Pre-Transplant Cytokine Levels as Signatures of Microvascular Inflammation in Kidney Allograft Biopsies.

BACKGROUND:  The presence of microvascular inflammation (MVI) characterized by leukocyte margination in the glomeruli (glomerulitis, Banff score 'g') and peritubular capillaries (peritubular capillaritis, Banff score 'ptc') is a hallmark histological feature of antibody-mediated rejection (AMR), even in the absence of circumferential C4d positivity. In this study, we assessed the efficacy of pre-transplant plasma cytokines as an ancillary screening tool to identify MVI in kidney allograft indication biopsies to facilitate better graft survival. METHOD:  This single-center prospective analytical study comprises 38 kidney transplant recipients whose peripheral blood was collected before transplant and assessed for the plasma cytokine concentrations of FOXP3, IL-6, TGF beta, and IL-17 using enzyme-linked immunosorbent assays (ELISA). Histopathological assessment was done in post-transplant indication biopsies, and Banff scores of 'g+ ptc' were calculated to categorize recipients into three MVI groups. The correlational, regression, and ROC curve analyses were used to assess the association and predictive ability of the cytokines with respect to MVI. RESULTS:  In our study cohort, 27 recipients had MVI=0, five had MVI=1, and six had MVI≥2. A significant difference in plasma cytokines was observed between these groups, and we found a strong negative correlation of FOXP3 with MVI, whereas a strong positive correlation of IL-6, TGF beta, and IL-17 was recorded with MVI. We have also assessed the predictive ability of these cytokines, FOXP3, IL-6, TGF-beta, and IL-17, through the ROC curve, which showed an AUC of 0.70, 0.76, 0.84, and 0.72, respectively. CONCLUSION:  Our findings suggest that the pre-transplant levels of cytokines FOXP3, IL-6, TGF-beta, and IL-17 could be measured to identify recipients at risk of post-transplant MVI, which could further serve as an additional tool for effective management of the kidney allograft.

Prevalence and risk factors for chronic pulmonary aspergillosis in chronic obstructive pulmonary disease patients with acute exacerbations.

Chronic obstructive pulmonary disease (COPD) patients often experience acute exacerbations requiring hospitalization. Recently, attention has focused on Aspergillus sensitization in the airways of these COPD patients. This study aimed to assess the prevalence of chronic pulmonary aspergillosis (CPA) in COPD patients with acute exacerbations and identify associated risk factors. A cross-sectional descriptive study was conducted at the Jawaharlal Institute of Postgraduate Medical Education and Research from January 2021 to June 2022. Sixty-one COPD patients presenting with acute exacerbations were included. Demographic details, blood investigations, and sputum examinations were performed for all patients. A high-resolution computed tomography thorax was conducted for eligible patients. The prevalence of CPA among patients with an acute exacerbation of COPD was found to be 9.8%, with chronic cavitary pulmonary aspergillosis being the most common presentation (50%). Among post-tubercular COPD patients, the prevalence of CPA was significantly higher at 22.7%. Hemoptysis (p<0.001) and a previous history of tuberculosis (p=0.008) were associated with Aspergillus sensitization. This study highlights the substantial prevalence of CPA in COPD patients with acute exacerbations, particularly in those with a history of tuberculosis. Early recognition and targeted management of CPA in COPD patients may improve outcomes and reduce hospitalization rates. Further large-scale multi-center studies are needed to validate these findings and comprehensively address the impact of CPA on all COPD patients.

Giant cell collagenoma: Report of a rare tumor and review of literature.

ABSTRACT: Giant cell collagenoma (GCC) is a rare benign dermal fibrous tumor. Although it has many clinicopathological differential diagnoses, it is often confused with cutaneous sclerotic fibroma/storiform collagenoma (SF/SC) and dermatofibroma. The following characteristic features point to GCC's diagnosis over the latter: the presence of peculiar multinucleated giant cells, and vimentin positivity of both single and multinucleated giant cells on immunohistochemistry. Most of the reported cases have mentioned that GCC is a variant of SF/SC. We report a rare case of GCC presenting as a slow-growing solitary firm nodule over the right ankle. To the best of our knowledge, only less than ten cases have been reported, including the index case. We have also reviewed the clinicopathological features of those cases and discussed the approach to the diagnosis.

