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 Table of Contents  
REVIEW ARTICLE
Year : 2017  |  Volume : 4  |  Issue : 1  |  Page : 21-28

Dermoscopy and confocal microscopy patterns of mucosal melanosis


1 Dermatology and Skin Cancer Unit, Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia; Dermatology Department, University of Modena and Reggio Emilia, Reggio Emilia, Italy
2 Pathology Unit, Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, Italy
3 Dermatology and Skin Cancer Unit, Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, Italy

Date of Web Publication19-Jun-2017

Correspondence Address:
Elvira Moscarella
Arcispedale S. Maria Nuova, IRCCS, Viale Risorgimento 80, 42100 Reggio Emilia
Italy
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2349-5847.208347

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  Abstract 


Melanosis is the most common cause of pigmentation of the mucosal areas. Mucosal melanoma is rare; however, at early stages, the differential diagnosis with benign melanosis can be challenging. Here, we provide a brief review of dermoscopy and reflectance confocal microscopy features of melanosis of the genital and oral mucosa.

Keywords: Dermoscopy, melanosis, reflectance confocal microscopy


How to cite this article:
Bombonato C, Longo C, Piana S, Moscarella E. Dermoscopy and confocal microscopy patterns of mucosal melanosis. Pigment Int 2017;4:21-8

How to cite this URL:
Bombonato C, Longo C, Piana S, Moscarella E. Dermoscopy and confocal microscopy patterns of mucosal melanosis. Pigment Int [serial online] 2017 [cited 2019 May 19];4:21-8. Available from: http://www.pigmentinternational.com/text.asp?2017/4/1/21/208347




  Dermoscopic and Confocal Microscopy Patterns of Melanosis of The Genital Mucosa Top


Introduction

The examination and evaluation of pigmented lesions located on the genital mucosa are considered problematic. First, especially in female patients, the lesion may be on difficult-to-examine locations; second, there are only a few studies describing the different dermoscopic patterns in this region. Pigmented lesions on the mucocutaneous junction and mucous membrane not only include benign and malignant melanocytic proliferations, such as nevi and melanoma, but also nonmelanocytic skin lesions such as basal cell carcinoma, squamous cell carcinoma, and seborrheic keratosis. Moreover, nonproliferative entities marked by increased pigmentation may occur, the most frequent being benign melanosis.[1],[2]

Estimates suggest that pigmented mucosal lesions are present in 10–12% of the general population and account for approximately 20% of vulvar disease.[3],[4],[5],[6] Because of the overlapping clinical and histological features between malignant and benign processes, pigmented vulvar lesions are often challenging. In this review, we summarize the distinguishing clinical characteristics of vulvar melanotic macules. We include dermoscopy and reflectance confocal microscopy (RCM) features. These noninvasive imaging techniques may aid in the diagnosis of pigmented vulvar lesions. Vulvar melanotic macules, also called melanosis, are the most frequent type of pigmented macule of the vulva. They are defined as a benign hyperpigmentation of the basal keratinocytes. The number of melanocytes is normal or slightly increased, but they are not arranged in nests. They usually occur in reproductive-aged women.[2],[3],[4],[5],[6],[7] The pathogenesis is largely unknown. When arising in children, the multisystem genodermatoses should be considered.[8],[9],[10],[11],[12] Clinically, vulvar melanosis presents as a single or more commonly multiple, asymmetric macules or patches with variable shades of tan-to-black color, irregular and poorly demarcated borders, and variable size from 1 mm to 1 cm. A predilection for the mucosal surfaces rather than keratinized, hair-bearing skin of the external genitalia has been observed [Figure 1].[13],[14],[15],[16],[17] Both the labia minora and labia majora can be involved. In a recent study, vulvar melanosis occurred more frequently on labia majora as compared to melanoma, most commonly found on labia minora.[7]
Figure 1: Clinical aspect of a vulvar melanosis in a 54-year-old patient. Multifocal brown, macular pigmentation of the vulva

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Dermoscopy

The examination and evaluation of pigmented lesions located on the mucosa are considered problematic. To avoid the transmission of infections, the use of polyvinyl chloride food wrap covering the dermatoscope with the interposition of oil or alcohol both between the glass plate and the film and between the film and the skin is recommended. In our opinion, the use and cleaning of the dermatoscope with isopropyl alcohol is sufficient to prevent nosocomial infection.

