Histopathological determinants of autofluorescence patterns in oral carcinoma

Meleti, Marco; Giovannacci, Ilaria; Vescovi, Paolo; Pedrazzi, Giuseppe; Govoni, Paolo; Magnoni, Cristina

doi:10.1111/odi.13304

Cited by 11 publications

(11 citation statements)

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“…Within this context, and following previous analyses performed on other anatomical sites (e.g., oral cavity) [21,24,25], we designed and conducted the present study, which attempts to evaluate the usefulness of AF for the diagnosis and the management of a heterogeneous group of NMSCs.…”

Section: Discussionmentioning

confidence: 99%

“…Gross architectural alterations (e.g., hyperkeratosis, neoangiogenesis) assoc with hyper-and hypofluorescence in pathologic tissues from the oral mucosa have recently described [21]. Only a few other papers have been published in this field, an our knowledge, this is the first work on NMSC autofluorescence and its histopatholo correlation [22] The aims of the present study are 1. to investigate the differences in AF inte between NMSC and healthy skin; 2. to analyze the histopathological determin possibly accounting for AF alterations in pathologic skin.…”

Section: Af Detection Systemmentioning

confidence: 93%

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Correlation between Autofluorescence Intensity and Histopathological Features in Non-Melanoma Skin Cancer: An Ex Vivo Study

Giovannacci

Meleti

Garbarino

et al. 2021

Cancers

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Non-melanoma skin cancer (NMSC) is the most common malignant tumor affecting fair-skinned people. Increasing incidence rates of NMSC have been reported worldwide, which is an important challenge in terms of public health management. Surgical excision with pre-operatively identified margins is one of the most common and effective treatment strategies. Incomplete tumor removal is associated with a very high risk of recurrence and re-excision. Biological tissues can absorb and re-emit specific light wave-lengths, detectable through spectrophotometric devices. Such a phenomenon is known as autofluorescence (AF). AF spectroscopy has been widely explored for non-invasive, early detection of NMSC as well as for evaluation of surgical margins before excision. Fluorescence-aided diagnosis is based on differences in spectral characteristics between healthy and neoplastic skin. Understanding the biological basis of such differences and correlating AF intensity to histological features could improve the diagnostic accuracy of skin fluorescence spectroscopy. The primary objective of the present pre-clinical ex vivo study is to investigate the correlation between the intensity of cutaneous AF and the histopathological features of NMSC. Ninety-eight lesions suggestive for NMSCs were radically excised from 75 patients (46 M; 29 F; mean age: 79 years). After removal, 115 specific reference points on lesions (“cases”; 59 on BBC, 53 on SCC and 3 on other lesions) and on peri-lesional healthy skin (controls; 115 healthy skin) were identified and marked through suture stitches. Such reference points were irradiated at 400–430 nm wavelength, and resulting emission AF spectra were acquired through spectrophotometry. For each case, AFIR (autofluorescence intensity ratio) was measured as the ratio between the number of photons emitted at a wavelength ranging between 450 and 700 nm (peak: 500 nm) in the healthy skin and that was captured in the pathological tissue. At the histological level, hyperkeratosis, neoangiogenesis, cellular atypia, epithelial thickening, fibrosis and elastosis were quantified by light microscopy and were assessed through a previously validated grading system. Statistical correlation between histologic variables and AFIR was calculated through linear regression. Spectrometric evaluation was performed on 230 (115 cases + 115 controls) reference points. The mean AFIR for BCC group was 4.5, while the mean AFIR for SCC group was 4.4 and the fluorescence peaks at 500 nm were approximately 4 times lower (hypo-fluorescent) in BCCs and in SCCs than in healthy skin. Histological variables significantly associated with alteration of AFIR were fibrosis and elastosis (p < 0.05), neoangiogenesis, hyperkeratosis and epithelial thickening. Cellular atypia was not significantly associated with alteration of AFIR. The intensity of fluorescence emission in neoplastic tissues was approximately 4 times lower than that in healthy tissues. Histopathological features such as hyperkeratosis, neoangiogenesis, fibrosis and elastosis are statistically associated with the decrease in AFIR. We hypothesize that such tissue alterations are among the possible biophysical and biochemical bases of difference in emission AF between neoplastic and healthy tissue. The results of the present evaluation highlighted the possible usefulness of autofluorescence as diagnostic, non-invasive and real-time tool for NMSCs.