A comparison between conventional and the Paris systems of reporting urinary cytopathology with a literature update.

INTRODUCTION: Owing to certain inherent limitations of earlier reporting systems, "The Paris System for Reporting Urinary Cytology (TPS)" was implemented in 2015 to standardize reporting urine cytology with more stringent cytomorphologic criteria. We share our post-TPS experience, comparing it with the conventional system (CS). AIM: To assess and compare the cyto-histopathologic/cystoscopic agreement between the conventional and the Paris systems (CS and TPS) for reporting urine cytology. MATERIALS AND METHODS: It is a cross-sectional study involving urine samples from 170 patients divided into two groups (CS and TPS). Of the 170 cases, 85 were reported according to the CS, and 85 were reported according to TPS with all the relevant clinical, radiologic, and cystoscopic findings. Using the kappa statistics, both groups were statistically analyzed for sensitivity, specificity, predictive values, and agreement. RESULTS: The sensitivity and specificity for high-grade urothelial carcinoma (HGUC) as per TPS were 83.33% and 94.59%, respectively, while they were 73.47% and 80.56% for the conventional system. The agreement for HGUC with TPS was 87.06% with a kappa value of 0.7416, while it was 76.5% with a kappa value of 0.53 for the CS. Implementing the TPS minimized usage of the atypical urothelial cells (AUC) category, increasing the clarity in detecting HGUC. CONCLUSION: TPS provides better agreement with histopathology than the CS for diagnosing HGUC, which is attributable to stringent TPS criteria that prompt cytopathologists to look more diligently for morphologic and numeric criteria.

Predictive accuracy of histopathological profile and immunohistochemical markers for the aging of abrasion: an autopsy-based study.

Wound age estimation is a crucial medicolegal task for forensic pathologists. The main objective of the current study was to evaluate the ability of the histopathological profile and immunohistochemical markers (CD14 and IL-8) to predict the age of abrasion and, furthermore, identify the relationship between the histopathological profile and immunohistochemical markers in abrasion aging. The study involved postmortem cases (n = 246) of abrasion injuries in which the injury infliction time was known. The test skin samples were taken from the abrasion site, and an adjacent area of uninjured skin was sampled for control. Hematoxylin and eosin stain was applied to tissue sections for the histopathological analysis. The semi-quantitative evaluation was made for expressing immunohistochemical markers CD14 and IL-8 on the infiltrating inflammatory cells. The study showed that the age of abrasion was significantly higher (p < 0.05) among the cases with positive staining than those with negative staining for both CD14 and IL-8. Additionally, the study found a significant association between the age of the abrasion and the IHC staining for IL-8. However, no significant association was seen between the age of abrasion and the CD-14 IHC staining. The odds ratio (95% confidence interval) for more than 72 h of the age of abrasion was compared to 0 to 72 h of the age of abrasion. The odds ratios were 39.00 (4.177-364.13) for the predominant mononuclear cell infiltration and 84.50 (9.287-768.814) for cases with the appearance of fibroblast, granulation tissue, and collagen deposition when compared to an unremarkable change on histopathological examination. Positive staining of immunohistochemical markers CD14 and IL-8 for the age of abrasion of more than 72 h showed a sensitivity of 40% and 80.95%, respectively, and specificity of 71.6% and 52.5%, respectively. The quantification of the histopathological changes of predominant mononuclear cell infiltration and the appearance of fibroblast, granulation tissue formation, and collagen deposition showed a significant correlation for the age of abrasion of more than 72 h. The immunohistochemical analysis revealed IL-8 as a more accurate marker than CD14 in identifying abrasions older than 72 h.

The urgency of Burkitt lymphoma diagnosis in fluid cytology-A tertiary care experience.

