Decoding molecular mechanisms: brain aging and Alzheimer's disease.

The complex morphological, anatomical, physiological, and chemical mechanisms within the aging brain have been the hot topic of research for centuries. The aging process alters the brain structure that affects functions and cognitions, but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease. Beyond these observable, mild morphological shifts, significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain. Understanding these changes is important for maintaining cognitive health, especially given the increasing prevalence of age-related conditions that affect cognition. This review aims to explore the age-induced changes in brain plasticity and molecular processes, differentiating normal aging from the pathogenesis of Alzheimer's disease, thereby providing insights into predicting the risk of dementia, particularly Alzheimer's disease.

Systemic Diseases and Heart Block.

Systemic diseases can cause heart block owing to the involvement of the myocardium and thereby the conduction system. Younger patients (<60) with heart block should be evaluated for an underlying systemic disease. These disorders are classified into infiltrative, rheumatologic, endocrine, and hereditary neuromuscular degenerative diseases. Cardiac amyloidosis owing to amyloid fibrils and cardiac sarcoidosis owing to noncaseating granulomas can infiltrate the conduction system leading to heart block. Accelerated atherosclerosis, vasculitis, myocarditis, and interstitial inflammation contribute to heart block in rheumatologic disorders. Myotonic, Becker, and Duchenne muscular dystrophies are neuromuscular diseases involving the myocardium skeletal muscles and can cause heart block.

Development and validation of the Atri-Risk Conduction Index risk score to predict risk of atrial fibrillation after typical atrial flutter ablation.

BACKGROUND: Identification of patients at risk for atrial fibrillation (AF) after typical atrial flutter (tAFL) ablation is important to guide monitoring and treatment. OBJECTIVE: The purpose of this study was to create and validate a risk score to predict AF after tAFL ablation METHODS: We identified patients who underwent tAFL ablation with no AF history between 2017 and 2022 and randomly allocated to derivation and validation cohorts. We collected clinical variables and measured conduction parameters in sinus rhythm on an electrophysiology recording system (CardioLab, GE Healthcare). Univariate and multivariate logistic regressions (LogR) were used to evaluate association with AF development. RESULTS: A total of 242 consecutive patients (81% male; mean age 66 ± 11 years) were divided into derivation (n =142) and validation (n = 100) cohorts. Forty-two percent developed AF over median follow-up of 330 days. In multivariate LogR (derivation cohort), proximal to distal coronary sinus time (pCS-dCS) ≥70 ms (odds ratio [OR] 16.7; 95% confidence interval [CI] 5.6-49), pCS time ≥36 ms (OR 4.5; 95% CI 1.5-13), and CHADS2-VASc score ≥3 (OR 4.3; 95% CI 1.6-11.8) were independently associated with new AF during follow-up. The Atri-Risk Conduction Index (ARCI) score was created with 0 as minimal and 4 as high-risk using pCS-dCS ≥70 ms = 2 points; pCS ≥36 ms = 1 point; and CHADS2-VASc score ≥3 = 1 point. In the validation cohort, 0% of patients with ARCI score = 0 developed AF, whereas 89% of patients with ARCI score = 4 developed AF. CONCLUSION: We developed and validated a risk score using atrial conduction parameters and clinical risk factors to predict AF after tAFL ablation. It stratifies low-, moderate-, and high-risk patients and may be helpful in individualizing approaches to AF monitoring and anticoagulation.

Aging-Related Protein Alterations in the Brain.

Aging is an intrinsic aspect of an organism's life cycle and is characterized by progressive physiological decline and increased susceptibility to mortality. Many age-associated disorders, including neurological disorders, are most commonly linked with the aging process, such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the effects of aging and AD on the molecular pathways and levels of different proteins in the brain, including metalloproteins, neurotrophic factors, amyloid proteins, and tau proteins. AD is caused by the aggregation of amyloid proteins in the brain. Factors such as metal ions, protein ligands, and the oligomerization state of amyloid precursor protein significantly influence the proteolytic processing of amyloid-ß protein precursor (AßPP). Tau, a disordered cytosolic protein, serves as the principal microtubule-associated protein in mature neurons. AD patients exhibit decreased levels of nerve growth factor within their nervous systems and cerebrospinal fluid. Furthermore, a significant increase in brain-derived neurotrophic factor resulting from the neuroprotective effect of glial cell line-derived neurotrophic factor suggests that the synergistic action of these proteins plays a role in inhibiting neuronal degeneration and atrophy. The mechanism through which Aß and AßPP govern Cu2+ transport and their influence on Cu2+ and other metal ion pools requires elucidation in future studies. A comprehensive understanding of the influence of aging and AD on molecular pathways and varying protein levels may hold the potential for the development of novel diagnostic and therapeutic methods for the treatment of AD.

