The differences between pure and mixed invasive micropapillary breast cancer: the epithelial-mesenchymal transition molecules and prognosis.

PURPOSE: Invasive micropapillary carcinoma (IMPC) of the breast is known for its high metastatic potential, but the definition of pure and mixed IMPC remains unclear. This retrospective cohort study aims to investigate the prognostic significance of the micropapillary component ratio and the expression of critical molecules of epithelial-mesenchymal transition (EMT), including E-cadherin (E-cad), N-cadherin (N-cad), CD44s, and ß-catenin (ß-cat), in distinguishing between pure and mixed IMPCs. METHODS: We analyzed 100 cases of locally advanced IMPC between 2000 and 2018 and excluded patients who received neoadjuvant chemotherapy. Pure IMPC was defined as having a micropapillary component of over 90%. A comprehensive recording of prognostic parameters was conducted. The IMPC areas were analyzed using the immunohistochemical (IHC) staining method on the microarray set for pure and mixed IMPC patients. Pearson's chi-square, Fisher's exact tests, Kaplan-Meier analysis, and Cox proportional hazards analysis were employed. RESULTS: The comparative survival analysis of the entire group, based on overall survival (OS) and disease-free survival (DFS), revealed no significant difference between the pure and mixed groups (P = 0.480, HR = 1.474 [0.502-4.325] and P = 0.390, HR = 1.587 [0.550-4.640], respectively). However, in the pure IMPC group, certain factors were found to be associated with a higher risk of short survival. These factors included skin involvement (P = 0.050), pT3&4 category (P = 0.006), a ratio of intraductal component (> 5%) (P = 0.032), and high-level expression of N-cad (P = 0.020). Notably, none of the risk factors identified for short OS in pure IMPC cases were observed as significant risks in mixed cases and vice versa. Furthermore, N-cad was identified as a poor prognostic marker for OS in pure IMPCs (P = 0.002). CONCLUSION: The selection of a 90% ratio for classifying pure IMPCs revealed significant differences in certain molecular and prognostic parameters between pure and mixed groups. Notably, the involvement of N-cadherin in the epithelial-mesenchymal transition (EMT) process provided crucial insights for predicting OS and DFS while also distinguishing between the two groups. These findings strongly support the notion that the pure IMPC subgroup represents a distinct entity characterized by unique molecular characteristics and behavioral patterns.

Cardiac Inflammatory Myofibroblastic Tumor Causing Pulmonary Artery Obstruction: A Rare Case Report.

Inflammatory myofibroblastic tumor (IMT) is a rare soft tissue tumor of the heart. In the literature, cardiac IMT is often described as an endocardial-based cavitary mass originating from the right side of the heart in infants and adolescents. In this article, we present a 5-year-old boy with a rare cardiac IMT who had no complaints and was diagnosed with murmur during his routine examination. Transthoracic echocardiography showed a homogeneous polypoid mass originating from the pulmonary valve, extending into the main pulmonary artery during systole and causing obstruction of the pulmonary artery and right ventricular outflow tract. Surgical resection of the tumor was performed successfully. There was no tumor recurrence in the control echocardiography at the postoperative first month.

BRAF V600E Mutation: A Significant Biomarker for Prediction of Disease Relapse in Pediatric Langerhans Cell Histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare disease presenting with usually a localized disease but sometimes a widespread aggressive disorder especially in children. Among the somatic mutations in RAF-MEK-ERK pathway, especially BRAF mutation has been detected so far in LCH. We aimed in this study to investigate the prognostic significance of the mutations of target genes playing a role in the RAF-MEK-ERK pathway in pediatric LCH. Mutation analyses were performed on tumor DNA extracted from formalin-fixed paraffin-embedded biopsy specimens of 38 pediatric LCH cases using a direct sequencing technique for BRAF, ARAF, MAP2K1, and MAP3K1 genes. The mutational status was correlated statistically with survival, clinical progression (disease relapse), and the established clinical prognostic parameters of LCH such as age, gender, localization, multisystem disease, central nervous system risk lesions, and risk organ or special-site involvement. BRAF V600E mutation was detected in 14 cases (36.8%), whereas ARAF mutation was found in only 1 case. No mutations were identified for MAP2K1 and MAP3K1 genes. The association of BRAF V600E mutation was significant in children with multisystem disease, younger age (<2 years), skin, and special organ involvement. BRAF V600E mutation was an independent predictive parameter for disease relapse. We therefore conclude that BRAF V600E mutation may be a significant marker for predicting disease progression in LCH and a candidate for targeted therapy for children with disease relapse and multisystem disease.

