Lymphocytic emperipolesis in breast carcinoma on cytology smears-A curious finding!

In this article, we discuss an intimidating finding of lymphocytic emperipolesis which was observed in breast carcinoma cells on cytology smears.

Bulldog Scalp Syndrome.

Bulldog scalp syndrome or cutis verticis gyrata (CVG) is a rare cutaneous disorder with an incidence of just 0.026 to 1 per 100,000 population and cosmetic problems should not be ignored as they can affect the quality of life of patients in social and psychological aspects. In CVG the scalp thickens to form folds resembling sulci and gyri just as the skin fold of bulldog. It is a clinical diagnosis with various etiologies. It is classified as primary essential or nonessential and secondary CVG. It can manifest with symptoms ranging from mild to severe intensity. Cosmetic problems are the major concern that can affect patients' social and psychological health. If the folds are heavy, they can cause mass symptoms. Thus, surgery remains the definitive treatment option for improving the cosmetic appearance. Both our cases have different etiologies, however, were managed surgically with removal of skin folds (gyrae) and scoring of aponeuroses of the scalp followed by stretching of the scalp and closure to improve appearance. The surgical team as well as patients were satisfied with the appearance of the scalp after healing. CVG though a rare disease with various etiologies is a benign condition with good prognosis with no reports of malignant transformation so far.

Circulating microRNA-590-5p functions as a liquid biopsy marker in non-small cell lung cancer.

Despite the availability of various diagnostic procedures, a tissue biopsy is still indispensable for the routine diagnosis of lung cancer. However, inaccurate diagnoses can occur, leading to inefficient cancer management. In this context, use of circulating microRNAs (miRNAs) may serve as diagnostic tools as liquid biopsies, and as biomarkers to better understand the molecular mechanisms involved in the progression of cancer. We identified miR-590-5p as a potential prognostic marker in the progression of non-small cell lung cancer (NSCLC). We were able to detect this miRNA in blood plasma samples of NSCLC patients through quantitative real-time PCR. Our data showed an ~7.5-fold downregulation of miR-590-5p in NSCLC patients compared to healthy controls, which correlated with several clinicopathological features. Further, overexpression of miR-590-5p led to decreased cell viability, proliferation, colony formation, migration, and invasion potential of lung cancer cells, whereas its knockdown showed the opposite effect. In addition, the levels of several proteins involved in the epithelial-to-mesenchymal transition negatively correlated with miR-590-5p levels in lung adenocarcinoma cells and tumors of NSCLC patients. Further, dual-luciferase reporter assays identified STAT3 as a direct target of miR-590-5p, which negatively regulated STAT3 activation and its downstream signaling molecules (eg, Cyclin D1, c-Myc, Vimentin, and ß-catenin) involved in tumorigenesis. Taken together, our study suggests that miR-590-5p functions as a tumor suppressor in NSCLC through regulating the STAT3 pathway, and may serve as a useful biomarker for the diagnosis/prognosis of NSCLC, and as a potential therapeutic target for the treatment of NSCLC.

Long Non-Coding RNAs as Strategic Molecules to Augment the Radiation Therapy in Esophageal Squamous Cell Carcinoma.

Intrinsic resistance to ionizing radiation is the major impediment in the treatment and clinical management of esophageal squamous cell carcinoma (ESCC), leading to tumor relapse and poor prognosis. Although several biological and molecular mechanisms are responsible for resistance to radiotherapy in ESCC, the molecule(s) involved in predicting radiotherapy response and prognosis are still lacking, thus requiring a detailed understanding. Recent studies have demonstrated an imperative correlation amongst several long non-coding RNAs and their involvement in complex cellular networks like DNA damage and repair, cell cycle, apoptosis, proliferation, and epithelial-mesenchymal transition. Additionally, accumulating evidence has suggested abnormal expression of lncRNAs in malignant tumor cells before and after radiotherapy effects in tumor cells' sensitivity. Thus, lncRNAs indeed represent unique molecules that can influence tumor cell susceptibility for various clinical interventions. On this note, herein, we have summarized the current status of lncRNAs in augmenting resistance/sensitivity in ESCC against radiotherapy. In addition, we have also discussed various strategies to increase the radiosensitivity in ESCC cells under clinical settings.

Calcifying Aponeurotic Fibroma of Leg Masquerading as Hemangioma in an Adolescent Male along with Review of Literature.

