Corded and hyalinized endometrioid carcinoma: Summary of clinical, histological, immunohistochemical and molecular data

Corded and hyalinized endometrioid carcinoma (CHEC) represents a potential pitfall for pathologists. This study aimed to provide a complete overview of all clinicopathological and molecular features of CHEC. Electronic databases were searched for all published series of CHEC. Clinical, histological, immunohistochemical and molecular data about CHEC were extracted and pooled. Six studies with 62 patients were identified; mean age was 49.8 years (range 19–83). Most cases showed FIGO stage I (68%), low grade (87.5%), and a favorable outcome (78.4%), with “no specific molecular profile” (NSMP). A subset of cases showed high-grade features (12.5%), p53 abnormalities (11.1%) or mismatch repair (MMR) deficiency (20%) and occurred at an older age (mean age>60 years). Common features of CHEC were: superficial localization of the corded component (88.6%), squamous/morular differentiation (82.5%), nuclear β-catenin accumulation (92%), partial/total loss of CKAE1/AE3 (88.9%), estrogen receptor (95.7%) and e-cadherin (100%), stromal changes such as myxoid (38.5%), osteoid (24%) and chondroid (4.5%), CTNNB1 mutations (57.9%), and POLE-wild-type (100%); 24.4% of cases showed lymphovascular space invasion. A minority of cases (16.2%) showed poor outcome despite a low-grade, NSMP phenotype; the molecular basis for the aggressiveness of these cases is still undefined. Further studies are necessary in this field

Recent Advances in Cervical Cancer Management: A Review on Novel Prognostic Factors in Primary and Recurrent Tumors

Background: Several pathological parameters, including tumor size, depth of stromal invasion, lympho-vascular space invasion and lymph node status, have been proposed as prognostic predictors in cervical cancer. However, given the high mortality and recurrence rate of cervical cancer, novel parameters that are able to provide additional prognostic information are needed in order to allow a better prognostic stratification of cervical cancer patients. Methods: A search was conducted on PubMed to identify relevant literature data regarding prognostic factors in cervical cancer. The key words “cervical cancer”, “prognostic factors”, “pathology”, and “outcome” were used. Results: The novel pathological grading system based on tumor budding and cell nest size appeared the most relevant prognostic factor in primary neoplasms. Moreover, other potentially useful prognostic factors were tumor size, depth of stromal invasion, lympho-vascular space invasion, perineural invasion, tumor-free distance and tumor-infiltrating lymphocytes. Prognostic factors related to advanced-stage cervical cancer, including lymph-nodes status, endometrial and cervical involvement as well as distant metastases, were also taken into consideration. Conclusions: According to our findings, tumor budding and cell nest size grading system, depth of stromal invasion, lympho-vascular space invasion, perineural invasion, tumor-free distance and tumor-infiltrating lymphocytes appeared the most relevant factors included in the pathology report

hemangioma of the umbilical cord with associated amnionic inclusion cyst two uncommon entities occurring simultaneously

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Let‐7a‐5p, mir‐100‐5p, mir‐101‐3p, and mir‐199a‐3p hyperexpression as potential predictive biomarkers in early breast cancer patients

Background: The aim of this study is to identify miRNAs able to predict the outcomes in breast cancer patients after neoadjuvant chemotherapy (NAC). Patients and methods: We retrospec-tively analyzed 24 patients receiving NAC and not reaching pathologic complete response (pCR). miRNAs were analyzed using an Illumina Next‐Generation‐Sequencing (NGS) system. Results: Event‐free survival (EFS) and overall survival (OS) were significantly higher in patients with up-regulation of let‐7a‐5p (EFS p = 0.006; OS p = 0.0001), mirR‐100‐5p (EFS s p = 0.01; OS p = 0.03), miR‐ 101‐3p (EFS p = 0.05; OS p = 0.01), and miR‐199a‐3p (EFS p = 0.02; OS p = 0.01) in post‐NAC samples, independently from breast cancer subtypes. At multivariate analysis, only let‐7a‐5p was significantly associated with EFS (p = 0.009) and OS (p = 0.0008). Conclusion: Up‐regulation of the above miRNAs could represent biomarkers in breast cancer

TCGA molecular subgroups of endometrial carcinoma in ovarian endometrioid carcinoma: A quantitative systematic review

