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 (>1,000 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 <2 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.

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.

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. Tissue Microarrays were constructed and stained with immunohistochemistry (IHC) for CD3, CD4, CD8, CD68, CD20, and FOXP3. Linear and logistic regression models were used to assess associations between risk factors and tumour features with IHC markers and total TILs, after adjusting for other covariates. RESULTS: A total of 226 invasive BC cases were included. Overall, LE-TIL (mean = 27.9, SD = 24.5) proportions were significantly higher than sTIL (mean = 13.5, SD = 15.8). Both sTILs and LE- TILs were predominantly composed of CD3, CD8, and CD68. We found higher TILs to be associated with high KI67/high grade and aggressive tumour subtypes, although these associations varied by TIL locations. Older age at menarche (≥ 15 vs. < 15 years) was associated with higher CD3 (OR: 2.06, 95%CI:1.26-3.37), but only for the intra-tumour stroma. CONCLUSION: The TIL enrichment in more aggressive BCs is similar to previously published data in other populations. The distinct associations of sTIL/LE-TIL measures with most examined factors highlight the importance of spatial TIL evaluations in future studies.

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.

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. METHODS: This was a census survey study conducted at the Aga Khan University Hospital, Nairobi, between November 2020 and February 2021 before the implementation of the COVID-19 vaccination. The SARS-CoV-2 nucleocapsid IgG test was performed using a chemiluminescent assay. RESULTS: One thousand six hundred thirty-one (1631) staff enrolled, totalling 60% of the workforce. The overall crude seroprevalence was 18.4% and the adjusted value (for assay sensitivity of 86%) was 21.4% (95% CI; 19.2-23.7). The staff categories with higher prevalence included pharmacy (25.6%), outreach (24%), hospital- based nursing (22.2%) and catering staff (22.6%). Independent predictors of a positive IgG result after adjusting for age, sex and comorbidities included prior COVID-19 like symptoms, odds ratio (OR) 2.0 [95% confidence interval (CI) 1.3-3.0, p = 0.001], a prior positive SARS-CoV-2 PCR result OR 12.0 (CI: 7.7-18.7, p<0.001) and working in a clinical COVID-19 designated area, OR 1.9 (CI 1.1-3.3, p = 0.021). The odds of testing positive for IgG after a positive PCR test were lowest if the antibody test was performed more than 2 months later; OR 0.7 (CI: 0.48-0.95, p = 0.025). CONCLUSIONS: The prevalence of anti- SARS-CoV-2 nucleocapsid IgG among HCWs and nonclinical staff was lower than in the general population. Staff working in clinical areas were not at increased risk when compared to staff working in non-clinical areas.

A Snapshot of the Landscape of Endocervical Adenocarcinoma in Kenya: What Has HPV Got to Do with It?

OBJECTIVE: To determine the frequency of the HPV associated endocervical adenocarcinomas diagnosed at a tertiary referral laboratory in Kenya over a one-year period and classify them by histologic subtypes according to the proposed criteria by IECC. MATERIALS AND METHODS: This was a collaborative cross-sectional descriptive study. Formalin-fixed parrafin embedded tissue blocks of 29 confirmed cases of endocervical adenocarcinoma diagnosed at AKUHN between July 2017 and July 2018 were analyzed for presence of 14 hrHPV subtypes including types 16 and 18 using GenomeMETM's GeneNavTm HPV One qPCR kit. Variables analyzed included age, histologic subtype and presence or absence of hrHPV. RESULTS: Twenty-nine cases were analyzed (median age=48years, range 23-70 years), of which 27(93.1%) were positive for hrHPV, with type 16 alone positive in 11(40.7%) cases and present alone or in combination with others including type 18 in 21(72.4%) cases. All hrHPV positive cases had either type 16 or 18. Twenty cases (69.0%) were classified as usual type adenocarcinoma, all positive for hrHPV. Other HPV associated adenocarcinomas identified were mucinous, signet ring cell type (4), villoglandular (2) and mucinous, NOS (1). There were only two cases of non-HPV associated adenocarcinoma. CONCLUSION: In this series, we show that the proportion of HPV associated endocervical adenocarcinoma in Kenya is high and is particularly driven by types 16 and 18. Policy makers, hospitals and laboratories in East Africa should make an effort to avail the various techniques of detecting hrHPV critical in screening and diagnosis of endocervical adenocarcinoma.

Geographic Variability of Nodular Lymphocyte-Predominant Hodgkin Lymphoma.

