The Expression of Mucin-4 (MUC4) in Sarcomas Apart From Sclerosing Epithelioid Fibrosarcoma and Low-Grade Fibromyxoid Sarcoma.

Background Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) are two rare but aggressive soft tissue sarcomas that can be difficult to distinguish due to histopathological similarities. The present study examines the diagnostic capacities of mucin-4 (MUC4), a transmembrane mucin, in identifying different types of sarcomas and broadens its evaluation to include a wide range of sarcomas. Methods Immunohistochemical (IHC) examination of tissue samples from various sarcomas was performed using a mouse anti-MUC4 monoclonal antibody. IHC was conducted on 4-mm thick formalin-fixed paraffin-embedded tissue sections after pressure cooker antigen retrieval with a mouse anti-MUC4 monoclonal antibody. Results MUC4 was shown to be highly expressed in SEF (n=13) and LGFMS (n=10), while focal positivity in synovial sarcoma (n=1). Other sarcomas, such as malignant peripheral nerve sheath tumors, fibrosarcoma, leiomyosarcoma, liposarcoma, and myxofibrosarcoma, exhibited no expression (n=0). These findings are consistent with previous research and support MUC4 specificity as a SEF and LGFMS marker. This study provides information on the diagnostic efficacy of MUC4, particularly in the context of certain subtypes. It not only helps our understanding of these unique instances, but it also provides context for histopathological and IHC findings in soft tissue sarcoma. Furthermore, this study investigates the influence of age and gender on MUC4 expression in a range of sarcomas, which was typically understudied in the literature and found no relation with expression of MUC4. Conclusion In conclusion, this study adds to our understanding of soft tissue sarcomas by emphasizing the crucial role of MUC4 in certain sarcoma subtypes while acknowledging the complex variety of the sarcoma landscape. Further research is needed to understand the molecular mechanism that governs marker expression patterns, as well as the therapeutic implications.

Acute Tubulointerstitial Nephritis and Secondary Renal Amyloidosis: A Rare Complication of Atezolizumab.

Lung cancer is the second most common malignancy in both genders and the most common cause of cancer-related deaths worldwide. Broadly, lung cancer is divided into two types: small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Non-small cell lung cancer accounts for 85% of the diagnoses of lung cancer. It is necessary to check for any targetable mutations, which can help in deciding the treatment plan for the patients. The patient we are reporting is a 70-year-old male with multiple co-morbidities diagnosed with non-small cell carcinoma, favoring adenocarcinoma on histopathology. He was started on Atezolizumab/Bevacizumab/Carboplatin/Paclitaxel (ABCP). He was switched to maintenance Atezolizumab/Bevacizumab after four cycles due to poor tolerance to carboplatin and paclitaxel. The patient presented with neutropenic colitis and acute kidney injury (AKI), requiring admission. workup revealed nephrotic range proteinuria with a high urinary albumin-to-creatinine ratio. He underwent a renal biopsy to ascertain the cause of his proteinuria, which showed marked acute and chronic tubulo-interstitial nephritis (TIN), amyloidosis, and global glomerulosclerosis. Secondary (AA) amyloidosis is characterized by the extracellular deposition of misfolded proteins. Although interstitial nephritis is a reported side effect of immune checkpoint inhibitors, AA amyloidosis is a rarer side effect. So, to determine the exact cause and early therapeutic intervention in immune checkpoint inhibitor-related kidney injury, large retrospective or prospective studies should be done.

Omega-3 long-chain polyunsaturated fatty acids: Metabolism and health implications.

Recently, omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have gained substantial interest due to their specific structure and biological functions. Humans cannot naturally produce these fatty acids (FAs), making it crucial to obtain them from our diet. This comprehensive review details n-3 LC-PUFAs and their role in promoting and maintaining optimal health. The article thoroughly analyses several sources of n-3 LC-PUFAs and their respective bioavailability, covering marine, microbial and plant-based sources. Furthermore, we provide an in-depth analysis of the biological impacts of n-3 LC-PUFAs on health conditions, with particular emphasis on cardiovascular disease (CVD), gastrointestinal (GI) cancer, diabetes, depression, arthritis, and cognition. In addition, we highlight the significance of fortification and supplementation of n-3 LC-PUFAs in both functional foods and dietary supplements. Additionally, we conducted a detailed analysis of the several kinds of n-3 LC-PUFAs supplements currently available in the market, including an assessment of their recommended intake, safety, and effectiveness. The dietary guidelines associated with n-3 LC-PUFAs are also highlighted, focusing on the significance of maintaining a well-balanced intake of n-3 PUFAs to enhance health benefits. Lastly, we highlight future directions for further research in this area and their potential implications for public health.