Calcifying aponeurotic fibroma (CAF) is a rare soft tissue tumor which falls under the WHO category of benign fibroblastic and myofibroblastic tumors. It typically occurs on the distal extremities (hands and foot) of children and adolescents. Other less common sites include wrists, ankles, trunk and rarely legs and arms. These tumors present as a painless soft tissue mass, arising in the subcutis, and are usually connected to tendons or aponeuroses. Computed tomography (CT) and magnetic resonance imaging (MRI) are the radiological investigations of choice; however, histopathology remains the diagnostic modality of choice for the diagnosis of CAF. We present a rare case of a 17-year-old boy who presented with a gradually progressive mass lesion on the leg which was later diagnosed as calcifying aponeurotic fibroma on histopathology.

Case of Undifferentiated Carcinoma with Osteoclast-like Giant Cells Associated with a Mucinous Cystic Neoplasm of the Pancreas: A Diagnostic Conundrum.

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is a rare histological subtype of pancreatic ductal adenocarcinoma according to the World Health Organization classification of digestive system tumors. This subtype is exceptionally uncommon, accounting for less than 1% of pancreatic malignant tumors. This paper presents a rare case of a 62-year-old female patient diagnosed with UC-OGC. The patient initially presented with symptoms, including epigastric pain and the presence of an abdominal mass, which led to further investigation and the eventual diagnosis of this unusual and challenging form of pancreatic cancer.

Isolated intramuscular cysticercosis of the forearm masquerading as malignancy.

A woman in her mid-20s presented to an Indian tertiary care hospital with pain in her left forearm. Extensive initial investigations led to a suspected diagnosis of a peripheral nerve sheath tumour; however, the pathological investigation of the excised tumour mass revealed it to be a case of isolated intramuscular cysticercosis in the forearm. Treatment for cysticercosis was commenced and the patient made a full recovery. Isolated intramuscular cysticercosis without the involvement of other organs is a rare presentation and has only been reported in a handful of case reports. We suggest that isolated intramuscular cysticercosis be considered a differential diagnosis in patients with isolated pain in their muscles and with no other symptoms, in patients with a presentation of solitary swelling and in patients at risk of parasitic infection. In addition, we emphasise the importance of histopathological examination due to the varied presentation of cysts.

Varied Clinical Presentations of Aggressive Angiomyxoma of the Vulva: A Rare Entity.

Objective: Aggressive Angiomyxoma (AA) of the vulva is a slow-growing mesenchymal tumour with a tendency to local invasion and recurrence. Case report: We report two cases of vulvoperineal masses that were diagnosed to be Aggressive Angiomyxomas after surgical excision. Both patients presented to the Gynaecology OPD of All India Institute of Medical Sciences, Bathinda, Punjab, India, in 2020 and 2022 with complaints of a mass coming out of introitus of three years duration and 14 years duration, respectively. The first patient was managed by surgical excision of the mass via abdominoperineal approach, while the second patient underwent vaginal hysterectomy along with the removal of the mass. Both patients were given GnRH analogues after the surgery to avoid any further recurrences and have been in remission on follow-ups so far. Conclusion: Due to its rare occurrence, clinicians should consider the possibility of AA while encountering patients with vulvovaginal masses to avoid misdiagnosis and delayed management.

Immune-Related Long Non-Coding RNA Signature Determines Prognosis and Immunotherapeutic Coherence in Esophageal Cancer.

Objectives: Aim of this study was to explore the immune-related lncRNAs having prognostic role and establishing risk score model for better prognosis and immunotherapeutic coherence for esophageal cancer (EC) patients. Methods: To determine the role of immune-related lncRNAs in EC, we analyzed the RNA-seq expression data of 162 EC patients and 11 non-cancerous individuals and their clinically relevant information from the cancer genome atlas (TCGA) database. Bioinformatic and statistical analysis such as Differential expression analysis, co-expression analysis, Kaplan Meier survival analysis, Cox proportional hazards model, ROC analysis of risk model was employed. Results: Utilizing a cutoff criterion (log2FC > 1 + log2FC < -1 and FDR < 0.01), we identified 3737 RNAs were significantly differentially expressed in EC patients. Among these, 2222 genes were classified as significantly differentially expressed mRNAs (demRNAs), and 966 were significantly differentially expressed lncRNAs (delncRNA). Through Pearson correlation analysis between differentially expressed lncRNAs and immune related-mRNAs, we identified 12 immune-related lncRNAs as prognostic signatures for EC. Notably, through Kaplan-Meier analysis on these lncRNAs, we found the low-risk group patients showed significantly improved survival compared to the high-risk group. Moreover, this prognostic signature has consistent performance across training, testing and entire validation cohort sets. Using ESTIMATE and CIBERSORT algorithm we further observed significant enriched infiltration of naive B cells, regulatory T cells resting CD4+ memory T cells, and, plasma cells in the low-risk group compared to high-risk EC patients group. On the contrary, tumor-associated M2 macrophages were highly enriched in high-risk patients. Additionally, we confirmed immune-related biological functions and pathways such as inflammatory, cytokines, chemokines response and natural killer cell-mediated cytotoxicity, toll-like receptor signaling pathways, JAK-STAT signaling pathways, chemokine signaling pathways significantly associated with identified IRlncRNA signature and their co-expressed immune genes. Furthermore, we assessed the predictive potential of the lncRNA signature in immune checkpoint inhibitors; we found that programed cell death ligand 1 (PD-L1; P-value = .048), programed cell death ligand 2 (PD-L2; P-value = .002), and T cell immunoglobulin and mucin-domain containing-3 (TIM-3; P-value = .045) expression levels were significantly higher in low-risk patients compared to high-risk patients. Conclusion: We believe this study will contribute to better prognosis prediction and targeted treatment of EC in the future.