OBJECTIVES: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) differs from classic Hodgkin lymphoma (CHL) in terms of clinicopathologic features, including Epstein-Barr virus (EBV) association. CHL geographic variability is well known, with higher frequencies of mixed-cellularity subtype and EBV positivity in low/middle-income countries (LMICs), but there are few well-characterized series of NLPHL from LMICs. METHODS: We detail clinicopathologic findings of 21 NLPHL cases received in consultation from Kenya and summarize reports of NLPHL with EBV testing published since 2000. RESULTS: Median age of consultation cases was 36 years, and male/female ratio was 3.2. All cases involved peripheral lymph nodes and showed at least some B-cell-rich nodular immunoarchitecture, with prominent extranodular lymphocyte-predominant (LP) cells and T-cell-rich variant patterns most commonly seen. LP cells expressed pan-B-cell markers, including strong OCT2; lacked CD30 and CD15 expression in most cases; and were in a background of expanded/disrupted follicular dendritic cell meshworks and increased T-follicular helper cells. LP cells were EBV negative in 18 cases. Historical cases showed a low rate of EBV positivity with no significant difference between LMICs and high-income countries. CONCLUSIONS: Unlike CHL, NLPHL shows few geographic differences in terms of clinicopathologic features and EBV association. These findings have implications for diagnosis, prognostication, and treatment of patients with NLPHL in LMICs.

Breast cancer risk factors in relation to molecular subtypes in breast cancer patients from Kenya.

BACKGROUND: Few studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations. METHODS: We conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based, and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors. RESULTS: The median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3, and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER-positive tumors, ER-negative patients were more likely to have higher parity (OR = 2.03, 95% CI = (1.11, 3.72), p = 0.021, comparing ≥ 5 to ≤ 2 children). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR = 0.45, 95% CI = 0.23, 0.87, p = 0.018, comparing ≥ 5 to ≤ 2 children); HER2-enriched patients were less likely to be obese (OR = 0.36, 95% CI = 0.16, 0.81, p = 0.013) or older age at menopause (OR = 0.38, 95% CI = 0.15, 0.997, p = 0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes. CONCLUSIONS: In Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies is needed to develop population and subtype-specific risk prediction/prevention strategies.

Comparative analysis of triple-negative breast cancer transcriptomics of Kenyan, African American and Caucasian Women.

PURPOSE: Triple-negative breast cancer (TNBC) patients of various ethnic groups often have discrete clinical presentations and outcomes. Women of African descent have a disproportionately higher chance of developing TNBCs. The aim of the current study was to establish the transcriptome of TNBCs from Kenyan (KE) women of Bantu origin and compare it to those TNBCs of African-Americans (AA) and Caucasians (CA) for identifying KE TNBC-specific molecular determinants of cancer progression and potential biomarkers of clinical outcomes. PATIENTS AND METHODS: Pathology-confirmed TNBC tissues from Kenyan women of Bantu origin (n = 15) and age and stage range matched AA (n = 19) and CA (n = 23) TNBCs of patients from Alabama were included in this study. RNA was isolated from paraffin-embedded tissues, and expression was analyzed by RNA sequencing. RESULTS: At clinical presentation, young KE TNBC patients have tumors of higher stages. Differential expression analysis identified 160 up-regulated and 178 down-regulated genes in KE TNBCs compared to AA and CA TNBCs. Validation analyses of the TCGA breast cancer data identified 45 KE TNBC-specific genes that are involved in the apoptosis (ACTC1, ERCC6 and CD14), cell proliferation (UHRF2, KDM4C, UHMK1, KCNH5, KRT18, CSF1R and S100A13), and Wnt signaling (BCL9L) pathways. CONCLUSIONS: In this study, we identified biomarkers that are specific for KE TNBC patients of Bantu origin. Further study with a larger sample size of matched tumors could confirm our findings. If biologically confirmed, these molecular determinants could have clinical and biological implications and serve as targets for development of personalized therapeutics for KE TNBC patients.

Clinicopathologic Features of Peripheral T-Cell Lymphoma in Sub-Saharan Africa.

