Renal Thrombotic Microangiopathy: A Complication of Paediatric Systemic Lupus Erythematosus That Requires Attention.

Systemic lupus erythematosus (SLE) is a multi-system disorder with a variety of clinical presentations. A wide range of renal vascular lesions (VL) is described predominantly in adult patients. The exact prevalence of renal VL in the pediatric SLE (pSLE) population is yet to be determined. A 10-year-old female patient with lupus nephritis (LN) presented with deteriorating kidney function. An exhaustive array of clinical-biochemical and pathological evaluations resulted in a diagnosis of class IV LN with thrombotic microangiopathy (TMA) associated with malignant hypertension and hypocomplementemia. Renal VL is overlooked or underreported in SLE patients, as it is neither accorded much importance in the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification nor in the activity and chronicity scoring. The TMA lesions in LN patients can be managed following the recently devised PLASMIC score; hence, reporting such VL has therapeutic implications.

Incidence and Malignancy Rates in Thyroid Nodules in North-East Indian Population by Bethesda System: A Single Institutional Experience of 3 Years.

Suvamoy ChakrabortyIntroduction Goiter is one of the most common conditions encountered clinically (up to 60% of population) with thyroid malignancy being one of the most common endocrine malignancies. The American Thyroid Association has advocated the need for validation of the Bethesda system of fine needle aspiration cytology (FNAC) in each center. The risk of malignancy (ROM) for Bethesda categories in the Indian population is limited. Objective As there are variations in the effectiveness of FNAC, this study aims to study the role of FNAC in evaluating thyroid nodules, estimating the risk of malignancy in thyroid nodules in the North-East Indian population, and correlating the FNAC findings with HPE (histopathological examination). Materials and Methods A total of 110 patients with thyroid nodules had visited the Department of Otorhinolaryngology during 2017-2020. Case records were retrieved, out of which only 66 patients had both FNAC and HPE reports. The FNAC of 66 patients were studied. Statistical Analysis Data were analyzed using STATA V14. Fischer's exact test was used to determine the association of Bethesda system in diagnosing thyroid malignancy. The percentage agreement between the FNAC and HPE was calculated using the Kappa statistics. The diagnostic validity of FNAC in the diagnosis of malignant thyroid nodule was reported. Results The sensitivity, specificity, PPV, and NPV of FNAC in diagnosing thyroid malignancy were 52%, 94.3%, 89%, and 69% respectively. The risk of malignancy (ROM) for Bethesda I to VI categories in our study was 20%, 25%, 67%, 40%, 78%, and 100% respectively ( p -value < 0.001, Fischer's exact test). Conclusion A specificity of 94.3% and PPV of 89% of FNAC makes it a good reliable tool in ruling in malignancy in our population. The higher ROM in indeterminate categories necessitates the need to consider thyroidectomy with or without intraoperative frozen section analysis in our population. Similar higher ROM has been reported in a few other Indian studies. These findings may suggest an increased ROM for Bethesda categories III and IV in the Indian population; however, the statement needs further validation from large multicentric studies with research to find the reason for the increased risk.

Prevalence of human papillomavirus infection in abnormal pap smears.

Objectives: This study was undertaken to study the prevalence of human papillomavirus (HPV) infection using the polymerase chain reaction (PCR) technique in abnormal cervical pap smears and to correlate the different cytological results with HPV infection. Material and Methods: A total of 1788 cervical pap smears of women more than 30 years of age conducted over a period of 1 year 3 months (June 2015-August 2016) were screened by liquid-based cytology. High-risk (HR)-HPV testing was performed by PCR in abnormal lesions. Inflammatory smears and some atypical squamous cells of undetermined significance (ASCUS)-reactive cases were excluded from HPV testing. Histopathological correlation was done wherever possible. Results: The overall prevalence of the intraepithelial lesions/malignancy was ASCUS. (ASCUS) - 79 (4.42%), atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) - 10 (0.56%), low-grade squamous intraepithelial lesion (LSIL) - 26 (1.45%), high-grade squamous intraepithelial lesion (HSIL) - 15 (0.84%), squamous cell carcinoma - 5 (0.28%), and adenocarcinoma - 1 case (0.06%). Overall, 136 (7.60%) samples were classified as abnormal. Seventy-seven samples were included for HR-HPV testing - 20 ASCUS, 10 ASC-H, 26 LSIL, 15 HSIL, and 6 malignant cases. A control group of ten samples with normal cervical cytology within the normal limit (Control) (WNLc) was tested for HR-HPV. HR-HPV was detected in 20% of samples of the WNLc group, 45% of the ASCUS group, 70% of the ASC-H group, 73.07% of the LSIL group, 86.67% of the HSIL, and 83.34% of the samples in the malignant group. Overall, HR-HPV was detected in 68.83% of abnormal cervical pap smears. Conclusion: Our study shows that the percentage of HR-HPV-positive case increases with the severity of cytologic morphology. HPV had 4 times higher positivity in squamous intraepithelial lesion as compared to ASCUS.

