Correlation of Serum Galactose-Deficient IgA1 and Oxford Class in Cases of IgA Nephropathy.

CONTEXT.­: Galactose-deficient immunoglobulin A1 (Gd-IgA1) deposition in the renal mesangium plays a role in the pathogenesis of IgA nephropathy. OBJECTIVE.­: To assess the serum Gd-IgA1 level in biopsy-proven IgA nephropathy cases on diagnosis and 3 months post treatment and its relation with histologic Oxford classification. DESIGN.­: In this hospital-based prospective cohort study, 40 cases and 20 controls were enrolled. Serum samples of biopsy-proven IgA nephropathy cases collected on the day of biopsy and 3 months post treatment were evaluated. Solid-phase ELISA (enzyme-linked immunosorbent assay) was performed for assessment of Gd-IgA1 level. All renal biopsies were scored by using Oxford Classification (C-MEST score). The association of serum Gd-IgA1 levels with other established prognostic parameters was assessed. To estimate the prognostic value of markers, logistic regression analysis and Kruskal-Wallis ANOVA (analysis of variance) were used. RESULTS.­: Significant difference was observed in the serum Gd-IgA1 level values in the IgA nephropathy cases and healthy controls (P = .001) at baseline. However, no significant correlation between serum Gd-IgA1 levels at baseline and 3 months of follow-up (P = .31) or between baseline levels and age, proteinuria, hematuria, or estimated glomerular filtration rate was noted. There was no significant correlation between C-MEST score and serum Gd-IgA1 levels at baseline (P > .05); however, the distribution of Gd-IgA1 at 3 months was found to differ significantly between different grades of S score (P = .008). CONCLUSIONS.­: Serum Gd-IgA1 levels may be of utility in predicting disease progression in IgA nephropathy cases. Measurement of serum Gd-IgA1 levels for the diagnosis and prognosis of IgA nephropathy may preclude the need for invasive renal biopsies.

Diagnostic accuracy of flow cytometry in detecting malignant epithelial cells in serous effusions.

INTRODUCTION: This study aims to evaluate diagnostic accuracy of flow cytometry (FCM) in detecting malignant epithelial cells in serous effusions. MATERIALS AND METHODS: Flow cytometric assessment of 96 serous fluids (86 ascitic, 10 pleural) was performed by using epithelial cell adhesion molecule (EpCAM) (in all 96 fluids) and MUC-1 (in a subgroup of 40 fluids) as epithelial markers and CD45 and CD14 as leucocyte markers. The percentage of EpCAM positivity and MUC-1 positivity was calculated in the CD14 and CD45 dual negative population by selective gating. The findings were then correlated with the defined gold standard criteria. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy for EpCAM was found to be 92.06%, 96.96%, 98.31%, 86.48%, and 93.75%, respectively, while that for MUC-1 was 79.16%, 93.75%, 95%, 71.4%, and 85%, respectively. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy for dual positivity for EpCAM and MUC-1 was found to be 83.3%, 100%, 100%, 80%, and 90% respectively. On combining FCM with cytomorphology the sensitivity, specificity, PPV, NPV, and diagnostic accuracy all increased greatly to 95.3%, 100%, 100%, 91.4%, and 96.8%, respectively. CONCLUSIONS: This study highlights the importance of multicolored flow cytometric analysis in detecting epithelial malignancies in effusions specially in cases belonging to the atypia of undetermined significance and suspicious for malignancy categories and in cases with strong clinical suspicion of malignancy with negative fluid cytology. We recommend the combined use of FCM and cytology for this specific subgroup of patients in routine clinical practice for fast and accurate reporting.

Post Covid Juvenile Dermatomyositis with Non Hodgkins Lymphoma in a Child: A Case Report.

