Educational needs and causes of false diagnosis of atypical squamous cells of unknown significance at a university hospital

The entity of atypical squamous cells of undetermined significance (ASCUS) in The Bethesda System 2001 for reporting cervical cytology is characterized by equivocal diagnosis, poor reproducibility and debatable management. This retrospective study was done to analyse the causes of false ASCUS if any and identify the educational needs as part of quality assurance programme. Cervical smears of all ASCUS cases reported over the one-year period were reviewed by the Cytopathologist. Relevant clinical data was retrieved. ASCUS was the most common type of abnormality representing 43.0 % cases among 294 abnormal smears reported during study period. 16.0% cases were found to be non ASCUS on review. The main four causes of over use of ASCUS diagnosis were poor quality smears and cellular atypia associated with Candida infection, atrophy and squamous metaplasia. Educational measures are being undertaken to avoid over diagnosis and improve the patient management (Afr J Reprod Health 2011; 15[1]: 111-114)

Fine-needle aspiration in suspected inflammatory breast cancer: case series with emphasis on approach to specimen adequacy

Objectives: To highlight the utility of a tangential approach in the fine-needle aspiration (FNA) technique for obtaining cellular material adequate for a conclusive diagnosis in diffusely enlarged breast without a discrete lump. Study Design: FNA was performed on 5 women clinically suspected to have inflammatory breast cancer (IBC). All had unilateral diffusely enlarged breasts with peau d’orange changes of the skin. No distinct lump was palpable. The procedure was performed using a 10 cm 3 syringe with a tangential approach of a 23-gauge needle in all 4 quadrants with extra passes in the antigravity areas. Rapid on-site evaluation for adequacy was done. Results: All women were of African descent within the age range of 34–57 years. One case had a recent history of lactation. FNA smears showed low-to-moderate cellularity. One case was suspicious and 4 were positive for ductal carcinoma. Core biopsy confirmed IBC in 3 cases. Two cases had a mastectomy; 1 of these cases had preoperative neoadjuvant chemotherapy. Conclusion: The approach of FNA used in these cases helped to establish the diagnosis of IBC in 4 women presenting with a diffusely enlarged and tender breast, resulting in the timely initiation of appropriate management. The technique needs to be assessed in a larger cohort of women with diffusely enlarged breast to evaluate its diagnostic utility

Diffuse Large B-Cell Lymphoma in Kenya: MYC, BCL2, and the Cell of Origin

Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most commonly diagnosed non-Hodgkin lymphoma in adults in Kenya. Cell of origin (COO) and double expression of MYC and BCL2 are two important prognostic factors for DLBCL. A small subset (5% to 10%) of DLBCL cases show positivity for CD5 and are associated with poor prognosis, whereas CD30 antigen, seen in up to 10% of cases, may be a useful target for therapy. We sought to determine the prevalence of MYC/BCL2 double expression, COO, and proportion of Epstein-Barr virus positivity among patients with DLBCL diagnosed at a tertiary referral laboratory in Kenya. Patients and Methods: All cases of DLBCL diagnosed from 2012 through 2015 in our pathology department were analyzed. Tumor tissue microarray sections were stained with CD20, CD3, CD5, CD30, BCL2, BCL6, CD10, MUM1, MYC, and Ki67, classified for COO on the basis of the Hans algorithm, and subjected to Epstein-Barr virus-encoded small RNAs in situ hybridization. Results: Among 165 DLBCL cases, the median age was 50 years, and there was no sex predilection. Only 18 (10.9%) cases showed double expression for MYC and BCL2. Germinal center B (GCB)-cell type DLBCL accounted for 67 cases (40.6%) and 97 cases (59.4%) were classified as non-GCB. The mean Ki67 proliferation index was significantly higher in the double-expressing (45%) and non-GCB groups (36%) compared with the non-double-expressing group (29%) and GCB group (26%). Sixteen cases (9.7%) were Epstein-Barr virus-encoded small RNAs positive, 12 (75%) of which were non-GCB. Conclusion: DLBCL in Kenya is seen in much younger patients with the poor prognostic non-GCB-type accounting for 59.4% of cases. MYC and BCL2 double expression was seen in fewer tumors than reported in the literature and in significantly older patients