Application Of New WHO Classification On Malignancies Of Sinonasal Tract: Correlation With Epidemiology And Survival In Pakistani Population.

Objectives: To analyse the clinicopathological characteristics of sinonasal malignancies in the light of the updates regarding head and neck tumours. METHODS: The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data of patients diagnosed with primary malignant tumours of the sinonasal tract between 2015 and 2020. Slides related to biopsies and resection specimens were retrieved from the institutional database and reviewed by two pathologists. Follow-up data was also obtained. Data was analysed using SPSS 20. RESULTS: Of the 245 samples, 144(58.7%) were epithelial tumours, 46(18.7%) neuroectodermal tumours, 41(16.7%) haematolymphoid tumours and 14(5.7%) were malignant soft tissue tumours. A heavy reliance was placed on immunohistochemical stains to diagnose poorly-differentiated tumours. Survival was dismal, especially with early and frequent spread to the brain (33.3% in cases of Sinonasal Undifferentiated Carcinoma). CONCLUSIONS: A wide array of sinonasal malignancies was seen. Updated knowledge of the malignancies prevalent in the region is imperative for timely diagnosis and treatment.

Identification of a Unique Morphological Pattern for the Diagnosis of Fungal Rhinosinusitis.

Fungal rhinosinusitis (FRS) is a relatively common, but often misdiagnosed disease of paranasal sinuses. The FRS is classified into invasive and non-invasive forms. The non-invasive form includes fungal ball and allergic FRS, and invasive form includes acute invasive FRS, chronic invasive FRS, and granulomatous FRS. Invasive fungal infections are associated with high morbidity and mortality, hence requiring urgent medical and surgical intervention. The histomorphology can help identify certain fungal organisms that cannot be cultured or are rarely visible in exudates. The morphologic diagnosis of tissue invasive and non-invasive fungal infection is essential for appropriate treatment. We analyzed cases of rhinosinusitis from 2017 to 2019 in Pathology Department at a tertiary care cancer hospital, Lahore, Pakistan. All clinical information was retrieved from patient records. Paraffin-embedded tissue blocks were stained with hematoxylin and eosin (H&E), special Grocott methenamine silver stain (GMS), and periodic acid Schiff stain (PAS) according to standard protocol. They were reviewed by two pathologists blinded by fungus status. A total of 169 cases of rhinosinusitis were reviewed. FRS comprised 146 (86.4%) of them. The mean age of patients with FRS was 32.8±14 years. The male:female ratio was 1.4:1. Maxillary sinus was the main site of involvement in 39 (27%) FRS cases. Aspergillus was identified in 117 (80.1%) cases of FRS. The culture reports were available in 44/146 (30.14%) FRS cases. They were negative in 22/44 (50.0%), and Aspergillus species were isolated in 18/44 (40.9%) cases of FRS. There were 84 (57.5%) cases of non-invasive FRS and 59 (40.4%) cases of invasive FRS. Among invasive FRS, there were 56 (38.4%) chronic granulomatous FRS cases including mixed patterns. Majority cases, 54 (96.4%), of chronic granulomatous FRS showed a unique crowded giant cell pattern comprising of foreign body and Langhans type giant cells. These giant cells were arranged closely forming irregular non-caseating granulomas surrounded by lymphocytes and fibrosis. Interestingly, the giant cells were scattered haphazardly without forming a granuloma as well. Fungal organisms were identified in all 56 cases of chronic granulomatous FRS. Histologically, predominant organism was Aspergillus in 48 (85.7%) on GMS and PAS stain. Our study observed a unique crowded giant cell pattern, which is a hallmark of invasive fungal infection. If pathologists are familiar with this unique pattern, they can make a quick and accurate diagnosis on histology. The physician can start antifungal treatment timely for better prognosis.

