Quest to develop a standard screening method for urothelial carcinoma using liquid-based cytology (The Paris System) and CK20.

Background: Bladder cancer, the most common malignancy of the urinary tract is a leading cause of morbidity and mortality. But cystoscopy, which is till now the mainstay of screening, is an invasive, high-cost method with low sensitivity especially for flat lesions. Aim: To find a non-invasive and effective screening method with liquid-based cytology (LBC) using The Paris System (TPS) and CK20 immunocytochemistry. Materials and Methods: It was a prospective study including the patients with clinical or cystoscopic diagnosis of urinary bladder space occupying lesions (SOL). Both conventional (CC) and liquid-based cytology slides were prepared from urine samples. Slides were evaluated by two trained pathologists and categorized according to TPS guidelines. CK20 immunocytochemistry (ICC) was also performed. Consequent formalin-fixed paraffin embedded sections were blindly examined by another pathologist and was taken as gold standard for comparison. Statistical Analysis: All the statistical analysis were done using MedCalc version 15.8 [Mariakerke, Belgium: MedCalc Software 2015]. Results: The study included 150 cases with a mean age of 62.4 years. Five cases revealed unsatisfactory smears. Rest of the cases were categorized as the following: 18.1% as NH-GUC, 8% as LGUN, 22.1% as AUC, 15.4% as SH-GUC, 32.9% as HGUC. Kappa value of CC and LBC were strong (0.854). LBC alone showed very low specificity (58%) and PPV (74.8%) which improved on application of ICC (specificity: 97.4%, PPV: 96.3%). Conclusion: We conclude that CK20 ICC offers potential for accurate, non-invasive detection and surveillance of bladder cancer and is a better tool when combined with liquid-based cytology, reported using The Paris System.

Spectrum of renal vascular lesions among patients with lupus nephritis: An experience from a tertiary care center.

Background: Lupus nephritis (LN) is the assemblage of glomerular, tubulointerstitial and vascular changes. Despite the fact that glomerular changes are overemphasized in pathological classification and scoring system, but the existence of vascular damage negatively impact the clinical course. Aims and Objective: This study was conducted to determine the clinicopathological spectrum of renal vascular lesions in lupus nephritis. Materials and Methods: Renal microvascular lesions in biopsy proven lupus nephritis were classified into 5 major categories-thrombotic microangiopathy, true vasculitis; lupus vasculopathy, uncomplicated vascular immune deposits, and arterial. Clinical details, laboratory parameters and histopathological variables were compared among all groups. Summary of chronic changes was also assessed. Results: Biopsies from 56 patients revealed thrombotic microangiopathy (2), lupus vasculopathy (3), uncomplicated vascular immune deposit (6), PAN type vasculitis (1) and arterial sclerosis (13). No renal vascular lesions were found in 35.18% of patients. At the time of biopsy, arterial sclerosis or lupus vasculopathy patients were older Nephritis subtype. Activity indices were higher in lupus vasculopathy group whereas patients with arteriosclerosis showed highest chronicity index. Conclusions: Renal vascular lesions are common in systemic lupus erythematosus patients with nephritis and may be associated with aggressive clinical course.

Heavy chain deposition disease in a case of clear cell renal cell carcinoma- A jack in the box.

Renal cell carcinoma (RCC) is the most common subtype of adult renal tumors, and its detection rate in the early stages has been increased in the dawn of advanced imaging modalities. Nephrectomy is the mainstay of treatment; determination of tumor category and staging is the primary concern of oncopathologists. Non-neoplastic renal parenchyma is overlooked majority of times and thus misses the opportunity to detect concomitant medical renal diseases which also predict the renal outcome in the postoperative era. Although any kind of glomerular or extraglomerular pathology may be encountered, vascular changes in the form of arterionephrosclerosis are the commonest one. Here, we take the opportunity to report an unusual association of heavy chain deposition disease (HCDD) with clear cell subtypes of renal cell carcinoma in a 48-year-old male of Indian ethnicity.

Leukemia cutis - A case of cutaneous manifestation of acute monoblastic leukemia.