BACKGROUND: Burkitt lymphoma (BL) is an aggressive high-grade B-cell non-Hodgkin lymphoma commonly diagnosed in young age and is known to involve extra nodal sites. But the involvement of body fluids by BL is an uncommon presentation. Rapid diagnosis of BL is vital to prevent complications like tumour lysis syndrome. Cytological examination of body fluids continues to be an indispensable tool for rapid diagnosis of BL. OBJECTIVES: In this study, we aim to study the clinical, cytomorphological and immunophenotypic characteristics of BL involving serous effusions and other fluids. MATERIALS AND METHODS: In this retrospective study, 17 cases reported as BL in fluid cytology from 2016 to 2022 were collected and reviewed. We performed a comprehensive analysis of the clinical data, cytomorphological features, immunophenotyping data along with the haematological workup of these cases. We have also compared with the histopathological diagnosis for those cases where biopsy was available. RESULTS: BL more commonly involved ascitic fluid (52%), followed by pleural fluid (4 cases) and cerebrospinal fluid (CSF; 4 cases). Primary diagnosis of BL in fluid was done in 88% of the cases. Bone marrow involvement was noted in two cases. Cytological smears showed discrete monomorphous population of medium-sized atypical lymphoid cells with frequent apoptotic bodies. Classic cytoplasmic punched out vacuoles were observed in 88% of the cases. Immunophenotyping data was available for 12 cases in which tumour cells showed positivity for CD20 (100%), CD10 (4 of 7 cases), BCL6 (3 of 5 cases) and cMYC (7 of 7 cases-100%) and were negative for Terminal deoxynucleotidyl transferase (TdT) (11 of 11 cases). Mean Ki67 labelling index was 95%. Histopathological diagnosis was available for 9 cases, and there was 100% agreement between cytological and histopathological diagnosis in 7 cases. CONCLUSION: Precise diagnosis of BL can be rendered in body fluids by identification of classic cytomorphological features and by performing supportive ancillary tests in fluids for immunophenotyping.

Congenital nephrotic syndrome with diffuse mesangial sclerosis caused by compound heterozygous mutation in LAMA5 gene.

A two-and-a-half-month-old female infant presented with generalized edema for 10 days. At presentation, she had periorbital puffiness, moderate ascites, and pedal edema. Laboratory investigations revealed serum albumin 1.3 g/dL, spot urine protein to creatinine ratio (Up:Uc) 20.87 mg/mg, total cholesterol 380 mg/dL, and serum creatinine 0.31 mg/dL. Exome sequencing revealed compound heterozygous variants in LAMA5 gene (NM_005560.6). There was a heterozygous likely pathogenic missense variant in exon 2: LAMA5: c.385C > A (depth 195 ×) and another heterozygous pathogenic variant in exon 31: LAMA5: c.3932_3936dup; parental segregation by Sanger sequencing proved that the variants were in trans. Kidney biopsy showed diffuse mesangial sclerosis (DMS). Our case adds LAMA5 gene to the constellation of genes causing DMS, in addition to the classically described WT1, LAMB2, and PLCE1 genes and to the list of genes causing congenital nephrotic syndrome (CNS).

Can combined non-invasive methods improve diagnosis of lung cancer?

Background: Lung cancer is the most common malignancy in both gender. Early diagnosis is needed to reduce morbidity and mortality. There is a debate about the most accurate investigating modality for the diagnosis of lung cancer. Methods: It is a retrospective cohort analysis to determine whether an approach of combined contrast-enhanced computed tomography (CECT) thorax with bronchoscopy method has higher sensitivity and specificity than combined CECT thorax with sputum cytology method. Records of patients with lung cancer who had visited the hospital within the last 6 months were retrospectively analyzed for their diagnostic modality. SPSS version 19 software was used for statistical analysis of the data. CECT scan thorax, bronchoscopy, and sputum cytology for lung cancer patients were analyzed. The CECT thorax plus bronchoscopy method was compared with the CECT thorax plus sputum cytology method. Their sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in diagnosing lung cancer were analyzed. Results: Sixty-two patients were considered, including 62.9% males with a mean age of 55.5 years. In patients diagnosed with lung cancer, CECT thorax combined with bronchoscopy method was found to have a sensitivity of 96.67% than CECT thorax combined with sputum cytology method with a sensitivity of 90% and the difference in sensitivity between all individual approaches as well as the combined method was statistically significant with a P = 0.00001 and Chi-square value of 86.5909 owing to the low sensitivity of sputum cytology. CECT thorax combined with sputum cytology approach had a better specificity than CECT thorax combined with bronchoscopy. Conclusion: Combined CECT thorax with sputum cytology method has a better specificity in diagnosing lung cancer than combined CECT thorax with bronchoscopy method.