Background: Ovarian endometrioid carcinoma (OEC) shares morphological and molecular features with endometrial endometrioid carcinoma (EEC). Several studies assessed the four TCGA groups of EEC, i.e. POLE-mutated (POLEmut), mismatch repair-deficient (MMRd), no specific molecular profile (NSMP) and p53-abnormal (p53abn), in OEC; however, it is unclear whether the TCGA groups have the same distribution and clinicopathological features between OEC and EEC. Objective: To assess the distribution and clinicopathological features of the TCGA groups in OEC. Methods: A systematic review and meta-analysis was carried out by searching 7 electronic databases from January 2013 to April 2021 for studies assessing the TCGA classification in OEC. Prevalence of each TCGA group in OEC and of FIGO grade 3 and stage>I was pooled using a random-effect model. Prevalence of TCGA groups was compared between OEC and EEC, extracting EEC data from a previous meta-analysis. Kaplan-Meier and Cox regression survival analyses were performed for progression-free survival (PFS). A significant p-value<0.05 was adopted. Results: Four studies with 785 patients were included. The frequency of the TCGA groups in OEC vs EEC was: POLEmut = 5% vs 7.6% (p = 0.594); MMRd = 14.6% vs 29.2% (p < 0.001); p53abn = 14% vs 7.8% (p = 0.097); NSMP = 66.4% vs 55.4% (p = 0.002). The pooled prevalence of FIGO grade 3 was: POLEmut = 19.2%; MMRd = 18.3%; p53abn = 38.1%; NSMP = 14.5%. The pooled prevalence of FIGO stage >I was: POLEmut = 31.6%; MMRd = 42.8%; p53abn = 48.5%; NSMP = 24.6%. Two-, 5- and 10-year PFS was: POLEmut = 100%, 100%, and 100%; MMRd = 89.1%, 82.2% and 73.3%; p53abn = 61.7%, 50.2% and 39.6%; NSMP = 87.7%, 79.6% and 65.5%. The hazard ratio for disease progression (reference = NSMP) was: POLEmut = not estimable (no events); MMRd = 0.825 (p = 0.626); p53abn = 2.786 (p = 0.001). Conclusion: The prognostic value of the TCGA groups was similar between OEC and EEC, despite the differences in the frequency and pathological features of each group

Clinico-pathological significance of TCGA classification and SWI/SNF proteins expression in undifferentiated/dedifferentiated endometrial carcinoma: A possible prognostic risk stratification

Background: Undifferentiated/dedifferentiated endometrial carcinoma (UEC/DDEC) is a heterogeneous entity, which may show any of the TCGA molecular signatures and loss of the switch/sucrose nonfermentable (SWI/SNF) proteins expression. Aim: To assess the clinico-pathological significance of the TCGA molecular groups and SWI/SNF proteins expression in UEC/DDEC, through a quantitative systematic review. Methods: Electronic databases were searched for all studies assessing the TCGA molecular groups, i.e. POLE-mutant, mismatch repair-deficient (MMRd), p53-abnormal (p53abn) and no specific molecular profile (NSMP), and/or the SWI/SNF proteins (SMARCA4/BRG1, SMARCB1/INI1, ARID1B) expression in UEC/DDEC. Student t-test, Fisher's exact test and Kaplan-Meier survival analysis with long-rank test were used to assess differences among groups; a p-value<0.05 was considered significant. Results: Eight studies were included in the systematic review. Among the TCGA groups, the mean patient age was significantly higher in the p53abn group than in the NSMP group (p = 0.048). The POLE-mutant group showed advanced FIGO stage (III-IV) significantly less commonly than the NSMP (p = 0.003) and MMRd (p = 0.008) groups, and a significantly better prognosis than the NSMP (p = 0.007), MMRd (p = 0.011) and p53abn (p = 0.045) groups.The SWI/SNF-deficient cases showed a significantly worse prognosis than the SWI/SNF-intact cases (p = 0.010), while no significant differences were found regarding patient age and FIGO stage. Conclusions: Among UEC/DDEC, POLE-mutant cases show good prognosis, while SWI/SNF-deficient cases show poor prognosis. The other TCGA molecular subtypes seem to be characterized by an intermediate biological behaviour. On this account, UEC/DDEC patients might be subdivided into three risk groups based on POLE and SWI/SNF status. Further studies are necessary in this field

Endometrial carcinoma with diffuse melanocytic differentiation: Clinicopathological and molecular analysis of a case with literature review and focus on differential diagnosis

Herein, we present a clinicopathological and molecular analysis of a case of endometrial carcinoma with diffuse melanocytic differentiation with literature review. A 72-year-old woman underwent hysterectomy due to a 14 cm endometrial mass. On histology, the tumor showed a serous carcinoma component and a solid component with giant eosinophilic and dyshesive multinucleated cells. Differential diagnosis included several entities, such as undifferentiated giant cell carcinoma and carcinosarcoma with rhabdomyoblasts. The solid component showed diffuse positivity for cytokeratin AE1/AE3, Melan A, Cathepsin K and S100, focal HMB45 positivity and loss of e-cadherin. The tumor was p53-abnormal, mismatch repair-proficient and POLE-wild-type. The patient had extrauterine metastases and was alive with disease at 12 months. Previous cases of endometrial and ovarian carcinomas with melanocytic differentiation (n = 7) did not show giant bizarre cells but showed melanin production; all cases were advanced and/or had unfavorable outcomes. In conclusion, endometrial carcinomas with melanocytic differentiation are highly aggressive tumors which should be distinguished from other entities. Being aware of this entity may help not to miss it