A Model to Predict Upstaging to Invasive Carcinoma in Patients Preoperatively Diagnosed with Low-Grade Ductal Carcinoma In Situ of the Breast

Background: We aimed to create a model of radiological and pathological criteria able to predict the upgrade rate of low-grade ductal carcinoma in situ (DCIS) to invasive carcinoma, in patients undergoing vacuum-assisted breast biopsy (VABB) and subsequent surgical excision. Methods: A total of 3100 VABBs were retrospectively reviewed, among which we reported 295 low-grade DCIS who subsequently underwent surgery. The association between patients’ features and the upgrade rate to invasive breast cancer (IBC) was evaluated by univariate and multivariate analysis. Finally, we developed a nomogram for predicting the upstage at surgery, according to the multivariate logistic regression model. Results: The overall upgrade rate to invasive carcinoma was 10.8%. At univariate analysis, the risk of upgrade was significantly lower in patients with greater age (p = 0.018), without post-biopsy residual lesion (p < 0.001), with a smaller post-biopsy residual lesion size (p < 0.001), and in the presence of low-grade DCIS only in specimens with microcalcifications (p = 0.002). According to the final multivariable model, the predicted probability of upstage at surgery was lower than 2% in 58 patients; among these 58 patients, only one (1.7%) upstage was observed, showing a good calibration of the model. Conclusions: An easy-to-use nomogram for predicting the upstage at surgery based on radiological and pathological criteria is able to identify patients with low-grade carcinoma in situ with low risk of upstaging to infiltrating carcinomas.

Intraductal papillary neoplasm of bile duct with invasive carcinoma as an intrahepatic cystic lesion, with successful preoperative diagnosis

An 82-year-old man presented to the emergency department with abdominal pain and febrile symptoms that had been present for 4 days. Blood tests showed elevated liver enzymes and white blood cell count, and abdominal contrast-enhanced CT revealed a 35 mm cystic lesion in the left lateral liver lobe. On closer examination, the cystic lesion was found to have contiguous bile duct dilatation and internal nodules. Furthermore, mucus production was observed during endoscopic retrograde cholangiopancreatography, which led to the diagnosis of intraductal papillary neoplasm of the bile duct (IPNB), with cystic infection. Although the patient was an older adult, there was no background disease that would have prevented surgery, and resection was performed. Pathological examination revealed type 1 IPNB, with invasive carcinoma. The number of reports of IPNB is expected to increase with an increasing older population in Asia, and we report the findings of this case.

Expression of CD4, CD8 Biomarkers in Invasive Carcinoma of Breast with Clinicopathological Correlation

Introduction: Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in various cancers, including invasive breast cancer (IBC). Aim and Objectives: To correlate the expression of CD4, CD8 T-lymphocytes in invasive carcinoma breast with established markers of prognosis like tumour size, grade, lymph node status and molecular subtypes mainly ER, PR, Her 2Neu, Ki67 status, mainly the triple negative breast cancers(TNBC). Methodology: 58 Invasive breast carcinoma proven tissue blocks were subjected to immunohistochemistry and morphometric analysis for positive CD4, CD8 T-lymphocytes were done. Results: Triple negative breast cancer subtype shows high TILs than other pathologic subtypes. Tumor interface CD8+ cells very well correlated with the pathological higher nodal stage. Majority CD4, CD8 positive cells were populated more towards the stromal and interface of the tumor microenvironment rather thatintratumoral. Conclusion: CD4+ and CD8+ counts may be a valuable independent prognostic tool in predicting the outcome in invasive breast cancer.

The ncRNA-Mediated Overexpression of Ferroptosis-Related Gene EMC2 Correlates With Poor Prognosis and Tumor Immune Infiltration in Breast Cancer

Ferroptosis is an iron-dependent programmed cell death process. Although ferroptosis inducers hold promising potential in the treatment of breast cancer, the specific role and mechanism of the ferroptosis-related gene EMC2 in breast cancer have not been entirely determined. The potential roles of EMC2 in different tumors were explored based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Tumor Immune Estimation Resource (TIMER), Shiny Methylation Analysis Resource Tool (SMART), starBase, and cBioPortal for cancer genomics (cBioPortal) datasets. The expression difference, mutation, survival, pathological stage, DNA methylation, non-coding RNAs (ncRNAs), and immune cell infiltration related to EMC2 were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify the differences in biological processes and functions among different related genes. The expression levels of core prognostic genes were then verified in breast invasive carcinoma samples using immunohistochemistry and breast invasive carcinoma cell lines using real-time polymerase chain reaction. High expression levels of EMC2 were observed in most cancer types. EMC2 expression in breast cancer tissue samples correlated with poor overall survival. EMC2 was mutated and methylated in a variety of tumors and affected survival. The LINC00665-miR-410-3p axis was identified as the most potential upstream ncRNA-related pathway of EMC2 in breast cancer. EMC2 levels were significantly positively correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. Our study offers a comprehensive understanding of the oncogenic roles of EMC2 across different tumors. The upregulation of EMC2 expression mediated by ncRNAs is related to poor prognosis and tumor immune infiltration in breast cancer.