Role of Mismatch Repair Deficiency Status and Microsatellite Instability in Relation to the Expression of Immune Checkpoint Proteins in Colorectal Cancer.

Introduction Colorectal cancer (CRC) is the third most common cancer in the world among men and second among women worldwide. One of the major molecular pathways responsible for the development of colorectal cancer (CRC) is the microsatellite instability (MSI) pathway. During carcinogenesis, the tumor cells express programmed death ligand-1 (PD-L1), which reduces the immunogenicity leading to the escape of immune attack. Anti-PD-L1 interaction is an upcoming line of research for the treatment of colorectal carcinoma patients. Materials and methods The present study was an ambispective study where the mismatch repair deficiency status (MMR) and programmed death ligand-1 (PD-L1) expression were studied using immunohistochemistry and then later analyzed and compared with the clinicopathological parameters and MSI status in relation to the expression of programmed death ligand-1 (PD-L1) in neoplastic and immune cells in a total of 55 biopsy specimen. MMR expression was reported as retained or loss of nuclear staining, and PD-L1 expression was taken as positive with a cut-off of more than or equal to 5% membranous positivity in both tumor cells and immune cells. Results The analysis showed a significant correlation of microsatellite instability (MSI) status with two of the clinicopathological parameters, which were the site of the tumor (p-value<0.001) and M stage (p-value<0.001). PD-L1 expression in neoplastic cells showed no significant correlation with the clinicopathological parameters, whereas PD-L1 expression in immune cells showed a significant association with gender (p-value=0.043). Also, MSI status showed a significant association with PD-L1 expression in tumor cells (p-value <0.001).

Clinicopathological, Immunological, and Laboratory Parameters of Childhood Lupus Nephritis: A Study from Northeast India.

Background Lupus nephrtis in children is associated with high morbidity and mortality. The incidence of childhood systemic lupus erythematosus (SLE) ranges from 3.3 to 8.8/100000 children with a higher Asian preponderance. The predominance of SLE in female pediatric patients increases gradually with age to the values observed in adults. Objectives To assess the clinical, immunological, and histopathological spectrum of childhood lupus nephritis in northeast India and explore the relationship between clinical, biochemical, serological, and histopathological findings. Materials and Methods A retrospective descriptive study was performed over 8 years. Histopathology slides were reviewed by two pathologists, whereas other details were collected from patients' records. Statistical Analysis Statistical analysis was based on the chi-square test and a p -value < 0.05 was considered statistically significant. Results Fifty-three cases of lupus nephritis were included in the study. The patients' age ranged from 5 to 18 years with a mean age of 14.5 years and a female: male ratio of 6.5:1. Edema and hypertension were the commonest clinical presentations, whereas proteinuria was the commonest presenting laboratory parameter. Amongst all the immunological markers, dsDNA was the commonest. Histopathologically, predominantly study population belonged to class IV lupus nephritis. The patients with class IV showed a statistically significant correlation with proteinuria and hematuria at the time of diagnosis. Immunological markers, namely, ANA and anti-ds-DNA positivity were significantly associated with advanced renal histopathology. Conclusion cSLE in northeast India presents mostly as Class IV LN presenting mostly with deranged laboratory parameters and preponderance of various immunological markers and clinical presentations.

A Comparative Study of Immunofluorescence on Formalin-Fixed, Paraffin-Embedded Versus Fresh Frozen Kidney Biopsy.

