Original articles

Vol. 117: Issue 3 - June 2025

The routine use of a digital tool for the tumor cell fraction quantification in molecular pathology: an international validation of QuANTUM

Authors

Vincenzo L’Imperio , Giulia Capitoli , Giorgio Cazzaniga , Mauro Mannino , Francesca Bono , Davide Seminati , Catarina Eloy , Joao Pinto , Elena Guerini Rocco , Matteo Fassan , Pasquale Pisapia , Francesco Pepe , Lara Pijuan , Jordi Temprana-Salvador , Antonio Polonia , Syed Ali Khurram , Emanuela Bonoldi , Alessandro Marando , Giuseppe Perrone , Fabio Pagni , PMMP SIAPEC collaborators

Key words: molecular pathology, computational pathology, tumor cell fraction, NGS, nonsmall cell lung cancer
DOI: 10.32074/1591-951X-1100
Publication Date: 2025-07-04

Abstract

Objective. The absolute and relative quantification of tumor cell fraction (TCF) in tissue samples for molecular pathology testing is time-consuming and poorly reproducible.
Methods. Here we report the results of an international survey on non-small cell lung cancer (NSCLC), validating the Qupath Analysis of Nuclei from Tumor to Uniform Molecular tests (QuANTUM) automated computational pipeline for TCF quantification.
Results. The TCF obtained with QuANTUM is reliable, as demonstrated by the comparison with the manual counting of cells (ground truth, GT) in cell blocks, small biopsies and surgical specimens (overall correlation of 0.89). The visual evaluation of QuANTUMprocessed images increased the pathologists’ agreement with GT and QuANTUM of +0.16, +0.21, +0.09 and +0.17, +0.29, +0.21 across the three sample types, respectively. An overall increase in cases classified as containing ≥100 tumor cells for all sample types was noted after QuANTUM (from 75 cases, 63% to 96 cases, 80% among cell blocks, p = 0.003).
Conclusions. QuANTUM is an easy-to-use and reliable tool for the TCF assessment and its employment significantly modifies the visual estimation by pathologists, improving the assessment of NSCLC cases for molecular analysis

Downloads

PDF
SUPPL. FILE
Authors

Vincenzo L’Imperio - Pathology, IRCCS Fondazione San Gerardo dei Tintori and Centro di Medicina Digitale, Dipartimento di Medicina e Chirurgia, University of Milano-Bicocca, Italy

Giulia Capitoli - Bicocca Bioinformatics Biostatistics and Bioimaging B4 Center, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

Giorgio Cazzaniga - Pathology, IRCCS Fondazione San Gerardo dei Tintori and Centro di Medicina Digitale, Dipartimento di Medicina e Chirurgia, University of Milano-Bicocca, Italy

Mauro Mannino - Pathology, IRCCS Fondazione San Gerardo dei Tintori and Centro di Medicina Digitale, Dipartimento di Medicina e Chirurgia, University of Milano-Bicocca, Italy

Francesca Bono - Pathology, IRCCS Fondazione San Gerardo dei Tintori and Centro di Medicina Digitale, Dipartimento di Medicina e Chirurgia, University of Milano-Bicocca, Italy

Davide Seminati - Pathology, IRCCS Fondazione San Gerardo dei Tintori and Centro di Medicina Digitale, Dipartimento di Medicina e Chirurgia, University of Milano-Bicocca, Italy

Catarina Eloy - Pathology Laboratory, Institute of Molecular Pathology and Immunology of University of Porto (IPATIMUP), Porto, Portugal; Pathology Department, Medical Faculty of University of Porto, Porto, Portugal;

Joao Pinto - Pathology Laboratory, Institute of Molecular Pathology and Immunology of University of Porto (IPATIMUP), Porto, Portugal

Elena Guerini Rocco - Division of Pathology, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Italy

Matteo Fassan - Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Surgical Pathology and Cytopathology Unit, Department of Medicine, DIMED, University of Padua, Padua, Italy

Pasquale Pisapia - Department of Public Health, University of Naples Federico II, Naples, Italy

Francesco Pepe - Department of Public Health, University of Naples Federico II, Naples, Italy

Lara Pijuan - Pathology Department, Bellvitge University Hospital, Barcelona, Spain

Jordi Temprana-Salvador - Pathology Department, Vall Hebron University Hospital, Barcelona, Spain

Antonio Polonia - Pathology Laboratory, Institute of Molecular Pathology and Immunology of University of Porto (IPATIMUP), Porto, Portugal; Escola de Medicina e Ciências Biomédicas, Universidade Fernando Pessoa, Porto, Portugal;

Syed Ali Khurram - School of Clinical Dentistry, Faculty of Health, University of Sheffield, Sheffield, UK

Emanuela Bonoldi - Department of Pathology, Grande Ospedale Metropolitano Niguarda, Milan, Italy

Alessandro Marando - Department of Pathology, Grande Ospedale Metropolitano Niguarda, Milan, Italy

Giuseppe Perrone - Thoracic Surgery Operative Research Unit, Fondazione Policlinico Universitario Campus Bio- Medico, Roma, Italy

Fabio Pagni - Pathology, IRCCS Fondazione San Gerardo dei Tintori and Centro di Medicina Digitale, Dipartimento di Medicina e Chirurgia, University of Milano-Bicocca, Italy

PMMP SIAPEC collaborators - SIAPEC Working Group

License

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Copyright

Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology

How to Cite
L’Imperio, V. ., Capitoli, G., Cazzaniga, G., Mannino, M., Bono, F., Seminati, D., Eloy, C., Pinto, J., Guerini Rocco, E. ., Fassan, M., Pisapia, P., Pepe, F., Pijuan, L., Temprana-Salvador, J. ., Polonia, A., Khurram, S. A., Bonoldi, E., Marando, A., Perrone, G., Pagni, F., & PMMP SIAPEC collaborators. (2025). The routine use of a digital tool for the tumor cell fraction quantification in molecular pathology: an international validation of QuANTUM. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 117(3). https://doi.org/10.32074/1591-951X-1100
  • Abstract viewed - 0 times
  • PDF downloaded - 0 times
  • SUPPL. FILE downloaded - 0 times