INTRODUCTION: Juvenile dermatomyositis (JDM), a rare multisystemic autoimmune disease of unknown cause, leads to chronic inflammation of both striated and smooth muscles. SARS - Co V2 virus infection in children generally remain asymptomatic. However, in some children it leads to a detailed immunological response named as multisystem inflammatory syndrome in children (MIS-C). Post recovery, occasionally, children are susceptible to other autoimmune disorders. CASE PRESENTATION: Our case post MIS-C developed JDM. 8-year-old malnourished child developed proximal myopathy of both upper and lower limbs post recovery from COVID 19. His disease severity increased within a short span of time and he went on to develop contractures and deformity of both upper and lower limbs. He developed an uncommon complication of JDM in form of highgrade non-Hodgkin's lymphoma. CONCLUSION: This case highlights the importance of long-term complications of COVID-19 in children which would gradually evolve in the next few years.

Mucocutaneous manifestations of COVID-19-associated mucormycosis: A retrospective cross-sectional study.

Background Cutaneous mucormycosis has shown a significant upsurge during the COVID-19 pandemic. Due to the rapid progression and high mortality of cutaneous mucormycosis in this context, it is important to identify it early. However, very few studies report detailed clinical descriptions of cutaneous mucormycosis in COVID-19 patients. Objectives To describe mucocutaneous lesions of COVID-19-associated mucormycosis based on clinical morphology and attempt to correlate them with radiological changes. Methods A retrospective cross-sectional study was conducted at a tertiary care centre from 1st April to 31st July 2021. Eligibility criteria included hospitalised adult patients of COVID-19-associated mucormycosis with mucocutaneous lesions. Results All subjects were recently recovering COVID-19 patients diagnosed with cutaneous mucormycosis. One of fifty-three (2%) patients had primary cutaneous mucormycosis, and all of the rest had secondary cutaneous mucormycosis. Secondary cutaneous mucormycosis lesions presented as cutaneous-abscess in 25/52 (48%), nodulo-pustular lesions in 1/52 (2%), necrotic eschar in 1/52 (2%) and ulcero-necrotic in 1/52 (2%). Mucosal lesions were of three broad sub-types: ulcero-necrotic in 1/52 (2%), pustular in 2/52 (4%) and plaques in 1/52 (2%). Twenty out of fifty-two patients (38%) presented with simultaneous mucosal and cutaneous lesions belonging to the above categories. Magnetic resonance imaging of the face showed variable features of cutaneous and subcutaneous tissue involvement, viz. peripherally enhancing collection in the abscess group, "dot in circle sign" and heterogeneous contrast enhancement in the nodulo-pustular group; and fat stranding with infiltration of subcutaneous tissue in cases with necrotic eschar and ulcero-necrotic lesions. Limitations The morphological variety of cutaneous mucormycosis patients in a single-centre study like ours might not be very precise. Thus, there is a need to conduct multi-centric prospective studies with larger sample sizes in the future to substantiate our morphological and radiological findings. Conclusions COVID-19-associated mucormycosis patients in our study presented with a few specific types of mucocutaneous manifestations, with distinct magnetic resonance imaging findings. If corroborated by larger studies, these observations would be helpful in the early diagnosis of this serious illness.

Value of whole-body MRI for the assessment of response to albendazole in disseminated neurocysticercosis: a prospective follow-up study.

BACKGROUND: Disseminated neurocysticercosis is defined as simultaneous involvement of the brain (≥3 cysts) and at least one additional body site/organ. We aimed to identify disseminated cystic lesions in other body parts and investigate the effect of albendazole. METHODS: We enrolled patients with multiple (≥3) neurocysticercosis brain lesions. Whole-body MRI (short tau inversion recovery coronal sequences) was performed to assess the number of lesions in the brain and other body parts at baseline and 3 months after albendazole therapy. RESULTS: We screened 35 patients with multiple brain neurocysticercosis. In 13 patients, whole-body MRI demonstrated disseminated neurocysticercosis lesions. Ten patients were treated with albendazole. We excluded three patients. Brain MRI showed a mean lesion count of 163.6±193.8. Whole-body MRI (excluding the brain) showed a mean lesion count of 629.9±486.1. After albendazole therapy, the lesion load of the brain reduced significantly (163.6±193.8 to 99±178.3; p=0.008). Similarly, whole-body MRI showed a significant reduction in extracerebral neurocysticercosis lesion load (629.9±486.1 to 183.4±301.9; p=0.005). Three patients had complete resolution, five patients showed ≥50% reduction and two patients had <50% reduction in extracerebral lesion load. CONCLUSION: Whole-body MRI should routinely be performed in multiple neurocysticercosis lesions of the brain. Albendazole treatment leads to a remarkable reduction in neurocysticercosis lesions throughout the body.

