False-Negative Cases on Confocal Microscopy Examination: A Retrospective Evaluation and Critical Reappraisal

Abstract

Background: Confocal microscopy is a second-level examination for dermoscopically equivocal melanocytic lesions. However, the number of false-negative cases on confocal microscopy and the scenarios in which confocal microscopy may fail have not been fully elucidated. Objective: To calculate the percentage of false-negative melanomas upon reflectance confocal microscopy examination in a large series of cases. Methods: A retrospective analysis on 201 melanomas, evaluated for dermoscopic/confocal criteria of melanoma, was carried out. Results: Twenty-three melanomas out of 201 cases (11.4%) revealed a low 7-point checklist score. On confocal examination, 22 out of 23 lesions have been diagnosed correctly as melanomas. Only 1 lesion did not display melanoma features, neither upon dermoscopy nor upon confocal microscopy examination. Seven lesions out of 201 cases (3.5%) were judged as negative on confocal examination, even if 6 of them were diagnosed as melanomas by clinical and/or dermoscopic evaluation. After histopathological revision, these cases were grouped into 5 categories: (1) amelanotic melanoma (n = 1), (2) hyperkeratotic melanomas (n = 2), (3) lentiginous melanomas (n = 2), (4) melanoma with small pagetoid cells (n = 1), (5) spitzoid melanoma (n = 1). Conclusion: Confocal and dermoscopic examination, along with patient-related information and clinical history, can lead to an optimal patient management.

Tips for difficult to diagnose hypomelanotic melanomas on reflectance confocal microscopy

“…By zooming mosaic images, we also noticed small hyper‐reflective nucleated (irregular cobblestone pattern) or focal small hyper‐reflective irregular cells without a visible nucleus in the epidermis, corresponding to malignant melanocytes which were difficult to differentiate from keratinocytes at first glance (Figure 1b,c). Melanomas with small pagetoid cells missed at RCM have already been reported in the literature as false‐negative cases 3,4 . Our series highlighted this aspect as even more relevant in HMs.…”

“…Reflectance confocal microscopy (RCM) has been shown to further improve the diagnostic accuracy of AHM detecting hyporeflective pagetoid cells and nests of weakly refractive melanocytes, besides well‐defined conventional criteria of pigmented melanoma 2 . However, RCM can still miss AHM 3,4 and a second expert opinion is helpful to reduce misdiagnosis due to difficult interpretation of its images 5 …”

Discriminating Nevi from Melanomas

“…Thus, placing RCM findings in context with patient-related information and clinical history will help avoid missing most of these melanomas. 39 …”

Confocal Microscopy and Lentigo Maligna: An in vivo Pilot Study for the Assessment of Response to Imiquimod Therapy

“…However, the operators should be aware of the possibility of false-negative and false-positive results on confocal microscopy examination. Therefore, confocal and dermoscopic examination should be considered, along with patient-related information and clinical history, to define an optimal patient management [24-26]. …”