Gemistocytic Differentiation in Isocitrate Dehydrogenase Mutant Astrocytomas: A Histopathological and Survival Analysis.

Gemistocytic differentiation is a rare histological feature seen in IDH mutant Astrocytomas. The 2021 World Health Organization (WHO) retains the diagnosis of IDH mutant Astrocytoma with its classical histology and tumors with the rare histological pattern of gemistocytic differentiation. Gemistocytic differentiation has historically been associated with a worse prognosis and shorter survival, and this prognostic difference has not been investigated in detail in our population. A population-based retrospective study included 56 patients with IDH mutant Astrocytoma with Gemistocytic differentiation and IDH mutant Astrocytoma diagnosed between 2010 and 2018 in our hospital. Demographic, histopathological, and clinical parameters were compared between the two groups. Gemistocyte percentage, perivascular lymphoid infiltrates, and Ki-67 proliferation index were also analyzed. A Kaplan-Meier analysis was done to analyze any prognostic difference in the overall survival time between the two groups. Patients with an IDH mutant Astrocytoma having gemistocytic differentiation had an average survival period of 2 years, while patients diagnosed with an IDH mutant Astrocytoma had an average survival time of approximately 6 years. There was a statistically significant decrease in survival time (p = 0.005) for patients with tumors with gemistocytic differentiation. The percentage of gemistocytes and the presence of perivascular lymphoid aggregates did not correlate with survival time (p = 0.303 and 0.602, respectively). Tumors with gemistocytic morphology had a higher mean Ki-67 proliferation index (4.4%) than IDH mutant Astrocytoma (2.0%, p = 0.005). Our data suggest that IDH mutant Astrocytoma with Gemistocytic differentiation is an aggressive variant of IDH mutant Astrocytoma associated with a shorter survival time and an overall worse prognosis. This data might be helpful to clinicians in the future management of IDH mutant Astrocytoma with Gesmistocytic differentiation as an aggressive tumor.

Blind Spot in the Radar of MEST-C Score: Type and Severity of Tubulointerstitial Nephritis in IgA Nephropathy.

Background: The updated version of predictive classification for immunoglobulin A nephropathy (IgAN) prognosis "The Oxford Classification" identifies five histopathological features including mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), tubular atrophy/interstitial fibrosis (T) and crescents (C), the MEST-C. However, few studies suggest that tubulointerstitial inflammation, which is not included in the MEST-C, is also linked to disease progression and is, consequently, a neglected determinant of prognosis among others. Therefore, there is a need to evaluate this histopathological parameter in patients with IgA nephropathy. Materials and Methods: This cross-sectional descriptive study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan. Data of histopathological and immunofluorescence proven renal biopsies (300) of IgA nephropathy patients from January 2016 through May 2022 were extracted using a convenient sampling technique. Biopsies were histologically reviewed for type and severity of tubulointerstitial inflammation, in addition to the MEST-C score. Renal biopsies of patients who had a history of transplant, autolyzed tissue, no glomeruli on histological examination, and/or a tubular atrophy/interstitial fibrosis score of 2 (T2) in MEST-C scoring were excluded. Data were analyzed using SPSS 20. An association between the variables was analyzed using the chi-square and Fischer exact tests. A p value less than 0.05 was considered statistically significant. Results: A total of 247/300 biopsies were eligible for inclusion. The mean age at the time of biopsy was 31.90 ± 12.48 with 63.6% in the age group between 21 and 40 years, and 69.6% were male. Tubulointerstitial inflammation was observed in 90.2% cases with 49.4% showing moderate while 4.5% showing severe degree of inflammation. A strong association of both the type and severity of tubulointerstitial inflammation was found with M, E, T, and C scores (p value < 0.05). Conclusion: The high-frequency and strong statistical association of tubulointerstitial inflammation with the M, E, T, and C scores in our study elucidate its prognostic role in the progression and management of IgA nephropathy.

Histopathological Characteristics and Prognosis of Malignant Acral Melanomas in Pakistani Patients.