Dermoscopy patterns have been described in four large studies and several reports.[7],[18],[19],[20],[21],[22] The most frequently detected pattern is the so-called ring-like pattern. Other common morphologies include parallel, homogeneous or structureless, reticular-like, and globular-like pattern.

The ring-like pattern is characterized by multiple round-to-ovoid structures, with regular hyperpigmented well-defined borders arranged in a grape-like manner in some areas. At dermoscopic–pathological correlation, it is characterized by the presence of “skipped” areas of pigmentation at the top of the dermal papillae [Figure 2].
Figure 2: Example of a vulvar melanosis dermoscopically featuring a ring-like pattern characterized by multiple round-to-oval structures

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The parallel pattern is composed of linear and curved streaks, lines, or globules running parallel to the skin surface. This parallel pattern may have a fingerprint-like aspect. It is observed mainly in cases with epithelial hyperpigmentation without prominent melanocytic hyperplasia [Figure 3].
Figure 3: (a) and (b) Example of vulvar melanosis dermoscopically featuring a parallel pattern

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The homogeneous or structureless pattern shows a diffuse homogeneous brown to gray-blue pigmentation with no additional dermoscopic criteria [Figure 4]. Histopathologically, a moderate-to-marked hyperpigmentation is observed along the basal cell layer, with no significant differences in the pigment distribution between the top and the bottom of the rete ridges.
Figure 4: Example of vulvar melanosis dermoscopically featuring a homogeneous pattern characterized by diffuse pigmentation in the absence of dots and globules, pigment network, and streaks

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The reticular-like pattern is similar to the pigment network observed in acquired-type nevi on the skin. It does not show a typical honeycomb polygonal disposition but a rather ovoid- or round-shaped honeycomb [Figure 5]. Histopathologically, it is correlated with the presence of melanin in the epidermal basal cells, the lines of the network resulting from the projection of the pigmented rete ridges to the skin surface. The epidermis is hyperacanthotic, with thick hyperpigmented epidermal crests with bridging of their base.
Figure 5: (a) and (b) Example of vulvar melanosis dermoscopically featuring a reticular-like pattern

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The globular-like pattern shows aggregated round-to-oval structures, tan-to-dark brown in color, similar to the globules of melanocytic lesions [Figure 6]. On histopathologic examination, the lesions show variable distribution of the melanin pigment along the epidermal basal layer and several melanophages in the dermis, with no increase in the number of melanocytes.
Figure 6: Example of vulvar melanosis dermoscopically featuring a globular-like pattern featuring aggregated round structures

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Reflectance confocal microscopy

The RCM features of vulvar melanosis show hyperreflective keratinocytes at the epithelial-chorion junction. These keratinocytes rim the dermal papillae that can be roundish (ringed pattern) and sometimes elongated (draped pattern).[23],[24],[25],[26],[27],[28],[29],[30] Dendritic cells are a possible finding in the epithelium of more than a third of cases. They are small in size and mainly confined in the basal layer of the epithelium around the dermal papillae, rendering possible, in the majority of cases, a differential diagnosis with malignant melanocytes that are preferentially located in the suprabasal layer (pagetoid scattering). The presence of gray color in dermoscopy has been associated to dendritic cells in RCM. A recent study suggested that the presence of gray color on dermoscopy, considered as an alerting feature for melanoma, could be related to the presence of melanin-laden inflammatory cells in the superficial dermis on RCM and, thus, when it is present as a “pure” feature not associated to other colors than brown or to atypical dermoscopical structures, it is related to the diagnosis of melanosis.[29]

Differential diagnosis

The differential diagnosis includes mainly vulvar nevi and melanoma.

