Mohs micrographic surgery for the treatment of invasive melanoma: A systematic review with meta-analyses.

BACKGROUND: The use of Mohs micrographic surgery (MMS) in melanoma treatment has divided opinion and evidence-based guidelines are lacking. OBJECTIVES: This systematic review aimed to analyse clinical outcomes for patients with invasive melanomas treated with Mohs rather than wide local excision (WLE). METHODS: Embase, MEDLINE and Cochrane databases (to 30 August 2023) were searched for studies using Mohs to treat invasive melanoma. Outcomes of interest were local recurrence and death from melanoma. RESULTS: Thirty-five articles involving 41,499 patients with invasive melanoma treated with Mohs were identified. Sixteen studies compared Mohs with WLE and 19 were Mohs-only, non-comparative studies. Patients treated with Mohs differed significantly from those undergoing WLE, in particular Mohs patients were older and had thinner melanomas. Two comparative studies using the same data source reported adjusted hazard ratios for melanoma-specific death and both showed no significant difference between Mohs and WLE-treated patients; 0.87 (95% CI 0.55-1.35) and 1.20 (95% CI 0.71-20.36). There was also no statistically significant difference in local recurrence risk; the unadjusted risk ratio for patients treated with Mohs was 0.46 (95% CI 0.14-1.51 p = 0.20) with moderate heterogeneity (I2 = 62%). No studies reported multivariable analyses for risk of local recurrence. Many studies generated from relatively few and often overlapping data sets have reported the use of Mohs to treat patients with invasive melanoma. Fewer studies were comparative between Mohs and WLE and these reported substantially different baseline risks of recurrence and death from melanoma between the groups. Mohs has generally been used for thinner melanomas in older patients; therefore, comparisons based on univariable analyses are likely to have been misleading. CONCLUSIONS: On the basis of currently available data, it is not possible to reliably assess whether outcomes differ if invasive melanomas with comparable features are treated with Mohs or WLE, and randomized trial evidence will be required for reliable conclusions to be reached.

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.

Lentigo maligna: defining margins and predictors of recurrence utilizing clinical, dermoscopic, confocal microscopy and histopathology features.

BACKGROUND: Lentigo maligna (LM) is a subtype of melanoma in situ with poorly defined margins and a high recurrence rate. The biological behaviour of LM appears to differ widely between cases, from biologically indolent to biologically active variants, with some patients experiencing multiple recurrences. It is not known whether this is secondary to inadequate margins, field cancerization or the innate biology of the lesion itself. OBJECTIVES: (a) Describe the margins of LM in detail by analysing LM in three zones, that is centre, edge and surround using reflectance confocal microscopy (RCM) and histopathology; (b) ascertain association of histological distance of LM and atypical melanocytic hyperplasia from the surgical margin with multi-recurrent (MR) disease and (c) identify features (clinical, dermoscopy, RCM and histopathology) associated with MR LM. METHODS: (1) Descriptive observational study comparing the centre, edge and surround of LM on histopathology and RCM; (2) retrospective cohort study comparing parameters associated with MR and non-recurrent (NR) LM. RESULTS: 30 patients (median follow-up time 6.2 years) were included. On histopathology, confluent or near confluent lentiginous proliferation, melanocyte density >15 per 0.5 mm and adnexal spread were best for distinguishing surround from edge of LM. On RCM, predominant melanocytes, lentiginous proliferation and pleomorphism distinguished surround from centre/edge. MR patients had a median histological distance of LM from the surgical margin of 2mm (versus NR patients with an average distance of 4mm). MR patients had a greater proportion of more florid features, compared with NR on histopathology at both the centre and the edge but were similar in the surround. CONCLUSION: These data may help pathologists and confocalists better define margins of LM. More florid features in MR patients, despite a similar background of sun-damaged skin, suggest the innate biology of the lesion rather than the field of cancerization may explain MR LM.

Flat scalp melanoma dermoscopic and reflectance confocal microscopy features correspond to histopathologic type and lesion location.

