing of the right upper lobe bronchus. Surgical resection of the lung mass was performed. Intraoperative frozen section examination indicated a malignant epithelial neoplasm consistent with adenocarcinoma. On permanent sections, histopathological evaluation demonstrated an epithelial tumor composed of complex and cribriform glandular structures within a desmoplastic stroma, accompanied by loss of polarity and nuclear enlargement, consistent with metastatic endometrioid carcinoma. In the wedge resection specimen obtained after frozen section examination, multiple microscopic lesions were identified in the non-neoplastic lung parenchyma. These lesions consisted of bland cells with round-to-ovoid nuclei arranged in whorled patterns along the alveolar septa. Immunohistochemical analysis supported the diagnoses of metastatic endometrioid carcinoma and MPMNs, respectively. Clinicians and pathologists should remain aware of MPMNs as incidental findings to avoid misinterpretation during the staging of metastatic pulmonary malignancies.

Background/Objective: Basal cell carcinoma (BCC) is the most common cutaneous malignancy, arising from epidermal basal cells or the outer root sheath of the pilosebaceous unit. Despite its generally indolent clinical behavior, BCC exhibits substantial histopathological heterogeneity, which may reflect underlying biological differences among its subtypes. This study aimed to evaluate the expression of Wnt/β-catenin pathway components and tumor-associated markers—including COX-2, Ki-67, tryptase, CD1a, and WNT3A—across different histopathological subtypes of BCC. Methods: This retrospective cross-sectional study included 100 formalin-fixed paraffin-embedded (FFPE) BCC specimens retrieved between January 2006 and September 2015. After the exclusion of three cases due to inadequate tissue quality, the tumors were classified into nodular (n = 60), infiltrative (n = 16), superficial (n = 9), and other subtypes (n = 12). The immunohistochemical expressions of COX-2, Ki-67, CD1a, intratumoral and peritumoral tryptase, β-catenin, and WNT3A were assessed and compared among the BCC subtypes. Results: No significant differences were observed among the BCC subtypes regarding age or sex distribution. The expression levels of COX-2, Ki-67, CD1a, and mast cell-associated markers (intratumoral and peritumoral tryptase) did not differ significantly among the groups (all p > 0.05). Conversely, β-catenin expression was significantly higher in the infiltrative subtype compared with the other histological variants (p = 0.001). WNT3A immunoexpression was uniformly negative across all evaluated cases. Conclusions: Most of the evaluated immunohistochemical markers did not differentiate among the BCC subtypes. However, the significantly increased β-catenin expression observed in the infiltrative subtype suggests a potential association with tumor growth patterns rather than serving as a specific discriminative marker, thereby highlighting the biological heterogeneity of BCC. Although WNT3A expression was uniformly negative in all cases, this finding should be interpreted cautiously and does not allow for definitive conclusions regarding its role in Wnt pathway activation. Overall, these results support the need for further investigation into the Wnt/β-catenin pathway heterogeneity in BCC.

Background and Objectives: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers and remains a leading cause of cancer-related mortality worldwide. EGFR-targeted tyrosine kinase inhibitors (TKIs) have substantially improved outcomes in EGFR-mutant NSCLC; however, primary and acquired resistance continues to limit their long-term efficacy. HER3 (receptor tyrosine-protein kinase ErbB3), a member of the ErbB receptor family, has been implicated in TKI resistance through heterodimerization with EGFR and HER2, leading to downstream PI3K/AKT pathway activation. Despite its biological plausibility as a resistance mediator, the clinical significance of HER3 expression as a prognostic and predictive biomarker in EGFR-mutant NSCLC has not been thoroughly characterized in real-world cohorts. Materials and Methods: This retrospective, single-center study included 52 patients diagnosed with EGFR-mutant NSCLC who received TKI therapy at Afyonkarahisar Health Sciences University between January 2011 and September 2023. HER3 protein expression was evaluated by immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tumor tissue sections using the Huabio anti-HER3 antibody (clone PD00-44, 1:2000 dilution). Staining in more than 30% of tumor cells was considered HER3-positive; membranous staining intensity was scored on a 1–3 scale. Progression-free survival (PFS1, PFS2) and overall survival (OS) were analyzed using the Kaplan–Meier method and log-rank test. Statistical significance was set at p < 0.05. Results: Of 52 patients (55.8% female; mean age 64.5 years), 59.6% received chemotherapy and 40.4% received an EGFR TKI as first-line treatment; erlotinib constituted 71.2% of targeted therapies. In the first-line TKI group, HER3-negative patients had a numerically longer median PFS1 compared with HER3-positive patients (14.0 vs. 7.1 months; p = 0.285); however, this difference did not reach statistical significance and should be interpreted with caution given the small sample size. In contrast, among patients receiving first-line chemotherapy, HER3 staining status did not meaningfully affect PFS1 (4.1 vs. 2.5 months; p = 0.063). In second-line treatment, HER3-positive patients who received TKI after prior chemotherapy demonstrated a PFS2 comparable to or slightly exceeding that of HER3-negative patients (21.8 vs. 19.8 months; p = 0.49), suggesting that the sequencing of chemotherapy before TKI may attenuate the adverse effect of HER3 positivity. Median OS was 15.1 months in HER3-negative patients and 12.7 months in HER3-positive patients (p = 0.824); this numerical difference of approximately 3 months did not reach statistical significance and should therefore be interpreted cautiously. Among patients receiving TKI in the first line, HER3-positive patients had a shorter median OS than HER3-negative patients (9.6 vs. 14.2 months), whereas those receiving TKI in the second line showed a trend toward longer OS in HER3-positive patients (20.5 vs. 17.2 months). Conclusions: HER3 expression was associated with reduced first-line TKI efficacy in EGFR-mutant NSCLC, suggesting a possible role for HER3 in primary TKI resistance; however, these findings are exploratory and did not reach statistical significance. The observation that HER3-positive patients who received chemotherapy before TKI demonstrated outcomes comparable to HER3-negative patients raises the hypothesis that treatment sequencing may potentially influence the impact of HER3 positivity, though this requires prospective validation before any clinical conclusions can be drawn. These results suggest that HER3 expression may warrant further investigation as a candidate biomarker for treatment sequencing decisions and as a potential therapeutic target in EGFR-mutant NSCLC. Prospective studies evaluating chemotherapy–TKI sequencing and HER3-directed agents such as patritumab deruxtecan (HER3-DXd) in HER3-positive patients are needed to confirm these preliminary observations.