Leukemia cutis is a comprehensive terminology for dermal manifestations of any type of leukemia either with accompanied or antecedent blood or bone marrow involvement. Although both myeloid and lymphoid neoplastic leukocytes can infiltrate the skin, the frequency is higher among children with congenital myeloid leukemia. However, the underlying pathogenesis of dermal tropism is not yet established. Clinical manifestation varies regarding appearance, site, and numbers. Skin biopsy is essential for the early establishment of the diagnosis and to guide for further testing and categorical management. We report the case of acute myeloid leukemia-cutis in a 22-year-old female where cutaneous manifestation preceded the hematological diagnosis of systemic leukemia.

Clinico-Hematological Profile in Hemoglobin SE Disease: A Case Series from a Tertiary Care Centre.

Hemoglobin SE (HbSE) disease are rare globally and there is paucity of literature regarding this condition. Cases reported in the Indian scenario so far have been limited to the tribal populations. This case series aims to highlight the rarity of this double heterozygous state and to raise awareness of its community prevalence beyond the tribal population. This is a case series over a 5-year observation period with six cases of double heterozygosity for HbS and HbE in our tertiary care centre. Four cases were in the 8-15 years' age group and 2 cases of 24-25 years' age group reported for initial evaluation due to easy fatigability and weakness: Two cases were siblings with history of consanguineous marriages in the family. Mild Pallor, variable icterus, spleen was just palpable in three of the cases and low MCV recorded in all cases. Sickling tests were positive and high performance liquid chromatography (HPLC) revealed both HbS > 50% and HbE fractions ≥ 25%. It's important to detect this rare condition, prevalent in consanguineous marriages as dreaded complications like sickling crisis may manifest during pregnancy and air travel. Detection and genetic counselling is important for prognosis, planning follow up and therapy for this uncommon double heterozygous state.

Utility of serum anti-phospholipase A2 receptor antibody as a biomarker in membranous nephropathy: An experience from a tertiary care center of Eastern India.

Background: Membranous nephropathy (MN) is a pattern of glomerular injury. Exact categorization into primary membranous nephropathy (PMN) or secondary membranous nephropathy (SMN) is essential for treatment. An endogenous podocyte antigen, M-type phospholipase A2 receptor (PLA2R) has been discovered to be involved in the pathogenesis of PMN. Aims and Objectives: In this article, we aimed to analyze renal tissue PLA2R and serum anti-PLA2R antibodies in MN cases and determined the diagnostic utility. Materials and Methods: The study was of prospective type carried out from March 2019 to August 2020. Analysis of cases of MN was performed with PLA2R paraffin immunoflourescence and serum anti-PLA2R antibody ELISA. Results: Overall sensitivity, specificity, PPV, and NPV of serum anti-PLA2R ELISA for PMN was 91.3%, 80%, 75%, and 93.3%, respectively, and of tissue PLA2R staining for PMN was 91.67%, 81.08%, 75.86%, and 93.75%, respectively. There was strong concordance between two methods. In the patients that were followed up, we found baseline serum anti-PLA2R antibody was less in complete remission group than that in non-remission group and the reduction in serum anti-PLA2R antibody was more in complete remission group than that in non-remission group. Conclusion: Routine light and immunofluorescence examination are incapable of giving exact categorical opinion regarding PMN and SMN. Serum anti-PLA2R antibody detection and renal tissue PLA2R analysis are sensitive and specific in detecting PMN. Baseline serum anti-PLA2R antibody and anti-PLA2R antibody quantification trends are related to prognosis of PMN. So they can be incorporated as additional biomarker.

Intestinal helminths-an outlander in a case of protein losing enteropathy.

Malabsorption is the major disease burden in tropical countries. Both primary and secondary forms exist and a secondary form overshadows the primary category. Intestinal parasitic infections lead to secondary form of tropical malabsorption in both native and travelers and presentation varies from mild glossitis to severe protein losing enteropathy. The underlying condition is often masked unless an endoscopic biopsy is performed. This is followed by a histopathological examination which unravels the etiology.