OBJECTIVES: Peripheral T-cell lymphomas (PTCLs) are heterogeneous, clinically aggressive, and rare. Subtype distribution varies by geographic location; however, data from sub-Saharan Africa (SSA) are lacking. We sought to elucidate clinicopathologic features of PTCL in SSA. METHODS: We reviewed PTCL consultation cases from three SSA countries. PTCL subtype was determined per 2017 World Health Organization classification. Cases with sufficient material were evaluated by polymerase chain reaction for human T-cell leukemia virus type 1 (HTLV-1) and T-cell receptor γ (TCRG) rearrangement. RESULTS: Among 32 cases, median age was 45 years and male-to-female ratio was 1.7. Thirty (94%) of 32 cases required additional workup for subclassification. PTCL, not otherwise specified (PTCL-NOS) was the most common subtype (13/32, 41%), followed by PTCL with T-follicular helper phenotype (6/32, 19%) and systemic anaplastic large cell lymphoma (6/32, 19%). Four (16%) of 25 cases were Epstein-Barr virus positive (EBV+) (2/2 extranodal natural killer/T-cell lymphoma, 1/13 PTCL-NOS, and 1/4 angioimmunoblastic T-cell lymphoma with EBV+ immunoblasts). Two (15%) of 13 patients with PTCL-NOS were human immunodeficiency virus positive. No cases with evaluable DNA (0/15) were HTLV-1 positive, and 9 of 10 showed clonal TCRG rearrangements. CONCLUSIONS: In comparison to Western studies, PTCLs from SSA show similar subtype distribution and male predominance but a younger age at diagnosis. Appropriate diagnosis of PTCL requires extensive ancillary testing not readily available in low-income countries, including much of SSA.

Loop electrosurgical excision procedure (LEEP) plus top hat for HIV-infected women with endocervical intraepithelial neoplasia in Kenya.

OBJECTIVE: To determine the utility of detecting endocervical cervical intraepithelial neoplasia (CIN) 2+ with endocervical curettage (ECC) and treating with loop electrosurgical excision procedure (LEEP) plus top hat (+TH) among women with HIV. METHODS: Cytology was followed by coloscopy-directed biopsy if participants had HSIL or ASC-H and biopsy plus ECC if there were glandular cells present. CIN2/3 on ECC and/or inadequate colposcopy (ENL) was treated with LEEP+TH, while CIN2/3 on ectocervix (ECL) received LEEP alone. Recurrent CIN2+ were compared over a 2-year follow-up. RESULTS: Of 5330 participants, 160 underwent ECC, 98 were CIN2/3 on ECC, and 77 received LEEP+TH. ECC detected 15 (9%) more women with CIN2/3 than biopsy alone. Women were more likely to have ENL if they were older (≥45 vs <35 years) (adjusted relative risk [aRR] 2.14; P = 0.009) and on antiretroviral treatment longer (≥2 vs <2 years) (aRR 3.97; P < 0.001). Over the 2-year follow-up, 35 (29%) ENL had recurrent CIN2+ after TH compared to 19 (24%) ECL after LEEP (hazard ratio 1.32; 95% confidence interval 0.75-2.31; P = 0.338). CONCLUSION: Among HIV-infected women, adding ECC did not increase detection of pre-cancerous disease significantly and treatment with LEEP+TH for ENL was comparable to treatment with LEEP for ECL.

Whole Genome Sequencing Reveals Virulence Potentials of Helicobacter pylori Strain KE21 Isolated from a Kenyan Patient with Gastric Signet Ring Cell Carcinoma.

Helicobacter pylori (H.pylori) infection is etiologically associated with severe diseases including gastric cancer; but its pathogenicity is deeply shaped by the exceptional genomic diversification and geographic variation of the species. The clinical relevance of strains colonizing Africa is still debated. This study aimed to explore genomic features and virulence potentials of H. pylori KE21, a typical African strain isolated from a native Kenyan patient diagnosed with a gastric cancer. A high-quality circular genome assembly of 1,648,327 bp (1590 genes) obtained as a hybrid of Illumina Miseq short reads and Oxford Nanopore MinION long reads, clustered within hpAfrica1 population. This genome revealed a virulome and a mobilome encoding more than hundred features potentiating a successful colonization, persistent infection, and enhanced disease pathogenesis. Furthermore, through an experimental infection of gastric epithelial cell lines, strain KE21 showed the ability to promote interleukin-8 production and to induce cellular alterations resulting from the injection of a functional CagA oncogene protein into the cells. This study shows that strain KE21 is potentially virulent and can trigger oncogenic pathways in gastric epithelial cells. Expended genomic and clinical explorations are required to evaluate the epidemiological importance of H. pylori infection and its putative complications in the study population.

Xpert® MTB/RIF assay on formalin-fixed paraffin-embedded tissues in the diagnosis of extrapulmonary tuberculosis.