BACKGROUND: Dermoscopy and Reflectance Confocal Microscopy (RCM) features of scalp melanoma according to lesion location and histopathology have not been fully investigated. OBJECTIVES: To reveal dermoscopic and RCM features of scalp melanoma according to lesion location and histopathology. METHODS: We retrospectively retrieved images of suspicious, atypical excised, flat melanocytic lesions of the scalp, assessed on dermoscopy and RCM at five centres, from June 2007 to April 2020. Lesions were classified according to histopathological diagnoses of nevi, lentigo maligna melanoma (LM/LMM) or superficial spreading melanoma (SSM). Clinical, dermoscopic and RCM images were evaluated; LM/LMM and SSM subtypes were compared through multivariate analysis. RESULTS: Two hundred forty-seven lesions were included. In situ melanomas were mostly LM (81.3%), while invasive melanomas were mostly SSM (75.8%). Male sex, baldness and chronic sun-damaged skin were associated with all types of melanomas and in particular with LM/LMM. LMs were mostly located in the vertex area and SSM in the frontal (OR: 8.8; P < 0.05, CI 95%) and temporal (OR: 16.7; P < 0.005, CI 95%) areas. The dermoscopy presence of pseudo-network, pigmented rhomboidal structures, obliterated hair follicles and annular-granular pattern were associated with LM diagnoses, whereas bluish-white veil was more typical of SSM. Observations on RCM of atypical roundish and dendritic cells in the epidermis were associated with SSM (42.4%) and dendritic cells with LM (62.5%) diagnoses. Folliculotropism on RCM was confirmed as a typical sign of LM. CONCLUSIONS: Flat scalp melanomas reveal specific dermoscopic and RCM features according to histopathologic type and scalp location.

Lentiginous melanoma (lentigo maligna and lentigo maligna melanoma) in Australia: clinicopathological characteristics, management and recurrence rates after 10-year follow-up at a tertiary centre.

BACKGROUND: Lentiginous melanoma or lentigo maligna is a slow-growing type of melanoma frequently arising in sun-damaged skin and often first diagnosed in the elderly. Few studies report long-term follow-up. OBJECTIVES: To define characteristics of lentiginous melanoma in situ (LM) and invasive lentiginous melanoma (LMM) in Australian patients managed at a tertiary centre and describe local recurrence or treatment failure rates after long-term follow-up. METHODS: Retrospective single-centre study of LM/LMM patients evaluated between January 2005 and March 2007. Medical and photographic records were reviewed. RESULTS: One hundred two patients were included, with a total of 117 lesions (70 LM and 47 LMM). Seventy-nine were new primary LM/LMM, and 38 were recurrences. Primary cases were mostly pigmented (71%), while 77% of recurrent cases were partially pigmented/light brown or amelanotic. The margins were clinically ill-defined in the majority of cases (64% of primary cases and 94% of recurrent cases). Dermoscopy of the primary LM/LMM showed either classic 'common' melanoma features (33%) or classic LM/LMM features (41%), while 95% of recurrent cases had no features for melanoma or LM/LMM. Primary cases that were initially excised (113, 97%) had mean histopathological clear margins of 4.9 mm (range 0.1-22 mm). The median follow-up time was 7.5 years (95% CI 5.2-10.0) with more than 10-year follow-up in 32% and 5-10 years in 24% of patients. There were 44 (38%) recurrences over the entire follow-up period. Half of the patients who recurred did so within the first 3.8 years after the first treatment. CONCLUSION: LM/LMM often recur late and are clinically subtle; therefore, careful monitoring and long-term follow-up are required.

Human surface anatomy terminology for dermatology: a Delphi consensus from the International Skin Imaging Collaboration.

