Diagnostic validation of a portable whole slide imaging scanner for lymphoma diagnosis in resource-constrained setting: A cross-sectional study.

Background: Telepathology utilizing high-throughput static whole slide image scanners is proposed to address the challenge of limited pathology services in resource-restricted settings. However, the prohibitive equipment costs and sophisticated technologies coupled with large amounts of space to set up the devices make it impractical for use in resource-limited settings. Herein, we aimed to address this challenge by validating a portable whole slide imaging (WSI) device against glass slide microscopy (GSM) using lymph node biopsies from suspected lymphoma cases from Sub-Saharan Africa. Material and methods: This was part of a multicenter prospective case-control head-to-head comparison study of liquid biopsy against conventional pathology. For the portable WSI scanner validation, the study pathologists evaluated 105 surgical lymph node specimens initially confirmed by gold-standard pathology between February and December 2021. The tissues were processed according to standard protocols for Hematoxylin and Eosin (H&E) and Immunohistochemistry (IHC) staining by well-trained histotechnicians, then digitalized the H& E and IHC slides at each center. The digital images were anonymized and uploaded to a HIPAA-compliant server by the histotechnicians. Three study pathologists independently accessed and reviewed the images after a 6-week washout. The agreement between diagnoses established on GSM and WSI across the pathologists was described and measured using Cohens' kappa coefficient (κ). Results: On GSM, 65.5% (n=84) of specimens were lymphoma; 25% were classified as benign, while 9.5% were metastatic. Morphological quality assessment on GSM and WSI established that 79.8% and 53.6% of cases were of high quality, respectively. When diagnoses by GSM were compared to WSI, the overall concordance for various diagnostic categories was 93%, 100%, and 86% for lymphoma, metastases, and benign conditions respectively. The sensitivity and specificity of WSI for the detection of lymphoma were 95.2% and 85.7%, respectively, with an overall inter-observer agreement (κ) of 0.86; 95% CI (0.70-0.95). Conclusions: We demonstrate that mobile whole slide imaging (WSI) is non-inferior to conventional glass slide microscopy (GSM) for the primary diagnosis of malignant infiltration of lymph node specimens. Our results further provide proof of concept that mobile WSI can be adapted to resource-restricted settings for primary surgical pathology and would significantly improve patient outcomes.

The distribution of reproductive risk factors disclosed the heterogeneity of receptor-defined breast cancer subtypes among Tanzanian women.

BACKGROUND: Recent epidemiological studies suggest that reproductive factors are associated with breast cancer (BC) molecular subtypes. However, these associations have not been thoroughly studied in the African populations. The present study aimed to investigate the prevalence of BC molecular subtypes and assess their association with reproductive factors in Tanzanian BC patients. METHODS: This hospital-based case-only cross-sectional study consisted of 263 histologically confirmed BC patients in Tanzania. Clinico-pathological data, socio-demographic characteristics, anthropometric measurements, and reproductive risk factors were examined using the Chi-square test and one-way ANOVA. The association among reproductive factors and BC molecular subtypes was analyzed using multinomial logistic regression. The heterogeneity of the associations was assessed using the Wald test. RESULTS: We found evident subtype heterogeneity for reproductive factors. We observed that post-menopausal status was more prevalent in luminal-A subtype, while compared to luminal-A subtype, luminal-B and HER-2 enriched subtypes were less likely to be found in post-menopausal women (OR: 0.21, 95%CI 0.10-0.41, p = 0.001; OR: 0.39, 95%CI 0.17-0.89, p = 0.026, respectively). Also, the luminal-B subtype was more likely to be diagnosed in patients aged ≤ 40 years than the luminal-A subtype (OR: 2.80, 95%CI 1.46-5.32, p = 0.002). Women who had their first full-term pregnancy at < 30 years were more likely to be of luminal-B (OR: 2.71, 95%CI 1.18-4.17, p = 0.018), and triple-negative (OR: 2.28, 95%CI 1.02-4.07, p = 0.044) subtypes relative to luminal-A subtype. Furthermore, we observed that breastfeeding might have reduced odds of developing luminal-A, luminal-B and triple-negative subtypes. Women who never breastfed were more likely to be diagnosed with luminal-B and triple-negative subtypes when compared to luminal-A subtype (OR: 0.46, 95%CI 0.22-0.95, p = 0.035; OR: 0.41, 95%CI 0.20-0.85, p = 0.017, respectively). . CONCLUSION: Our results are the first data reporting reproductive factors heterogeneity among BC molecular subtypes in Tanzania. Our findings suggest that breast-feeding may reduce the likelihood of developing luminal-A, luminal-B, and triple-negative subtypes. Meanwhile, the first full-term pregnancy after 30 years of age could increase the chance of developing luminal-A subtype, a highly prevalent subtype in Tanzania. More interventions to promote modifiable risk factors across multiple levels may most successfully reduce BC incidence in Africa.

Ki-67, p53 and BCL-2 Expressions and their Association with Clinical Histopathology of Breast Cancer among Women in Tanzania.

This study associated Ki-67, p53, and BCL-2 markers with clinical histopathological (CH) features using currently available limited data on these markers in Tanzania. Retrospective chart review study was conducted among females with confirmed breast cancer (BC) at Muhimbili National Hospital in Tanzania between 2016 and 2017. Inclusion criteria were met by 76 patients with a mean age of 51.32 ± 14.28 years. Of these, 86.4% were stage III and IV, whereas 83.5% cases had grade 2 and grade 3. Upon immunostaining, 85.5% and 57.9% were Ki-67 and BCL-2 positive respectively. Log-linear analysis showed no statistically significant association among biomarkers expression and CH features. However, multinomial linear regression showed higher possibility for association between high expression of Ki-67, low expression of p53 and high expression of BCL-2 with age, grade, stage and tumor (T) stage. BCL-2 was positively correlated with Ki-67 expression contrary to p53, which was negatively correlated with BCL-2. Conclusively, there is evidence of correlation between the studied markers with CH features. However, studies with larger sample sizes will likely reveal significant associations that will validate the role of these markers as tools for evaluating treatment response in individualized therapeutic schemes in Tanzania.