BACKGROUND: Diagnosis of extrapulmonary tuberculosis continues to be a challenge due to the complexity of the causative organism and the wide array of pathologic features seen in this infection. Xpert MTB/RIF can be used on fresh or frozen tissue specimens for diagnosis of tuberculosis with good results. However, there is little data on its use with formalin-fixed paraffin-embedded (FFPE) tissues. OBJECTIVES: The aim of this study was to demonstrate the potential utility of Xpert MTB/RIF and to compare its performance to Ziehl-Neelsen staining for the detection of Mycobacterium tuberculosis from FFPE tissues using histological features from haematoxylin and eosin staining as the gold standard. METHODS: Eighty randomly selected archival FFPE tissues exhibiting histological features of tuberculosis were included in the study. After deparaffinisation and lysis, all the tissue specimens were subjected to the Xpert® MTB/RIF assay. The outcome measures were proportions of positively identified cases by each test. RESULTS: Using histology as the gold standard, the sensitivity of Ziehl-Neelsen staining was 20.3% (95% confidence interval: 12% - 30.8%), and the sensitivity of the Xpert® MTB/RIF assay was 53.2% (95% confidence interval: 41.6% - 64.9%); the difference was statistically significant (p = 0.002). None of the cases tested positive for rifampicin resistance. CONCLUSION: With prior deparaffinisation and lysis, FFPE tissues are amenable to testing by Xpert® MTB/RIF assay. A validation study to determine the clinical utility, analytical optimisation and cost implications of this assay for FFPE tissues is recommended.

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.

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.

Difficulties in diagnosis of Riedel's thyroiditis on aspiration cytology: A case report and brief review of the literature.

Riedel's thyroiditis (RT) is a rare disorder characterized by extensive fibrosis extending to the extrathyroidal tissues. An elderly male presented with diffuse moderate thyromegaly and hoarseness of voice for two years. Radiology showed extrathyroidal extension around trachea with compression and deviation suggestive of malignancy. Thyroid was hard and non tender. Ultrasound guided Fine Needle Aspiration (FNA) from multiple foci on both sides using thinner needle yielded moderately cellularity showing follicular cells, lymphoplasmacytic infiltrate, scant colloid and fibrous tissue fragments. Hurthle cells were absent. Adiagnosis of chronic thyroiditis was given with possibility of RT in view of clinical and radiological findings. A core biopsy showed similar picture as cytology. Guided FNA from multiple foci using thinner needle helped to obtain adequate material allowing a confident diagnosis. This case adds to the meagre literature available on the cytologic diagnosis of RT and highlights the diagnostic challenge due to suspicious radiology findings.

Task Sharing and Shifting to Provide Pathology Diagnostic Services: The Kenya Fine-Needle Aspiration Biopsy Cytology and Bone Marrow Aspiration and Trephine Biopsy Training Program.

PURPOSE: Fine-needle aspiration biopsy (FNAB) cytology is a simple, inexpensive, and accurate diagnostic test for benign, infectious, and malignant lesions of the breast, thyroid, lymph nodes, and other organs. Similarly, bone marrow aspiration and trephine (BMAT) biopsy procedures are relatively simple and inexpensive techniques that are important for diagnosing and monitoring many hematologic diseases including leukemias and lymphomas. However, the scarcity of pathologists in Kenya limits patient access to these simple diagnostic tests. We describe a task sharing and shifting program that sought to improve the provision of FNABs and BMAT biopsies in tertiary public hospitals in Kenya. METHODS: Between January 2016 and February 2017, we trained pathologists, pathology residents, and technologists from the University of Nairobi and Aga Khan University Hospital, Nairobi, in FNAB and BMAT biopsies, who in turn trained pathologists, medical officers (MO), clinical officers (CO), and technologists at five tertiary public hospitals. The program involved curriculum development, training workshops, the establishment of new and strengthening existing FNAB and BMAT biopsy clinics, interim site visits, audits, and stakeholder workshops. RESULTS: Fifty-one medical personnel at the tertiary hospitals were trained. The FNAB numbers increased by 41% to 1,681, with 139 malignant diagnoses (7.1%). BMAT biopsy numbers increased by 268% to 140, with 34 malignant cases. Between 60% and 100% of the FNAB and BMAT biopsy procedures were performed by MO and CO over the project period. One new FNAB and two new BMAT biopsy clinics were established. CONCLUSION: This project demonstrates a successful model of task sharing and shifting from specialist pathologists to MO and CO that improved access to important FNAB and BMAT biopsy services in a low-resource setting.

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 > 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.

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

INTRODUCTION: Data examining mammographic 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 cross-sectional study included women with pathologically confirmed breast cancers (n = 123). Pretreatment mammograms of the unaffected breast 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 (P < 0.01). Higher dense and nondense areas were observed in obese women (P-trend < 0.01). Estrogen receptor (ER) positive patients (73%) had higher PD and dense area than ER-negative patients (P ≤ 0.02). Triple negative breast cancer (TNBC) patients (17%) had lower PD and dense area (P ≤ 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.