BACKGROUND: There is no internationally vetted set of anatomic terms to describe human surface anatomy. OBJECTIVE: To establish expert consensus on a standardized set of terms that describe clinically relevant human surface anatomy. METHODS: We conducted a Delphi consensus on surface anatomy terminology between July 2017 and July 2019. The initial survey included 385 anatomic terms, organized in seven levels of hierarchy. If agreement exceeded the 75% established threshold, the term was considered 'accepted' and included in the final list. Terms added by the participants were passed on to the next round of consensus. Terms with <75% agreement were included in subsequent surveys along with alternative terms proposed by participants until agreement was reached on all terms. RESULTS: The Delphi included 21 participants. We found consensus (≥75% agreement) on 361/385 (93.8%) terms and eliminated one term in the first round. Of 49 new terms suggested by participants, 45 were added via consensus. To adjust for a recently published International Classification of Diseases-Surface Topography list of terms, a third survey including 111 discrepant terms was sent to participants. Finally, a total of 513 terms reached agreement via the Delphi method. CONCLUSIONS: We have established a set of 513 clinically relevant terms for denoting human surface anatomy, towards the use of standardized terminology in dermatologic documentation.

The smart approach: feasibility of lentigo maligna superficial margin assessment with hand-held reflectance confocal microscopy technology.

BACKGROUND: Lentigo maligna may be challenging to clear surgically. OBJECTIVE: To evaluate feasibility of using superficial skin cuts as RCM imaging anchors for attaining negative surgical margins in lentigo maligna. METHODS: Included patients presented with lentigo maligna near cosmetically sensitive facial structures. We evaluated, with hand-held-RCM, microscopic clearance of melanoma beyond its dermoscopically detected edges. Evaluated margins were annotated using shallow skin cuts. If a margin was positive at 'first-step' RCM evaluation, we sequentially advanced the margin radially outward at that segment by 2-mm intervals until an RCM-negative margin was identified. Prior to final surgical excision, we placed sutures at the outmost skin cuts to allow comparison of RCM and histopathological margin assessments. Primary outcome measure was histopathological verification that RCM-negative margins were clear of melanoma. RESULTS: The study included 126 first-step margin evaluations in 23 patients, median age 70 years (range: 43-91). Seventeen patients (74%) had primary in-situ melanoma and six (26%) invasive melanoma, mean thickness 0.3 mm (range 0.2-0.4 mm). Six cases (26%) showed complete negative RCM margins on 'first-step', 11 (48%) were negative at 'second-step', and four (17%) at 'third-step'. In two additional cases (9%), margins clearance could not be determined via RCM due to widespread dendritic cells proliferation. The RCM-negative margins in all 21 cases proved clear of melanoma on histopathology. Of the 15 cases that returned at 1-year follow-up, none showed any residual melanoma on dermoscopic and RCM examinations. Interobserver reproducibility showed fair agreement between bedside RCM reader and blinded remote-site reader, with Spearman's rho of 0.48 and Cohen's kappa of 0.43; using bedside reader as reference, the remote reader's sensitivity was 92% and specificity 57% in positive margin detection. CONCLUSIONS: Margin mapping of lentigo maligna with hand-held-RCM, using superficial skin cuts, appears feasible. This approach needs validation by larger studies.

Dermoscopy vs. reflectance confocal microscopy for the diagnosis of lentigo maligna.

BACKGROUND: Several dermoscopic and in vivo reflectance confocal microscopy (RCM) diagnostic criteria of lentigo maligna (LM)/lentigo maligna melanoma (LMM) have been identified. However, no study compared the diagnostic accuracy of these techniques. OBJECTIVE: We evaluated the diagnostic accuracy of dermoscopy and RCM for LM/LMM using a holistic assessment of the images. METHODS: A total of 223 facial lesions were evaluated by 21 experts. Diagnostic accuracy of the clinical, dermoscopic and RCM examination was compared. Interinvestigator variability and confidence level in the diagnosis were also evaluated. RESULTS: Overall diagnostic accuracy of the two imaging techniques was good (area under the curve of the sROC function: 0.89). RCM was more sensitive (80%, vs. 61%) and less specific (81% vs. 92%) than dermoscopy for LM/LMM. In particular, RCM showed a higher sensitivity for hypomelanotic and recurrent LM/LMM. RCM had a higher interinvestigator agreement and a higher confidence level in the diagnosis than dermoscopy. CONCLUSION: Reflectance confocal microscopy and dermoscopy are both useful techniques for the diagnosis of facial lesions and in particular LM/LMM. RCM is particularly suitable for the identification of hypomelanotic and recurrent LM/LMM.