Background Immunofluorescence techniques done on formalin-fixed, paraffin-embedded tissue can serve as salvage techniques in cases where immunofluorescence on the frozen section may not be adequate or available. The present study was undertaken to assess the diagnostic utility of paraffin immunofluorescence by proteinase K digestion on renal biopsy compared to fresh frozen immunofluorescence. Methodology The paraffin immunofluorescence by proteinase K digestion of paraffin-embedded renal biopsy (IF-FFPE) was standardized and compared with the immunofluorescence on fresh frozen tissue (IF-Frozen). A total of 50 cases of the native renal biopsy were included in the study, and their intensity for fluorescein isothiocyanate-labeled IgA, IgG, IgM, C3, kappa, and lambda was compared. Results A total of 50 cases of the native renal biopsy were included in the study, and their intensity for fluorescein isothiocyanate-labeled antibodies of IgA, IgG, IgM, C3, kappa, and lambda was compared. The difference of 2+ intensity of antibodies between IF-FFPE and IF-Frozen was noted mainly in lupus nephritis (15%), followed by IgA nephropathy (10%) and membranoproliferative glomerulonephritis (7%). IF-FFPE showed a sensitivity of 90.3%, 91.8%, 82.7%, 81.1%, 92.1%, and 94.6% for IgA, IgG, IgM, C3, kappa, and lambda, respectively, whereas specificity was 100% for IgA, IgG, C3, kappa, and lambda and 95.2% for IgM. Conclusions Immunofluorescence techniques done on formalin-fixed, paraffin-embedded tissue can serve as salvage techniques in kidney biopsies.

The G-protein-coupled estrogen receptor, a gene co-expressed with ERα in breast tumors, is regulated by estrogen-ERα signalling in ERα positive breast cancer cells.

GPER is a seven transmembrane G-protein-coupled estrogen receptor that mediates rapid estrogen actions. Large volumes of data have revealed its association with clinicopathological variables in breast tumors, role in epidermal growth factor (EGF)-like effects of estrogen, potential as a therapeutic target or a prognostic marker, and involvement in endocrine resistance in the face of tamoxifen agonism. GPER cross-talks with estrogen receptor alpha (ERα) in cell culture models implicating its role in the physiology of normal or transformed mammary epithelial cells. However, discrepancies in the literature have obfuscated the nature of their relationship, its significance, and the underlying mechanism. The purpose of this study was to assess the relationship between GPER, and ERα in breast tumors, to understand the mechanistic basis, and to gauge its clinical significance. We mined The Cancer Genome Atlas (TCGA)-BRCA data to examine the relationship between GPER and ERα expression. GPER mRNA, and protein expression were analyzed in ERα-positive or -negative breast tumors from two independent cohorts using immunohistochemistry, western blotting, or RT-qPCR. The Kaplan-Meier Plotter (KM) was employed for survival analysis. The influence of estrogen in vivo was studied by examining GPER expression levels in estrus or diestrus mouse mammary tissues, and the impact of 17ß-estradiol (E2) administration in juvenile or adult mice. The effect of E2, or propylpyrazoletriol (PPT, an ERα agonist) stimulation on GPER expression was studied in MCF-7 and T47D cells, with or without tamoxifen or ERα knockdown. ERα-binding to the GPER locus was explored by analysing ChIP-seq data (ERP000380), in silico prediction of estrogen response elements, and chromatin immunoprecipitation (ChIP) assay. Clinical data revealed significant positive association between GPER and ERα expression in breast tumors. The median GPER expression in ERα-positive tumors was significantly higher than ERα-negative tumors. High GPER expression was significantly associated with longer overall survival (OS) of patients with ERα-positive tumors. In vivo experiments showed a positive effect of E2 on GPER expression. E2 induced GPER expression in MCF-7 and T47D cells; an effect mimicked by PPT. Tamoxifen or ERα-knockdown blocked the induction of GPER. Estrogen-mediated induction was associated with increased ERα occupancy in the upstream region of GPER. Furthermore, treatment with 17ß-estradiol or PPT significantly reduced the IC50 of the GPER agonist (G1)-mediated loss of MCF-7 or T47D cell viability. In conclusion, GPER is positively associated with ERα in breast tumors, and induced by estrogen-ERα signalling axis. Estrogen-mediated induction of GPER makes the cells more responsive to GPER ligands. More in-depth studies are warranted to establish the significance of GPER-ERα co-expression, and their interplay in breast tumor development, progression, and treatment.