Vulvar nevi are uncommon; in a study of 301 new patients in a gynecology practice, the prevalence of melanocytic nevi on the vulvar skin was only 2.3%.[3] A small subset of nevi with peculiar histopathologic features has been described, termed “atypical melanocytic nevi of the genital type” (AMNGT).[29] Vulvar nevi may present during childhood and they appear, in most cases, as symmetric macules and flat-topped or dome-shaped papules, ranging in color from pink to dark brown-black, or rarely, blue. Common nevi are well-demarcated with regular borders and uniform pigmentation, ranging from 5 mm to 9 mm. Compared with common vulvar nevi, AMNGT are more frequently located on the labia minora[7] and have an equal distribution between mucosal surfaces and hair-bearing skin of the external genitalia in adults. AMNGT may have alarming clinical features, such as dark pigmentation, irregular borders, and large size. There are not many reports focused on the dermoscopic patterns of nevi of the mucosal membranes. The predominant dermoscopic patterns of vulvar nevi are the globular and homogeneous pattern.[7] These can be difficult to distinguish from the globular-like and the homogeneous pattern of vulvar melanosis. However, when only brown-to-gray color is present with no other dermoscopic features, the diagnosis of a benign pigmentation should be favored.[7],[18],[19],[20],[21],[22] Globular pattern is defined by the presence of aggregated roundish-to-oval structures, tan-to-dark brown in color, corresponding histopathologically to the dermal nests of melanocytes. The homogeneous pattern is characterized by the presence of homogeneous pigmentation in the absence of other dermoscopic structures. In AMNGT, a mixed pattern, defined as the combination of two or more dermoscopic patterns, has been observed most frequently. These lesions are frequently excised to exclude melanoma.[7] Only two studies up to now have examined the RCM features of vulvar nevi.[26],[31] RCM showed focal cytological atypia and architectural irregularity without clear features of malignancy in case of AMNGT.[31] Further studies are needed to clarify the RCM features of vulvar nevi.

Mucosal melanoma accounts for approximately 1.3–1.4% of all melanomas. Compared with cutaneous melanoma, the mean age of detection of mucosal melanomas is 10 years later. There is no evidence for racial predilection of mucosal melanoma; they account for 1.3% of melanomas in whites, whereas 11.8% of all melanomas in blacks are mucosal. Mucosal melanoma has a poorer prognosis than cutaneous melanoma, and more than the half of the patients develop advanced disease.[32]

Vulvar melanoma accounts for 2% of all melanomas in females.[1],[2],[3] Most melanomas are located on the labia minora or clitoris.[1] The disease can affect women of all ages but is more common in the older population, with almost half of the patients aged 70 years or older, with a prevalence in the white population (almost 90% of the cases).[31],[32],[33],[34],[35],[36] Clinically, early mucosal melanomas present brown-black macules with shades of gray. The diameter is larger than 1 cm, and multifocal growth is possible. Advanced mucosal melanoma presents as blackor brown nodules combined frequently with the macular part at the basis of a tumor. In cases of amelanotic melanoma, red is the dominant color. Early stages of vulvar melanoma can be seen in differential diagnosis with benign melanotic macules. A recent study highlighted that in vulvar melanomas, a dermoscopic combination of blue, gray, or white color and structureless areas are highly predictive of melanoma.[21] In more advanced stages, a multicomponent pattern composed of irregular dots and globules, multiple colors, a blue-white veil, and atypical vessels can be found, similar to melanomas of the skin [Figure 7] and [Figure 8].[21] In a study by Ronger-Savle et al.,[20] the investigators propose a scoring algorithm for vulvar pigmented lesions, which has sensitivity and specificity values of 100 and 94%, respectively. Different clinical and dermoscopic variables are included. In detail, two points are given for a clinically palpable lesion, for lesions showing dermoscopically a multicomponent pattern, or for each of the following criteria: blue-whitish veil, white veil, irregular globules, and peppering. Unilateral and unifocal, irregular pattern, more than three colors, and irregular vessels count each for 1 point. A total score ≥4 is defined as a threshold for the diagnosis of melanoma. Blum et al. developed two other algorithms for management of mucosal lesions: the first with a sensitivity of 100% and a specificity of 82.2%, respectively, and the second had a lower specificity (64.3%).
Figure 7: Dermoscopic aspect of a vulvar melanoma in a 68-year-old woman

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Figure 8: Clinical (a) and (b) Dermoscopic aspect of vulvar melanoma