Detection of desmoplastic melanoma with dermoscopy and reflectance confocal microscopy.

BACKGROUND: Desmoplastic melanoma (DM) is frequently misdiagnosed clinically and often associated with melanoma in situ (MIS). OBJECTIVE: To improve the detection of DM using dermoscopy and reflectance confocal microscopy (RCM). METHODS: A descriptive analysis of DM dermoscopy features and a case-control study within a melanoma population for RCM feature evaluation was performed blindly, using data obtained between 2005 and 2015. After retrospectively identifying all DM cases with RCM data over the study period (n = 16), a control group of non-DM melanoma patients with RCM data, in a ratio of at least 3 : 1, was selected. The control group was matched by age and primary tumour site location, divided into non-DM invasive melanomas (n = 27) and MIS (n = 27). Invasive melanomas were selected according to the melanoma subtypes associated with the DM cases. The main outcomes were the frequency of melanoma-specific features on dermoscopy for DM; and the odds ratios of RCM features to distinguish DM from MIS and/or other invasive melanomas; or MIS from the combined invasive melanoma group. RESULTS: At least one of the 14 melanoma-specific features evaluated on dermoscopy was found in 100% of DMs (n = 15 DM with dermoscopy). Known RCM melanoma predictors were commonly found in the DMs, such as pagetoid cells (100%) and cell atypia (100%). The RCM feature of spindle cells in the superficial dermis was more common in DM compared with the entire melanoma control group (OR 3.82, 95% CI 1.01-14.90), and particularly compared to MIS (OR 5.48, 95% CI 1.11-32.36). Nucleated cells in the dermis and the RCM correlate of dermal inflammation were also significant RCM features favouring DM over MIS, as well as invasive melanoma over MIS. CONCLUSION: Dermoscopy and RCM may be useful tools for the identification of DM. Certain RCM features may help distinguish DM from MIS and other invasive melanomas. Larger studies are warranted.

Analysis of an electrical impedance spectroscopy system in short-term digital dermoscopy imaging of melanocytic lesions.

BACKGROUND: Electrical impedance spectroscopy (EIS) is a noninvasive diagnostic technique that measures tissue impedance. OBJECTIVES: To evaluate the effect of adding an EIS measurement at baseline to suspicious melanocytic lesions undergoing routine short-term sequential digital dermoscopy imaging (SDDI). METHODS: Patients presented with suspicious melanocytic lesions that were eligible for short-term SDDI (with no clear feature of melanoma on dermoscopy). EIS measurement was performed at the first visit following dermoscopic photography. Normally, an EIS score of ≥ 4 is considered positive; however, this protocol investigated a higher cut-off in combination with SDDI. When the EIS score was ≥ 7 the lesion was excised immediately owing to the high risk of melanoma. Lesions with a score < 7 were monitored with standard SDDI over a 3-month period. RESULTS: From a total of 160 lesions analysed, 128 of 154 benign lesions received an EIS score of 0-6, giving a specificity of the EIS method for the diagnosis of melanoma of 83·1% [95% confidence interval (CI) 76·3-88·7]. Five of the six melanomas found in this study had an EIS score ≥ 7, with a sensitivity for melanoma diagnosis of 83·3% (95% CI 35·9-99·6). When EIS 0-6 lesions were subsequently followed up with SDDI, one additional melanoma was detected (EIS = 6) giving a sensitivity for the diagnosis of melanoma overall of 100% (95% CI 54·1-100; six of six malignant melanomas excised) and a specificity of 69·5% (95% CI 61·5-76·6; 107 of 154 benign lesions not excised). CONCLUSIONS: If utilizing a protocol where an EIS score ≤ 3 requires no SDDI and ≥ 7 requires immediate excision, it reduced the need for SDDI by 46·9% (n = 75/160; 95% CI 39·0-54·9).

The value of reflectance confocal microscopy in diagnosis of flat pigmented facial lesions: a prospective study.

