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

Abstract

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.

Keywords: BL, Burkitt Lymphoma; CAP, College of American Pathologists; DLBCL, Diffuse Large B-cell Lymphoma; GSM, Glass slide microscopy; H&E, Hematoxylin and Eosin staining; HL, Hodgkin’s Lymphoma; IHC, Immunohistochemistry; LMICs, Low-and-middle income countries; Lymphoma diagnosis; NPV, Negative predictive value; PPV, Positive predictive value; Portable whole slide imaging scanner; Resource-limited setting; Validation; WSI, Whole slide imaging.

Fig. 1

Schematic flow chart of the study participants.

Fig. 2

Diagnostic algorithm proposed by Naresh et al, (2011) to be used for the differential diagnosis of aggressive B-cell lymphomas in limited-resource settings with a high incidence of BL.

Fig. 3

A: Photograph of Alexapath mobile scanner workstation. B: Photomicroscopy of H&E stained biopsy highlighting sub-optimal quality (non-diagnostic); 100x original magnification. C: IHC stained Non-Hodgkin lymphoma demonstrating sub-optimal quality, 100x original magnification. D: IHC-stained BL demonstrating optimal quality with nearly 100% immunostaining with Ki-67, 100x original magnification. E: H&E-stained DLBCL displaying optimal quality photomicroscopy, 200x original magnification. F: A photograph showing a local biomedical engineer trying to fix a technical problem with the Alexapath scanner.