Gallbladder Cancer in Simple Cholecystectomy Specimens-an Analysis of 8227 Gallbladders from an Endemic Region.

Gallbladder cancers (GBCs) detected at pathological examination for suspected benign gallbladder disease are known as incidental GBCs. These post-cholecystectomy GBCs (PCGBCs) constitute a small fraction of all cholecystectomies. The proportion of these PCGBCs is unknown in endemic regions like North India. We planned to study the proportion and epidemiology of these PCGBCs in a high-volume center in North India. We reviewed the histopathology reports of gallbladder specimens for a 5-year period between 1 January 2014 and 31 December 2018, from a prospectively maintained pathology database. Patient demographics, place of referral (academic/non-academic center), and tumor characteristics were recorded. Descriptive statistics are used to demonstrate the distribution of various factors. Of the 8227 gallbladder specimens examined, cancer was found in 162 specimens. Thus, the proportions of GBC in these cases were 1.96%. The T stage of the tumor was T1a in 6 (3.8%), T1b in 35 (22.2%), T2 in 61 (38.8%), and T3 in 55 (35%). Liver bed margins were positive in 32/103 (31%). Of the evaluable 108 cystic duct margins, 16 (14.8%) were positive. Both margins were positive in 7/77 (9%) specimens and at least one margin was positive in 26/77 (33.7%) patients. This is the first study to demonstrate the high proportion of PCGBCs in high incidence area. This study provides a compelling reason to investigate this high PCGBC numbers. Routine histopathological evaluation of gallbladder should be done with diligence as this could alter the prognosis of a patient, especially in areas of high GBC incidence.

Cytomorphology of pituitary carcinoma metastatic to liver diagnosed by fine-needle aspiration: A rare case report and review of literature.

Pituitary carcinomas (PCs) are rare entities constituting about 0.1-0.2% of all pituitary neoplasms. They are diagnosed by the presence of craniospinal or systemic metastasis in pituitary adenomas (PAs). The distant metastatic sites include liver, followed by bone, lung, and lymph nodes. The diagnosis of PC is rarely made on fine-needle aspiration cytology (FNAC) with only six cases reported till date; hence, the cytologic features are not well defined. Herein, we report a case of PA having high Ki-67 proliferation index and p53 expression, presenting with liver lesion 6 weeks post-surgery and diagnosed on FNA. Detailed cytomorphologic features are defined and compared. We emphasize that FNAC, along with clinic-radiologic correlation, is a cost-effective, safe, and diagnostically accurate method of diagnosing PC metastases.

Laboratory perspectives for Leprosy: Diagnostic, prognostic and predictive tools.