BACKGROUND: Flat pigmented facial lesions are difficult to diagnose even with dermatoscopy. It is controversial how additional information obtained by in vivo reflectance confocal microscopy (RCM) impacts the diagnosis and management. OBJECTIVE: To examine what in vivo reflectance confocal microscopy of flat pigmented facial lesions adds to clinical examination using dermatoscopy including digital dermatoscopic monitoring. METHODS: We prospectively collected 70 cases of flat pigmented facial lesions and recorded diagnoses and management decisions by experts based on direct clinical examination aided by dermatoscopy including digital dermatoscopic monitoring and by remote experts who reviewed the corresponding confocal images. The expert confocal readers were blinded to the clinical and dermatoscopic appearance of the lesion. RESULTS: The sensitivity of dermatoscopy plus digital dermatoscopic monitoring was 95.0% (95% CI 75.13% to 99.87%) and the specificity was 84.0% (95% CI 70.89% to 92.83%). The sensitivity of RCM was 95.0% (95% CI 75.13% to 99.87%) and the specificity was 82.0% (95% CI 68.56% to 91.42%). CONCLUSION: Although most flat pigmented facial lesions can be managed by clinical examination and dermatoscopy alone, confocal microscopy is a useful adjunct in selected lesions. If RCM is not correlated with clinical and dermatoscopic information, there is risk of overdiagnosis of actinic keratosis, however.

Histological examination confirms clinical clearance of actinic keratoses following treatment with ingenol mebutate 0·05% gel.

BACKGROUND: To date, studies with ingenol mebutate gel have used clinical clearance, not histological clearance, as a primary efficacy endpoint. OBJECTIVES: This phase I, multicentre, single-arm, open-label study sought to confirm histologically the clinical clearance of actinic keratoses (AKs) to support a treatment effect deep in the epidermis. METHODS: Patients (n = 108) aged ≥ 18 years with histologically confirmed AK within a 25-cm2 contiguous treatment area on the trunk and extremities received ingenol mebutate 0·05% gel for two consecutive days and were followed up on day 3 and week 8. One AK was randomly preselected at day 1 for clinical and histological evaluation at week 8 and for reflectance confocal microscopy (RCM) in a subset of patients. The primary endpoint was clinical and histological clearance of AKs at week 8. RESULTS: The observed agreement rate between clinical and histological assessments of clearance of a single AK was 81·9% and the positive predictive value of a clinical assessment of clearance was 87%. Agreement between the two pathologists was 88%. The common composite 8-week complete clearance rate was 41% (95% confidence interval 32-50). Observed agreement rates between RCM and pathologist I and II assessments of clearance were 72·9% and 81·4%, respectively. Overall, 30 patients (27·8%) experienced 38 adverse events (AEs). Application-site pain (four patients, 3·7%) was the most common treatment-related AE inside the treatment area. CONCLUSIONS: Ingenol mebutate achieves histopathological clearance of AKs that correlates with observed clinical clearance. Clinical clearance is a good predictor for histological clearance.

Dermoscopy and in vivo confocal microscopy are complementary techniques for diagnosis of difficult amelanotic and light-coloured skin lesions.

BACKGROUND: Amelanotic melanomas are often difficult to diagnose. OBJECTIVES: To find and test the best methods of diagnosis using dermoscopy and reflectance confocal microscopy (RCM) tools. METHODS: We selected consecutive, difficult-to-diagnose, light-coloured and amelanotic skin lesions from three centres (in Australia and Italy). Dermoscopy and RCM diagnostic utility were evaluated under blinded conditions utilizing 45 melanomas (16 in situ, 29 invasive), 68 naevi, 48 basal cell carcinomas (BCCs), 10 actinic keratoses, 10 squamous cell carcinomas (SCCs) and 13 other benign lesions. RESULTS: Sensitivity and specificity for melanoma with dermoscopy pattern analysis by two blinded observers and their 'confidence in diagnosis' were low. The amelanotic dermoscopy method had the highest sensitivity (83%) for a diagnosis of malignancy (melanoma, BCC or SCC), but specificity was only 18%. Multivariate analysis confirmed the utility of RCM features previously identified for the diagnosis of BCC and melanoma (highest odds ratio for melanoma: epidermal disarray, dark and/or round pagetoid cells). RCM sensitivity was 67% and 73% for melanoma and BCC diagnosis, respectively, and its specificity for nonmalignant lesion diagnosis was 56%. RCM reader confidence was higher than for dermoscopy; 84% of melanomas would have been biopsied and biopsy avoided in 47% of benign lesions. All melanomas misclassified by either dermoscopy or RCM were detected by the other tool. CONCLUSIONS: Dermoscopy and RCM represent complementary/synergistic methods for diagnosis of amelanotic/light-coloured skin lesions.