Background Malignant melanoma is a common cancer in Scandanavian countries due to increased exposure to ultraviolet light. Very limited data is available on malignant melanomas in Pakistani population and further studies are needed to determine its incidence in our population. Objective The main objective of our study was to determine histopathological characteristics and prognosis of malignant foot melanomas in Pakistani patients. Material and methods After approval by the Institutional Review Board, we performed a retrospective study of 59 consecutive cases of malignant acral melanoma from the year 2016-2019. The follow-up of in-house cases was available in hospital archives. The follow-up of diagnostic patients was done through direct communication. The histological features were assessed, and the prognosis was determined in terms of recurrence, metastasis, and death. Results The main histological features assessed were Breslow thickness <1 (n=3), >1-2 (n=9), >2-4 (n=12), >4 (n=36), ulceration was present in 65% (n=39), and pathological stage 1 (n=3), stage 2 (n=9), stage 3 (n=12) and stage 4 (n=36). The margin was involved in 28.3% (n=17) cases. Recurrence was observed in 47.4% (n=28), metastasis in 55.9 % (n=33), and death was observed in 49.1% (n=29). The mean follow-up duration of 3.4 years ± 0.20 (Range 3 to 6 years). The recurrence-free survival was 2.9 ± 0.24 years, metastasis-free survival was 2.8 ± 0.237 years, and disease-specific survival was 3.4 ± 0.203 years.  Conclusion Malignant acral melanoma is fatal with high mortality rates. In our part of the world, acral melanoma has poor prognosis compared to non-acral melanomas. When compared with acral melanomas in other parts of the world prognosis is even worst. Early diagnosis and treatment are crucial in terms of patient management.

Prognostic significance of minor high grade component in non-invasive papillary urothelial carcinoma of urinary bladder: (A study of 273 consecutive cases over a period of 3 years).

PURPOSE: Our study aimed to determine the prognostic significance of minor high-grade components (HGC) in non-invasive papillary urothelial carcinomas compared with pure low-grade and high-grade tumors. MATERIAL AND METHODS: We retrospectively retrieved 273 in-house cases of non-invasive papillary urothelial carcinomas (pTa) from 2016 to 2018 for which follow up data was available in hospital archives. We stratified our data into four main groups (G). G1, pure low-grade (n = 164); G2, HGC ≤5 % (n = 17); G3, HGC >5 % to ≤25 % (n = 14); and G4, pure high-grade (n = 78). Prognosis was assessed in terms of recurrence, grade and stage of progression, metastasis, and death. The mean follow up duration was 34.72 ± 20 months (range 20-60 months). RESULTS: All four groups showed no difference in tumor recurrence (G1 81.7 %, G2 88.2 %, G3 92.9 %, G4 92.3 % p-value 0.183). In terms of grade progression, there was no significant difference in G2 35.3 % and G3 35.7 % and both groups showed worst prognosis compared to G1 16.5 % p-value 0.04. Regarding stage progression (G1 6.7 %, G2 23.5 %, G3 28.6 %, G4 41% p-value 0.001), metastasis (G1 5.5 %, G2 5.9 %, G3 7.1 %, G4 17.9 % p-value 0.01) and death (G1 4.3 %, G2 5.9 %, G3 7.1 %, G4 15.4 % p-value 0.02) there was no significant difference in G2 and G3 and both groups showed worst prognosis than G1 and better than G4. CONCLUSION: Urothelial carcinomas with minor high-grade component ≤25 % behaved worst than pure low grade and better than pure high grade and should be treated as distinct grade entity.

Expression of NKX2.2 in Non-Ewing Tumors With Round Cell Morphology.

