Fifth edition WHO classification: mature B-cell neoplasms.

We present a review of mature B-cell neoplasms as described in the fifth edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5). Entities have expanded, and definitions are increasingly reliant on genomic and other technologies. However, the WHO-HAEM5 employs a hierarchical structure with family (class)-level definitions that group several specific entities.

Single-cell-guided identification of logic-gated antigen combinations for designing effective and safe CAR therapy.

Unlabelled: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematological malignancies. However, its application in solid tumors remains limited because single targets are unlikely to suffice due to tumor antigen heterogeneity and off-tumor toxicities. To overcome these obstacles, we developed , a computational approach that utilizes single-cell transcriptomics data from patient tumors to systematically identify the cancer-specific antigen circuits with logic gates ("AND," "OR," and "NOT") that target the majority of cancer cells in a tumor while sparing normal cells and tissues as much as possible.

Moving the dial on diagnostics: an update from the Lancet Commission on diagnostics.

The Lancet Commission on diagnostics made recommendations for ten topics: national strategy (including national essential diagnostics lists), access in primary care, workforce, regulatory framework, national financing, affordability, appropriate use of technology, needs in conflict or fragile situations, advocacy, and an international alliance with oversight capabilities. Since 2021, progress in these areas has benefitted greatly from the adoption of a World Health Assembly resolution on diagnostics and the work of a broad coalition, as assessed by literature surveys by subject matter experts, quantitative findings (where feasible), and an anonymous survey of knowledgeable and engaged individuals. Greater progress was observed where there was political will and the production of diagnostics coincided with industrial policy goals, also in areas where changing the legal and health policy frameworks was involved.

Molecular profile of non-small cell lung cancer in a predominantly Black African population in Kenya: A single institution review.

Introduction: Targeted therapies for patients with non-small cell lung cancer (NSCLC) have significantly improved the outcomes for patients with oncogenic driver mutations. Testing for epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangement, c-ros oncogene 1 (ROS1) rearrangement and programmed death ligand 1 (PDL 1) testing are now highly recommended for all patients with NSCLC. There are clear geographical differences in the rate of driver mutations with higher EGFR mutation rates in the Asian population in comparison to the Caucasian population.

Adenomatoid Tumor of the Testis: A Report of Two Cases and Literature Review.

Testicular adenomatoid tumor is a rare benign condition that can resemble testicular malignancies in its clinical presentation, potentially leading to overtreatment, such as radical orchidectomy. In our two case reports, we aim to better understand the behavior of this disease by examining its clinical presentation, as well as radiological, intraoperative, and pathological findings.

Whole exome-seq and RNA-seq data reveal unique neoantigen profiles in Kenyan breast cancer patients.

Background: The immune response against tumors relies on distinguishing between self and non-self, the basis of cancer immunotherapy. Neoantigens from somatic mutations are central to many immunotherapeutic strategies and understanding their landscape in breast cancer is crucial for targeted interventions. We aimed to profile neoantigens in Kenyan breast cancer patients using genomic DNA and total RNA from paired tumor and adjacent non-cancerous tissue samples of 23 patients.

Kinetics of naturally induced binding and neutralising anti-SARS-CoV-2 antibody levels and potencies among SARS-CoV-2 infected Kenyans with diverse grades of COVID-19 severity: an observational study.

Background: Given the low levels of coronavirus disease 2019 (COVID-19) vaccine coverage in sub-Saharan Africa (sSA), despite high levels of natural severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) exposures, strategies for extending the breadth and longevity of naturally acquired immunity are warranted. Designing such strategies will require a good understanding of naturally acquired immunity.

Methods: We measured whole-spike immunoglobulin G (IgG) and spike-receptor binding domain (RBD) total immunoglobulins (Igs) on 585 plasma samples collected longitudinally over five successive time points within six months of COVID-19 diagnosis in 309 COVID-19 patients.

The Association between the JAK-STAT Pathway and Hypertension among Kenyan Women Diagnosed with Breast Cancer.

Background: Breast cancer is the most common malignant tumor in women worldwide, and disproportionately affects Sub-Saharan Africa compared to high income countries. The global disease burden is growing, with Sub-Saharan Africa reporting majority of the cases. In Kenya, breast cancer is the most commonly diagnosed cancer, with an annual incidence of 7,243 new cases in 2022, representing 25.

Development of an online teaching platform to improve access to postgraduate pathology training in sub-Saharan Africa.

Background: Resource barriers to the provision of accessible training in cancer diagnosis in lower- and middle-income countries (LMICs) limit the potential of African health systems. Long-term provision via teaching visits from senior pathologists and trainee foreign placements is unsustainable due to the prohibitive costs of travel and subsistence. Emerging eLearning methods would allow pathologists to be trained by experts in a cheaper, more efficient, and more scalable way.

Post-vaccination SARS-CoV-2 IgG spike antibody responses among clinical and non-clinical healthcare workers at a tertiary facility in Kenya.

Introduction: Following the coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, vaccination became the main strategy against disease severity and even death. Healthcare workers were considered high-risk for infection and, thus, were prioritised for vaccination.

Methods: A follow-up to a SARS-CoV-2 seroprevalence study among clinical and non-clinical HCWs at the Aga Khan University Hospital, Nairobi, we assessed how vaccination influenced SARS-CoV-2 anti-spike IgG antibody responses and kinetics.

Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer.

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples.