Accuracy of optical coherence tomography for the diagnosis of superficial basal cell carcinoma: a prospective, consecutive, cohort study of 168 cases.

BACKGROUND: Superficial basal cell carcinoma (sBCC) can be safely treated topically. Potentially noninvasive imaging techniques, such as optical coherence tomography (OCT), may be useful to diagnose and manage patients with sBCC and obviate the need for biopsy. OBJECTIVES: To evaluate in OCT (i) the sensitivity and specificity for sBCC diagnosis, (ii) the accuracy in determining BCC depth and (iii) the role in management of sBCC mimickers. METHODS: A prospective, consecutive cohort of lesions for which sBCC was considered in the differential diagnosis. These lesions underwent clinical, dermoscopic and OCT assessment. Diagnosis and its confidence were recorded for each modality and were correlated with the histopathological diagnosis (punch biopsy). Interpretation of the OCT images and assessment of individual features were performed blinded to the biopsy results. RESULTS: In total, 168 lesions were recruited: 52% were sBCC, 26% were other BCC variants and the remaining lesions were actinic keratosis, squamous cell carcinoma in situ, other benign inflammatory processes and two other malignant tumours. The sensitivity and specificity of OCT for diagnosis of sBCC were 0·87 and 0·80, respectively. There was excellent correlation between OCT and biopsy for tumour depth amongst tumours ≤ 0·4 mm (Pearson correlation r = 0·86, P < 0·001), but the correlation was less as depth increased (Pearson correlation r = 0·71, P < 0·001 for all tumours < 1·0 mm). CONCLUSIONS: OCT has good diagnostic accuracy for diagnosing sBCC and measuring depth in tumours ≤ 0·4 mm. Potentially OCT can reduce the need for biopsy in clinically suspected sBCCs. However, careful follow-up is required in such cases as there is a small risk (5%) of misdiagnosis.

In vivo confocal microscopy for the oral cavity: Current state of the field and future potential.

Confocal microscopy (CM) has been shown to correlate with oral mucosal histopathology in vivo. The purposes of this review are to summarize what we know so far about in vivo CM applications for oral mucosal pathologies, to highlight some current developments with CM devices relevant for oral applications, and to formulate where in vivo CM could hold further application for oral mucosal diagnosis and management. Ovid Medline® and/or Google® searches were performed using the terms 'microscopy, confocal', 'mouth neoplasms', 'mouth mucosa', 'leukoplakia, oral', 'oral lichen planus', 'gingiva', 'cheilitis', 'taste', 'inflammatory oral confocal', 'mucosal confocal' and 'confocal squamous cell oral'. In summary, inclusion criteria were in vivo use of any type of CM for the human oral mucosa and studies on normal or pathological oral mucosa. Experimental studies attempting to identify proteins of interest and microorganisms were excluded. In total 25 relevant articles were found, covering 8 main topics, including normal oral mucosal features (n=15), oral dysplasia or neoplasia (n=7), inflamed oral mucosa (n=3), taste impairment (n=3), oral autoimmune conditions (n=2), pigmented oral pathology/melanoma (n=1), delayed type hypersensitivity (n=1), and cheilitis glandularis (n=1). The evidence for using in vivo CM in these conditions is poor, as it is limited to mainly small descriptive studies. Current device developments for oral CM include improved probe design. The authors propose that future applications for in vivo oral CM may include burning mouth syndrome, intra-operative mapping for cancer surgery, and monitoring and targeted biopsies within field cancerization.