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).

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.

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.

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.

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.

Cytology of primary nocardiosis of the lymph node: A rare report.

Primary nocardiosis of the lymph node is a rare presentation even in an immunocompromised individual, with few case reports in the literature. In addition, Nocardia farcinica as observed in our case, is rarely documented, making it an interesting report. This paper clearly illustrates the subtle morphological clues that can be used to diagnose nocardial infection.

How fine needle aspiration cytology and flow cytometry helped in diagnosing a high-grade B-cell lymphoma masquerading as leukaemia.

High-grade B-cell lymphoma (HGBL) has recently been introduced into the category of aggressive, mature B-cell lymphomas. It is biologically different from diffuse large B-cell lymphoma and Burkitt lymphoma and exhibits an aggressive course. Leukaemic presentation, though known in various types of mature B-cell and mature T-cell lymphomas, is rare in high-grade B-cell lymphoma. We report one such case of a high-grade B-cell lymphoma which was masquerading as acute leukaemia with a soft tissue infiltration, with added emphasis on the role of fine needle aspiration cytology and flow cytometry in the diagnosis, and their therapeutic significance.

Comparison of the quality of the microwave cell-block method with the conventional cell-block method in processing body fluid samples.

INTRODUCTION: Conventional cell blocks (CCB) prepared from cytological specimens are very useful but the method is relatively time-consuming. Suitable modifications in cell-block techniques are beneficial for improving the turnaround time. We share our experience of a rapid microwave cell-block (MCB) technique. AIM AND OBJECTIVES: To study the quality of routine and immunohistochemical (IHC) staining of cell-block sections from serous body fluids prepared by the MCB technique compared with the CCB technique. METHOD: A total of 177 serous body fluid samples were processed by routine centrifugation technique, and the sediments were used for cell-block preparations by both conventional and rapid microwave methods. Cell-block sections were stained with haematoxylin and eosin stain. Haematoxylin and eosin staining quality was analysed using three parameters (cellularity, morphology and staining intensity). IHC for epithelial membrane antigen and calretinin were also performed, and the quality of staining was evaluated on 62/177 samples. Results were analysed using appropriate statistical tests. RESULTS: The time taken for processing cell blocks by the MCB method was 1 hour and 18 minutes compared to 13 hours and 45 minutes by CCB. The quality of sections by both methods showed good agreement for cellularity and intensity of staining, and moderate agreement for morphology. A 100% concordance was noted for distinguishing benign and malignant samples on morphology as well as with IHC stain results. CONCLUSION: Although the techniques are comparable in terms of quality of routine and IHC staining, we recommend using the MCB technique due to its short turnaround time.

The utility of fine needle aspiration cytology in orbital haematolymphoid neoplasms.

BACKGROUND: Orbital hematolymphoid lesions are rare and usually encountered in elderly patients. Orbital lesions are not easy to biopsy: hence fine needle aspiration cytology (FNAC) can be a very good diagnostic modality for these lesions. MATERIALS AND METHODS: Cases of orbital masses subjected to FNAC dating from 2013 to 2020 were retrieved from our archives. A total of 16 cases with biopsy confirmation were included. All clinical details, the type of procedure, details of the immunocytochemistry (ICC) performed on smear, follow-up biopsy, and their haematological work-up were analysed in detail. RESULTS: Sixteen biopsy-confirmed cases had been diagnosed as orbital haematolymphoid lesions on cytomorphology and further categorised with ancillary studies including ICC. In twelve instances, the cytology impression was congruent with the histopathological diagnosis and eight of the sixteen cases (50%) proved to be primary orbital lymphoma. Four were secondary orbital lymphomas and the remaining four included one case each of plasmacytoma, myeloid sarcoma, Rosai-Dorfman disease and angiolymphoid hyperplasia with eosinophilia. CONCLUSION: FNAC is a minimally invasive procedure for diagnosing most of the haematolymphoid orbital lesions and it has a rapid turnaround time. The accuracy of cytomorphology combined with ICC on smears/cell blocks can be as good as a biopsy for exact categorisation. Additionally, aspirate smears are preferred samples for cytogenetics compared to formalin-fixed tissue blocks, as molecular cytogenetics techniques are frequently employed for diagnostic, prognostic, and therapeutic purposes.

Descriptive study of the histopathological subtypes and programmed death-ligand 1 in metaplastic breast carcinoma.

Metaplastic Breast Carcinoma (MBC) is a rare heterogeneous group of tumors, the incidence of which is less than 1% of breast tumors. These are a unique set of tumors with varying subtypes, poor prognosis, and an increased chance of distant metastasis. We aimed to study the clinical, histomorphological, and immunohistochemical (IHC) features of Metaplastic Breast Carcinoma (MBC). This was a descriptive study of cases diagnosed as MBC at a tertiary care center in Southern India from January 2015 to December 2019. A total of 20 cases were diagnosed whose clinical, histomorphological, and IHC features were studied. PD-L1and CD8 IHC were performed and analyzed in 12 cases. The median age of presentation was 50 years. Seventy percent (14/20) patients were postmenopausal women. On excision, 75% (15/20) showed mixed typed MBC, the remainder showing epithelial type MBC. Metastasis to axillary lymph node was seen only in 20% (4/20) of the cases. Thirty percent (6/20) of the cases belonged to stage 3 disease and 5% (1/20) of the cases belonged to stage 4 disease with liver metastasis. Estrogen receptor (ER), Progesterone receptor (PR) were negative in all the cases, Her2neu was positive in three cases. Ki67 labeling index was greater than 14% in all the cases. PD-L1was positive in 41.5% of the cases and intratumoral CD8 positive lymphocytes were increased in 83.3% of the cases. MBCs are tumors occurring in elderly postmenopausal women, presenting with large tumor size, have lesser chances of lymph node metastasis, and a higher chance of recurrence and hematogenous spread. They are negative for ER, PR, Her-2 neu, with a high Ki67 index and a strong PDL-1 expression.

Takayasu arteritis (TA) first presenting with intestinal ischemia: a case report and review of gastrointestinal tract involvement (ischemic and non-ischemic) associated with TA.

Takayasu arteritis (TA) is a large vessel vasculitis involving the aorta and its major branches. Insidious inflammation usually results in gradual arterial narrowing; however, critical organ ischemia is rare. We describe a young male with TA who presented with acute mesenteric ischemia requiring intestinal resection, followed by critical limb ischemia. In our literature review, we identified intestinal gangrene as a rare manifestation of TA. However, intestinal ischemia as the first manifestation of TA has been scarcely reported in the literature. Also, ischemia of the intestine occurring together with critical limb ischemia is extremely unusual. Rheumatologists should be aware of TA as a rare cause of gastrointestinal vasculitis in young adults, which can be easily suspected by routinely examining all the peripheral pulses.