Systemic Diseases and Heart Block.

Systemic diseases can cause heart block owing to the involvement of the myocardium and thereby the conduction system. Younger patients (<60) with heart block should be evaluated for an underlying systemic disease. These disorders are classified into infiltrative, rheumatologic, endocrine, and hereditary neuromuscular degenerative diseases. Cardiac amyloidosis owing to amyloid fibrils and cardiac sarcoidosis owing to noncaseating granulomas can infiltrate the conduction system leading to heart block. Accelerated atherosclerosis, vasculitis, myocarditis, and interstitial inflammation contribute to heart block in rheumatologic disorders. Myotonic, Becker, and Duchenne muscular dystrophies are neuromuscular diseases involving the myocardium skeletal muscles and can cause heart block.

Sensitivity and Specificity of Wearables for Atrial Fibrillation in Elderly Populations: A Systematic Review.

PURPOSE OF REVIEW: This study aims to evaluate the sensitivity and specificity of wearable devices for AF detection in older adults, as well as examine the incidence of AF across various studies, contextual factors impacting AF detection, and safety and adverse events associated with wearable use. RECENT FINDINGS: A systematic search of three databases identified 30 studies on wearables for AF detection in older adults, encompassing 111,798 participants. Both PPG-based and single-lead electrocardiography-based wearables show scalable potential for screening and managing AF. The results of this systematic review demonstrate that wearable devices, such as smartwatches, can effectively identify arrhythmias like AF in older adults, with scalable potential in PPG-based and single-lead electrocardiography-based wearables. As wearable technologies continue to gain prominence in healthcare, it is crucial to understand their challenges and incorporate them as preventative and monitoring tools for AF detection in elderly populations to improve patient care and prevention techniques.

The Impact of a Place-Tailored Digital Health App Promoting Exercise Classes on African American Women's Physical Activity and Obesity: Simulation Study.

BACKGROUND: The increasing prevalence of smartphone apps to help people find different services raises the question of whether apps to help people find physical activity (PA) locations would help better prevent and control having overweight or obesity. OBJECTIVE: The aim of this paper is to determine and quantify the potential impact of a digital health intervention for African American women prior to allocating financial resources toward implementation. METHODS: We developed our Virtual Population Obesity Prevention, agent-based model of Washington, DC, to simulate the impact of a place-tailored digital health app that provides information about free recreation center classes on PA, BMI, and overweight and obesity prevalence among African American women. RESULTS: When the app is introduced at the beginning of the simulation, with app engagement at 25% (eg, 25% [41,839/167,356] of women aware of the app; 25% [10,460/41,839] of those aware downloading the app; and 25% [2615/10,460] of those who download it receiving regular push notifications), and a 25% (25/100) baseline probability to exercise (eg, without the app), there are no statistically significant increases in PA levels or decreases in BMI or obesity prevalence over 5 years across the population. When 50% (83,678/167,356) of women are aware of the app; 58.23% (48,725/83,678) of those who are aware download it; and 55% (26,799/48,725) of those who download it receive regular push notifications, in line with existing studies on app usage, introducing the app on average increases PA and decreases weight or obesity prevalence, though the changes are not statistically significant. When app engagement increased to 75% (125,517/167,356) of women who were aware, 75% (94,138/125,517) of those who were aware downloading it, and 75% (70,603/94,138) of those who downloaded it opting into the app's push notifications, there were statistically significant changes in PA participation, minutes of PA and obesity prevalence. CONCLUSIONS: Our study shows that a digital health app that helps identify recreation center classes does not result in substantive population-wide health effects at lower levels of app engagement. For the app to result in statistically significant increases in PA and reductions in obesity prevalence over 5 years, there needs to be at least 75% (125,517/167,356) of women aware of the app, 75% (94,138/125,517) of those aware of the app download it, and 75% (70,603/94,138) of those who download it opt into push notifications. Nevertheless, the app cannot fully overcome lack of access to recreation centers; therefore, public health administrators as well as parks and recreation agencies might consider incorporating this type of technology into multilevel interventions that also target the built environment and other social determinants of health.