The curious case of T-cell mediated renal allograft rejection after Covid-19 infection.

ABSTRACT: Our case illustrates the possible explanation of renal allograft rejection in a patient who had recovered from Covid-19 infection in the post-transplant period, which ultimately led to the death of the patient. A 27-year-old male patient received renal allograft from his mother, with an uneventful post-transplant period. Three years after the transplantation he contracted Covid-19 infection. The patient recovered from Covid-19 infection after being treated according to the treatment protocol. Subsequently, in the next 2 weeks, he presented with heavy proteinuria and a rise in serum creatinine level. Renal biopsy examination showed features of acute T-cell mediated rejection (TCMR) without any evidence of antibody-mediated rejection. He was given all due care but he deteriorated quickly leading to his death. This case highlights the inter-relation between Covid-19 infection and acute TCMR of the renal allograft, where renal biopsy serves as an indispensable tool in understanding its pathophysiology.

Diagnostic and prognostic utility of SF-1 in adrenal cortical tumours.

Background and Aims: Superior imaging techniques have increased the recognition of adrenal pathology. Distinguishing benign from malignant adrenocortical tumors is not always easy. Several criteria and immunohistochemical markers have been discovered which help to differentiate between adrenocortical adenoma (ACA) and adrenocortical carcinoma (ACC). Our aim here was to evaluate the diagnostic and prognostic role of steroidogenic factor-1 (SF-1) in adult adrenocortical tumors (ACT) diagnosed using the Weiss criteria. In this cohort, we have also analyzed Ki67 and p53 expression and the extent of agreement between SF-1 and Ki-67. Methodology: This was a retrospective, observational study comprising 24 cases of adult ACT over 10 years. Immunohistochemical staining for SF-1, Ki67, and p53 was done in all the cases, and the results correlated with the morphological diagnosis made using Weiss criteria. Results: SF-1 was 100% sensitive and 80% specific as a marker of malignancy. Increased SF-1 expression correlated with worse survival. There was a moderate degree of agreement between Ki-67 labeling-index and SF-1 as a marker of malignancy with the kappa coefficient being 0.75. The sensitivity of p53 was lower than Ki67 in diagnosing ACC. Conclusion: In adult ACTs, SF-1 has diagnostic significance and prognostic implication. SF-1 is a crucial, dosage-dependent survival factor in ACC. There is a moderate extent of agreement between Ki-67 and SF-1 as a marker of malignancy.

Role of light and immunofluorescence microscopy to differentiate primary and secondary membranous nephropathy.

Context: Membranous nephropathy (MN) causes nephrotic syndrome, mostly primary but may be associated with SLE, infections, cancer, or drug. Aims: To estimate clinical, serological, light microscopic, and direct immunofluorescence (DIF) findings to differentiate primary and secondary MN. Settings and Design: Prospective, cross-sectional, single-center study in a tertiary care hospital. Methods and Material: Total 51 cases from September 2019 to February 2020. Laboratory Data: Blood glucose, urine analysis, urea, creatinine, albumin, cholesterol, HBsAg, Anti HCV, ASO, ANA, MPO ANCA, PR3 ANCA, dsDNA, PLA2R, C3, and C4. Clinical parameters: age, sex, BP, skin lesions, arthralgia, edema, obesity. Renal biopsies examined with H and E, PAS, silver methanamine, MT stains. DIF done with IgG, IgM, IgA, C3c, C1q, kappa, and lambda. Statistical Analysis Used: Statistical software (Graph Pad PRISM 6) and Chi-square test). Results: Among 51 cases, 25 are primary and 26 are secondary MN with 22 being lupus nephritis, with 2 being post-infectious and the remaining 2 being proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMIDD) with kappa chain restriction. Mean age was 37 ± 12.18 and 30.69 ± 13.92 years for primary and secondary MN, respectively. Significant male preponderance in primary MN. Serum C4 significantly low in secondary MN (15.34 ± 9.59). Microscopic hematuria present in secondary MN. Mesangial and endocapillary hypercellularity are significant in secondary MN. IgG and kappa are significantly intense in primary whereas IgA, C3c, and C1q are significantly intense in secondary MN. Conclusions: Reliable differentiation between primary and secondary MN has important therapeutic implications.

