One of the biggest challenges in cancer surgery is the accurate definition of tumour margins, to ensure complete removal of the tumour while preserving an adequate margin of healthy tissue. This challenge is even greater in oral cancer due to variations in tumour invasion patterns between patients. Determining both the tumour margin and the pattern of invasion is strongly associated with prognosis and risk of recurrence.
This project focuses on oral squamous cell carcinoma (OSCC), the eighth most common cancer worldwide, with a five-year survival rate below 60% [1]. Surgery is the main treatment, and both tumour margins and the pattern of invasion are key factors influencing outcomes. The “Worst Pattern of Invasion” (WPOI) is a histopathological classification used to evaluate how aggressively a tumour infiltrates surrounding tissues. Studies have shown that WPOI is strongly associated with prognosis and recurrence risk [6–8].
However, this classification is not fully understood or consistently implemented in clinical practice, possibly because histology examines complex three-dimensional invasion fronts in two-dimensional sections. It remains unclear whether observed tumour islands are truly isolated or still connected to the main tumour mass [8]. This limitation complicates tumour evaluation.
Phase-contrast micro-computed tomography (micro-CT) is a high-resolution imaging technique that enables rapid three-dimensional visualisation of tissue morphology [2–8]. Although not yet approved for clinical diagnosis, micro-CT is increasingly used in research to assess soft tissue, tumour margins, and structural details [2, 9, 10]. Emerging studies also indicate potential applications in breast cancer diagnosis [7]. Thus, micro-CT could become a valuable imaging modality for histological cancer evaluation, improving clinical decision-making and patient outcomes. However, its integration into clinical practice requires further research, particularly with larger sample sizes and improved soft tissue contrast.
Five patients were included in the study, and micro-CT imaging was performed in all cases. Image quality assessment, based on a modified Likert scale, led to the exclusion of three cases. For the remaining two, micro-CT-based assessment of deep margins was feasible, but not sufficiently accurate when compared with histopathology. This limitation was attributed to insufficient contrast in whole-tumour specimens (2–4 cm thick). To address this, a second round of micro-CT scanning was performed using 2 mm-thick paraffin-embedded tissue blocks from the same tumours. This significantly improved image quality, allowing all five cases to be included and enabling tumour margin assessment in four out of five cases.
This study is the first to compare micro-CT and synchrotron imaging for three-dimensional visualisation of oral cancer tissue. It advances our understanding of tumour margins and invasion patterns, and these insights may provide a foundation for future research aimed at improving tumour assessment, optimising prognosis, and reducing treatment-related complications. Ultimately, this imaging approach has the potential to enhance surgical precision and reduce the need for follow-up treatments.
References
1. Chinn, S.B. and J.N. Myers, Oral Cavity Carcinoma: Current Management, Controversies, and Future Directions. J Clin Oncol, 2015. 33(29): p. 3269-76.
2. Papazoglou, A.S., et al., Volumetric Tissue Imaging of Surgical Tissue Specimens Using Micro Computed Tomography: An Emerging Digital Pathology Modality for Nondestructive, Slide Free Microscopy-Clinical Applications of Digital Pathology in 3 Dimensions. Am J Clin Pathol, 2023. 159(3): p. 242-254.
3. Vågberg, W., et al., Cellular-resolution 3D virtual histology of human coronary arteries using x-ray phase tomography. Sci Rep, 2018. 8(1): p. 11014.
4. Schmidt-Christensen, A., et al., Structure-function analysis of time-resolved immunological phases in metabolic dysfunction-associated fatty liver disease (MASH) comparing the NIF mouse model to human MASH. Scientific Reports, 2024. 14(1): p. 23014.
5. Westöö, C., et al., Distinct types of plexiform lesions identified by synchrotron-based phase-contrast micro-CT. Am J Physiol Lung Cell Mol Physiol, 2021. 321(1): p. L17-l28.
6. Haggmark, I., K. Shaker, and H.M. Hertz, In Silico Phase-Contrast X-Ray Imaging of Anthropomorphic Voxel-Based Phantoms. IEEE Trans Med Imaging, 2021. 40(2): p. 539-548.
7. Qiu, S.Q., et al., Micro-computed tomography (micro-CT) for intraoperative surgical margin assessment of breast cancer: A feasibility study in breast conserving surgery. Eur J Surg Oncol, 2018. 44(11): p. 1708-1713.
8. van Ineveld, R.L., et al., 3D imaging for driving cancer discovery. Embo j, 2022. 41(10): p. e109675.
9. Marshall, K., et al., Anatomical characterization of the inguinal lymph nodes using microcomputed tomography to inform radical inguinal lymph node dissections in penile cancer. J Surg Oncol, 2020. 122(8): p. 1785-1790.
10. Yoshida, M., et al., Pathological Evaluation of Rectal Cancer Specimens Using Micro Computed Tomography. Diagnostics (Basel), 2022. 12(4).
For further information about this HALRIC pilot project, please contact:
Tobias Todsen
Rigshospitalet
Tobias.Todsen@regionh.dk
Fatemeh Makouei
Rigshospitalet
fatemeh.makouei@regionh.dk