Limitations of Unipolar Signals in Guiding Successful Outflow Tract Premature Ventricular Contraction Ablation.

BACKGROUND: Unipolar electrograms (UniEGMs) are commonly used to annotate earliest local activation of focal arrhythmias. However, their utility in guiding premature ventricular contractions (PVCs) ablation may be limited when the PVC source is less superficial. OBJECTIVES: The authors sought to compare bipolar electrograms (BiEGMs) vs UniEGMs in guiding successful ablation of right ventricular outflow tract (RVOT) vs intramural outflow tract (OT) PVCs. The authors hypothesized that: 1) earliest bipolar local activation time (LATBi) would better guide mapping and ablation, vs UniEGM dV/dt (LATUni) or QS morphology; and 2) LAT differences using bipolar vs unipolar EGMs (ΔLATBi-Uni) would be greater for intramural OT than RVOT PVCs. METHODS: Consecutive patients undergoing successful PVC ablation 2017 to2020 requiring only RVOT or RVOT+left ventricular OT (RVOT+LVOT) ablation were retrospectively analyzed. BiEGMs and UniEGMs at successful ablation sites were compared. RESULTS: Of 70 patients, 50 required RVOT-only, and 20 required RVOT+LVOT ablation for acute and long-term PVC suppression. Mean ΔLATBi-Uni was lower for RVOT vs RVOT+LVOT groups (9.3 ± 6.4 ms vs 17.4 ± 9.9 ms; P < 0.01). QS UniEGM was seen in 78% of RVOT, compared with 53% of RVOT+LVOT patients (P < 0.016). RVOT+LVOT sites most frequently included the posteroseptal RVOT and adjacent LVOT (73%), and 43% lacked a QS unipolar EGM. ΔLATBi-Uni ≥15 ms best distinguished sites in which RVOT-only vs RVOT+LVOT ablation achieved acute PVC suppression (area under the curve: 0.77). CONCLUSIONS: Earliest BiEGM activation guides successful ablation of OT PVCs better than UniEGM-guided analysis, especially when an intramural PVC source is present.

Status of COVID-19 vaccination around South Asia.

The public health sector and the global economy are facing the challenges of the epidemic of coronavirus disease 19 (COVID-19) since December 2019. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an emerging outbreak and spreading rapidly across the globe. The COVID-19 pandemic of unprecedented proportions has devastated almost all countries and pervaded globally. However, various vaccines have been developed to achieve immunity against the virus and limit transmissibility. By 18 November 2021, 52.6% of the world population got first dose of the COVID-19 vaccine. South Asia shares 15% fully vaccinated and 22.6% partially vaccinated population in the world. The 56.5% of South Asian Association Regional Cooperation (SAARC) regions, consisting of Pakistan, Afghanistan, Bangladesh, India, Sri Lanka, Nepal, Maldives, and Bhutan, got the first shot of COVID-19 vaccine, whereas 30.5% were fully vaccinated. India has the highest percentage of the vaccinated population of about 46.5% among SAARC countries. Although South Asian countries have unstable multiple socio-economic factors, including poverty, overpopulation, low literacy about medical care and medical systems, etc., the increasing trend in vaccination status has been observed. The high percentage of health budgets of SAARC countries was utilized for purchasing COVID-19 vaccines. This report observes that South Asian countries have been significantly tackling the threats of COVID-19.

International Society of Urological Pathology (ISUP)-Grade Grouping in Prostatic Adenocarcinoma and its Prognostic Implications.

In this study, we evaluated the association of ISUP/WHO-grade groups with various pathological prognostic parameters and cancer-specific survival in patients with prostatic adenocarcinoma. We found 27 (15.7%) cases of grade group 1, 22 (12.8%) grade group 2, 30 (17.4%) grade group 3, 40 (23.3%) grade group 4 and 53 (30.8%) grade group 5 prostatic adenocarcinoma. We found that high-grade tumors (grade 3-5) had a higher frequency of perineural invasion and higher tumor volumes (>50%). Moreover, a significant association of tumor grade was noted with cancer-specific survival of patients, signifying prognostic significance of grade grouping in prostatic adenocarcinoma.