Three shades of black - secondary thrombotic microangiopathy.

Thrombotic microangiopathy is a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ damage. Wide age distribution and the heterogeneity in presentation demand a deeper understanding into the pathogenesis of TMA. Primary TMA is distinct from TMA associated with secondary causes and remains clinically occult till a precipitating factor aggravates it. The extent and severity of renal damage caused by each of them is also distinct. The first alerting signal could be the presence of schistiocytes on peripheral smear and arteriolar thrombi on light microscopy. Thus in secondary TMA, identification of the underlying disorder is indispensible for targeted management.

Fine-needle aspiration cytology of juvenile granulosa cell tumour: A case report with summary of prior published cases.

Juvenile granulosa cell tumours (JGCT) are uncommon tumours of the ovary and can present diagnostic difficulty both on histology and cytology because of its rarity. Here we present the fine-needle aspiration cytology (FNAC) findings of a 4 year-old girl who came with a large abdominal mass and bleeding per vaginum. FNAC from the mass showed features suggestive of granulosa cell tumour (GCT) and which was later confirmed on histology to be of juvenile type. Only two cases of cytological findings of JGCT have been described earlier, both of which were recurrent cases and at metastatic sites. The main cytological feature in our case was presence of thick colloid like fluid containing apparent bubbles along with small clusters of uniform cells with eosinophilic cytoplasm and fine vacuolation. The presence of these secretions corresponding to the macrofollicles on histology has not been reported earlier.

Comparison of Frozen Section and Squash Cytology as Intra-Operative Diagnostic Tool in Pediatric CNS Tumors.

Background: Pediatric central nervous system (CNS) tumors have a different histological spectrum as compared to adults with the infantile group having even more varied and distinct histological profiles. Intra-operative diagnosis is especially important as it guides the neurosurgeon to tailor an approach which is best suited for a particular case. The aim of the study was to evaluate the diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value of frozen section (FS) and squash cytology and to find out the degree of correlation (kappa value) between the two procedures. Materials and Methods: A prospective study was conducted on 55 pediatric patients with clinicoradiologically diagnosed CNS lesions for a period of 2.5 years. Intra-operative squash smears and FS were made and stained with hematoxylin and eosin stain. Diagnosis made subsequently on paraffin embedded sections was taken as the gold standard. Results: Although the specificity (90%) and positive predictive value (96%) were comparable between the two procedures, sensitivity (91.4%) and negative predictive value (75%) of FS was more as compared to squash cytology. Both the diagnostic modalities showed substantial agreement (k = 0.728). Conclusion: Even though the histological spectrum of pediatric CNS tumors is more varied than adults, FS gives a reasonable intra-operative diagnosis and better results when compared to squash alone.

Cutaneous Vesiculobullous Lesions: A Clinicopathologic Study.

Vesiculobullous disorders could be either immunobullous or non-immunobullous. The spectrum was analyzed using histopathology, direct immunofluorescence (DIF), and salt-split technique. Among the 104 patients analyzed, 77 (74%) were immunobullous and 25 (24%) were having non-immunobullous diseases. Bullous pemphigoid (20.2%) is the commonest among immunobullous lesions, and epidermolysis bullosa (11.5%) was the most frequent non-immunobullous lesion. Involvement of the hair and nail and a positive family history were common relationships for non-immunobullous disorders. Immunobullous lesions showed DIF positivity whereas non-immunobullous lesions were DIF negative. Perilesional DIF was more sensitive and specific than lesional DIF. The commonest antibody was immunoglobulin G (IgG) (78.9%) followed by complement 3c (C3c) (38.1%), immunoglobulin A (IgA) (25%), and immunoglobulin M (IgM) (6.6%). No lesion should be considered non-immunobullous unless both lesional and perilesional DIF results were negative.

Utility of tru-cut biopsy in diagnosis of palpable pediatric soft tissue neoplasms.

