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Whole slide imaging of tumour microenvironment in classical Hodgkin’s lymphoma: development of a clinical prediction model based on programmed death-ligand 1 and tumorous Reed-Sternberg cells
  1. Antonio Santisteban Espejo1,2,3,
  2. Irene Bernal-Florindo3,4,
  3. Pedro Montero-Pavon4,
  4. Jose Perez-Requena1,
  5. Lidia Atienza-Cuevas1,3,
  6. Ana Villalba-Fernandez1,
  7. Marcial Garcia-Rojo3,4
  1. 1Department of Pathology, Puerta del Mar University Hospital, Cadiz, Spain
  2. 2Deparment of Medicine, Faculty of Medicine, University of Cadiz, Cadiz, Spain
  3. 3Institute of Research and Biomedical Innovation of Cadiz, INiBICA, Cadiz, Spain
  4. 4Department of Pathology, Jerez de la Frontera University Hospital, Jerez de la Frontera, Spain
  1. Correspondence to Dr Antonio Santisteban Espejo, Department of Pathological Anatomy, University Hospital Puerta del Mar, Cadiz 11009, Spain; antoniosantistebanespejo{at}


Aims The prognostic impact of programmed death-ligand 1 (PD-L1) cells in classic Hodgkin lymphoma (cHL) tumour microenvironment remains undefined.

Methods Model development via Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines were followed. PD-L1+ and CD30+ tumoral Reed-Sternberg cells were quantified through whole slide imaging and digital image analysis in 155 digital histopathological slides of cHL. Univariate and multivariate survival analyses were performed. The analyses were reproduced for patients with advanced stages (IIB, III and IV) using the Advanced-stage cHL International Prognostic Index.

Results The PD-L1/CD30 ratio was statistically significantly associated with survival outcomes. Patients with a PD-L1/CD30 ratio above 47.1 presented a shorter overall survival (mean OS: 53.7 months; 95% CI: 28.7 to 78.7) in comparison with patients below this threshold (mean OS: 105.4 months; 95% CI: 89.6 to 121.3) (p=0.04). When adjusted for covariates, the PD-L1/CD30 ratio retained prognostic impact, both for the OS (HR: 1.005; 95% CI: 1.002 to 1.008; p=0.000) and the progression-free survival (HR: 3.442; 95% CI: 1.045 to 11.340; p=0.04) in a clinical and histopathological multivariate model including the male sex (HR: 3.551; 95% CI: 0.986 to 12.786; p=0.05), a percentage of tumoral cells ≥10.1% (HR: 1.044; 95% CI: 1.003 to 1.087; p=0.03) and high risk International Prognostic Score (≥3 points) (HR: 6.453; 95% CI: 1.970 to 21.134; p=0.002).

Conclusions The PD-L1/CD30 ratio identifies a group of cHL patients with an increased risk of treatment failure. Its clinical application can be performed as it constitutes an easy to implement pathological information in the diagnostic work-up of patients with cHL.

  • lymphoma
  • pathology, molecular
  • image processing, computer-assisted
  • hematologic diseases

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • Handling editor Vikram Deshpande.

  • ASE and IB-F contributed equally.

  • Contributors Conception, design and data analysis and interpretation: ASE and IB-F. Financial support: MG-R. Provision of study materials or patients: AV-F, JP-R, LA-C, PM-P and MG-R. Manuscript writing, final approval of manuscript and accountable for all aspects of the work: all authors. Author acting as guarantor: MG-R.

  • Funding This work was supported by a postdoctoral grant (RH-0145-2020) from the Andalusia Health System.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.