Hematotoxicity and functional impacts related to chemotherapy with doxorubicin and cyclophosphamide for invasive ductal breast carcinoma: a study in clinical records

Objective: To evaluate the occurrence of hematological and functional toxicities during chemotherapy with doxorubicin and cyclophosphamide in women with breast invasive ductal carcinoma. Methods: This was a descriptive, cross-sectional and quantitative study, involving the data collection in clinical records of 119 women undergoing chemotherapy for breast invasive ductal carcinoma in an oncology outpatient clinic, carried out between February 2014 and February 2015. Results: The investigated toxicities and their respectively occurrences in patients exposed to doxorubicin and cyclophosphamide were hemoglobinemia (26,5%), leukopenia (21,6%), neutropenia (10,8%), thrombocytopenia (none) and reduced hematocrit (28,4%), in addition to fatigue (93,1%), fever (20,6%), gain (35,3%) and weight loss (22,5%). In these variables, there were no significant differences between the exposed and not exposed patients. The association with taxanes showed a significant reduction in hematocrit values (p=0.019) and the toxicities distributed by age group were not significant within the exposed group. Conclusions: Exposure to doxorubicin and cyclophosphamide was not associated with an increase in the occurrence of hematotoxicities and functional impacts in women with breast ductal invasive carcinoma, except when associated with taxane agents.

Pancreatic medullary carcinoma developed on a pancreatic intraductal papillary mucinous neoplasm with loss of MSH2 and MSH6 expression: a case report

Background Pancreatic medullary carcinoma (PMC) is a rare pancreatic tumor, usually showing the presence of microsatellite instability, mostly MLH1 silencing, and a wild-type KRAS mutation status. We report here a PMC arising from a Pancreatic Intraductal Papillary Mucinous Neoplasm (IPMN), both having KRAS and TP53 mutations. Case presentation We report the case of a 73-year-old woman presenting with right iliac fossa pain. MRI revealed a 16 mm diameter mass in the pancreas, leading to a pancreatic duct stricture and upstream a dilatation of the distal pancreatic duct of Wirsung. A fine needle aspiration was performed, and pathology analysis revealed malignant glandular cells. The patient underwent distal pancreatectomy. Gross examination revealed an12 mm indurated white lesion, adjacent to a cystic lesion extending into the rest of the pancreatic body. Microscopically, the cystic area represented a mixed (gastric-type and pancreatobiliary-type) IPMN, involving the main and secondary pancreatic ducts with low-grade and high-grade dysplasia. In the periphery of this IPMN, a 14mm associated invasive carcinoma was observed, characterized by focal gland formation and by poorly differentiated cells with a syncytial appearance, associated with a dense lymphoplasmocytic and neutrophilic infiltrate. Immunohistochemical analyses showed loss of MSH2 and MSH6 expression. Microsatellite instability was confirmed by molecular test. Molecular analysis was performed both on the invasive carcinoma and on the high-grade dysplasia IPMN, revealing the same mutation profile with KRAS and TP53 mutations. The proposed diagnosis was mixed IPMN with associated invasive medullary carcinoma that presented loss of MSH2 and MSH6 expression. Conclusions The present case reports for the first time, at the best of our knowledge, the coexistence of IPMN lesions and PMC, both having the same molecular alterations. It also describes the second case of PMC with microsatellite instability, MSH2 and MSH6 silenced.

Florid Mesothelial Hyperplasia Associated with Abdominal Wall Endometriosis Mimicking Invasive Carcinoma

Florid mesothelial hyperplasia typically occurs in the pelvis, abdomen, or chest associated with an underlying neoplastic or inflammatory process. These lesions are of clinical significance because they can mimic a neoplasm. Early reports were published in the 1970s, but only a few case series of such lesions have been published in the gynecologic pathology literature. Here, we report a case of florid mesothelial hyperplasia with an infiltrative growth pattern, mimicking an invasive carcinoma. The lesion was associated with endometriosis forming a mass lesion in the abdominal wall. Histologically, tubular arrangements and nests of mesothelial cells, some with artifactual slit-like spaces, formed a stellate lesion adjacent to endometrial glands and stroma. Cytologic atypia was mild and reactive, and positive immunostaining for calretinin, WT-1, and cytokeratin 5 identified the lesion as mesothelial and benign. We describe in detail the histologic findings in this case and review the pertinent literature. We discuss the clinically importance of this diagnostic pitfall and the path to arriving at the correct diagnosis.

The association between serum ferritin levels and malignant intraductal papillary mucinous neoplasms

Background Serum ferritin levels are elevated in many malignancies. In this study, we showed the performance of serum ferritin in identifying malignant intraductal papillary mucinous neoplasms (IPMNs). Methods A total of 151 patients with pathologically confirmed IPMNs were enrolled. Serum tumor biomarker (carbohydrate antigen 19–9 (CA19–9) and carcinoembryonic antigen (CEA)) levels and serum ferritin levels were recorded. Lesion location, tumor size, diameter of the main pancreatic duct (MPD), mural nodule, and IPMN type, were collected from imaging examinations. IPMNs with high grade dysplasia and associated invasive carcinoma were considered malignant IPMNs. Results Serum ferritin levels in patients with malignant IPMNs were higher than those in patients with nonmalignant IPMNs (p < 0.05). Serum ferritin was an independent factor for the occurrence of malignant IPMNs (odds ratio (OR) = 1.18, 95% confidence interval (CI):1.01–1.39). A similar trend was found between high serum ferritin (> 149 ng/ml) and malignant IPMNs (OR = 5.64, 95% CI:1.78–17.92). The area under the curve (AUC) of serum ferritin was higher than that of CEA and CA19–9 in identifying malignant IPMNs (AUC = 0.67 vs. AUC = 0.58, 0.65). The combination of serum ferritin with IPMN type showed a similar performance to MPD diameter and the combination of serum CA19–9 with IPMN types in identifying malignant IPMNs (AUC = 0.78 vs. AUC = 0.79, 0.77) and invasive carcinoma (AUC = 0.77 vs. AUC = 0.79, 0.79). Conclusions Elevated serum ferritin is a factor associated with malignant IPMNs. Serum ferritin may be a useful marker for identifying malignancy in IPMNs.