Evolution of Frozen Section in Carcinoma Breast: Systematic Review.

Background: The frozen section (FS) has been a good technique in surgical management of breast lesions since many years. But complete agreement and cooperation have not been achieved everywhere among surgeons and pathologists especially in the developing countries. FS undergoes continuous criticism due to various shortcomings but continued to be evaluated especially in developing countries. Objectives: This review was conducted to synthesize information on the use of frozen section in carcinoma breast. Data Sources. The MEDLINE database for frozen section since its origin and its implication in recent breast surgery techniques was studied. Study Eligibility Criteria. Sixty-five articles were reviewed with complete analysis on FS in both benign and malignant breast lesions. Study Appraisal and Synthesis Methods. The analysis of frozen section was done as a diagnostic tool in breast lesions, margin status in breast conservative surgery in carcinoma breast, and sentinel lymph node and use of immunohistochemistry for sentinel lymph node FS. Results: It was analysed that the FS gives accurate results in margin status analysis, decreasing rerecurrence. Conclusion: The accuracy of FSA, low recurrence rate, avoidance of reoperation, and good cosmesis are the key points of its use in breast conservative surgery. Its use in sentinel lymph node biopsy (SLNB) is equivocal. However, application of immunohistochemistry on frozen section of SLNB is an evolving trend in today's era.

A diagnostic and prognostic value of blood-based circulating long non-coding RNAs in thyroid, pancreatic and ovarian cancer.

Several studies have demonstrated the potential of circulating long non-coding RNAs (lncRNAs) as promising cancer biomarkers. Herein, we addressed the regulatory role of circulating lncRNAs and their potential value as diagnostic/prognostic markers for thyroid, pancreatic and ovarian cancers. Furthermore, we analyzed and measured the clinical implications and association of lncRNAs with sensitivity, specificity, and area under the ROC curve (AUC). Based on our meta-analysis, we found that GAS8-AS1 could discriminate thyroid cancer from non-cancer and other cancers with higher accuracy (AUC = 0.746; sensitivity = 61.70 %, and specificity = 90.00 %). Similarly, for ovarian cancer, lncRNA RP5-837J1.2 was found to have ideal diagnostic potential with critical clinical specifications of AUC = 0.996; sensitivity = 97.30 % and specificity = 94.60 %. Whereas we could not find any lncRNA having high diagnostic/prognostic efficiency in pancreatic cancer. We believe that lncRNAs mentioned above may explore clinical settings for the diagnosis and prognosis of cancer patients.

Circulating Long Non-Coding RNAs LINC00324 and LOC100507053 as Potential Liquid Biopsy Markers for Esophageal Squamous Cell Carcinoma: A Pilot Study.