Context: Soft tissue neoplasms are infrequent in children with sarcomas accounting for approximately 7% of all pediatric malignancies. Morphologic diagnosis is challenging due to overlapping features. Subtyping and categorization of these lesions are difficult on fine-needle aspiration cytology (FNAC) alone owing to tumor heterogeneity and limited material in some cases. Tru-cut biopsies obtain adequate tumor tissue for ancillary studies besides conventional histology. Aim: The study aims to explore the role of tru-cut biopsy to arrive at a definitive diagnosis. The study also highlights the correlation between FNAC and histopathology on tru-cut biopsy besides explaining the significance of a panel of immunohistochemistry (IHC) markers for histological categorization and subtyping. Materials and Methods: A total of 61 children from infancy to 18 years were included in the study. Closed biopsy procedures like FNAC and tru-cut biopsy were performed, and the tru-cut biopsy specimen was subjected to a panel of immunohistochemical markers. Results: Fisher's exact test for sensitivity and specificity towards detection of malignancy was 83% and 86%, respectively for FNAC. For tru-cut biopsy, sensitivity was 94% and specificity was 91%. The two-sided P value (<0.0001) was extremely significant. Cohen's Kappa coefficient value for tru-cut biopsy was 0.772 suggesting a substantial strength of agreement. Tru-cut with IHC had a Kappa value of 0.866 suggesting greater agreement with histopathology. Conclusion: Tru-cut biopsy is a simple, safe, and reliable adjunct to the FNAC. Instead, immunohistochemistry enhances the diagnostic accuracy.

Histoplasmosis masquerading as tuberculosis: A report of three cases in immunocompetent children.

The most common cause of granulomatous lymphadenitis in countries like ours is mycobactrium tuberculosis followed by atypical mycobacterial infection, fungal infections, parasitic infection, cat scratch disease, lymphogranuloma venereum (inguinal lymphadenopathy), and leprosy Here, we present three cases of lymphadenopathy due to histoplasmosis in immunocompetent children. Two of them presented with fever, lymphadenopathy, initially diagnosed as granulomatous lymphadenitis consistent with tuberculosis on FNAC and were put on antitubercular drugs. However, their condition gradually became worse. As the patients continued to deteriorate, subsequent lymph node biopsies were done and diagnosed as histoplasmosis. Third case presented with acute loss of vision with hepatosplenomegaly and lymphadenopathy. Initially considered as acute leukemia, but eventually established as histoplasmosis. Histoplasmosis should be considered as one of the possible causes of granulomatous lymphadenitis in children.

Clinicopathological Spectrum of Henoch-Schönlein Purpura Vasculitis: An Experience from a Tertiary Care Center.

Henoch-Schönlein purpura (HSP) is a small vessel vasculitis with multiorgan involvement. Renal involvement is the key factor predicting morbidity. We have aimed to analyze the clinicopathological spectrum of HSP vasculitis and HSP nephritis to assess the risk factors associated with kidney involvement. This retrospective study was performed in the department of pathology with collaboration of department of dermatology and department of nephrology of a tertiary care center. All clinical details along with biopsy findings were retrieved. Starting materials of the study were cases of leukocytoclastic vasculitis with only perivascular IgA deposit of more than ++ in the absence of other immunoglobulin and trace complements. To investigate the possible factors that are influential on the development of biopsy-proven HSP nephritis, we divided the whole study population in two groups -group 1: with and group 2: without biopsy-proven nephritis. One-way analysis of variance was carried out during comparative analysis between two groups using IBM SPSS statistics software, version 19 and MedCalc software, version 12.3.0.0. HSP vasculitis comprised 11.6% (n = 19) of total cutaneous vasculitis in 2 years (164 cases) with a mean age of 13.52 ± 8.10 (range: 4-33 years). Three cases developed de novo kidney disease (15.79%). A correlation analysis revealed that predictors were seasonal variation (P = 0.018), severe gastrointestinal involvement (P = 0.03), and subcutaneous edema (P = 0.005). Various clinical and laboratory parameters were associated with renal consequences. Occult nephritis was the most common presentation with crescent as a constant histopathological feature.