The diagnosis of leprosy poses several challenges. The bacillary load, serology, and tissue response are determined by the host immune status, which make individual tests unsuitable across the spectrum. The sensitivity of tests for identifying paucibacillary cases remains limited, on the other hand, many tests lack specificity in differentiating contacts from diseased cases. Nonetheless, a plethora of laboratory tests have been added to the armamentarium of the clinicians dealing with leprosy. In the current review, we critically analyze the tests available for diagnosis, prognostication, and prediction of treatment response in leprosy. We discuss in brief the conventional tests available and detail the newer serologic and molecular tests added over the past few years with an attempt to suggest the pros and cons of each, and the tests best fit for each clinical scenario. Slit skin smears and skin or nerve biopsies are primarily performed to exclude clinical mimics, confirm a diagnosis, and immunologically subtype the case. Antibody titres of phenolic glycolipid-1 and its synthetic variants can be measured in serum and saliva and provide noninvasive means to detect leprosy with good specificity. Conventional, quantitative, real-time, and other variants of PCR can detect M. leprae DNA and have been used to effect in blood, tissue, and urine samples. T helper I and II cytokine signatures can be used to differentiate the subtypes of leprosy. Newer machine learning algorithms use combinations of these tests to predict the development of leprosy in contacts. Tests to detect treatment response, antimicrobial drug resistance, and predict the onset of reactions in leprosy can be used to advantage. We compare the characteristics of these tests and suggest an algorithm for leprosy diagnosis optimally utilizing them in various clinical settings.

Impact of COVID 19 pandemic on patients requiring renal biopsy.

INTRODUCTION: The disruption of healthcare services in coronavirus disease (COVID)19 pandemic was widespread particularly due to lockdown curbs. This study was undertaken to see the effect of this pandemic on subjects requiring renal biopsy. MATERIALS AND METHOD: Renal biopsies performed during the COVID 19 pandemic between April 2020 and December 2020 (Group 1) were compared with those in pre-COVID period between June 2019 and February 2020 (Group 2). Indication of biopsies, syndromic diagnosis and all baseline laboratory characteristics were retrieved from the hospital records. RESULTS: 130 and 191 patients were biopsied in groups 1 and 2, respectively. Patients in group 1 were younger compared with group 2 (32.55 ± 15.60 and 36.37 ± 16.96 years, respectively, p value 0.038). The mean serum creatinine value in group 1 was significantly higher than in group 2 (3.21 ± 2.08 and 2.68 ± 2.02 mg/dl respectively, p value: 0.023). Group 1 comprises a significantly higher percentage of rapidly progressive renal failure patients (RPRF) (39.3 vs 28, p value 0.046). A higher percentage of nephrotics was biopsied in group 2 vs group 1 (46.9 vs 30.4 respectively, p value 0.008). The treatment protocol remained similar in both the groups. Evaluation of the transplant biopsies revealed a nonsignificant higher number of rejections in group 1 (11 out of 18) as compared to group 2 (5 out of 16), p value 0.100. Combined rejection saw a lesser use of rATG in group 1. CONCLUSION: COVID pandemic induced restrictive measures could have led to selective high risk patients with RPRF as presumptive diagnosis and higher creatinine values getting biopsied. Higher rejections were noticed in transplant recipients pointing towards the need of establishing a more efficient support system for managing such patients.

Fatal allograft mucormycosis complicating severe COVID-19 infection and bacterial pyelonephritis.

We herein present a case of live related kidney transplant recipient who initially developed severe coronavirus (COVID-19) disease associated with E.coli related pyelonephritis and graft dysfunction, who improved over one week only to deteriorate in the second week, with fever, oligoanuria and refractory shock. A postmortem allograft biopsy revealed angioinvasive mucormycosis. With the resurgence of mucormycosis during the COVID-19 pandemic, the transplant team should add allograft mucormycosis as a rare differential for severe graft dysfunction and oligoanuria in the COVID-19-infected kidney transplant recipient.

Perineal warty plaques: A case of verrucous porokeratosis.

Nonvenereal genital dermatoses form an important category of disorders, and verrucous porokeratosis is a rare and less recognized entity among the same. We present the case of a young adult male with warty growths over scrotum and buttocks for a year. Characteristic cornoid lamellae with typical differentiating features were seen in the histopathology, establishing the diagnosis. This case emphasizes the rare nonvenereal cause for a condition clinically mimicking condyloma acuminata.

Recurrent proteinuria with graft dysfunction: a diagnostic and clinical conundrum.