Background Round cell sarcomas pose diagnostic challenges due to overlapping histopathological features, necessitating precise immunohistochemical markers for accurate categorization. NKX2.2 has emerged as a sensitive diagnostic tool, particularly in Ewing sarcoma. This study extends this understanding to various round-cell sarcomas, shedding light on the potential diagnostic utility of NKX2.2 beyond its established role. The nuanced exploration of NKX2.2 expression aims to enhance diagnostic strategies, prognostic assessments, and therapeutic developments in the landscape of sarcoma research. Methodology Cases were retrieved from the surgical pathology and consultation files of Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan. Representative hematoxylin and eosin-stained slides of six different types of already confirmed tumors, including lymphoblastic lymphoma, neuroblastoma, rhabdomyosarcoma, synovial sarcoma, Wilms tumor, and Ewing sarcoma, were reviewed by a panel of pathologists. Immunohistochemistry, utilizing a rabbit anti-NKX2.2 monoclonal antibody, was performed on formalin-fixed paraffin-embedded tissue sections. The presence of NKX2.2 was defined as moderate or high nuclear immunoreactivity in at least 5% of cells. Results The histopathological examination revealed characteristic features in each sarcoma subtype, aligning with established diagnostic criteria. In Lymphoblastic lymphoma, T-cell lineage was confirmed through TdT expression, while the atypical finding of focal NKX 2.2 expression hinted at genetic diversity. Neuroblastoma exhibited the expected salt and pepper chromatin pattern, with NKX 2.2 expression raising questions about its prognostic significance. Rhabdomyosarcoma presented primitive cells expressing desmin, and NKX 2.2 focal expression echoed previous subtype-associated studies. Synovial sarcoma displayed both monophasic and biphasic growth patterns and TLE1 expression, with NKX 2.2 variation suggesting tumor heterogeneity. In Wilms tumor, the characteristic WT1 expression was observed, while NKX2.2's absence reaffirmed its irrelevance in this context. Ewing sarcoma displayed the anticipated homogenous cell population, strong NKX2.2 expression, and CD99 positivity across various sites. Furthermore, age and gender impact on this range of sarcomas found no significant relation with an expression of NKX2.2. Conclusion In conclusion, the diverse expression profiles of diagnostic markers discovered in this study, particularly the atypical expression of NKX2.2 beyond its established role in Ewing sarcoma, signify a significant advancement. This unique finding accentuates the potential diagnostic importance of NKX2.2 in various sarcomas, presenting a novel dimension to our understanding of these malignancies.

Angiomatoid Fibrous Histiocytoma: A Tumor With Uncertain Behavior and Various Clinicopathological Presentations.

Background Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of uncertain differentiation, which has various clinical and morphological presentations. Although it behaves in a benign manner, it has malignant potential. Aim To share various histological patterns and survival data in our population of this rare entity. Materials and methods We studied 25 patients who reported AFH from January 2011 to December 2021. Clinical information, gross and histological features, immunohistochemical results, and survival data were compiled and analyzed. Results Among 25 cases reported as AFH, the majority (68%) were males with a mean age of 31.8 years at the time of diagnosis. The most common location was the lower extremity, especially the thigh (56%), and the mean size of the lesion was 55 mm. Most of the lesions were superficial (84%). Grossly, the majority of lesions (76%) had a solid appearance. Microscopically, classic spindle cell morphology was the most common (76%) with a lymphoid cuff and intralesional hemorrhage. Mild cellular atypia was seen in most (92%) of the cases, while some biopsies (8%) had a high-grade morphology. The majority of patients were alive, while one patient died of the disease. Conclusion AFH is an under-recognized entity with various clinical and histological presentations and a low malignant potential.

Agro-active endo-therapy treated Xylella fastidiosa subsp. pauca-infected olive trees assessed by the first 1H-NMR-based metabolomic study.

Xylella fastidiosa is a xylem-limited bacterium causing a range of economically important plant diseases in hundreds of crops. Over the last decade, a severe threat due to Olive Quick Decline Syndrome (OQDS), caused by Xylella fastidiosa subspecies pauca, affected the Salento olive groves (Apulia, South-East Italy). Very few phyto-therapeutics, including a Zn/Cu citric acid biocomplex foliar treatment, were evaluated to mitigate this disease. However, the traditional foliar applications result in the agro-actives reaching only partially their target. Therefore the development of novel endo-therapeutic systems was suggested. Metabolite fingerprinting is a powerful method for monitoring both, disease progression and treatment effects on the plant metabolism, allowing biomarkers detection. We performed, for the first time, short-term monitoring of metabolic pathways reprogramming for infected Ogliarola salentina and Cima di Melfi olive trees after precision intravascular biocomplex delivery using a novel injection system. Upon endo therapy, we observed specific variations in the leaf content of some metabolites. In particular, the 1H NMR-based metabolomics approach showed, after the injection, a significant decrease of both the disease biomarker quinic acid and mannitol with simultaneous increase of polyphenols and oleuropein related compounds in the leaf's extracts. This combined metabolomics/endo-therapeutic methodology provided useful information in the comprehension of plant physiology for future applications in OQDS control.

