2021 international consensus statement on optical coherence tomography for basal cell carcinoma: image characteristics, terminology and educational needs.

BACKGROUND: Despite the widespread use of optical coherence tomography (OCT) for imaging of keratinocyte carcinoma, we lack an expert consensus on the characteristic OCT features of basal cell carcinoma (BCC), an internationally vetted set of OCT terms to describe various BCC subtypes, and an educational needs assessment. OBJECTIVES: To identify relevant BCC features in OCT images, propose terminology based on inputs from an expert panel and identify content for a BCC-specific curriculum for OCT trainees. METHODS: Over three rounds, we conducted a Delphi consensus study on BCC features and terminology between March and September 2020. In the first round, experts were asked to propose BCC subtypes discriminable by OCT, provide OCT image features for each proposed BCC subtypes and suggest content for a BCC-specific OCT training curriculum. If agreement on a BCC-OCT feature exceeded 67%, the feature was accepted and included in a final review. In the second round, experts had to re-evaluate features with less than 67% agreement and rank the ten most relevant BCC OCT image features for superficial BCC, nodular BCC and infiltrative and morpheaphorm BCC subtypes. In the final round, experts received the OCT-BCC consensus list for a final review, comments and confirmation. RESULTS: The Delphi included six key opinion leaders and 22 experts. Consensus was found on terminology for three OCT BCC image features: (i) hyporeflective areas, (ii) hyperreflective areas and (iii) ovoid structures. Further, the participants ranked the ten most relevant image features for nodular, superficial, infiltrative and morpheaform BCC. The target group and the key components for a curriculum for OCT imaging of BCC have been defined. CONCLUSION: We have established a set of OCT image features for BCC and preferred terminology. A comprehensive curriculum based on the expert suggestions will help implement OCT imaging of BCC in clinical and research settings.

[Confocal line-field OCT]. / Konfokale Line-Field-OCT.

Optical coherence tomography (OCT) and confocal laser microscopy (CLSM) are established non-invasive methods in clinical dermatological routine diagnosis. Whereas CLSM is especially useful to distinguish between nevi and melanoma, OCT is suitable for the diagnosis and differentiation of non-melanoma skin cancer. Line-field confocal optical coherence tomography (LC-OCT) is a new innovative device, which has better cellular resolution than OCT and a higher penetration depth than CLSM. Similar to CLSM, LC-OCT also allows 3D images in real time to be taken. Therefore LC-OCT is very useful for the examination of skin lesions of all kinds, since it unites the features of CLSM and OCT.

Line-field confocal optical coherence tomography for the in vivo real-time diagnosis of different stages of keratinocyte skin cancer: a preliminary study.

BACKGROUND: The treatment of keratinocyte cancers (KC) strictly depends on their differentiation and invasiveness. Non-invasive diagnostic techniques can support the diagnosis in real time, avoiding unnecessary biopsies. This study aimed to preliminarily define main imaging criteria and histological correlations of actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) using the novel device line-field confocal optical coherence tomography (LC-OCT). METHODS: Dermoscopy and LC-OCT images of 73 histopathologically confirmed lesions (46 AKs, 11 BD and 16 SCCs) were included in the study. Exemplary lesions (10 AKs, 5 BD and 5 SCCs) were additionally investigated with optical coherence tomography and reflectance confocal microscopy. RESULTS: Most common LC-OCT findings of KC in the descriptive statistics were hyperkeratosis/parakeratosis, disruption of stratum corneum, broadened epidermis, basal and suprabasal keratinocyte atypia, dilated vessels/neoangiogenesis and elastosis/collagen alterations. In the univariate multinomial logistic regression, a preserved DEJ was less common in SCC compared with AK and BD, BD displayed marked keratinocyte atypia involving all epidermal layers (bowenoid pattern), while SCC showed ulceration, increased epidermal thickness, keratin plugs, acantholysis, not visible/interrupted DEJ and epidermal bright particles. LC-OCT increased the diagnostic confidence by 24.7% compared with dermoscopy alone. CONCLUSIONS: Our study describes for the first time specific LC-OCT features of different stages of KC and their histopathological correlates, focusing on keratinocyte morphology and architecture of the epidermis and DEJ. LC-OCT may open new scenarios in the bedside diagnosis, treatment planning and follow-up of KC.

Line-field optical coherence tomography: in vivo diagnosis of basal cell carcinoma subtypes compared with histopathology.