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Section: Discussionmentioning

confidence: 99%

Section: Af Detection Systemmentioning

confidence: 93%

Correlation between Autofluorescence Intensity and Histopathological Features in Non-Melanoma Skin Cancer: An Ex Vivo Study

Giovannacci

Meleti

Garbarino

et al. 2021

Cancers

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“…2G, H). Notably, in a few patients with highly keratinized dysplastic or cancerous epithelium, AFI might yield a false negative with increased fluorescence, representing the contribution of keratin (Meleti et al 2020).…”

Section: Optical Imaging Techniques In the Diagnosis Of Opmds Maligna...mentioning

confidence: 99%

Optical Imaging in the Diagnosis of OPMDs Malignant Transformation

Deng

Sun

et al. 2022

J Dent Res

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Oral potentially malignant disorders (OPMDs) are a heterogeneous group of oral lesions with a variable risk of malignant transformation to oral squamous cell carcinoma. The current OPMDs malignant transformation screening depends on conventional oral examination (COE) and is confirmed by biopsy and histologic examination. However, early malignant lesions with subtle mucosal changes are easily unnoticed by COE based on visual inspection and palpation. Optical techniques have been used to determine the biological structure, composition, and function of cells and tissues noninvasively by analyzing the changes in their optical properties. The oral epithelium and stroma undergo persistent structural, functional, and biochemical alterations during malignant transformation, leading to variations in optical tissue properties; optical techniques are thus powerful tools for detecting OPMDs malignant transformation. The optical imaging methods already used to detect OPMDs malignant transformation in vivo include autofluorescence imaging, narrowband imaging, confocal reflectance microscopy, and optical coherence tomography. They exhibit advantages over COE in detecting biochemical or morphologic changes at the molecular or cellular level in vivo; however, limitations also exist. This article comprehensively reviews the various real-time in vivo optical imaging methods used in the adjunctive diagnosis of OPMDs malignant transformation. We focus on the principles of these techniques, review their clinical application, and compare and summarize their advantages and disadvantages. Finally, we conclude with a discussion of current challenges and future directions of this field.

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“…VELscope™ produces a cone of blue light with a distinctive spectrum excitation light in the wavelength range of 400 to 460 nm to illuminate oral tissue. While normal healthy oral mucosa emits a pale green AF, architectural alterations of the mucosa exhibit an AF pattern that can vary, based on the thickness of the keratin layer and other subepithelial changes, from reduction or loss of autofluorescence (LAF; seen in OSCC) to gain of fluorescence (GF; seen in leukoplakia or verrucous carcinoma; Meleti et al, 2020; Tiwari, Kuja, & Farah, 2020a; Yamamoto et al., 2017).…”

Section: Introductionmentioning

confidence: 99%

Gene expression analysis of autofluorescence margins in leukoplakia and oral carcinoma: A pilot study

et al. 2020

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Objectives Autofluorescence is considered a useful technique in the early detection of oral mucosal alterations. However, its efficacy to discriminate tumor margins is still under debate. The purpose of this pilot study was to confirm the existence of molecular divergence from the center of a lesion compared to white light and autofluorescence (VELscopeTM) visualized margins in leukoplakia and oral carcinoma. Materials and methods Molecular divergence from the center of the lesion to white light and VELscopeTM defined margins was compared in patients with leukoplakia (n = 3) and oral carcinoma (n = 4). Expression profiling of 45 selected genes was performed through custom‐made TaqMan arrays. Gene Ontology was used for biological pathway analysis. Results Irrespective of pathology, the greatest molecular divergence existed between the center of the lesion and both white light and VELscopeTM margins. VELscopeTM and white light margins were also molecularly distinct in oral carcinoma samples. Indeed, the white light margin retained molecular abnormalities observed in the center of the lesion thus suggesting the existence of a "partially transformed" cell population. Conclusion Despite the limited low number of patients, our data confirm the benefit of combining autofluorescence with conventional oral examination in identifying surgical margins during biopsy procedures for leukoplakia and oral carcinoma.

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Histopathological determinants of autofluorescence patterns in oral carcinoma

Cited by 11 publications

References 12 publications

Correlation between Autofluorescence Intensity and Histopathological Features in Non-Melanoma Skin Cancer: An Ex Vivo Study

Correlation between Autofluorescence Intensity and Histopathological Features in Non-Melanoma Skin Cancer: An Ex Vivo Study

Optical Imaging in the Diagnosis of OPMDs Malignant Transformation

Gene expression analysis of autofluorescence margins in leukoplakia and oral carcinoma: A pilot study

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