Body Mass Index and Other Risk Factors Effects on Colon Cancer Prognosis in Pakistan.

Introduction: Asian developing countries share the burden of colorectal cancer (CRC) with rising mortality rates. This prospective study aims to apprehend the clinical relevance of age, gender, lifestyle choices (dietary habits and addiction) and body mass index (BMI) to the occurrence and progression of colon cancer (CC). Methods: A cohort of non-cancer (NC) and CC patients of South-Central Asian origin registered for screening colonoscopy or surgery at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH and RC), Lahore, Pakistan, from 2015 to 2020 was identified. BMI (Kg/m2) was classified according to the World Health Organization criteria as underweight (<18.5 Kg/m2), normal weight (18.5-24.9 Kg/m2) and overweight (≥25 Kg/m2). Results: Among 236 participants, 99 (41.9%) belonged to the NC group, and 137 (58.1 %) participants had CC Overall, participants included 74 women and 162 men aged 20-85 years (mean ± SD; 49.9 ± 14.9). Notably, 46.0% of cancer patients had a family history of cancer. There was a direct relationship between CC with abnormal BMI (underweight and overweight), positive smoking history and positive family history of cancer. Conclusion: Being underweight or overweight is a potential risk factor for CC patients. The overall survival in patients with CC is clinically associated with lifestyle choices before CC diagnosis. A balanced diet, walking and other forms of exercise should be strongly recommended to the community and those undergoing screening colonoscopy.

Diagnosis on Excision Biopsy of Breast Tissues Labeled As Fibroepithelial Tumors on Trucut Samples in a Developing Country.

INTRODUCTION: Fibroadenomas (FAs) and phyllodes tumors (PTs) are less prevalent but allied to have malignant transformation in many instances. It is a challenge to diagnose the phyllodes by conventional trucut biopsy technique. OBJECTIVE: To evaluate the histological characteristics of tumors labeled as fibroepithelial lesions of breast tissues on trucut biopsy and compare with a diagnosis on excision biopsy. METHODS AND MATERIALS: It was a descriptive cross-sectional study that was carried out in Shaukat Khanum Memorial Hospital and Research Centre within six years from January 2015 to January 2021. In trucut samples, stromal cellularity, stromal cell nuclear atypia, mitotic count, stromal overgrowth, the enhancement of stromal cellularity adjacent to epithelium were scrutinized. In each category, the activity was seen as absent, mild, moderate, or severe. Mitotic activity was graded as 0-1, 0-5, 5-10, >10. RESULTS: A total of 125 patients were registered for the study. The mean age of patients in our study was 33.86 ± 9.95 years. The mean size was 41.02 ± 27.38 mm with a mean lump duration of 7.52 ± 5.34 months. In the FA group, the trucut sampling report showed the stromal cellularity as mild in 62 (69.7%) and stromal cell nuclear atypia as absent in 68 (76.4%) cases. But in the phyllodes tumor group, the stromal cellularity was severe in 10 (27.8%) patients and stromal cell nuclear atypia was severe in five (13.9%). The ultimate outcome showed that 89 (71.2%) patients had FA and 36 (28.8%) had PT at excision. CONCLUSION: Assessment of tumor size, stromal cellularity, mitoses, and enhancement of stromal cellularity adjacent to epithelium are useful markers for diagnosing the PT in trucut needle biopsy.

C4d at Crossroads Between Post-Infectious Glomerulonephritis and C3 Glomerulopathy.