Comprehensive Immunohistochemical Analysis of Epithelial-Mesenchymal Transition Biomarkers in the Invasive Micropapillary Cancer of the Breast.

Background: Invasive micropapillary carcinoma (IMPC) of the breast is commonly associated with a poor prognosis due to its high incidence of lymphovascular invasion and lymph node metastasis (LNM). Our study is aimed at investigating the prognostic significance of the expressions of E-cadherin (E-cad), N-cadherin (N-cad), CD44s, and ß-catenin (ß-cat). In addition, it is aimed at deciphering the consistency of these markers between the IMPC, the invasive breast carcinoma, no-special type (IBC-NST), and LNM components in the same IMPC cases. Methods: Sixty-two IMPC cases with LNM from 1996 to 2018 were analyzed. Immunohistochemical staining was performed separately on the three regions for each patient. Statistical analyses included Kaplan-Meier, Cox regression, and McNemar's statistical tests. Results: Loss of CD44 expression in IMPC, IBC-NST, and LNM areas was associated with poor prognosis in overall survival (OS) (p = 0.010, p < 0.0005, p = 0.025). Loss of CD44 expression in the IBC-NST, gain of N-cad expression in the IMPC, and loss of ß-cat expression in the LNM areas were indicators of poor prognosis in disease-free survival (DFS) (p = 0.005, p = 0.041, p = 0.009). Conclusion: Our evaluation of this rare subtype, focusing on the expression of key epithelial-mesenchymal transition (EMT) molecules, revealed that it shares characteristics with the IBC-NST component within mixed tumors. Notably, contrary to expectations, a reduction in CD44 expression was found to adversely affect both OS and DFS. By conducting staining procedures simultaneously across three regions within the same patient, a novel approach has provided valuable insights into the mechanisms of EMT.

Platelet to lymphocyte and neutrophil to lymphocyte ratios in endometrial pathologies.

OBJECTIVES: Aim of this study was to evaluate the relationship between platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), and endometrial pathologies. MATERIAL AND METHODS: The database of our institution was reviewed. Cases with endometrial pathology including endometrial cancer (EC), endometrial hyperplasia with atypia and without atypia, normal endometrial findings, between January 2015 to January 2020, were collected. Their CBC results and clinicopathologic data were determined. The relation between the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and endometrial pathologies was evaluated. RESULTS: NLR was significantly higher in patients with endometrial cancer compared to other endometrial pathologies including endometrial hyperplasia with and without atypia and patients with normal endometrial findings. NLR cut-off value was determined 3.55 to discriminate cancer among other endometrial pathologies. PLR had not a significant difference between the endometrial pathologies. CONCLUSION: NLR seems to be an effective and simple marker to discriminate endometrial cancer among endometrial pathologies by contrast with PLR.

Evaluation of Epithelioid Trophoblastic Tumor in the Light of Literature.

Epithelioid trophoblastic tumors (ETTs) are extremely rare gestational trophoblastic neoplasia and a subtype of the placental site trophoblastic tumors (PSTTs). To our knowledge, there have been only 110 patients diagnosed with the ETT. ETT is generally seen in the reproductive period, following term pregnancy. Generally, as in PSTT, ß-HCG levels are normal or slightly elevated. The most common complaint is abnormal vaginal bleeding. At the time of diagnosis, findings of metastasis can be seen in 50% of the cases. Transvaginal ultrasonography (TV-USG) and computed tomography (CT) are used for imaging in the literature. Surgical treatment and follow-up are sufficient in the early stages. We present a case of a 37-year-old ETT patient who suffered from irregular vaginal bleeding.

Villitis of Unknown Etiology in the Placenta of a Pregnancy Complicated by COVID-19.

Villitis of unknown etiology (VUE) is noninfectious chronic villitis thought to be associated with fetal growth restriction and stillbirth. COVID-19 and the pandemic SARS-CoV-2 infection can cause an increased risk in pregnant women for potential maternal and fetal complications from an immunological mechanism. We report a 39-week-gestational-age infant delivered to a 37-year-old mother diagnosed with SARS-CoV-2 infection at 37 weeks gestation. The placental examination showed the morphological features of VUE. We showed immunohistochemically that macrophages and CD4-positive T cells predominated in the villous tissue, although elevated numbers of CD8-positive cells were also present. We hypothesize that VUE may represent a maternal anti-viral immune response, in this case to SARS-CoV-2.