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer in the general population. Treatments vary from Mohs surgery to topical therapy, depending on the subtype. Dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) have gained a foothold in daily clinical practice to optimize diagnosis and subtype-oriented treatment. The new technique of line-field confocal OCT (LC-OCT) allows imaging at high resolution and depth, but its use has not yet been investigated in larger studies. AIM: To evaluate the main LC-OCT criteria for the diagnosis and subtyping of BCC compared with histopathology, OCT and RCM. METHODS: In total, 52 histopathologically confirmed BCCs were evaluated for imaging criteria. Their frequency, predictive values and ROC curves were calculated. A multinominal regression with stepwise variables selection to distinguish BCC subtypes was performed. RESULTS: Nodular BCCs were mainly characterized by atypical keratinocytes, altered dermoepidermal junction (DEJ), tumour nests in the dermis, dark clefting, prominent vascularization and white hyper-reflective stroma. Superficial BCCs showed a thickening of the epidermis due to a series of tumour lobules with clear connection to the DEJ (string of pearls pattern). Infiltrative BCCs were characterized by elongated hyporeflective tumour strands, surrounded by bright collagen (shoal of fish pattern). The overall BCC subtype agreement between LC-OCT and conventional histology was 90.4% (95% CI 79.0-96.8). CONCLUSION: LC-OCT allows noninvasive, real-time identification of BCCs and their subtypes in vertical, horizontal and three-dimension mode compared with histology, RCM and OCT. Further larger studies are needed to better explore the clinical applications of this promising device.

[Noninvasive diagnostic imaging in pediatric skin lesions]. / Nichtinvasive bildgebende Diagnostik bei Hauterkrankungen im Kindesalter.

Optical coherence tomography (OCT) and reflectance confocal laser microscopy (RCM) allow noninvasive imaging diagnostics of the skin. Since the indication for a biopsy in children is generally made cautiously, OCT and KLM can be helpful in the clarification of pediatric skin lesions. In addition, biopsies only represent a snapshot of a small area of the skin, while noninvasive methods allow several locations to be examined over time, so that dynamic changes and the course of therapy can also be determined. In pediatric dermatology, these diagnostic methods are particularly suitable for the clarification of atypical pigment lesions, for infectious dermatoses such as scabies or tinea, and for the diagnosis of inflammatory and degenerative dermatoses.

Dynamic optical coherence tomography shows characteristic alterations of blood vessels in malignant melanoma.

BACKGROUND: Dynamic optical coherence tomography (D-OCT) allows in vivo visualization of blood vessels in the skin and in malignant tumours. Vessel patterns in malignant melanoma may be associated with tumour stage. OBJECTIVE: The aim of this study was to describe blood vessel patterns in melanomas and to correlate them with stage. METHODS: One hundred fifty-nine malignant melanomas were assessed in a multicentre study. Every tumour was imaged using D-OCT prior to surgery and histologic evaluation. The tumour data such as thickness and ulceration as well as the staging at primary diagnosis and a follow-up of at least 40 months resulted in a stage classification. The vessel patterns were assessed according to predefined categories, compared with healthy adjacent skin, and correlated to stage. RESULTS: Melanomas contained more blood vessels in different patterns compared with healthy adjacent skin. In particular, irregular vascular shapes such as blobs, coils, curves and serpiginous vessels were more common in melanomas. In addition, these patterns were significantly more often found in high-risk and metastatic melanomas than in low-risk lesions. CONCLUSION: In melanomas, the density of the blood vessels is increased, and irregular vascular patterns are more frequent. At higher stages, especially in metastatic melanomas, these atypical vessels are significantly more common.

Evaluation of two histological classifications for actinic keratoses - PRO classification scored highest inter-rater reliability.