OBJECTIVE: Isocitrate dehydrogenases (IDHs) are rate-limiting enzymes in the intracellular tricarboxylic acid (TCA) cycle. IDH1/2 mutation may have an oncogenic effect and has also enabled the discovery of new therapeutic approaches for treating changes caused by this mutation. Genetic alterations and changes in DNA methylation are known to contribute to the pathogenesis of endometrial cancer. Still, there is no information yet about a relationship between IDH 1 mutation and endometrial cancer. In this study, aimed to evaluate the frequency of IDH1 mutations in endometrial cancer and its effect on prognosis. MATERIAL AND METHODS: For this study, we reviewed the files of 150 patients diagnosed with endometrial cancer who were treated and monitored between January 2012 and December 2020. 104 patients had adequate tumor tissue available in the pathology laboratory. The IDH-R132H mutation was assessed using immunohistochemistry. The primary endpoints were defined as overall survival (OS) and event-free survival (EFS). RESULTS: The study included 104 patients diagnosed with endometrial cancer. The patients expressing mutant IDH had a significantly higher rate of stage 4 disease (p=0.008), distant metastasis (p=0.034), and recurrence (p=0.037). The 3-year and 5-year event-free survival rates were significantly shorter in this group, with a p-value of 0.044. CONCLUSIONS: This is the first study showing that the IDH1-R132H mutation can be detected in patients with endometrial cancer. Our findings indicate that this mutation is a poor prognostic factor for these patients. We believe that the results of our study will form the basis of treatment studies targeting this mutation in endometrial cancer patients with the IDH1-R132H mutation.

Objective: This study aimed to analyze the demographic characteristics, clinical preliminary diagnoses, biopsy indications, and histopathological findings of adult bone marrow biopsies to construct a framework that aids clinicians and pathologists in evaluating bone marrow biopsy results. Materials and Methods: Bone marrow biopsy reports from 900 cases referred to the Department of Internal Diseases Hematology at Afyonkarahisar Health Sciences University from January 1, 2017, to December 31, 2021, were retrospectively analyzed. Patients with insufficient material (18) and those sent for treatment response evaluation (184) were excluded, resulting in 698 patients being included in the study. Data analysis was performed using SPSS v26, employing the McNemar test to assess clinicopathological concordance, with a significance level set at p< 0.05. Results: Of the 698 patients analyzed, 388 (55.6%) were male and 310 (44.4%) were female, with ages ranging from 18 to 87 years. The most common indications for biopsy were lymphoma (16.09%), pancytopenia (16.05%), and anemia with a high sedimentation rate (14.06%). The most frequently noted preliminary diagnosis was myeloma (22.02%), followed by lymphoma (16.09%) and acute leukemia (10.03%). Significant clinicopathological concordance was observed in diagnoses such as aplastic anemia and lymphoplasmacytic lymphoma, whereas discordance was noted in conditions such as follicular lymphoma and acute myeloid leukemia (AML), reflecting the complexity and challenge of accurate diagnosis in hematologic conditions. Conclusion: This study documented a high incidence of lymphoma and myeloma as preliminary diagnoses, with myeloma confirmed in 52% of cases with an initial suspicion based on clinical presentation. Notable discrepancies between clinical suspicion and histopathological findings were evident in conditions such as follicular lymphoma and acute myeloid leukemia (AML), with a significant discordance rate. These findings highlight the need for enhanced diagnostic precision and the development of sophisticated diagnostic algorithms to improve the predictive accuracy of preliminary clinical diagnoses. Ultimately, this study calls for a refined approach to the clinical and pathological evaluation of bone marrow biopsies to better support therapeutic decision making and patient management.