Systemic Diseases and Heart Block.

Systemic diseases can cause heart block owing to the involvement of the myocardium and thereby the conduction system. Younger patients (<60) with heart block should be evaluated for an underlying systemic disease. These disorders are classified into infiltrative, rheumatologic, endocrine, and hereditary neuromuscular degenerative diseases. Cardiac amyloidosis owing to amyloid fibrils and cardiac sarcoidosis owing to noncaseating granulomas can infiltrate the conduction system leading to heart block. Accelerated atherosclerosis, vasculitis, myocarditis, and interstitial inflammation contribute to heart block in rheumatologic disorders. Myotonic, Becker, and Duchenne muscular dystrophies are neuromuscular diseases involving the myocardium skeletal muscles and can cause heart block.

Quality of Life in Patients Undergoing Cardiac Surgery: Role of Coping Strategies.

Adaptive coping strategies are used to reduce stress in patients undergoing cardiac surgery. These strategies have a major role in physical health, psychological health, quality of life and also affect an individual's response to the disease. The current study was conducted to comprehend the impact of coping strategies on the quality of life of patients suffering from cardiac disease. A purposive convenient sampling method was used to collect data from different hospitals in South Punjab. We applied Carver's Brief Coping Orientation to Problem Experienced (Brief COPE) inventory and the WHO quality of life scale. A cross-sectional research design was proposed for the study. The findings of the study showed that coping strategies and quality of life are associated with each other, and the use of emotion-focused and problem-focused coping strategies have a significant impact on patients experiencing cardiac surgery. Demographic details of patients also revealed the differences in both variables. Implications and future recommendations have also been discussed.

Morphological Spectrum of Vesiculobullous Skin Lesions: An Institutional Perspective.

Introduction A vesiculobullous lesion of the skin encompasses a group of dermatological disorders with protean clinicopathological features. They usually occur as a part of the spectrum of various infectious, inflammatory, drug-induced, genetic, and autoimmune disorders. Therefore, accurate diagnosis of these lesions is essential for appropriate management and to reduce the associated morbidity and mortality. The conventional skin punch biopsy is the mainstay in the diagnosis of dermatological diseases, especially when combined with confirmatory tests, such as direct immunofluorescence (DIF). Our study evaluated the clinicopathological spectrum of vesiculobullous lesions. Methods We studied 150 cases of vesiculobullous lesions at the Department of Histopathology, Liaquat National Hospital and Medical College Karachi, Pakistan. Written and informed consent was taken from the patients followed by skin punch procedure in which three biopsies were obtained, which included one biopsy from the lesion and two peri-lesional biopsies. One peri-lesional biopsy was sent in cryomatrix for DIF studies, whereas the other two were sent in formalin to follow the standard tissue-processing protocol. Results Our results showed that most patients belonged to the geriatric age group of more than 50 years (44.7%), and 54.7% of the patients were females. Total 74.7% of the patients had generalized lesions, followed by lower limbs (9.3%) and trunk (7.3%) involvement. Most patients were diagnosed with bullous pemphigoid (31.3%), followed by pemphigus vulgaris (27.3%), dermatitis herpetiformis (15.3%), Darier's disease (14.7%), pemphigus foliaceus (4.7%), epidermolysis bullosa (2%), linear immunoglobulin A dermatosis (2%), paraneoplastic pemphigus (0.7%), and drug reactions (0.7%). DIF studies were applied on 60 cases, out of which complement protein C3c was the most commonly deposited protein (53.3%). Conclusion Our study emphasized the diagnostic role of skin punch biopsy in the proper evaluation of vesiculobullous skin lesions. Histopathology is the cornerstone diagnostic tool in this regard, with DIF being a useful adjunct.

Safety and efficacy of left atrial appendage closure using an epicardial suture snaring device: Systematic review and current status.