BACKGROUND: Despite the availability of advanced technology to detect and treat esophageal squamous cell carcinoma (ESCC), the 5-year survival rate of ESCC patients is still meager. Recently, long non-coding RNAs (lncRNAs) have emerged as essential players in the diagnosis and prognosis of various cancers. OBJECTIVE: This pilot study focused on identifying circulating lncRNAs as liquid biopsy markers for the ESCC. METHODOLOGY: We performed next-generation sequencing (NGS) to profile circulating lncRNAs in ESCC and healthy individuals' blood samples. The expression of the top five upregulated and top five downregulated lncRNAs were validated through quantitative real-time PCR (qRT-PCR), including samples used for the NGS. Later, we explored the diagnostic/prognostic potential of lncRNAs and their impact on the clinicopathological parameters of patients. To unravel the molecular target and pathways of identified lncRNAs, we utilized various bioinformatics tools such as lncRnome, RAID v2.0, Starbase, miRDB, TargetScan, Gene Ontology, and KEGG pathways. RESULTS: Through NGS profiling, we obtained 159 upregulated, 137 downregulated, and 188 neutral lncRNAs in ESCC blood samples compared to healthy individuals. Among dysregulated lncRNAs, we observed LINC00324 significantly upregulated (2.11-fold; p-value = 0.0032) and LOC100507053 significantly downregulated (2.22-fold; p-value = 0.0001) in ESCC patients. Furthermore, we found LINC00324 and LOC100507053 could discriminate ESCC cancer patients' from non-cancer individuals with higher accuracy of Area Under the ROC Curve (AUC) = 0.627 and 0.668, respectively. The Kaplan-Meier and log-rank analysis revealed higher expression levels of LINC00324 and lower expression levels of LOC100507053 well correlated with the poor prognosis of ESCC patients with a Hazard ratio of LINC00324 = 2.48 (95% CI: 1.055 to 5.835) and Hazard ratio of LOC100507053 = 4.75 (95% CI: 2.098 to 10.76)]. Moreover, we also observed lncRNAs expression well correlated with the age (>50 years), gender (Female), alcohol, tobacco, and hot beverages consumers. Using bioinformatics tools, we saw miR-493-5p as the direct molecular target of LINC00324 and interacted with the MAPK signaling pathway in ESCC pathogenesis. CONCLUSION: This pilot study suggests that circulating LINC00324 and LOC100507053 can be used as a liquid biopsy marker of ESCC; however, multicentric studies are still warranted.

Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung Cancer.

Dysregulated expression profiles of microRNAs (miRNAs) have been observed in several types of cancer, including non-small cell lung cancer (NSCLC); however, the diagnostic and prognostic potential of circulating miRNAs in NSCLC remains largely undefined. Here we found that circulating miR-320a was significantly down-regulated (~5.87-fold; p < 0.0001) in NSCLC patients (n = 80) compared to matched control plasma samples from healthy subjects (n = 80). Kaplan-Meier survival analysis revealed that NSCLC patients with lower levels of circulating miR-320a had overall poorer prognosis and survival rates compared to patients with higher levels (p < 0.0001). Moreover, the diagnostic and prognostic potential of miR-320a correlated with clinicopathological characteristics such as tumor size, tumor node metastasis (TNM) stage, and lymph node metastasis. Functionally, depletion of miR-320a in human A549 lung adenocarcinoma cells induced their metastatic potential and reduced apoptosis, which was reversed by exogenous re-expression of miR-320a mimics, indicating that miR-320a has a tumor-suppressive role in NSCLC. These results were further supported by high levels of epithelial-mesenchymal transition (EMT) marker proteins (e.g., Beta-catenin, MMP9, and E-cadherin) in lung cancer cells and tissues via immunoblot and immunohistochemistry experiments. Moreover, through bioinformatics and dual-luciferase reporter assays, we demonstrated that AKT3 was a direct target of miR-320a. In addition, AKT3-associated PI3K/AKT/mTOR protein-signaling pathways were elevated with down-regulated miR-320a levels in NSCLC. These composite data indicate that circulating miR-320a may function as a tumor-suppressor miRNA with potential as a prognostic marker for NSCLC patients.

LncRNA ZFAS1 inhibits triple-negative breast cancer by targeting STAT3.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with fewer treatment options than other types of invasive breast cancer due to the loss of the estrogen, progesterone receptors and low levels of the HER2 protein, resulting in a poor prognosis for these patients. Here, we found that the expression of the lncRNA, ZFAS1, was significantly downregulated (∼3.0-fold) in blood samples of TNBC patients (n=40) compared to matched healthy controls (n=40). Functionally, silencing of ZFAS1 promoted cell proliferation and colonization of human MDA-MB-231 TNBC cells by inhibiting the expression levels of the cyclin-dependent kinase (CDK) inhibitors p21 (CDKN1A) and p27 (CDKN1B) compared to the scrambled siRNA control cells. Further, we found that downregulation of ZFAS1 led to decreased protein levels of the epithelial markers, E-cadherin, Claudin-1, and Zo-1, with increased protein levels of the mesenchymal markers, Slug and ZEB1. In addition, by utilizing the bioinformatic tools such as RAID v2.0 (RNA Interactome Database Version 2.0), AnnoLnc (Annotate human lncRNA database), and GEPIA (Gene Expression Profiling Interactive Analysis), we identified a strong negative correlation between ZFAS1 and signal transducer and activator of transcription 3 (STAT3) gene expression (R = -0.11, p-value = 0.0002). Further, we observed that decreased ZFAS1 expression significantly (p < 0.05) increased STAT3 and phosphorylated STAT3 (at Ser727 residue) protein levels in TNBC cells. The composite data indicate that ZFAS1 may function as a tumor-suppressor lncRNA with potential as a diagnostic/prognostic marker and may offer a new target for the treatment of TNBC patients.