Clinicopathological Profile of Immunoglobulin A Nephropathy: A Study from Northeast India.

Immunoglobulin A (IgA) nephropathy is the most common primary glomerulopathy, with wide variation in its prevalence as well as clinical symptoms. Among the laboratory parameters, increased serum creatinine (SCr) levels, mean arterial pressure (MAP), and a decreased estimated glomerular filtration rate (eGFR) point toward poorer renal function. The Oxford 2016 scoring system for IgA nephropathy identified various histopathological variables, which serve as indicators of renal outcomes. There is a paucity of studies on the prevalence as well as the various clinical laboratory parameters correlating with the 2016 Oxford scoring system in northeastern India. The present study showed that IgA nephropathy was more common in the second and third decades, more prevalent in females, and mostly presented with edema. Nephrotic proteinuria, higher SCr, MAP, and decreased eGFR levels at presentation suggested poorer renal function in most subjects. The endocapillary hypercellularity, segmental sclerosis, tubular atrophy, and crescent variables of the 2016 Oxford scoring system showed a statistically significant relationship with various laboratory parameters at presentation.

Immunoglobulin A Nephropathy in a SARS-CoV-2-Positive Patient With Coexistent Metabolic Syndrome.

SARS-CoV-2 viral infection though primarily affects the respiratory system, but concurrent renal involvement is been reported in the medical literature. Acute kidney injury (AKI) is a common finding in SARS-CoV-2-positive patients. An isolated case of IgA nephropathy in a SARS-CoV-2 virus-infected patient has been already reported in the medical literature. Incidence of metabolic syndromes is on the rise considering the change in lifestyle and food habits and the global pandemic of obesity. Renal manifestations of metabolic syndrome are myriad with IgA nephropathy being an occasional manifestation in such patients. We reported a case of IgA nephropathy in a patient in her fourth decade of life diagnosed as metabolic syndrome with concomitant SARS-CoV-2 infection that progressed to chronic kidney damage (CKD) subsequently. In this case report, we postulate that cytokine storm along with hypoxemia secondary to SARS-CoV-2 infection may accelerate the declining renal function however further studies are necessary to confirm this hypothesis considering the rarity of such cases.

Hepatosplenic T Cell Lymphoma: Diagnostic Conundrum.

Hepatosplenic T cell lymphoma (HSTCL) is a very rare and aggressive peripheral T cell lymphoma that comprises less than 1% of Non-Hodgkin lymphomas (NHL). It is derived from cytotoxic T-cells, usually of γδ T cell receptor type, and is characterized by primary extranodal disease with typical sinusoidal infiltration of the liver, spleen and bone marrow by medium-sized lymphoid cells. HSTCL occurs more frequently in immunocompromised patients, especially in those receiving long-term immunosuppressive therapy. The differential diagnosis is varied, and the clinical course is dismal with a poor response to currently available therapies. Herein we report a case of HSTCL in a 20-year-old immunocompetent male who presented with fever, pallor, weight loss, bicytopenia, hepatomegaly, and massive splenomegaly, highlighting the diagnostic conundrum and pointers towards an accurate diagnosis. The key role for diagnosis was the combination of morphologic finding of atypical lymphoid cells in the bone marrow, typical immunophenotypic profile on flow cytometry and the pattern of involvement of the liver and the spleen, even in the absence of full-fledged diagnostic panels and tools. The report of this case is an endeavor to emphasize the high index of suspicion for timely detection of such a rare entity.

Cold spot assessment in Epithelial-Mesenchymal Transition: a histological predictor of tumor recurrence in oral cavity squamous cell carcinoma.

