1. In vivo dermoscopic and confocal microscopy multi-step algorithm to detect in situ melanomas
S. Borsari1, R. Pampena1, E. Benati1, C. Bombonato1, A. Kyrgidis1, E. Moscarella1, A. Lallas2, G. Argenziano3, G. Pellacani4, C. Longo1,4
Affiliations:
Dermatology and Skin Cancer Unit, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy
First Department of Dermatology, Aristotle University, Thessaloniki, Greece
Dermatology Unit, Second University of Naples, Naples, Italy
Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy
British Journal of Dermatology. DOI: /bjd.16364

2. Introduction What’s already known?
The incidence of cutaneous melanoma has been increasing at a steady rate over the last decade, with intraepidermal tumors constituting the majority of the burden.
Although several dermoscopic features of early melanoma have been identified, in situ melanoma (MIS) can be challenging to distinguish from benign pigmented lesions.
Reflectance confocal microscopy (RCM) improves the diagnostic accuracy in skin cancer detection when combined with dermoscopy even for difficult-to-diagnose lesions. While RCM criteria of melanoma have been extensively identified, data on confocal diagnostic features for MIS are still lacking.

3. Introduction Aims to identify the RCM diagnostic features of MIS
to develop a diagnostic score for MIS while combining dermoscopic and confocal criteria

4. Methods
TEST SET: 333 consecutive lesions (120 MIS and 213 nevi) excised to rule out a melanoma
Retrieved from the database of the Skin Cancer Unit of Reggio Emilia (Italy) from 2011 to 2016
No acral and facial lesions
Dermoscopic ad RCM examination
VALIDATION SET: 100 lesions (50 MIS and 50 nevi)

5. Methods
Clinicians analized dermoscopic and RCM images of all lesions, in blind for histopathology, to assess the presence of several features:
DERMOSCOPIC EVALUATION:
Atipical pigment network
Blue-whitish veil
Atypical vessels
Irregular dots/globules
Peripheral streaks
Irregular pigmentation
Regression
RCM EVALUATION:
Epidermis
- pagetoid infiltration (yes/no)
- pagetoid cell shape (roundish, dendritic, both)
- pagetoid cell location (central, peripheral, widespread)
Dermal-epidermal junction and upper dermis:
- architectural pattern (ringed, meshwork, clod,
nonspecific; regular or irregular)
- junctional/dermal nesting (dense, demnse and sparse,
sheet-like)
- citological atypia (focal or widespread)
- melanophages

6. Results Dermoscopic and RCM features predicting MIS diagnosis:
Multivariate logistic regression
P-value
OR (95% CI)
Atypical network
0.001
3.437 ( )
Regression
<0.001
4.168 ( )
Pagetoid cells
0.007
2.829 ( )
Cytologic atypia
- focal (<25%)
- widespread
0.008
3.390 ( )
8.439 ( )
Dense nests
0.012
0.300 ( )
Melanophages
0.021
0.435 ( )
Dermoscopy
RCM

7. Results
A score for predicting MIS was developed assigning – 1 to + 2 points to each criterion statistically positively and negatively associated with MIS.
An overall score of +2 or higher signifies melanoma with a sensitivity of 92.5% and a specificity of 61%, and must therefore lead to the surgical removal of that lesion.
Diagnostic accuracy of this algorithm was confirmed by the validation set (sensitivity 92%, specificity 58%).

8. Example
A dermoscopically atypical lesion characterized by dermoscopic regression (+1 point) and epidermal pagetoid spread (+1 point) at confocal examination.

9. Example
Upon RCM, moving down to the dermal-epidermal junction, we observe widespread cytological atypia (on the left, +2 points) and melanophages inside dermal papillae (on the right, -1 point). The total makes 3, strongly suggestive for MIS diagnosis. Histopathology confirmed the diagnosis.

10. Discussion What does this study add?
RCM is a valid support to reduce the grey zone between nevi and MIS.
Pagetoid spreading in epidermis and cytologic atypia at dermal- epidermal junction are confirmed as confocal positive predictors for melanoma diagnosis. Remarkably, in MIS, the confocal finding of junctional cytologic atypia, especially widespread, have a higher weight compared to pagetoid spreading alone.
A high number of MIS was analized.

11. Conclusions
Our multi-step diagnostic algorithm is able to detect MIS with high sensitivity and specificity.
Dermoscopic and confocal criteria of the algorithm are highly reproducible.
Including only 5 dermoscopic and confocal criteria that are organized in a multi-step fashion (dermoscopic examination followed by confocal assessment, as routinely performed during patients’ care), our new algorithm proves to be easily applicable in the daily clinical practice.

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