Oral Melanoacanthoma: Case Series of 33 Cases and Review of the Literature

Abstract

Background

Oral melanoacanthoma (OM) is a rare, reactive, and benign proliferation of two cell types: keratinocytes and melanocytes. Biopsy is mandatory to not only confirm the diagnosis but also, rule out other entities, as clinical correlation simply, is not definitive.

Aim of the study

We present a large series of OM with analysis of demographics, clinical appearance, histologic presentation, and review of the literature. To the best of our knowledge, this is the largest series of oral OM reported to date.

Materials and Methods

Following IRB approval, cases diagnosed as OM within the archives of the University of Florida Oral Pathology Biopsy Service (1998–2020) were included. Patient age, gender, location, clinical appearance, clinical impression, and duration of each lesion was collected.

Results

A total of 33 cases were included with a mean age of 38.7 years (range of 5–73), and a female: male ratio of 2.6:1. The most common location in descending order was the buccal mucosa (n = 16, 48%), followed by palate (n = 11, 33%), tongue and labial mucosa (n = 2 each, 6%), maxillary and mandibular gingiva (n = 1 each, 3%). The lesions were most frequently brown/black in color, and most often described as macular. All cases were asymptomatic and reported duration was ranged from one week to twelve months. Clinical impression in descending order was pigmented macules (n = 15, 45%), melanosis (n = 4, 12%), nevus (n = 3, 9%), melanoma (n = 2, 6%), melanoacanthoma (n = 1, 3%), and racial pigmentation (n = 1, 3%). Ethnicity was only documented in only 6 out of 33 cases, of which 5 cases were African-American and one Caucasian. The majority of cases (n = 28, 84%) demonstrated hyperplastic/acanthotic surface epithelium with less common, atrophic (n = 4, 12.1%) or spongiotic epithelium (n = 2, 6.06%).

Conclusion

The demographics and clinical presentation of OM in our series was similar to previous findings but encompasses wider variability of histologic presentation. Awareness of OM in the clinical and histologic differential diagnosis of pigmented lesions should be reinforced as many patients are concerned for melanoma and clinicians are often unware of this condition.

Introduction

Oral Melanoacanthoma (OM) is an uncommon benign mixed epithelial proliferation characterized by the mucosal pigmentation with dendritic melanocytes dispersed among the epitheli with acanthosis and spongiosis [1]. OM is generally asymptomatic and usually arises as a focal pigmented macule mostly on the buccal mucosa (51%), followed by the palate (22%), lips (15%) and gingiva (5%). It occurs most commonly in patients with higher levels of skin pigmentation, with a strong female predilection in the third or fourth decade of life [2]. The lesion is dark black to brown in color and often exhibits a radial increase in size. It often reaches a diameter of several centimeters within a period of few weeks resulting in potential clinical misdiagnosis as a melanoma [3].

OM demonstrates dendritic melanocytes extending from the basal cell layer throughout the spinous cell layer with acanthosis. Often the diagnosis can be made on biopsy only, but immunohistochemistry can also be utilized to confirm melanocytic activity using markers such as HMB-45, S-100, or Melan-A [4].

The aim of this article is to expand the literature regarding the clinical and histologic features of OM. To the best of our knowledge, this is the largest single-center case series of OM with a focus on demographics, clinical appearance, and histologic presentation.

Material and Methods

With IRB approval, institutional 22-year retrospective review of oral melanoacanthomas between the years 1998 and 2020 were queried from the University of Florida Oral and Maxillofacial Pathology Biopsy Service database. Focusing on demographics, clinical appearances, histological presentation and results of any IHC testing performed were recorded.

The original slides, accession sheets, and biopsy reports of all cases were reviewed by board certified oral pathologists (IB, MI, DC, SF).

Results

A total of 33 cases were included in the database. The mean age was 38.7 years old, with an age range (5–73). Of the 33 cases, 24 lesions were occurred in females and nine lesions were found in males, with a female: male ratio of 2.6:1. Figure 1 shows the age distribution by decades of life. The most common site of involvement was buccal mucosa (n = 16, 48%), followed by palate (n = 11, 33%), tongue and labial mucosa (n = 2 each, 6%) and maxillary and mandibular gingiva (n = 1 each, 3%). The intra-oral locations are depicted in Fig. 2.