BACKGROUND: Actinic keratoses (AKs) can histologically be classified by the extent of atypical keratinocytes throughout the epidermis or their pattern of basal proliferation. Currently, no data on the inter-rater reliability of both scores is available. OBJECTIVE: To evaluate the inter-rater reliability of the two classification schemes; histological grade (AK I-III) and basal proliferation (PRO I-III). METHODS: Histological images of 54 AKs were classified by 21 independent dermatopathologists with regard to basal proliferation (PRO I-III), histological grade (AK I-III) and assumed risk of progression into invasive carcinoma. RESULTS: Overall, of the 54 AKs 16.7% (9/54) were classified as AK I, 66.7% (36/54) as AK II, and 16.7% (9/54) as AK III. With regards to basal growth pattern, 25.9% (14/54) were classified as PRO I, 42.6% (23/54) as PRO II, and 31.5% (17/54) as PRO III. We observed a highly significant inter-rater reliability for PRO-grading (P < 0.001) which was higher than for AK-grading (Kendall's W coefficient: AK = 0.488 vs. PRO = 0.793). We found substantial agreement for assumed progression risk for AKs with worsening basal proliferation (k = 0.759) compared to moderate agreement (k = 0.563) for different AK-gradings. CONCLUSIONS: Histological classification of basal growth pattern (PRO) showed higher inter-rater reliability compared to the established classification of atypical keratinocytes throughout epidermal layers. Moreover, experienced dermatopathologists considered basal proliferation to be more important in terms of progression risk than upwards directed growth patterns. It should be considered to classify AKs according to their basal proliferation pattern (PRO I-III).

[Optical coherence tomography for skin pathologies]. / Optische Kohärenztomographie bei Pathologien der Haut.

Optical coherence tomography (OCT) has become established in routine diagnosis in dermatology only in the last few years. The reason is that the skin is a challenge for OCT as a strong scattering medium, because only a very small proportion of photons is reflected and can be used for imaging. In addition, in most cases a visual assessment or a biopsy is sufficient. Nevertheless, the main field of application in dermatology is the diagnostics of epithelial skin tumors. The OCT is suitable for the early recognition of small, clinically and light microscopically unspecific basal cell carcinomas as well as for the differential diagnosis of other tumors and precancerous lesions. Using OCT, the preoperative measurement of tumor spread, observation of the course and treatment control of non-surgical procedures are possible; therefore, in many cases a biopsy or treatment control can be avoided. Dynamic OCT is a newly developed add on technique to visualize and quantify the superficial blood vessels of the skin. First studies are focused on the evaluation of tumor vessels, wound healing and monitoring of laser therapy. In ophthalmology, OCT diagnostics of basal cell carcinomas on the eyelids as well as for planning and control of eyelid interventions can be of interest.

Optical coherence tomography of basal cell carcinoma: influence of location, subtype, observer variability and image quality on diagnostic performance.

BACKGROUND: We previously described the principal results from an observational, prospective, multicentre, clinical trial of the diagnostic value of optical coherence tomography (OCT) for basal cell carcinoma (BCC) in a clinical setting. In this trial, much additional useful information was gathered that warranted further analysis, presented here. OBJECTIVES: To investigate the influence of candidate diagnostic criteria, OCT image quality, lesion location, and observer confidence and interobserver variability on the diagnostic performance of OCT, and to assess its potential use for diagnosis of BCC subtypes. METHODS: A total of 234 clinically unclear 'pink lesions' were evaluated in three steps: after clinical examination, after adding dermoscopy and after adding OCT. In addition to the diagnoses (including lesion subtype), observers recorded which of 15 diagnostic criteria the OCT image contained, their confidence in the diagnoses, the OCT image quality and the anatomical location of the lesion. RESULTS: Diagnostic performance of OCT did not depend on the lesion's anatomical location. Good OCT image quality was correlated with improved diagnostic performance, but diagnostic performance for lesions with mediocre image quality was still better than by clinical and dermoscopic examination. The main reason for reduced image quality was superficial scales and crusting. Observer confidence in diagnosis was correlated with diagnostic performance. Interobserver diagnostic performance was consistently higher than clinical examination and dermoscopy across all sites. BCC subtype could be determined with moderate accuracy, but further independent image markers are required. CONCLUSION: OCT is useful in the diagnosis of BCC.

Optical coherence tomography for margin definition of basal cell carcinoma before micrographic surgery-recommendations regarding the marking and scanning technique.

BACKGROUND/PURPOSE: Mohs Micrographic Surgery (MMS) is the preferred therapeutic treatment for high-risk basal cell carcinoma (BCC). Optical Coherence Tomography (OCT) is a non-invasive imaging technique that enables the diagnosis of BCC. We thought to determine the margins of BCCs with OCT, prior to MMS, to reduce the number of surgical steps. METHODS: Different permanent markers were tested on the skin regarding line width, resistance against disinfection and brightness in the OCT image. The visible tumor margins of BCCs were defined by dermoscopy, adding a safety margin of 2 mm and labeled using the selected pen, causing a signal shadow in OCT. Scans of the center and of entire margin were performed. If parts of the BCC were visible outside the margin, another 2 mm were added and the scan was repeated until the tissue outside the labeling looked tumor free. RESULTS: Eight out of ten BCCs were totally excised in a single stage when margin delineation was done by OCT. Macroscopic margins were enlarged after OCT scanning in four patients, saving further stages of MMS. CONCLUSION: OCT may help to better define the microscopic dimensions of BCCs and therefore reduce the number of stages of MMS.