The index case is a 45-year old male with unknown cause for native kidney disease, who received a kidney from his wife. Antithymocyte globulin (ATG) was used for induction, and tacrolimus, mycophenolate mofetil and prednisolone were prescribed for maintenance. His baseline serum creatinine was 0.9 mg/dl. Two years after the transplant, the patient developed 3+ proteinuria on routine urinalysis with stable graft function. His 24-hour urinary protein was 2.3 grams, serum albumin was 3.0 g/dl, and the total cholesterol was 251 mg/dl. The tacrolimus C0 levels were maintained between 6 and 8 ng/ml range. Allograft biopsy revealed diffuse thickening of glomerular basement membranes, with the immunofluorescence showing 2+ granular positivity along the loops for IgG and C3. Further, tissue staining for PLA2R and THD7A were both negative. Also, no donor-specific antibodies (DSA) were detected, and serum PLA2R antibody assay was also negative. The patient was managed conservatively with losartan 50 mg and atorvastatin 20 mg, with subsequent reports of proteinuria of 1.5-2.0 grams/day. After 52 months of renal transplant, the patient presented with a serum creatinine of 2.06 mg/dl and proteinuria of 6.8 grams/day. A repeat allograft biopsy revealed thickened glomerular basement membranes with spikes on silver staining. (Figure 1a) Further, immunofluorescence studies showed 2+-3+ granular positivity for IgG, C3, with the added findings of C4d positivity on the peritubular capillaries and tissue PLA2R positivity on the basement membranes by immunohistochemistry. (Figures 1b-d) The biopsy also revealed peritubular capillaritis and acute tubular injury. Antibodies to donor Class II (HLA DR) were positive with a mean fluorescence intensity (MFI) of 6885, but serum PLA2R antibodies remained negative. Based on these findings, the patient was treated with pulse methylprednisolone, 5 sessions of plasma exchange at 40 ml/kg with 5% human albumin and fresh frozen plasma replacement, intravenous immunoglobulin (at 100 mg/kg × 5) and rituximab (two doses of 1 g 2 weeks apart). Subsequently, the serum creatinine settled to 1.6 mg/dl, and DSA reduced to < 500 MFI. Three months after discharge, the serum creatinine is 1.5 mg/dl, 24-hour urine protein is 982 mg/day and follow-up DSA remains negative.

Molecular classification and stratification of adult diffuse gliomas: A tertiary care center study.

BACKGROUND: Diffuse gliomas in the adult population are the most common primary central nervous system (CNS) tumors. The World Health Organization incorporated isocitrate dehydrogenase (IDH) mutations and 1p/19q co-deletion with histopathological features into an "integrated diagnosis" in the revised classification of tumors of CNS. These molecular subgroups of diffuse gliomas are found to stratify patients into prognostically distinct groups better than the histological classification. The objectives of the current study were to assess the frequency of IDH mutation, ATRX expression loss, p53 overexpression, and 1p/19q co-deletion detection in adult diffuse gliomas (Grade II, III, and IV) and to correlate them with clinicopathological and histopathological features. MATERIALS AND METHODS: The current study was a tertiary care hospital-based retrospective case series of 112 cases of adult diffuse gliomas. Immunohistochemistry (IHC)-based molecular detection was performed for IDH-1, ATRX, and p53 and fluorescent in situ hybridization (FISH) was performed for 1p/19q co-deletion detection. RESULTS: IDH-1 mutation was present in 30.4% (n = 34/112) cases, ATRX expression was lost in 18% (n = 19/104) cases, p53 was mutated in 39.3% (n = 42/107) cases and 1p19q was co-deleted in 25% (n = 4/16) cases. In the IDH1 mutant cases, with retained ATRX, FISH for 1p/19q co-deletion was performed and was co-deleted in four cases. CONCLUSION: The results of the present study indicate that IHC including IDH1/2, ATRX, and p53 is useful for the molecular classification of diffuse gliomas, which could be useful for the evaluation of prognosis, especially Grade III and II. Although the immunohistochemical approach does not replace genetic testing completely, it is a practical and powerful means of assessing molecular genetic changes. IDH mutations are the established markers of better prognosis in diffuse gliomas.