Inflammatory Myofibroblastic Tumor of the Testis in a Patient With Cecal Carcinoma.

Inflammatory myofibroblastic tumors (IMTs) are uncommon tumors that can be classified among fibroinflammatory disorders. IMTs are diagnosed after excluding all other entities, which can be considered differential diagnoses of IMTs. Microscopic examination of IMTs shows multiple myofibroblastic spindle cells, which are surrounded by inflammation. IMTs have lesser chances of progression to malignancy. The case defined below is one of the few cases in the literature that reports the presentation of IMT and another malignancy. We describe a 72-year-old man who was found to have cecal carcinoma and later diagnosed with an IMT of the testis. IMTs are generally benign tumors with a tendency for local recurrence. Patients affected by IMTs usually get diagnosed only after more than one biopsy. IMT is diagnosed only after ruling out other differential diagnoses. They rarely show invasiveness and metastasize. The presence of metastasis, recurrence, and other malignancies probably indicate poor prognosis and poor survival. The course of IMTs is usually benign, with good outcomes after surgery. IMTs have been known to recur, invade, or metastasize in sites such as paranasal sinuses, mediastinum, and the abdomen. In the case that we researched, vimentin and smooth muscle actin were strongly positive in the spindle-shaped cells, whereas anaplastic lymphoma kinase-1 was negative.

Bacillary Positive Tuberculous Body Fluid Smears: A Perspective on How Fast to Use Acid Fast.

Background Tuberculous effusions are common. Classically, they are described as bacteria poor and lymphocyte rich. Our experience, however, has been more varied. We compiled this rare group of bacteria-positive tuberculous fluids to document their cytologic spectrum and to look for possible predictors of bacillary positivity. Methods Fifty-one cases of bacillary positive fluids were identified and their clinicopathological details were noted. Per case, the smear background was assigned as either clear, caseous, suppurative, granular proteinaceous or frankly hemorrhagic. Fine, punched-out vacuoles in the smear background were also noted. The bacillary load in each case was classified from scanty to 3+. Eventually, the clinicopathologic variables were tabulated for frequency and studied for any association with bacillary presence. Results Only 19 of the 51 patients had a history of tuberculosis. Retropositive patients comprised a small proportion (9.8%) and did not always indicate strong (3+) bacillary positivity. The granular proteinaceous background was the most frequent (35%) pattern. Only a suppurative background was associated with strong bacillary positivity. Fine vacuoles were seen almost always with caseous and granular proteinaceous backgrounds but without statistical significance. Conclusion Tuberculous effusions can have diverse smear backgrounds, not necessarily one rich in caseous material. When tuberculosis is known or clinically suspected, non-classical findings such as abundant neutrophils or suppurative background should not dissuade one from requisitioning mycobacterial stains. In fact, acid-fast stains should probably routinely accompany Giemsa slides of clinically idiopathic effusions in endemic areas since it is still the cheapest and fastest method for a conclusive diagnosis.

Dermoscopic features of basal cell carcinoma in skin of color: A retrospective cross-sectional study from Puducherry, South India.