INTRODUCTION: The LARIAT epicardial suture snaring device has been fraught with technical challenges and procedural complications. Over time, technique modification and improved operator experience have helped overcome many of these challenges. METHODS AND RESULTS: Studies reporting left atrial appendage epicardial closure over a 12-year period from 2009 to 2020 were evaluated. The primary efficacy outcome evaluated was left atrial appendage closure with residual flow ≤1 mm. Safety outcomes evaluated were periprocedural and long term complications after device placement. Nine studies consisting of 1430 patients were included in this analysis, of which 1386 (97%) underwent successful device placement. The mean age was 69.3 years, with a mean CHADS2 -VASC score of 3.78. Primary efficacy end point was achieved in 95.8% patients immediately after device placement, and in 92.8% patients on long term follow-up. Early procedural complications consisted of pericardial effusion 5.6%, cardiac perforation 2.7%, pericarditis 2.6%, and need for open heart surgery 1.5%. Long term complications consisted of all-cause mortality 2.3%, stroke 1.5%, and left atrial appendage thrombus 2.3%. Reduced complications were noted using micropuncture needles (2.20% vs. 10.14%; p < .0001), a longer duration pericardial drainage, and use of anti-inflammatory medications (1.58% vs. 8.4%). Oral anticoagulation use decreased from 44.7% to 22.9% post device implantation, and to 8.5% on last clinical follow up. CONCLUSIONS: The LARIAT device is effective in epicardial closure of the left atrial appendage. Improvement in device techniques such as use of micropuncture needle, prophylactic colchicine, and maintenance of a pericardial drain have helped improve safety over time.

Triple-Negative Metaplastic Breast Carcinoma: Association of Epidermal Growth Factor Receptor Expression With Prognostic Parameters and Clinical Outcome.

Introduction Metaplastic breast carcinoma (MBC) is one of the rare special subtypes of breast carcinoma associated with poor prognostic features compared with invasive ductal carcinoma. Moreover, therapeutic options are limited in MBC owing to frequent triple-negative profiles of these tumors. Epidermal growth factor receptor (EGFR) is a proto-oncogene that is overexpressed in many human cancers, and is a potential therapeutic target. Therefore, in this study, we evaluated the expression of EGFR in MBC by immunohistochemistry, and its association with clinicopathological and prognostic parameters. Methods We conducted a retrospective observational study in the Department of Histopathology at Liaquat National Hospital and Medical College, Pakistan, over a period of seven years. A total of 61 cases with a histopathological diagnosis of MBC were included in the study. All slides were reviewed by histopathologists for diagnostic confirmation. Histopathological parameters, such as tumor size, grade, and nodal metastasis, were recorded. The representative tissue blocks were also retrieved and immunohistochemical studies were performed for cytokeratin 5/6 (CK5/6), Ki67, and EGFR. Results The mean age of the patients was 44.48 ± 13.01 years. The mean tumor size was 5.72 ± 2.72 cm, with most of the cases belonging to tumor (T)-stage T3. Axillary metastasis was present in 57.4% cases, and the perinodal extension was present in 11.5% cases. Most tumors were grade III (85.2%), with a mean Ki67 index of 39.67% ± 20.38%. Most of the cases were nonbasal (83.6%), owing to the absent CK5/6 expression. Tumor recurrence was noted in 14.8% cases, with a median follow-up of 43 (13-83) months and median disease-free survival of 36 (12-60) months. Positive EGFR expression was noted in 52.5% cases. A significant association of EGFR expression was noted with tumor grade, mean Ki67 index, axillary metastasis, and nodal (N)-stage. Cases with positive EGFR expression were found to have higher grade (grade III), with higher Ki67 index, higher frequency of axillary metastasis, and higher N-stage. Moreover, cases with positive EGFR expression had lower disease-free survival compared to cases with negative EGFR expression. Conclusion We found that a significant proportion of triple-negative MBC expressed EGFR. Moreover, EGFR overexpression was associated with poor pathological parameters and lower disease-free survival. Therefore, EGFR can be considered a potential prognostic biomarker and therapeutic target in triple-negative MBC; however, the correlation between gene amplification and protein overexpression is required to better uncover the role of EGFR as a therapeutic target.

Mucinous Breast Carcinoma: Clinicopathological Comparison With Invasive Ductal Carcinoma.