BACKGROUND: Post-infectious glomerulonephritis (PIGN) (immune complex-mediated glomerulonephritis) and C3 glomerulopathy are sub-types of glomerulonephritis (GN) with hypercellularity. Both have overlapping clinical and morphologic features on a kidney biopsy, however, the treatment and prognosis of these diseases are quite different making their distinction of utmost importance. Immune complex-mediated glomerulonephritis arises from glomerular deposition of immune-complexes (Igs) and C3 as a result of activation of classical (CP) and lectin pathways (LP). C4d is produced as a result of activation of the CP/LP. On the other hand, C3 glomerulopathy results from activation of alternative pathway of complement. AIM: To distinguish between PIGN and C3 glomerulopathy with the help of C4d IHC stain. MATERIALS AND METHODS: We studied 28 biopsies reported as GN with hypercellularity from January 2015 to January 2020. Clinical information, histological features and immunofluorescence patterns were analyzed. C4d IHC was performed on all the biopsies. Six known cases of immune complex-mediated GN were selected to act as a positive control for C4d staining. RESULTS: Amongst 28 cases originally reported as GN with hypercellularity, 18 were labeled as post-infectious GN and 10 as C3 glomerulopathy based on clinical information and serological findings. 13 of 18 (72.2%) cases of PIGN had mild to moderate (1-2+) C4d staining, 2 (11.1%) had strong (3+) staining and 3 (16.7%) cases were negative for C4d staining. In the 10 biopsies of C3 glomerulopathy, mild (1+) C4d staining was noted only in 3 (30%) biopsies. C4d had moderate to strong (2-3+) staining in the control group. CONCLUSION: C4d IHC stain can be helpful in distinguishing PIGN from C3 glomerulopathy.

Müllerian Adenosarcoma: A Single-Centre Experience of 59 Cases of This Rare Entity.

Background and objective Müllerian adenosarcomas (MA) are rare biphasic tumors with benign epithelial and sarcomatous stromal components. There is very limited cohort study data on MA in the South Asian countries and no such study has been attempted in Pakistan. Our aim was to evaluate the clinicopathological characteristics of MA and to review the published literature on the condition. Additionally, we also analyzed the impact of various prognostic factors on the overall survival (OS) of patients with MA. Materials and methods This was a retrospective observational study performed at the Shaukat Khanum Memorial Hospital and Research Centre, Lahore from 2003 to 2020. A total of 59 histologically confirmed cases of MA were included in the study and critically reviewed. Results The mean age of the patients was 54 ±16 years, and the most common tumor location was the uterine corpus (48, 81.4%), followed by the cervix (eight, 13.6%), ovary (two, 3.4%), and vagina (one, 1.7%). Sarcomatous overgrowth (SO) was seen in 22 (37.3%) patients, and high-grade cytology was observed in 18 (30.5%) patients. Furthermore, lymphovascular invasion (LVI) was present in six (10.2%) patients, and myometrial invasion was noted in 25 (42.4%) patients. The follow-up details of 29 patients were available, and death was recorded in 13 (44.8%) patients with a median OS of three years. Conclusion MA is a rare and diagnostically challenging entity due to its wide differential diagnosis. It is essential to take note of different morphological features such as SO, cytological features, LVI, and heterologous differentiation because of their significant prognostic impact.

Frequency Of Non-Diabetic Renal Disease In Type 2 Diabetes Mellitus Patients Undergoing Renal Biopsy.

BACKGROUND: Diabetes mellitus has become a major emerging health concern. Its burden, estimated to be 451 million in 2017, has been projected to rise to 693 million by 2045. This will bring a rise in the prevalence of its associated complications. There is a wide spectrum of non-diabetic renal disease (NDRD) known to be present in diabetic patients with variable prevalence. However, the majority of diabetes mellitus (DM) patients with renal disease are yet not biopsied and the diagnosis of diabetic nephropathy (DN) is presumed on clinical grounds. METHODS: It is a retrospective cross-sectional study. We selected a total of 126 cases of renal biopsies with a history of type 2 diabetes mellitus. Demographic data was collected from the medical records and pathology reports while all cases were evaluated by reviewing the archived slides. RESULTS: Patients were categorized into group 1 with isolated NDRD, group 2 showing NDRD mixed with DN and group 3 with isolated DN. Thirty-four (27%) cases had isolated NDRD (group 1), 14 (11%) had NDRD mixed with DN and 78 (62%) patients had isolated DN. NDRD, either alone or in combination with DN, was found to be present in 48 patients with an overall prevalence of 38%. CONCLUSION: Our study concludes that NDRD is frequent in type 2 diabetes mellitus patients. Renal biopsy remains the key diagnostic tool in such cases, providing crucial information for proper management of the underlying pathology.

Symmetric and asymmetric impact of oil price, FDI and economic growth on carbon emission in Pakistan: Evidence from ARDL and non-linear ARDL approach.