There are conflicting data regarding the prognostic effect of microvascular density (MVD) in breast cancer and its molecular subtypes. It is thought that high levels of FOXP3 + T cells in breast cancer are associated with poor prognosis. However, data regarding FOXP3 show significant variability in the literature. In our study, we aim to measure MVD and FOXP3 + T cells in breast cancer cases and investigate their relationship with each other and their effects on breast cancer patients’ clinical and prognostic features. In our study, the results of 207 female breast cancer patients whose excisional tumoral tissue was obtained are presented. The study evaluated the findings under a light microscope using antibodies against CD34 for measuring MVD and FOXP3 for measuring FOXP3-positive T cells. CD34 ≥ 17 was categorized as high MVD, and CD34 < 17 was classified as low MVD. FOXP3 + cell count ≥ 20/mm2 was categorized as high FOXP3 positivity and < 20/mm2 as low FOXP3 positivity. The SPSS program (version 22) was used to evaluate the results statistically, and p < 0.05 was considered significant. The median age was 54.0 (27–86) years, and the median follow-up period was 60.0 (IQR: 42.6–86.5) months. In the high MVD group, a higher progesterone receptor (PR) positivity rate was detected (p = 0.035). High FOXP3 positivity was significantly associated with high nuclear grade (p = 0.003). High FOXP3 positivity was significantly associated with PR negativity and high Ki67 values ​​(p = 0.009, p = 0.012, respectively). No statistically significant correlation was found between MVD elevation and FOXP3 positivity (r = 0.063, p = 0.36). A weakly significant positive correlation was detected between high Ki67 and FOXP3 positivity (r = 0.0146, p = 0.04). A weak inverse correlation was detected between high FOXP3 positivity and PR percentage values ​​(r=-0.182, p = 0.01). While there was no significant difference in disease-free survival in cases with high MVD and high FOXP3 + T cells compared to groups with low levels, the results were not mature enough because the median values ​​in overall survival could not be reached. A significant correlation was found between high FOXP3 positivity and some aggressive tumor features; no effect on survival was detected. In contrast to literature data on luminal A breast cancer, high MVD in the luminal B (HER2-) subgroup was associated with a lower risk of recurrence. Our study is the first in the literature to evaluate the relationship between MVD measured using CD34 and FOXP3 positive T cells in breast cancer. Our study found no correlation between MVD and FOXP3 positivity, while literature data show significant correlations in some other cancers.

Objective: Tumor protein 53 (p53), were included in the new FIGO 2023 staging system. Tumor protein 53 (p53) was incorporated into the new FIGO 2023 staging system. This study aimed to assess recurrence rates, overall survival (OS), and progression-free survival (PFS) in endometrial cancer patients with p53 mutations treated in the radiation oncology clinic. Material and Method: 260 patients were included in the study. The patients were divided into 2 groups according to the p53 mutation: p53 abnormal (p53 mutant) and p53 wild type. The Kaplan-Meier method was used to evaluate OS and PFS. Survival rates; were compared in terms of p53 mutations. Patients who underwent surgery for EC between January 1, 2008, and January 1, 2023, were included if their postoperative pathology reports evaluated p53 mutations, and they were referred to the radiation oncology clinic. Results: In our study; OS of EC was 84.2%, PFS was 88.8%. Total of 29 patients (%11.2) with recurrence were detected in the follow-up of the patients. The OS of p53 wild type patients was 88.6% and p53 mutant patients was 61% (p

Background: To emphasize the effect of molecular markers on prognosis in endometrial cancer, in addition to the International Federation of Gynecology and Obstetrics (FIGO) 2009 classification. Methods: The records of 160 patients with endometrial cancer between 2008 and 2022 were retrospectively reviewed. Staging was done according to FIGO 2009 criteria. Patients were divided into 4 groups according to molecular classification. If one had polymerase epsilon (POLE) mutation, the patient was included in POLE ultramutated (POLEmut) group. In case of intakt POLE, but abnormal staining of mismatch repair (MMR), the group was diagnosed as mismatch repair defciency (MMRd). If there was only p53 abnormal results detected, that group was p53-abnormal (p53mut). If no mutation at all, that group was categorized as non-specific molecular profile (NSMP). The Kaplan-Meier method was used to evaluate overall survival and progression-free survival. Survival rates were compared for molecular markers. Results: According to the molecular analysis, 4 patients (2.5%) were classifed as POLEmut group, 53 patients (33.1%) in the MMRd group, 18 patients (11.3%) had p53mut, and 85 patients (53.1%) into the NSMP group. 5-year overall survival was 79.4%, 5-year progression-free survival was 90%. 5-year overall survival was 75% in POLEmut group, 84.9% in MMRd group, 38.9% in p53mut group and 84.7% in NSMP group (p = 0.001). 5-year progression-free survival was 100% in POLEmut group, 96.2% in MMRd group, 77.8% in p53mut group and 88.2% in NSMP group (p = 0.082). Conclusion: Our study shows the prognostic value of the molecular endometrial cancer classification. Patients with p53mut have a poor progression-free survival, POLEmut endometrial cancer have a good prognosis. In this study, we wanted to demonstrate the importance of molecular markers in endometrium cancer and their contribution to prognosis.