Objectives: To investigate clinical implications of epithelial mesenchymal transition (EMT) expression in oral cavity squamous cell carcinoma (OSCC). Materials and. Methods: E-cadherin and vimentin expression was studied in 50 newly diagnosed cases of OSCC who underwent surgical excision. EMT expression at non cold spot infiltrative margin and cold spot was studied and correlated with prognostic factors and disease-free survival (DFS). Results: EMT expression at the cold spot and non-cold spot infiltrative margin showed significant results with nodal status (P < 0.001, P < 0.009 respectively). On multivariate analysis, only EMT at the cold spot correlated significantly with prognostic factors (P < 0.030). The factors affecting DFS on Kaplan Meier index were EMT expression and differentiation (P < 0.002, P < 0.016 respectively) which proved significant in cox regression analysis. Conclusion: The study reveals that EMT expression at the cold spot is a significant biomarker for predicting lymph-node metastasis and tumor recurrence in OSCC.

Papillary cystadenocarcinoma of the parotid gland: a rare sub-variant of salivary gland adenocarcinoma.

Papillary cystadenocarcinoma of the salivary gland is a very rare malignant neoplasm accounting for only 2% of all salivary gland lesions. In 1991 it was first included as a separate entity in the World Health Organization (WHO) classification of salivary gland tumors and in 2017 WHO Classification, the tumor was clubbed as a sub-variant of adenocarcinoma, not otherwise specified. It most commonly occurs in the major salivary glands. Herein we report a case of salivary papillary cystadenocarcinoma in a 54-year-old female, who presented with rapid enlargement of the right parotid swelling. Based on radiology and fine-needle aspiration cytology, a working diagnosis of the malignant tumor involving the superficial lobe of the right parotid gland was made. In view of the malignant nature of the swelling, superficial parotidectomy was done. The histopathology and immunohistochemistry of the mass confirmed the diagnosis of papillary cystadenocarcinoma of the right parotid. With the revised 2017 WHO classification of salivary gland tumors, it is important to report all rare subtypes in order to understand their biology and behavior.

Evaluation of Hematological Parameters in Predicting Intensive Care Unit Admission in COVID-19 Patients.

Hematological parameters like total leukocyte count (TLC), neutrophil, lymphocyte, and absolute eosinophil counts (AEC), and neutrophil-to-lymphocyte ratio (NLR) are known to predict the severity of novel coronavirus disease 2019 (COVID-19) patients. In the present study, we aimed to study the role of complete blood count parameters in triaging these patients requiring intensive care unit (ICU) admission. A retrospective study was done over a period of 2 months. Patients, who were ≥ 18 years of age with COVID-19 confirmed on SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) and whose routine hematology counts were sent within 24 h of admission, were included in the study. Cut-off values of 47.5 years for age, 11.3 × 109/L for TLC, and 9.1 for NLR were predictive of disease severity among COVID-19 patients. Relative neutrophilia ≥ 70% (p < 0.007), relative lymphopenia ≤ 20% (p < 0.002), AEC ≤ 40/cumm (p < 0.001), and NLR ≥ 9.1 (p < 0.001) were significantly associated with ICU admission. Routine hematological parameters are cost-effective and fast predictive markers for severe COVID-19 patients, especially in resource-constrained health care settings to utilize limited ICU resources more effectively.

Papillary cystadenocarcinoma of the parotid gland: a rare sub-variant of salivary gland adenocarcinoma

Papillary cystadenocarcinoma of the salivary gland is a very rare malignant neoplasm accounting for only 2% of all salivary gland lesions. In 1991 it was first included as a separate entity in the World Health Organization (WHO) classification of salivary gland tumors and in 2017 WHO Classification, the tumor was clubbed as a sub-variant of adenocarcinoma, not otherwise specified. It most commonly occurs in the major salivary glands. Herein we report a case of salivary papillary cystadenocarcinoma in a 54-year-old female, who presented with rapid enlargement of the right parotid swelling. Based on radiology and fine-needle aspiration cytology, a working diagnosis of the malignant tumor involving the superficial lobe of the right parotid gland was made. In view of the malignant nature of the swelling, superficial parotidectomy was done. The histopathology and immunohistochemistry of the mass confirmed the diagnosis of papillary cystadenocarcinoma of the right parotid. With the revised 2017 WHO classification of salivary gland tumors, it is important to report all rare subtypes in order to understand their biology and behavior.

Role of Coagulation Profile in Predicting Disease Severity Among Patients of COVID-19.