Introduction Invasive ductal carcinoma (IDC) is the most common histological subtype of breast cancer. Conversely, many special types of breast carcinoma were described with varying prognosis and hormone receptor status. Mucinous carcinoma (MC) is a rare special subtype of breast cancer, and only a few studies have evaluated the clinicopathological and hormone receptor profile of this type of breast cancer. Therefore, in this study, we compared the clinicopathological characteristics of MC with IDC in our population. Methods A retrospective observational study was conducted in the Department of Histopathology, Liaquat National Hospital and Medical College, from January 2013 till December 2020, for eight years. During this period, 38 cases of MC were diagnosed and 1268 cases of IDC were identified. All specimens were grossed according to standard protocols and representative sections were submitted from tumors, resection margins, and lymph nodes. Slides were examined by histopathologists to determine tumor type and grade. Immunohistochemical (IHC) stains were applied to evaluate estrogen receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth factor receptor 2 (HER2/neu) statuses. Results The mean age of the patients with MC was 56.47±13.90 years, and most of the patients were above 50 years of age. The mean tumor size was 34.89±19.70 mm. Most tumors were grade 1 (68.4%) with a low mean Ki67 index (15.21±14.06%). Axillary metastasis was present in 31.6% of cases and all of them were nodal (N)-stage N1. ER, PR, and HER2/neu positivity were noted in 94.7%, 78.9, and 10.5% cases, respectively. Compared with IDC, a significant association of MC was noted with age, Ki67 index, tumor (T)-stage, N-stage, and tumor grade. MC cases had a higher mean age than IDC cases. Comparative analysis revealed that MC had a lower frequency of axillary metastasis, a lower mean Ki67 index, and a lower tumor grade than IDC. About biomarker status, MC was noted to have a higher frequency of ER and PR expression, and a lower frequency of HER2/neu expression than IDC. Conclusion MC is a rare subtype of breast cancer. However, it is important to recognize this subtype of breast cancer as it is associated with a prognostically better pathological profile, such as lower tumor grade and Ki67 index, lower frequency of axillary metastasis, higher expression of ER and PR, and lower expression of HER2/neu.

Diagnostic Accuracy of Intraoperative Touch Imprint Cytology for the Diagnosis of Axillary Sentinel Lymph Node Metastasis of Breast Cancer: Comparison With Intraoperative Frozen Section Evaluation.

Introduction The intraoperative frozen section is a recommended method to detect breast cancer metastasis to axillary sentinel lymph nodes (SLNs); however, frozen section is not widely available and requires an experienced staff. Alternatively, touch imprint cytology (TIC) is a simple and cost-effective technique to detect metastasis. Therefore, in this study, we assessed the diagnostic accuracy of TIC for detecting SLN metastasis and compared it with intraoperative frozen section evaluation. Methodology A retrospective study was conducted in the Department of Histopathology, Liaquat National Hospital and Medical College, for a duration of two years. A total of 114 patients undergoing surgery for primary breast cancer were included in the study. All patients had clinically and radiologically negative axillary lymph nodes. SLN sampling was done using radioactive dye and sent for intraoperative consultation. The SLNs were sliced at 4-mm intervals and two TIC slides and three step-levels for frozen section were prepared, and the results were compared with final (paraffin) section histology. Results The sensitivity, specificity, and diagnostic accuracy of TIC was 83.7%, 98.5%, and 92.1%, respectively. Alternatively, the sensitivity, specificity, and diagnostic accuracy of frozen section was 93.9%, 100%, and 97.4%, respectively. The sensitivity of TIC and frozen section for detecting micrometastasis was 14.3% and 57.1%, respectively, with a diagnostic accuracy of 90.3% and 95.8%, respectively. Alternatively, with respect to macrometastasis, the sensitivity and specificity of TIC were 95.2% and 98.5%, respectively, while the sensitivity and specificity of frozen section were 100%. Conclusion TIC is a quick and effective technique for detecting breast cancer metastasis in axillary SLNs. Although frozen section had an overall higher sensitivity than TIC, the sensitivity of TIC for detecting macrometastasis was comparable to the frozen section. Therefore, we conclude that TIC is a good alternative to the frozen section in facilities where the frozen section is not available.

CD30-Positive Anaplastic Variant of Diffuse Large B-cell Lymphoma: Frequency and Association With Clinicopathological Parameters.