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The RCM imaging of mucosal melanoma is characterized by four major features: presence of pagetoid bright cells in the epithelium (mainly roundish- or spindle-shaped with plump body), high density of basal hyperreflective dendritic cells, loss of the normal architecture of the chorion papillae, and sheet-like proliferation of atypical cells in the chorion.[23],[24],[25] The diagnosis of early invasive melanoma can be very difficult because the architecture of the epithelium and epithelium-chorion junction can be mostly preserved and only few atypical melanocytes can be observed in the epithelium. In these cases, melanocytes could have a similar size as keratinocytes; thus, the differential diagnosis with vulvar melanosis can be challenging.[23],[24],[25] Therefore, it is important to look for the presence of dendrites that characterize the melanocytes. However, hyperreflective dendritic cells can also correspond to the Langerhans cells that are a frequent finding in inflamed and even normal mucosa. The differential diagnosis with melanoma is sometimes challenging because some melanoses present Langerhans cells around the chorion papillae and among the papillae and in the upper layers of the epithelium. In melanoses the presence of roundish large medium-reflective cells corresponding to melanophages. When we find them, they are usually numerous and can be distinguished from an initial spread of melanocytes toward the chorion, because they are less reflective and associated with edged-papillae and a normal epithelium that are not found in case of invasive melanoma. Moreover, the presence of a homogeneous hyperreflective rim around the papillae is usually not found in melanoma and favors the diagnosis of melanosis.


  Dermoscopic and Confocal Microscopy Patterns of Oral Mucosa Melanotic Macules Top


Introduction

Oral melanotic macules are found primarily in adults over 40 years of age. Some authors report a slight female predilection, whereas others describe both sexes being affected equally. The most common site is the vermilion border, followed by the gingiva, the buccal mucosa, and the palate.

The pigmented lesions of the oral mucosa can be the result of exogenous factors such as the outcome of tattoo pigment, amalgam from dental restorations, or pencil lead. In smokers, the melanosis can be caused by tobacco.[37] A lot of systemic drugs can also induce oral pigmentation. Endogenous pigmentation can be associated with numerous physiological conditions and syndromes,[38],[39],[40] and in addition, can be caused by deposit of hemoglobin, hemosiderin, and bilirubin. Postinflammatory pigmentation can result from chronic trauma or inflammation. Although uncommon, acquired melanocytic nevi can present in the oral cavity.[41],[42] Both primary and metastatic melanomas have been reported in the oral cavity, but these are rare events.[43],[44] The color of mucosal pigmentation can vary from brown to blue or black depending on the depth of the pigment within the mucosa [Figure 9]. Because of the great variety of oral pigmented lesions, especially for their etiology, the diagnosis can be difficult, and clinical examination alone cannot be enough. In this case, dermoscopy, confocal microscopy, and biopsy can help the clinicians.
Figure 9: Clinical and dermoscopy features of oral melanosis. (a) Brown macules on the vermilion border of the lower lip in a 35-year-old woman. (b) Dermoscopy showing a globular pattern

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Dermoscopy

Mucosal melanosis can reveal different dermoscopy patterns. A general finding is the regularity of these mucosal lesions. They can display a homogenous, globular, or variant of reticular pattern with usually regular border [Figure 4]. The frequency of dermoscopic patterns differs in different studies.

In a study by Lin et al.,[22] they identified four main patterns: a dotted globular pattern (25%), a homogeneous pattern (25%), a fish scale-like pattern (18%), defined as multiple curves of semicircles, U-shaped or V-shaped and arranged like scales of fish, and a hyphal pattern (18%) presented with less regularly curved or flexed lines of different lengths, mimicking fungal hyphae.

On the basis of dermoscopy, Mannone et al.[19] considered only three types of mucosal melanosis: structureless, parallel, and reticular types.

A regular parallel pattern, formed by lines, dots, or globules, and ring-like patterns, is the main dermoscopy features of mucosal melanosis, indicating benignity.

Frequently, mucosal melanosis displays a homogenous pattern, which is also found in mucosal melanoma. In case of a large lesion with a homogenous pattern, more than one color or gray-blue color, biopsy is recommended to exclude melanoma.

Reflectance confocal microscopy

In a recent review, Maher et al.[45] found only one paper in which RCM was used to investigate benign and malignant oral mucosal pigmented pathologies including melanomas. In a study by Debarbieux et al.,[23] 56 labial or genital benign and malignant pigmented lesions, including 22 lip and two gingival melanocytic macules and two lip melanomas, were examined. On the basis of this study, melanotic macules of the lip commonly have ringed, polycyclic, or “draped” papillae. Lip melanotic macules had dendritic cells that were commonly found in the basal layer at a very low density and their shape was stellate, triangular, or fusiform.