Dynamic optical coherence tomography of skin blood vessels - proposed terminology and practical guidelines.

BACKGROUND: Dynamic optical coherence tomography (D-OCT) has recently been introduced in dermatology. In contrast to 'Standard' OCT imaging, which exclusively relies on the morphological analysis of the tissue, D-OCT allows the in vivo visualization of blood flow. Preliminary D-OCT data showed differences in the vascularization of nevus to melanoma transition, suggesting that this technology may help to differentiate between benign and malignant lesions. OBJECTIVE: Several factors may influence the quality of D-OCT imaging. Therefore, standard operating procedures as well as a common terminology are required for better validation and comparison of the images. METHODS: Here, we present practical guidelines for optimal image acquisition and a proposed terminology on vascular patterns observed by D-OCT. RESULTS: Dynamic OCT allows the morphologic distinction of different vascular shapes (e.g. dots, blobs, curves, lines), their distribution and organization within skin lesions. CONCLUSION: D-OCT adds functional information on skin microvasculature and the vascular networks within lesions.

In vivo microvascular imaging of cutaneous actinic keratosis, Bowen's disease and squamous cell carcinoma using dynamic optical coherence tomography.

BACKGROUND: A clear distinction between actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) cannot reliably be made by clinical and dermoscopic evaluation alone. Dynamic optical coherence tomography (D-OCT) is a novel angiographic variant of OCT that allows for non-invasive, in vivo evaluation of the cutaneous microvascular morphology. OBJECTIVE: To investigate the microvascular structures of AK, BD and invasive SCC using D-OCT in order to gain insights into the microvascular morphology of lesions in the spectrum of keratinocyte skin cancers. METHODS: Forty-seven patients with a total of 54 lesions (18 AK, 12 BD and 24 SCC) were included in the study. D-OCT still images of AK, BD and SCC at three predefined skin depths were prepared and randomized, creating a study set of 162 D-OCT images. Three observers performed blinded evaluations of the randomized study set assessing multiple parameters including the different types of vascular morphology. Non-blinded quantitative measurements of vascular diameter were also performed. RESULTS: The blinded observer analysis suggests that D-OCT evaluation of the vascular morphology may aid in distinguishing AK, BD and SCC lesions. We identified two vascular shapes that presented significantly differently across the lesion types, namely 'blobs' and 'curves'. A strong presence of blobs at 300 µm skin depth was characteristically seen in a third of BD cases, while not or only slightly present in AK and SCC lesions. Vascular curves were predominantly present in AK lesions. CONCLUSION: We identified various vascular D-OCT features that may aid in non-invasively differentiating subtypes within the keratinocyte skin cancer spectrum.

Shining into the White: The Spectrum of Epithelial Tumors from Actinic Keratosis to Squamous Cell Carcinoma.

Actinic keratosis, Bowen disease, and invasive squamous cell carcinoma represent different steps within the disease continuum of squamous neoplasia. Although these stages of squamous neoplasia share common findings, reflectance confocal microscopy may be applied for their differentiation and distinction from other benign or malignant lesions. Hyperkeratosis represents the most important limitation in the evaluation of squamous neoplasia as it may impair the analysis of deeper epidermal and dermal structures significantly.

Fluorescence (Multiwave) Confocal Microscopy.

In addition to reflectance confocal microscopy, multiwave confocal microscopes with different laser wavelengths in combination with exogenous fluorophores allow fluorescence mode confocal microscopy in vivo and ex vivo. Fluorescence mode confocal microscopy improves the contrast between the epithelium and the surrounding soft tissue and allows the depiction of certain structures, like epithelial tumors, nerves, and glands.

Optical coherence tomography of actinic keratoses and basal cell carcinomas - differentiation by quantification of signal intensity and layer thickness.