Pattern and trends of Helicobacter pylori genotypes in gastric cancer: A Kenyan 8-year study

Background: Notable geographic and temporal variations in the prevalence and genotypes of Helicobacter pylori, in relation to gastric pathologies, have been observed; however, their significance and trends in African populations is scarcely described. The aim of this study, was to investigate the association of H. pylori and its respective CagA and vacuolating cytotoxin A (VacA) genotypes with gastric adenocarcinoma, and to describe the trends of H. pylori genotypes over an 8-year period (2012–2019). Materials and methods: A total of 286 samples of gastric cancer cases and benign controls (one-to-one matching), from three main cities in Kenya, between 2012 and 2019 were included. Histologic evaluation, and CagA and VacA genotyping using PCR, was performed. Distribution of H. pylori genotypes was presented in proportions. To determine association, a univariate analysis was conducted using a Wilcoxon rank sum test for continuous variables, and a Chi-squared test or Fisher’s exact test for categorical data. Results: The VacA s1m1 genotype was associated with gastric adenocarcinoma, {odds ratio (OR) = 2.68 [confidence interval (CI) of 95%: 0.83–8.65]; p = 0.108}, whilst VacA s2m2 was associated with a reduced probability of gastric adenocarcinoma [OR = 0.23 (CI 95%: 0.07–0.78); p = 0.031]. No association between cytotoxin associated gene A (CagA) and gastric adenocarcinoma was observed. Conclusion: Over the study period, an increase in all genotypes of H. pylori was seen, and although no predominant genotype was noted, there was significant year-to-year variation, with VacA s1 and VacA s2 showing the greatest variation. VacA s1m1 and VacA s2m2 were associated with increased, and reduced risk of gastric cancer, respectively. Intestinal metaplasia and atrophic gastritis did not appear to be significant in this population

Immunophenotypic expression profile of multiple myeloma cases at a tertiary hospital in Nairobi Kenya

Introduction: Multiple myeloma (MM) is a plasma cell neoplasm that constitutes 10–15% of all hematopoietic neoplasms. Kenya is placed among the top five African countries for MM incidence and MM-related mortality. Prior studies have suggested that the aberrant expression of Cyclin D1, CD56, CD117 and Ki-67 on neoplastic plasma cells is useful in disease prognostication. The prevalence and significance of expression of these markers in a cohort of MM cases in Kenya has not been studied previously. Methods: A retrospective cross-sectional study was carried out at the Aga Khan University Hospital, Nairobi. The study population included 83 MM cases with available trephine blocks archived between 1st of January 2009 and 31st of March 2020. Immunohistochemical expression of Cyclin D1, CD56, CD117, and Ki-67 was analyzed and scored. The biomarkers were described using frequencies based on the positive and negative results. Fisher’s exact test was used to determine the association between the immunophenotypic markers and categorical variables. Results: Of the 83 selected cases, expression of Cyclin D1, CD56, CD117 and Ki- 67 was identified in 28.9, 34.9, 7.2, and 50.6%, respectively. Cyclin D1 positivity was significantly associated with hypercalcemia. Absence of CD117 expression was noted to be associated with adverse risk parameters including an IgA isotype or light chain disease, International Staging System (ISS) stage III disease, abnormal baseline serum free light chains (sFLC) and a high plasma cell burden. Conclusion: Cyclin D1 expression was congruent with previously reported studies. The frequency of CD56 and CD117 expression was lower than previously reported. This may be due to differences in disease biology between the study populations. Approximately half of cases were Ki-67 positive. Our data showed limited associations between the expression of studied markers and clinicopathologic variables. However, this could be attributed to the small study sample size. We would recommend further characterization of the disease in a larger prospective study with the inclusion of survival outcomes and cytogenetic studies