Introduction Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma and is the most common type of non-Hodgkin's lymphoma (NHL) worldwide. The World Health Organization (WHO) classification of hematopoietic tumors has recognized three morphological variants of DLBCL: centroblastic, immunoblastic, and anaplastic. Some studies have shown that the anaplastic variant of DLBCL is associated with aggressive clinicopathological features. Anaplastic DLBCL is rare, and the clinicopathological characteristics of this subtype of DLBCL are not widely studied in our population. Therefore, in this study, we evaluated the frequency of the anaplastic variant of DLBCL and its association with other clinicopathological parameters. Methods A retrospective study was conducted in the Department of Histopathology at the Liaquat National Hospital and Medical College over a period of six years, from January 2015 to December 2020. All cases diagnosed as DLBCL based on morphology and immunohistochemical (IHC) profile were included in the study. The diagnosis of anaplastic DLBCL was rendered based on morphology (large bizarre pleomorphic cells in a cohesive or sheet-like growth pattern), combined with CD30 IHC expression. Results The mean age of the patients was 52.90 ±16.42 years, and the mean Ki67 index was 73.18 ±16.52%. Of the 220 cases of DLBCL, 47.3% cases were germinal center B-cell (GCB) subtype, and 59.1% cases were nodal. BCL-2, BCL-6, MUM1, c-MYC, and CD10 positivity were noted in 60%, 45.5%, 40.9%, 44.1, and 38.6% cases, respectively. Only 14 cases (6.4%) were recognized as anaplastic variants of DLBCL according to the previously defined criterion. The only significant association of anaplastic-variant DLBCL was noted with a lack of BCL-2 expression. No significant association of anaplastic-variant DLBCL was noted with age, gender, Ki67 index, DLBCL subtype, or any other IHC marker expression. Conclusion We found a low frequency of the anaplastic variant of DLBCL in our study. No significant association of this DLBCL variant was noted with any of the clinicopathological parameters, except for the lack of BCL-2 expression. Alternatively, from a pathological perspective, it is important to recognize this variant of DLBCL as it often mimics other CD30-positive lymphoma and undifferentiated carcinoma.

Clinicopathological Features of Primary Neuroendocrine Tumors of Gastrointestinal/Pancreatobiliary Tract With Emphasis on High-Grade (Grade 3) Well-Differentiated Neuroendocrine Tumors.

Introduction The two broad subcategories of neuroendocrine neoplasms (NENs) are well-differentiated neuroendocrine tumors (WDNETs) and poorly differentiated neuroendocrine carcinomas (PDNECs), based on tumor architecture and cytology. Grade 3 WDNETs are a subset of WDNETs that not only are high grade by mitotic activity or proliferative index but exhibit a well-differentiated histology. In this study, we evaluated the clinicopathological features of primary neuroendocrine tumors of the gastrointestinal (GI)/pancreatobiliary tract with emphasis on high-grade WDNETs, as it is a newly defined entity. Methods We conducted a retrospective observational study, including a total number of 122 cases of primary GI and pancreatobiliary tract NENs. Slides and blocks of all cases were retrieved from the departmental archives. Immunohistochemical stains including Ki67 were applied to selected tissue blocks of all cases. Tumors were then evaluated for their histological differentiation and tumor grade. Results Our results showed that the mean age of patients was 46.8 ± 17.1 years. Majority of the NENs were GI tract origin (86.9%). The most common site of tumor in gastroenteropancreatic tract was the small bowel (31.1%), followed by the stomach (26.2%). Ninety five percent of the tumors were WDNETs, of which the most common grade was G2. The mean Ki67 index was 15.8 ± 23.8. Grade 3 WDNETs were noted to have an older mean age than grades 1 and 2 WDNETs. Ten out of 102 (9.8%) WDNETs of GI tract were grade 3, compared with four out of 14 (28.6%) of pancreatobiliary tract.  Conclusion In this study, we found that high-grade (grade 3) WDNETs were more frequent in pancreatobiliary tract than GI tract. Moreover, high-grade WDNETs were associated with a higher mean age than low-grade (grade 1-2) WDNETs. It is extremely important to recognize this subset (high grade) of WDNETs and to distinguish it from PDNECs, as the latter are known to be associated with a worse overall survival. Despite high mitotic rate/proliferative index, high-grade WDNETs are characterized by organoid architecture and monomorphic cell population.