BACKGROUND: Previous studies have shown that actinic keratoses (AKs) and basal cell carcinomas (BCCs) can be diagnosed by optical coherence tomography (OCT) based on morphological characteristics. There is a lack of systematic studies that give standardized information on signal intensity and layer thickness of AKs and BCCs. OBJECTIVE: The aim of this study was to find out if AKs and BCCs can be objectively diagnosed through standardized measurement of signal intensity and layer thickness and to use OCT as a non-invasive objective method for the diagnosis and evaluation of AKs and BCCs. Additionally, tumour and skin layer thickness were investigated in correlation with histology. METHODS: In this experimental study, 301 lesions (188 BCCs and 113 AKs) of 125 patients were clinically as well as dermoscopically diagnosed and investigated with OCT before therapy. Normal perilesional skin served as control. RESULTS: It is possible to differentiate BCCs and AKs from normal skin in OCT due to the decrease of local signal intensity in affected skin layers in relation to adjacent healthy skin. In AKs, a strong thickness increase of the stratum corneum and epidermis compared to normal skin were observed. For the distinction between AKs and BCCs, a drop of signal intensity in the dermis of AKs towards BCCs and a thicker epidermis of AKs in contrast to BCCs were registered. All results are statistically highly significant (P < 0.0001). Besides, a strong correlation of tumour and skin layer thickness of BCCs and AKs in OCT with histology was found. CONCLUSION: Through standardized measurement of signal intensity and layer thickness, BCCs and AKs can be objectively diagnosed and distinguished from each other with OCT. This will further improve the use of OCT as a non-invasive objective method for the diagnosis and treatment monitoring of these diseases.

Comparison of different optical coherence tomography devices for diagnosis of non-melanoma skin cancer.

PURPOSE: To compare the diagnostic imaging ability of three different optical coherence tomography (OCT) devices in non-melanoma skin cancer (NMSC). METHODS: Thirty actinic keratoses (AKs) and 27 basal cell carcinomas (BCCs) of 29 patients were examined with three different OCT devices, VivoSight® , Callisto® and Skintell® . RESULTS: Complete data sets were available for 16 BCCs and 10 AKs of 18 patients. All OCT devices were able to discriminate BCCs and AKs significantly from perilesional normal skin due to lower signal intensities as well as a thicker stratum corneum and epidermis in AKs. A significant decrease in the signal intensity and thickness of all skin layers was noted with Skintell® in contrast to VivoSight® and Callisto® . OCT comparisons revealed only slight differences between VivoSight® and Callisto® . Regarding BCC tumor thickness VivoSight® and Callisto® correlated well, histology did not correlate with the three OCT devices, whereas Skintell® showed no correlation with VivoSight® , Callisto® or histology. CONCLUSION: All tested OCT devices could identify BCCs and AKs objectively through standardized measurement of signal intensity and skin layer thickness. Due to their technical specifications (resolution, penetration depth), each of the OCT systems offers additional and special information on NMSC.

The sensitivity and specificity of optical coherence tomography for the assisted diagnosis of nonpigmented basal cell carcinoma: an observational study.

BACKGROUND: The diagnostic criteria for basal cell carcinoma (BCC) using optical coherence tomography (OCT) have been described previously, but the clinical value of these findings remains unknown. OBJECTIVES: To investigate the diagnostic value of OCT for BCC in a typical clinical setting. The primary efficacy end point was a diagnosis of BCC for each lesion. Secondary end points were the diagnosis of other possible conditions. METHODS: This was an observational, prospective, multicentre study in which consecutive patients with nonpigmented pink lesions suspicious for BCC underwent clinical assessment, dermoscopy and OCT, with the diagnosis recorded at each stage. Once all diagnoses had been recorded, the histological results were disclosed. In total 164 patients with 256 lesions were recruited. Histology was missing for 21 lesions, leaving 235 lesions in 155 patients for analysis. RESULTS: Sixty per cent of lesions (141 of 235) were identified as BCC by histology. A slight increase of sensitivity was noted following OCT, which did not reach statistical significance. The specificity increased significantly from 28·6% by clinical assessment to 54·3% using dermoscopy and to 75·3% with the addition of OCT (P < 0·001). The positive predictive value for the diagnosis of BCC using OCT was 85·2% [95% confidence interval (CI) 78·6-90·4], and the negative predictive value was 92·1% (95% CI 83·6-97·0). The accuracy of diagnosis for all lesions increased from 65·8% with clinical evaluation to 76·2% following additional dermoscopy and to 87·4% with the addition of OCT. CONCLUSIONS: OCT significantly improved the diagnostic specificity for BCC compared with clinical assessment and dermoscopy alone.