Mammographic Breast Density and Breast Cancer Molecular Subtypes: The Kenyan-African Aspect

Introduction: Data examiningmammographic breast density (MBD) among patients in Sub-Saharan Africa are sparse.We evaluated how MBD relates to breast cancer characteristics in Kenyan women undergoing diagnostic mammography. Methods: This crosssectional study included women with pathologically confirmed breast cancers ( = 123). Pretreatment mammograms of the unaffectedbreast were assessed to estimate absolute dense area (cm2), nondense area (cm2), and percent density (PD). Relationships between density measurements and clinical characteristics were evaluated using analysis of covariance. Results: Median PD and dense area were 24.9% and 85.3 cm2. Higher PD and dense area were observed in younger women ( \u3c 0.01). Higher dense and nondense areas were observed in obese women (-trend \u3c 0.01). Estrogen receptor (ER) positive patients (73%) had higher PD and dense area than ER-negative patients ( ≤ 0.02). Triple negative breast cancer (TNBC) patients (17%) had lower PD and dense area ( ≤ 0.01) compared with non-TNBCs. No associations were observed between MBD and tumor size and grade. Conclusions: Our findings show discordant relationships between MBD and molecular tumor subtypes to those previously observed in Western populations. The relatively low breast density observed at diagnosis may have important implications for cancer prevention initiatives in Kenya. Subsequent larger studies are needed to confirm these findings

Sentinel Lymph Node Biopsy Pathology and 2-Year Postsurgical Recurrence of Breast Cancer in Kenyan Women

Purpose: The goal of this study was to describe the pathologic findings and early follow-up experience of patients who underwent a sentinel lymph node biopsy (SLNB) at Aga Khan University Hospital (AKUH) between 2008 and 2017. Patients and Methods: We performed a retrospective analysis of women with breast cancer who underwent an SLNB at AKUH between 2008 and 2017. The SLNB was performed on patients with stage I and stage II breast cancer, and identification of the sentinel lymph node was made by radioactive tracer, blue dye, or both, per availability and surgeon preference. Demographic, surgical, and pathologic data, including immunohistochemistry of the surgical sample for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, were abstracted from the patient records. Follow-up data were available for a subset of patients. Results: Between 2008 and 2017, six surgeons performed SLNBs on 138 women, 129 of whom had complete records and were included in the study. Thirty-one of 129 (24%) had a positive SLNB, including 10 of 73 (14%) with stage I and 21 of 56 (38%) with stage II disease. Seventy-eight patients (60%) received systemic adjuvant chemotherapy and 79 (62%) received radiation therapy, and of the 102 patients who were estrogen receptor positive, 86 (85%) received endocrine therapy. Seventy-nine patients were observed for \u3e 2 years, and, of these, four (5.1%) had a regional recurrence. Conclusion: The SLNB positivity rates were similar to those of high-income country (HIC) cohorts. However, preliminary data suggest that recurrence rates are elevated at AKUH as compared with those of HIC cohorts, perhaps because of a lower use of radiotherapy and chemotherapy at AKUH compared with HIC cohorts or because of differences in the characteristics of the primary tumor in patients at AKUH as compared with those in HICs

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+. P16 immunohistochemistry was performed on the baseline cervical biopsy with a positive result defined as strong abnormal nuclear expression in a continuous block segment of cells (at least 10–20 cells). Results: Among the 200 women with CIN2+ randomized to cryotherapy, 160 (80%) had a baseline cervical biopsy specimen available, of whom 94 (59%) were p16-positive. p16 expression at baseline was associated with presence of any one of 14 hrHPV genotypes [Odds Ratio (OR)  =  3.2; 95% Confidence Interval (CI), 1.03–9.78], multiple lifetime sexual partners (OR  =  1.6; 95% CI, 1.03–2.54) and detectable plasma HIV viral load (\u3e1,000 copies/mL; OR  =  1.43; 95% CI, 1.01– 2.03). Longer antiretroviral therapy duration (≥2  years) at baseline had lower odds of p16 expression (OR  =  0.46; 95% CI, 0.24–0.87) than \u3c2  years of antiretroviral therapy. Fifty-one women had CIN2+ recurrence over 2-years, of whom 33 (65%) were p16-positive at baseline. p16 was not associated with CIN2+ recurrence (Hazard Ratio  =  1.35; 95% CI, 0.76–2.40). Conclusion: In this population of women with HIV and CIN2+, 41% of lesions were p16 negative and baseline p16 expression did not predict recurrence of cervical neoplasia during two-year follow up