Recurrent proteinuria with graft dysfunction: a diagnostic and clinical conundrum.

The index case is a 45-year old male with unknown cause for native kidney disease, who received a kidney from his wife. Antithymocyte globulin (ATG) was used for induction, and tacrolimus, mycophenolate mofetil and prednisolone were prescribed for maintenance. His baseline serum creatinine was 0.9 mg/dl. Two years after the transplant, the patient developed 3+ proteinuria on routine urinalysis with stable graft function. His 24-hour urinary protein was 2.3 grams, serum albumin was 3.0 g/dl, and the total cholesterol was 251 mg/dl. The tacrolimus C0 levels were maintained between 6 and 8 ng/ml range. Allograft biopsy revealed diffuse thickening of glomerular basement membranes, with the immunofluorescence showing 2+ granular positivity along the loops for IgG and C3. Further, tissue staining for PLA2R and THD7A were both negative. Also, no donor-specific antibodies (DSA) were detected, and serum PLA2R antibody assay was also negative. The patient was managed conservatively with losartan 50 mg and atorvastatin 20 mg, with subsequent reports of proteinuria of 1.5-2.0 grams/day. After 52 months of renal transplant, the patient presented with a serum creatinine of 2.06 mg/dl and proteinuria of 6.8 grams/day. A repeat allograft biopsy revealed thickened glomerular basement membranes with spikes on silver staining. (Figure 1a) Further, immunofluorescence studies showed 2+-3+ granular positivity for IgG, C3, with the added findings of C4d positivity on the peritubular capillaries and tissue PLA2R positivity on the basement membranes by immunohistochemistry. (Figures 1b-d) The biopsy also revealed peritubular capillaritis and acute tubular injury. Antibodies to donor Class II (HLA DR) were positive with a mean fluorescence intensity (MFI) of 6885, but serum PLA2R antibodies remained negative. Based on these findings, the patient was treated with pulse methylprednisolone, 5 sessions of plasma exchange at 40 ml/kg with 5% human albumin and fresh frozen plasma replacement, intravenous immunoglobulin (at 100 mg/kg × 5) and rituximab (two doses of 1 g 2 weeks apart). Subsequently, the serum creatinine settled to 1.6 mg/dl, and DSA reduced to < 500 MFI. Three months after discharge, the serum creatinine is 1.5 mg/dl, 24-hour urine protein is 982 mg/day and follow-up DSA remains negative.

Programmed Death Ligand-1 Expression in Gliomas: A Study of Histopathological and Molecular Associations.

BACKGROUND: Gliomas are aggressive tumors with limited treatment options. Immunotherapy targets are under evaluation as new therapeutic targets in gliomas. AIMS AND OBJECTIVES: The aims of the study were to analyze expression of PDL1 in adult diffuse gliomas in World Health Organization grade II, III, and IV and to corelate its expression with demographic features, IDH-1, ATRX, and p-53 mutation status. MATERIALS AND METHODS: This was a case series that included 30 cases of adult diffuse glioma. In all cases, a composite diagnosis including histologic type, grade, and molecular alterations was rendered. PDL1 testing was done by immunohistochemistry using PDL1 SP-263 antibody. RESULTS: PDL1 expression was identified in 33.3% cases in tumor cells and in 6.67% cases in immune cells. All neoplasms with PDL1 expression were astrocytic tumors. PDL1 expression was significantly associated with IDH-1 immunonegative gliomas (P = 0.013). CONCLUSION: PDL1 is a novel therapeutic target in gliomas. The current study is an attempt to evaluate the expression of PDL1 over the varied spectrum of gliomas.