Several studies have examined the impact of economic growth on carbon emission; however, the symmetric and asymmetric impact of oil price along with FDI on carbon emission has not studied in the case of Pakistan. For this purpose, the long and short-run impact of per capita income, FDI, and oil price on carbon emissions investigated by employing the ARDL and non-linear ARDL cointegration methodology, along with Granger causality in the context of Pakistan for 1971-2014. This study confirms the EKC hypothesis for Pakistan under both methodologies, whereas symmetric results show that economic growth and FDI intensify carbon emission in both the long and short-run, while oil price increase emission in the short-run and reduces emission in the long-run. Whereas asymmetric results in the long-run show that an increase in oil price reduces emissions and decrease in oil price intensify emissions. The causality analysis also supports the above findings and suggests a feedback effect between economic growth and carbon emission in Pakistan. This study provides implications for policymakers, where the descending flow of FDI allows limited space to Pakistan in FDI selection; however, the presence of emission convergence and adoption of carbon pricing may facilitate Pakistan in achieving its environmental targets. While diversifying the overall energy mix towards more renewable/clean energy along with formulating favorable policies for the adoption of renewable energy like solar by the industrial and residential consumers can further reduce the overall emission levels.

Renal Transplant Pathology: Demographic Features and Histopathological Analysis of the Causes of Graft Dysfunction.

BACKGROUND: Renal transplant has emerged as a preferred treatment modality in cases of end-stage renal disease; however, a small percentage of cases suffer from graft dysfunction. AIM: To evaluate the renal transplant biopsies and analyze the various causes of graft dysfunction. MATERIALS AND METHODS: 163 renal transplant biopsies, reported between 2014 and 2019 and who fulfilled the inclusion criteria, were evaluated with respect to demographics, clinical, histological, and immunohistochemical features. RESULTS: Of 163 patients, 26 (16%) were females and 137 (84%) were males with a mean age of 34 ± 7 years. 53 (32.5%) cases were of rejection (ABMR and TCMR), 1 (0.6%) was borderline, 15 were of IFTA, and rest of 94 cases (57.7%) belonged to the others category. SCr (serum creatinine) in cases of rejection was 3.85 ± 0.55 mg/dl. Causes of early graft dysfunction included active ABMR (7.1 ± 4.7 months), acute TCMR (5.5 months), and acute tubular necrosis (after 6 ± 2.2 months of transplant) while the causes of late rejection were CNIT and IFTA (34 ± 4.7 and 35 ± 7.8 months, respectively). CONCLUSION: Renal graft dysfunction still remains a concerning area for both clinicians and patients. Biopsy remains the gold standard for diagnosing the exact cause of graft dysfunction and in planning further management.

Proteomics analysis of colon cancer progression.

BACKGROUND: The aim of this pilot study was to identify proteins associated with advancement of colon cancer (CC). METHODS: A quantitative proteomics approach was used to determine the global changes in the proteome of primary colon cancer from patients with non-cancer normal colon (NC), non-adenomatous colon polyp (NAP), non-metastatic tumor (CC NM) and metastatic tumor (CC M) tissues, to identify up- and down-regulated proteins. Total protein was extracted from each biopsy, trypsin-digested, iTRAQ-labeled and the resulting peptides separated using strong cation exchange (SCX) and reverse-phase (RP) chromatography on-line to electrospray ionization mass spectrometry (ESI-MS). RESULTS: Database searching of the MS/MS data resulted in the identification of 2777 proteins which were clustered into groups associated with disease progression. Proteins which were changed in all disease stages including benign, and hence indicative of the earliest molecular perturbations, were strongly associated with spliceosomal activity, cell cycle division, and stromal and cytoskeleton disruption reflecting increased proliferation and expansion into the surrounding healthy tissue. Those proteins changed in cancer stages but not in benign, were linked to inflammation/immune response, loss of cell adhesion, mitochondrial function and autophagy, demonstrating early evidence of cells within the nutrient-poor solid mass either undergoing cell death or adjusting for survival. Caveolin-1, which decreased and Matrix metalloproteinase-9, which increased through the three disease stages compared to normal tissue, was selected to validate the proteomics results, but significant patient-to-patient variation obfuscated interpretation so corroborated the contradictory observations made by others. CONCLUSION: Nevertheless, the study has provided significant insights into CC stage progression for further investigation.