Background Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), affects the coagulation cascade. In this retrospective study, we aimed to analyze the association of different coagulation parameters including that of D-dimer, fibrinogen, prothrombin time (PT), and activated partial thromboplastin time (aPTT) with severity in COVID-19 patients. Methodology A total of 90 patients positive for SARS-CoV-2 on real-time reverse transcription-polymerase chain reaction (rRT-PCR) were included in the study. The patients were categorized as severe and non-severe, and their D-dimer, fibrinogen, PT, and aPTT values on admission were evaluated. The association of the coagulation parameters with disease severity was analyzed by independent t-test and Chi-square test. The cut-off values of these parameters were calculated to predict the disease severity by receiver operator characteristic (ROC) curve. Results Out of 90 patients admitted, 42 patients were categorized as severe and the rest 48 patients were categorized as non-severe. D-dimer, fibrinogen, and PT in the severe group were significantly higher than the non-severe group with p-values of <0.001, 0.005, and <0.001, respectively. Cut-off values of 0.99 mg/L for D-dimer,349.5 mg/dL for fibrinogen, and 13.05 seconds for PT were predictive of disease severity among COVID-19 patients. Conclusion Severe COVID-19 patients showed significantly higher levels of D-dimer and fibrinogen and prolongation of PT as compared to non-severe COVID-19 patients. Higher levels of D-dimer and fibrinogen, and prolonged PT are predictive of increased disease severity among COVID-19 patients.

Enhancement pattern of differentiated and undifferentiated gastric carcinoma on multiphasic contrast-enhanced computed tomography.

PURPOSE: To study the enhancement pattern of differentiated and undifferentiated gastric carcinoma on multiphasic contrast-enhanced computed tomography (CT). MATERIAL AND METHODS: Seventy patients with biopsy-proven gastric cancer underwent multiphasic contrast-enhanced CT. The CT protocol include plain, arterial, portal venous, and hepatic venous phase. Tumour size, location, peak-enhancement characteristics, and staging were evaluated. RESULTS: The peak-enhancement type was 'arterial' in 20 out of 28 within the differentiated-type GCAs and 'portalvenous' in 37 out of 42 within the undifferentiated-type GCAs (c2 statistic with Yates correction = 23.3981, p < 0.00001). The maximum attenuation value was statistically significant for the arterial phase between differentiated and undifferentiated GCAs (p < 0.05). CONCLUSIONS: Assessing peak-enhancement in a multiphasic CT can help identify the histological subcategory of gastric carcinomas that has prognostic significance. Arterial phase peak-enhancement is frequently seen in differentiated carcinomas whereas venous phase peak-enhancement is seen in undifferentiated carcinomas.

Study of Programmed Death Ligand 1 and EGFR/HER2 Expression in Non-Small-Cell Lung Carcinoma With a Clinicopathological Spectrum.

Non-small-cell lung carcinoma (NSCLC) is a disease characterized by the upregulation of programmed death ligand 1 (PD-L1) along with alterations in epidermal growth factor receptor (EGFR) and HER2-neu (HER2) amplification in addition to EGFR mutation. In the present study, the expression of PD-L1 and EGFR and HER2-neu in NSCLC was studied and their expression in relation to various clinicopathological parameters was analysed. We studied 49 core biopsy specimens of NSCLC for PD-L1, EGFR and HER2-neu expressions using immunohistochemistry. Scoring was based on the intensity and percentage of tumour cells expressing the immunomarkers. PD-L1, EGFR and HER2-neu expression was seen in 20.4%, 32.7% and 14.2% of NSCLC, respectively. The analysis showed no significant difference in PD-L1 expression in relation to any clinicopathological parameters. Low or negative EGFR expression was significantly associated with positive lymph node status (P=0.04). HER2-neu expression showed a significant difference in relation to tumour histology (adenocarcinoma; P=0.01). Also, there was no difference noted with PD-L1 expression in relation to EGFR and HER2-neu expression. As our study has a small number of cases, the validation of the predictive and prognostic value of these markers in lung cancer patients requires further studies.

Cerebral Astroblastoma: A Rare Tumor.