Ethnicity and Breast Cancer Characteristics in Kenya

Purpose: There are no published data from specific regions of sub-Saharan Africa describing the clinical and pathological characteristics and molecular subtypes of invasive breast cancer by ethnic group. The purpose of this study was to investigate these characteristics among the three major ethno-cultural groupings in Kenya. Methods: The study included women with pathologically confirmed breast cancer diagnosed between March 2012 and May 2015 at 11 hospitals throughout Kenya. Sociodemographic, clinical, and reproductive data were collected by questionnaire, and pathology review and immunohistochemistry were performed centrally. Results: The 846 cases included 661 Bantus (78.1%), 143 Nilotes (16.9%), 19 Cushites (2.3%), and 23 patients of mixed ethnicity (2.7%). In analyses comparing the two major ethnic groups, Bantus were more educated, more overweight, had an older age at first birth, and had a younger age at menopause than Nilotes (p \u3c 0.05 for all comparisons). In analyses restricted to definitive surgery specimens, there were no statistically significant differences in tumor characteristics or molecular subtypes by ethnicity, although the Nilote tumors tended to be larger (OR for ≥ 5 cm vs. \u3c 2 cm: 3.86, 95% CI 0.77, 19.30) and were somewhat more likely to be HER2 enriched (OR for HER2 enriched vs. Luminal A/B: 1.41, 95% CI 0.79, 2.49). Conclusion: This case series showed no significant differences in breast cancer tumor characteristics or molecular subtypes, but significant differences in sociodemographic characteristics and reproductive factors, among the three major ethnic groups in Kenya. We suggest further evaluation of ethnic differences in breast cancer throughout the genetically and culturally diverse populations of sub-Saharan Africa

Breast Cancer knowledge, perceptions and practices in a rural Community in Coastal Kenya

Background: Data on breast healthcare knowledge, perceptions and practice among women in rural Kenya is limited. Furthermore, the role of the male head of household in influencing a woman’s breast health seeking behavior is also not known. The aim of this study was to assess the knowledge, perceptions and practice of breast cancer among women, male heads of households, opinion leaders and healthcare providers within a rural community in Kenya. Our secondary objective was to explore the role of male heads of households in influencing a woman’s breast health seeking behavior. Methods: This was a mixed method cross-sectional study, conducted between Sept 1st 2015 Sept 30th 2016. We administered surveys to women and male heads of households. Outcomes of interest were analysed in Stata ver 13 and tabulated against gender. We conducted six focus group discussions (FGDs) and 22 key informant interviews (KIIs) with opinion leaders and health care providers, respectively. Elements of the Rapid Assessment Process (RAP) were used to guide analysis of the FGDs and the KIIs. Results: A total of 442 women and 237 male heads of households participated in the survey. Although more than 80% of respondents had heard of breast cancer, fewer than 10% of women and male heads of households had knowledge of 2 or more of its risk factors. More than 85% of both men and women perceived breast cancer as a very serious illness. Over 90% of respondents would visit a health facility for a breast lump. Variable recognition of signs of breast cancer, limited decision- autonomy for women, a preference for traditional healers, lack of trust in the health care system, inadequate access to services, limited early-detection services were the six themes that emerged from the FGDs and the KIIs. There were discrepancies between the qualitative and quantitative data for the perceived role of the male head of household as a barrier to seeking breast health care. Conclusions: Determining level of breast cancer knowledge, the characteristics of breast health seeking behavior and the perceived barriers to accessing breast health are the first steps in establishing locally relevant intervention programs