Toluidine blue versus frozen section for assessment of mucosal tumor margins in oral squamous cell carcinoma

Algadi, Hana’a Hezam; Abou-Bakr, Amany A; Jamali, Omer Mohammed; Fathy, L M

doi:10.1186/s12885-020-07644-0

Cited by 10 publications

(6 citation statements)

References 36 publications

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“…Additionally, the field of view is limited by the probe’s size and its acoustic penetration depth. Most other techniques for in-vivo assessment primarily reveal only the tumor’s mucosal extent ( 9 , 11 , 13 ). As no superior in-vivo technique has emerged thus far, ex-vivo margin assessment remains crucial for margin control.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of an MR-based digital specimen for tongue cancer resection specimens: a novel approach for margin evaluation

de Koning,

Dankbaar,

de Keizer

et al. 2024

Front. Oncol.

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ObjectiveThis study explores the feasibility of ex-vivo high-field magnetic resonance (MR) imaging to create digital a three-dimensional (3D) representations of tongue cancer specimens, referred to as the “MR-based digital specimen” (MR-DS). The aim was to create a method to assist surgeons in identifying and localizing inadequate resection margins during surgery, a critical factor in achieving locoregional control.MethodsFresh resection specimens of nine tongue cancer patients were imaged in a 7 Tesla small-bore MR, using a high-resolution multislice and 3D T2-weighted Turbo Spin Echo. Two independent radiologists (R1 and R2) outlined the tumor and mucosa on the MR-images whereafter the outlines were configured to an MR-DS. A color map was projected on the MR-DS, mapping the inadequate margins according to R1 and R2. We compared the hematoxylin-eosin-based digital specimen (HE-DS), which is a histopathological 3D representation derived from HE stained sections, with its corresponding MR-images. In line with conventional histopathological assessment, all digital specimens were divided into five anatomical regions (anterior, posterior, craniomedial, caudolateral and deep central). Over- and underestimation 95th-percentile Hausdorff-distances were calculated between the radiologist- and histopathologist-determined tumor outlines. The MR-DS’ diagnostic accuracy for inadequate margin detection (i.e. sensitivity and specificity) was determined in two ways: with conventional histopathology and HE-DS as reference.ResultsUsing conventional histopathology as a reference, R1 achieved 77% sensitivity and 50% specificity, while R2 achieved 65% sensitivity and 57% specificity. When referencing to the HE-DS, R1 achieved 94% sensitivity and 61% specificity, while R2 achieved 88% sensitivity and 71% specificity. Range of over- and underestimation 95HD was 0.9 mm - 11.8 mm and 0.0 mm - 5.3 mm, respectively.ConclusionThis proof of concept for volumetric assessment of resection margins using MR-DSs, demonstrates promising potential for further development. Overall, sensitivity is higher than specificity for inadequate margin detection, because of the radiologist’s tendency to overestimate tumor size.

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Section: Discussionmentioning

confidence: 99%

Feasibility of an MR-based digital specimen for tongue cancer resection specimens: a novel approach for margin evaluation

de Koning,

Dankbaar,

de Keizer

et al. 2024

Front. Oncol.

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“…Apart from iodine staining, staining with toluidine blue has also been researched. However, the studies of concern [ 51 , 52 ] stained the resection specimen, but only after the resection was completed. These studies concluded that this stain is highly sensitive to SCC in the resection margins but has a low PPV.…”

Section: Discussionmentioning

confidence: 99%

Intraoperative Techniques That Define the Mucosal Margins of Oral Cancer In-Vivo: A Systematic Review

de Koning,

Adriaansens,

Noorlag

et al. 2024

Cancers

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Background: This systematic review investigates techniques for determining adequate mucosal margins during the resection of oral squamous cell carcinoma (SCC). The primary treatment involves surgical removal with ≥5 mm margins, highlighting the importance of accurate differentiation between SCC and dysplasia during surgery. Methods: A comprehensive Embase and PubMed literature search was performed. Studies underwent quality assessment using QUADAS-2. Results: After the full-text screening and exclusion of studies exhibiting high bias, eight studies were included, focusing on three margin visualization techniques: autofluorescence, iodine staining, and narrow-band imaging (NBI). Negative predictive value (NPV) was calculable across the studies, though reference standards varied. Results indicated NPVs for autofluorescence, iodine, and NBI ranging from 61% to 100%, 92% to 99%, and 86% to 100%, respectively. Autofluorescence did not significantly enhance margins compared to white light-guided surgery, while iodine staining demonstrated improvement for mild or moderate dysplasia. NBI lacked comparison with a white light-guided surgery cohort. Conclusions: We recommend studying and comparing the diagnostic accuracy of iodine staining and NBI in larger cohorts of patients with oral SCC, focusing on discriminating between SCC and (severe) dysplasia. Furthermore, we advise reporting the diagnostic accuracy alongside the treatment effects to improve the assessment of these techniques.

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“…The specimen imaging techniques are agnostic to the fluorescent agent used and may thus also apply beyond paniatumumab-IRDye800CW ( 20), (21) (22). It is worth mentioning that non-fluorescent optical dyes have been investigated for margin analysis with promising results (23,24) (25).…”

Section: Discussionmentioning

confidence: 99%

Fluorescent Molecular Imaging Can Improve Intraoperative Sentinel Margin Detection in Oral Squamous Cell Carcinoma

et al. 2022

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In head and neck cancer, a major limitation of current intraoperative margin analysis is the ability to detect areas most likely to be positive based on specimen palpation, especially for larger specimens where sampling error limits detection of positive margins. This study aims to prospectively examine the clinical value of fluorescent molecular imaging to accurately identify "the sentinel margin," the point on a specimen where tumour lies closest to the resected edge in real-time during frozen section analysis. Methods:Eighteen patients with oral squamous cell carcinoma were enrolled into a prospective clinical trial and infused intravenously with 50mg of panitumumab-IRDye800CW 1-5 days prior to surgery. Resected specimens were imaged in a closed-field near-infrared optical imaging system in near-real time, and custom designed software was used to identify locations of highest fluorescence on deep and peripheral margins. The surgeon identified the sentinel margin blinded to optical specimen mapping, and then the regions of highest fluorescence were identified and marked for frozen analysis. Final pathology based on specimen reconstruction was used as reference standard. Results:Resected specimens were imaged in the operating room and fluorescence had a higher interobserver agreement with pathology (Cohen kappa value 0.96) than the surgeon (Cohen kappa values of 0.82) for the location of the closest margin.

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Toluidine blue versus frozen section for assessment of mucosal tumor margins in oral squamous cell carcinoma

Cited by 10 publications

References 36 publications

Feasibility of an MR-based digital specimen for tongue cancer resection specimens: a novel approach for margin evaluation

Feasibility of an MR-based digital specimen for tongue cancer resection specimens: a novel approach for margin evaluation

Intraoperative Techniques That Define the Mucosal Margins of Oral Cancer In-Vivo: A Systematic Review

Fluorescent Molecular Imaging Can Improve Intraoperative Sentinel Margin Detection in Oral Squamous Cell Carcinoma

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