BACKGROUND: Dermoscopy is useful in the diagnosis of basal cell carcinoma (BCC). However, most descriptions of the dermoscopic features of BCCs are in Caucasians (skin types I-III) and there is a paucity of data in dark-skinned Indian patients. AIMS: The aim of this study was to describe the various dermoscopic features of BCC in dark-skinned patients from South India and correlate these with the histopathologic subtypes. METHODS: A retrospective observational study of biopsy-proven cases of BCC was conducted at a tertiary care center in South India using nonpolarized contact dermoscopy. RESULTS: Sixty BCCs in 35 patients predominantly of skin phototypes IV or V were studied. These included 32 nodular, 27 superficial and 1 infiltrative type of BCC. The most common dermoscopic features noted were maple leaf-like areas (61.7%), blue-white veils (53.4%), ulceration (48.4%) and short fine telangiectases (46.7%). Ulceration, blue-white veils and arborizing vessels were significantly associated with nodular BCCs, while maple leaf-like areas, red-white structureless areas, multiple small erosions and spoke wheel areas were noted with superficial BCCs. LIMITATIONS: The limitations of this study include its retrospective nature, the use of only nonpolarized light for examination, the lack of other histopathological variants of BCC as well as the lack of a comparison group. CONCLUSION: We report a dermoscopic study of BCC in dark-skinned patients from Puducherry, South India. The blue-white veil was observed in half of the patients and was significantly associated with nodular BCCs. The addition of the blue-white veil to the diagnostic criteria for pigmented BCC could improve the diagnostic accuracy of dermoscopy in Indian patients.

Disseminated rhinosporidiosis masquerading as soft tissue round cell tumour diagnosed by fine needle aspiration cytology.

Rhinosporidium seeberi belongs to the eukaryotic class Mesomycetozoea and causes chronic granulomatous lesions known as rhinosporidiosis. Rhinosporidiosis frequently involves the nasal cavity and nasopharynx through transepithelial invasion. Atypical presentations of this disease at other body sites have been reported, including the subcutis, visceral organs, bones, and genitals. Only a few cases of cutaneous and subcutaneous involvement have been reported to date. This chronic granulomatous condition is known for its recurrence following autoinoculation unless the correct diagnosis and appropriate treatment are given. We describe a case of an immunocompetent adult who had undergone fine needle aspiration cytology (FNAC) of mass-like swellings in the right thigh and right calf at another healthcare centre and had been diagnosed with a small round blue cell tumour. FNAC at our centre confirmed a rare case of rhinosporidiosis that was clinically mimicking a soft tissue neoplasm of the lower extremity, and the erroneous interpretation of the prior cytology studies had resulted in misinterpretation of the individually dispersed pathogenic organisms as individual malignant cells. FNAC of rhinosporidiosis can lead to early diagnosis and prompt treatment of this pathogen when it presents at unanticipated body sites.

Clinicopathological Spectrum of Cutaneous Lymphomas and Distinction of Early Mycosis Fungoides from its Mimics-A Retro-Prospective Descriptive Study from Southern India.

Background: Cutaneous lymphomas (CLs) could be either primary (PCL) or secondary; the former comprises cutaneous T-cell lymphomas (CTCLs) and cutaneous B-cell lymphomas (CBCLs). Mycosis fungoides (MF) is the most common PCL. Diagnosis of early MF and distinguishing it from benign inflammatory mimics is challenging. This study aims to assess the clinicopathological spectrum of CL and to characterize early MF from its mimics using clinical characteristics, histopathological features, and ancillary techniques. Materials and Methods: This retro-prospective descriptive study was conducted in a tertiary-care institute, for over 5 years. Clinically as well as histopathologically suspected and biopsy-proven CL and their mimics were included. Cases were reviewed and subgrouped based on clinical and histopathological parameters and immunohistochemistry (IHC). Data were analyzed using descriptive statistics and a Chi-square test at a 5% level of significance. Results: Among PCL, CTCL comprised 84% (21/25) and CBCL was 16% (4/25); the most common CTCL was MF at 81% (17/21). Histologically, atypia of dermal infiltrate (100%), epidermotropism (91.7%), basal alignment of lymphocytes (91.7%), clear haloed cells (91.7%), wiry collagen (66.7%), grandiosity sign (50%), eccrine infiltration (66.7%), and follicular infiltration (50%) were significantly associated with early MF. Spongiosis (84.6%), pigment incontinence (84.6%), exocytosis (76.9%), and parakeratosis (76.9%) were significantly associated with inflammatory mimics. There was no significant difference in the downregulation pattern of CD7 (P = 0.206) between early MF and its mimics. The four cases of CBCL in our study were plasmablastic lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, and lymphoblastic lymphoma. Conclusion: MF was the most common PCL. Histological parameters showed a significant difference, whereas IHC did not show any significant difference between early MF and its mimics.