On the other hand, in lip melanomas, dendritic cells were found in moderate-to-numerous amounts in the basal layer and were shaped either roundish or fusiform.

Differential diagnosis

Physiological pigmentation results not from an increase in number of melanocytes, but rather from greater melanocytic activity.[38] Darker-skinned and the elderly are more commonly affected. The color can range from light brown to almost black, and the most common location is the attached gingiva, even if it can be noted anywhere in the oral cavity, including the tips of the fungiform papillae on the dorsal tongue. The diagnosis can be made clinically and no treatment is necessary.

Smoker’s melanosis is a phenomenon of increased melanin pigmentation seen in cigarette smokers.[37] This pigmentation is probably due to an increase of melanin production in response to heat or exposure to tobacco smoke, and this phenomenon is postulated to have a protective effect against the harmful components of tobacco smoke.[38] The most common location is the labial gingiva. Diagnosis is made by correlating the clinical appearance with the patient’s smoking history.

Amalgam tattoo is one of the most common etiologies of intraoral pigmentation and may be mistaken for a melanocytic lesion.[38],[41],[46] They appear as gray-blue macules that range in size from a few millimeters to >1 cm and can be single or multiple, but almost always asymptomatic. They can be located on the gingiva or on edentulous mucosa, but can also be seen on the hard palate, buccal mucosa, and floor of the mouth. Radiographic evaluation may be positive. If a patient has a history of dental amalgam restorations and shows a mucosal blue-gray color pigmentation, a biopsy may be unnecessary. Otherwise, it would be better to do a biopsy.

Oral melanotic macules, also called focal melanosis, are benign mucosal macules uniformly tan-to-dark brown in color, <1 cm in size,[47] and generally solitary. The color is typically a result of increased melanin deposition and is not dependent on solar exposure. The lower lip is the most common site of occurrence (33%); still, buccal mucosa, gingiva, and palate can be involved. There is a female predominance and any age can be involved; buccal mucosa lesions may occur more frequently in blacks.[38] The diagnosis rests on both the clinical presentation of a solitary lesion along with the microscopic features (where an increased melanin deposition predominantly in the basal cell layer is found). A biopsy is requested on melanotic macules that exhibit recent onset, increased size, or irregular pigmentation.[43],[44]

Oral melanoacanthoma is an uncommon benign pigmented tumor of the oral mucosa most commonly seen in black women in the third to fourth decades. The color can range from brown to almost black, and most lesions are solitary and asymptomatic. This lesion is remarkable for the rapid increase in size to several centimeters. The etiology is still unknown, even if trauma is supposed to be the cause in some cases.[44],[48],[49] A biopsy to rule out melanoma is indicated because of the worrisome appearance of a rapidly growing darkly pigmented lesion. Melanocytic nevi are uncommon, and they are located on the hard palate, gingiva, buccal mucosa, and lip. They appear as pigmented macules or papules ranging in color from brown to black or blue, even if 15% of the intraoral nevi are amelanotic and present as a solitary sessile mucosal-colored lesion that can be mistaken for a fibroma.[44],[50] Most of them are thought to be acquired, and the average age at diagnosis is 35 years with a female ratio.[51] The most common oral nevi are intramucosal nevi, and the second most common is the blue nevus that present as a small (<1 cm) blue-black macule or dome-shaped papule, most commonly on the palate.[51] There are no reports of malignant transformation of both these types of nevi to melanoma.

Primary intraoral melanoma is extremely rare, accounting for <1% of all melanomas,[52] and the incidence is relatively stable. They are seen in the sixth to seventh decades, and a male preponderance is noted. The most common sites are the palate and the maxillary alveolus.[43],[44] To date, no precursor lesion is known for intraoral melanoma, although a prior history of pigmentation in the area has been noted in about one-third of the patients.[44] Patients often present at an advanced stage with pain, mobile teeth, bone involvement, and also nodal metastases.

Financial support and sponsorship

This research was kindly supported by Italian Ministry of Health (Project Code: NET-2011-02347213).

Conflicts of interest

There are no conflicts of interest.



 
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