Population-specific Mutation Patterns in Breast Tumors from African American, European American, and Kenyan Patients.

Unlabelled: Women of African descent have the highest breast cancer mortality in the United States and are more likely than women from other population groups to develop an aggressive disease. It remains uncertain to what extent breast cancer in Africa is reminiscent of breast cancer in African American or European American patients. Here, we performed whole-exome sequencing of genomic DNA from 191 breast tumor and non-cancerous adjacent tissue pairs obtained from 97 African American, 69 European American, 2 Asian American, and 23 Kenyan patients.

P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV.

Background: The expression of p16 protein, a surrogate marker for high-risk human papillomavirus (hrHPV), is associated with cervical dysplasia. We evaluated correlates of p16 expression at treatment for high-grade cervical lesions and its utility in predicting the recurrence of cervical intraepithelial lesions grade 2 or higher (CIN2+) following cryotherapy among women with HIV.

Methods: This is a subgroup analysis of women with HIV in Kenya with baseline cervical biopsy-confirmed CIN2+ who were randomized to receive cryotherapy and followed every six-months for two-years for biopsy-confirmed recurrence of CIN2+.

Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer.

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results.

Spatial analyses of immune cell infiltration in cancer: current methods and future directions: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer.

Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based).

Metastatic breast cancer in Kenya: survival, prognosis and management at a tertiary referral centre.

There has been an increase in breast cancer in Africa with up to 77% of patients diagnosed with advanced disease. However, there is little data on survival outcomes and prognostic factors affecting survival in patients with metastatic breast cancer (MBC) in Africa. The study objective was to establish the survival of patients with MBC at a single tertiary health facility, the clinical and pathological characteristics affecting survival and describe the treatment modalities used.

Training health workers in clinical breast examination for early detection of breast cancer in low- and middle-income countries.

Background: Most women living in low- and middle-income countries (LMICs) present with advanced-stage breast cancer. Limitations of poor serviceable health systems, restricted access to treatment facilities, and lack of breast cancer screening programmes all likely contribute to the late presentation of women with breast cancer living in these countries. Women are diagnosed with advanced disease and frequently do not complete their care due to a number of factors, including financial reasons as health expenditure is largely out of pocket resulting in financial toxicity; health system failures, such as missing services or health worker lack of awareness on common signs and symptoms of cancer; and sociocultural barriers, such as stigma and use of alternative therapies.

Tumour Infiltrating Lymphocytes (TILs) and immune composition in breast cancer patients from Kenya: Spatial distributions and associations with risk factors and tumour characteristics.

Background: The immune landscape of breast cancer (BC) in patients from Sub Saharan Africa is understudied. Our aims were to describe the distribution of Tumour Infiltrating Lymphocytes (TILs) within the intratumoural stroma (sTILs) and the leading/invasive edge stroma (LE-TILs), and to evaluate TILs across BC subtypes with established risk factors and clinical characteristics in Kenyan women.

Methods: Visual quantification of sTILs and LE-TILs were performed on Haematoxylin and eosin -stained pathologically confirmed BC cases based on the International TIL working group guidelines.

Adaptive immune receptor features related to breast cancer tissue in Kenyan patients: high immunoglobulin gene expression and high levels of gamma-delta T-cells.

Background: Characterization of the breast cancer (BC) immune response may provide information for a point of intervention, such as application of immunotherapeutic treatments. In this study, we sought to recover and characterize the adaptive immune receptor (IR) recombination reads from genomics files representing Kenyan patients, to better understand the immune response specifically related to those patients.

Methods: We used a previously applied algorithm and software to obtain productive IR recombination reads from cancer and adjacent normal tissue samples representing 22 Kenyan BC patients.

Seroprevalence, correlates and kinetics of SARS-CoV-2 nucleocapsid IgG antibody in healthcare workers and nonclinical staff at a tertiary hospital: A prevaccine census study.

Background: Healthcare workers and nonclinical staff in medical facilities are perceived to be a high-risk group for acquiring SAR-CoV-2 infection, and more so in countries where COVID-19 vaccination uptake is low. Serosurveillance may best determine the true extent of SARS-CoV-2 infection since most infected HCWs and other staff may be asymptomatic or present with only mild symptoms. Over time, determining the true extent of SARS-CoV-2 infection could inform hospital management and staff whether the preventive measures instituted are effective and valuable in developing targeted solutions.

Promoting Best Practice in Cancer Care in Sub Saharan Africa.

Promoting best practice in the management of a cancer patient is rooted in the application of new knowledge derived through various sources including population science, laboratory advances, and translational research. Ultimately, the impact of these advances depends on their application at the patient's bedside. A close collaboration between the oncologist and the pathologist is critical in underwriting progress in the management of the cancer patient.

A pilot phase Ib/II study of whole-lung low dose radiation therapy (LDRT) for the treatment of severe COVID-19 pneumonia: First experience from Africa.

Background: Low dose radiation therapy (LDRT) has been used for non-malignant conditions since early 1900s based on the ability of single fractions between 50-150 cGy to inhibit cellular proliferation. Given scarcity of resources, poor access to vaccines and medical therapies within low and middle income countries, there is an urgent need to identify other cost-effective alternatives in management of COVID-19 pneumonia. We conducted a pilot phase Ib/II investigator-initiated clinical trial to assess the safety, feasibility, and toxicity of LDRT in patients with severe COVID-19 pneumonia at the Aga Khan University Hospital in Nairobi, Kenya.