Astroblastoma is a rare neuroepithelial tumor of the central nervous system, which accounts for only 0.45-2.8% of all neuroglial tumors. These tumors have distinct radiological, histopathological, immunohistochemical, and molecular features. We describe a case of astroblastoma of the left temporal lobe in a 38-year-old female, who presented with complaints of headache and occasional episodes of vomiting.

Tumour Behaviour of Low-Grade Papillary Urothelial Carcinoma: A Single-Centre Retrospective Study.

Background and objective Carcinoma of the urinary bladder is the most common urological cancer, and it accounts for 3.9% of all cancer cases in men. Patients with the subset of noninvasive low-grade papillary urothelial carcinoma (LG-UrCa) are at higher risk for tumour recurrence. In this study, we aimed to analyse the histopathological features of LG-UrCa and to correlate those with recurrence potential as well as disease stage and grade progression. Materials and methods We conducted a retrospective study from January 2016 to December 2018. All cases with presenting biopsy initially reported as LG-UrCa were included in the study. All cases with initial biopsy reported as high-grade papillary urothelial carcinoma (HG-UrCa) were excluded from the study. We used the 2016 World Health Organization/International Society of Urological Pathology (WHO/ISUP) guidelines for the classification of papillary urothelial neoplasm. Results A total of 48 initially diagnosed cases of LG-UrCa were identified. Two out of 48 cases were reclassified as high-grade urothelial carcinoma and were excluded from the study. The mean age of patients at presentation was 56.7 years. The mean duration of follow-up was 19.8 months. The mean size of initial tumours was 3.4 cm. Tumour recurrence was encountered in 14 (30.4%) of 46 patients. Out of the four patients who had high-grade progression (8.7%), two also developed TNM stage progression. These two patients eventually underwent radical cystectomy. Patients with larger initial tumour sizes were found to have an increased tumour recurrence rate (p=0.009). Patients with multiple lesions at initial diagnosis had a significantly higher tumour recurrence rate than those with a single tumour (p=0.02). There was no significant difference with regard to intravesical Bacillus Calmette-Guérin (BCG) and tumour recurrence (p=0.065). None of the clinicopathological parameters were significantly associated with the grade and/or stage progression. Conclusion Based on our findings, patients with larger initial tumour size and tumour multiplicity at presentation had an increased tumour recurrence rate.

Expression of PDL1 and Her2neu in Gastric and Gastroesophageal Junction Adenocarcinoma.

The process of tumorigenesis in gastric carcinoma involves multiple genetic alterations including overexpression of PD-L1, amplification of Her2neu, and mutation of p53. In the present study, the expressions of PD-L1 and Her2neu were analyzed in relation to clinicopathological parameters including p53 in gastric and gastroesophageal junction adenocarcinoma. We examined 100 biopsy and resection samples of gastric and gastroesophageal junction carcinomas for PD-L1, Her2neu, and p53 protein expressions using immunohistochemistry. Scorings were done based on intensity and percentage of tumor cells expressing the markers. Follow-up and survival analyses were done wherever data was available. PD-L1 and Her2neu were seen in 37% and 38% respectively. The analysis showed PD-L1 expression was significantly associated with depth of invasion (p = 0.0007), nodal metastasis (p = 0.0003), and AJCC staging (p = 0.0085). Her2neu negative including equivocal expression was significantly associated with histological grading (p = 0.0043), Lauren classification (p = 0.0042), depth of invasion (p = 0.04), and nodal metastasis (p = 0.017). Combined analysis of PD-L1 and Her2neu showed significant association with histological grading (p = 0.017), Lauren classification (p = 0.005), depth of invasion (p = 0.0035), and nodal metastasis (p = 0.00073). Univariate Cox regression analysis showed that depth of invasion, nodal metastasis, distant metastasis, AJCC staging, and p53 were negative prognostic factors for patients' overall survival. In multivariate analysis, distant metastasis and Her2neu negativity including equivocal cases were independent prognostic factors. PD-L1 positivity was seen in cases with advanced pathological features, which suggest its role in the tumorigenesis of gastric and gastroesophageal junction adenocarcinoma. Her2neu positivity showed no correlation with advanced pathological features as well as no prognostic significance, which could be attributed to tumor heterogeneity, endoscopic nature of the biopsies, and non-confirmation of equivocal cases by fluorescent in situ hybridization.