In vivo intraoral reflectance confocal microscopy of an amalgam tattoo

The majority of oral pigmentations are benign lesions such as nevi, melanotic macules, melanoacanthomas or amalgam tattoos. Conversely, mucosal melanomas are rare but often lethal; therefore, excluding oral melanomas in this setting is crucial. Reflectance confocal microscopy is a non-invasive, in vivo imaging system with cellular resolution that has been used to distinguish benign from malignant pigmented lesions in the skin, and more recently in the mucosa. However, lesions located posteriorly in the oral cavity are difficult to assess visually and difficult to biopsy due to their location. Herein we present a patient with previous multiple melanomas presenting with an oral amalgam tattoo in the buccal mucosa, which was imaged using an intraoral telescopic probe attached to a commercially available handheld RCM. In this case report we describe this novel probe, the first RCM description of an amalgam tattoo and we discuss its differences with the findings described in oral melanomas.


Introduction
The majority of oral pigmentations are benign lesions such as nevi, melanotic macules, melanoacanthomas or amalgam tattoos [1,2]. Conversely, mucosal melanomas are rare, but often lethal [2]. Reflectance confocal microscopy (RCM) allows imaging with cellular resolution and has excellent diagnostic accuracy to diagnose cutaneous melanoma [3]. However, RCM can be challenging to perform in the oropharynx using the current probes.
The majority of oral pigmentations are benign lesions such as nevi, melanotic macules, melanoacanthomas or amalgam tattoos. Conversely, mucosal melanomas are rare but often lethal; therefore, excluding oral melanomas in this setting is crucial. Reflectance confocal microscopy is a non-invasive, in vivo imaging system with cellular resolution that has been used to distinguish benign from malignant pigmented lesions in the skin, and more recently in the mucosa. However, lesions located posteriorly in the oral cavity are difficult to assess visually and difficult to biopsy due to their location. Herein we present a patient with previous multiple melanomas presenting with an oral amalgam tattoo in the buccal mucosa, which was imaged using an intraoral telescopic probe attached to a commercially available handheld RCM. In this case report we describe this novel probe, the first RCM description of an amalgam tattoo and we discuss its differences with the findings described in oral melanomas.

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Observation | Dermatol Pract Concept 2017;7(4):4 During imaging, the patient was awake and tolerated the procedure well. Superficially, RCM showed an overall normal epithelium with focal areas of epithelial disarray (Figure 2a

Conclusions
In the last decade, RCM imaging has expanded its use beyond the skin and has been applied to the oral and genital mucosa, specifically to distinguish mucosal melanomas from benign lesions [1,6,7]. Indeed, RCM features suggesting mucosal melanomas include suprabasal dendritic or large round cells, dendritic cells in the epithelial-connective tissue junction, and epithelial disarray [1,6,7]. In our case, RCM showed numerous suprabasilar dendritic cells along with epithelial disarray. However, these findings occurred focally, and we also noted numerous bright dots and plump cells suggesting a reactive lymphohistiocytic infiltrate. To better characterize these findings, immunohistochemical stains for melanocytes and Langerhans cells were performed. These showed normal numbers of melanocytes within the basal and suprabasilar epithelium (Figure 2f) Herein we present a patient with previous multiple melanomas presenting with an oral amalgam tattoo in the buccal mucosa, which was imaged using a novel intraoral telescopic probe attached to a commercially available handheld RCM.

Case
A woman in her 70s was referred by her dentist for a pigmented lesion on the oral mucosa. She had a history of four cutaneous melanomas -three in situ and one invasive (Breslow 0.25 mm)-excised four years prior. At physical examination, she presented with a 3 mm asymptomatic bluish papule on the left buccal mucosa (Figure 1a, asterisk). To evaluate this location, a handheld RCM (Vivascope3000, Caliber ID, Rochester, NY) fitted with a telescopic probe was used ( Figure   1b). The probe was designed to be sufficiently small (12 mm) and long (~150 mm) to allow access inside the oral cavity [4]. The probe consists of a telescope and an objective lens of numerical aperture 0.7, providing a ~0.75 x 0.75 mm field of view, ~4 μm optical sectioning and ~1 μm lateral resolution, allowing imaging to a depth of ~300 μm. Enclosing the lens there is a cap with a coverslip, which provides contact to the mucosa and keeps the tissue gently flattened and still during the imaging procedure (Figure 1b, arrowheads). Two caps are used: a shorter cap allows for imaging in the deeper epithelium/mucosal-submucosal junction and a longer cap in the superficial lamina propria. We acquired images and videos that were converted into videomosaics [5]. Langerhans cells are difficult to distinguish from melanocytes on RCM [8], and have a low specificity on the oral mucosa since they occur in normal mucosa and in reactive processes such as amalgam tattoos [1]. Histologically amalgam tattoos reveal small granules deposited between the collagen fibers and can present with a foreign-body reaction [2]. Although the presence of epidermal disarray and suprabasilar dendritic cells on RCM was suggestive of melanoma, the coexisting presence of bright dots and plump cells brings into consideration the differential diagnosis a reactive process such as an amalgam tattoo. However, since the RCM features of mucosal melanomas and other mucosal conditions are limited, larger studies are needed to increase the meaning of using this new probe with high-resolution images.