Fig. 1.

Bar graph distribution of OM by gender (n = 33) and by age (decades of life)

Fig. 2.

Bar graph showing the intra-oral locations of the case series (n = 33)

The majority of lesions are solitary and if multifocal-ipsilateral the buccal mucosa the most common location. Figure 3A and B. One case exhibited bilateral involvement. Figure 3C and D. Three cases presented with multiple lesions involving different areas inside the oral cavity in African American females (Figs. 4, 5).

Fig. 3.

A and B Solitary with the buccal mucosa is the most common location. C and D Bilateral involvement

Fig. 4.

Multifocal presentation of OM in 69yo AA female

Fig. 5.

Multifocal presentation of OM in 38yo AA female

In the 11 out of 33 cases, where color of the lesion was provided, 81.8% were black/brown and 18.2% bluish. All lesions were described as asymptomatic. Half of the cases were with unknown duration but when available, it ranged from one week to twelve months. The lesions were most commonly described as being present for an average of 4.7 months (n = 48.8%). None of the lesions was described as a recurrent lesion.

The most common clinical description provided was that of diffuse macules, with irregular borders. The clinical impression in descending order of frequency was pigmented macule (n = 15, 45%), melanosis (n = 4, 12%), nevus (n = 3, 9%), melanoma (n = 2, 6%), melanoacanthoma (n = 1, 3%), and racial pigmentation (n = 1, 3%). In this series, ethnicity was only documented in 6 out of 33 cases, of which five were African-American and one Caucasian. More than 80% of the biopsy procedures were excisional and no follow up information.

Histomorphology

All slides were reviewed and evaluated for histologic features consistent with OM including epithelial hyperplasia/acanthosis (n = 27, 81.8%), where the epithelium forms long and anastomosing rete ridges. Figure 6, A. Epithelial atrophy was less common (n = 4, 12.1%) and some showed a minor degree of hyperkeratosis secondary to local irritation (Fig. 6B). The surface epithelium was parakeratinized in all but two cases, which demonstrated an orthokeratinized layer. Spongiotic epithelium (n = 2, 6.06%) was rarely identified.

Fig. 6.

A Acanthotic epithelial proliferation with long anastomosing rete ridges ×10. B Atrophic epithelium with lichenoid pattern of inflammation, ×10

Mild acanthosis and widening of rete ridges were seen in almost all cases. Benign dendritic melanocytes with clear cytoplasm, well-defined nuclei and pigment-laden dendritic processes were scattered throughout the epithelium, chiefly within the basal cell layer. Figure 7A. Multiple areas of melanin incontinence were also noted within the lamina propria and superficial connective tissue. In the underlying connective tissue, a focally mild to moderate chronic inflammatory cell infiltrate was also present. There was no atypia or dysplasia or mitotic activity.

Fig. 7.

A Pigment-laden dendritic processes were scattered throughout the lesional epithelium (arrows) ×20. B and C Spongiotic features of keratinocytes involving almost all epithelial cell layers, ×20 and ×40. D Dendritic melanocytes stained with melanocytic marker HMB45 where they infiltrate all epithelium layers

The spongiotic epithelial appearance occurred less frequently in our case series with only two cases demonstrating this feature. In these two cases, the entire epithelium was involved with acantholytic like spongiosis and the spinous cells lost their shape and formed rounded cells as shown in Fig. 7B and C. HMB-45 stains clearly demonstrated dendritic melanocytes throughout the epithelialium layers (Figure 7D).

Discussion

The term melanoacanthoma was first explained by Bloch in 1926 as melanoepithelioma. In 1960, Mishima and Pinkus initiated the term melanoacanthoma [5]. Tomich and Zunt recommended the term melanoacanthosis, and Horlick et al. suggested in 1988 the phrase “mucosal melanotic macule, reactive type”, since the term melanoacanthoma is indicative of a neoplastic process [6, 7].

The etiology is still uncertain, but most of the authors favor trauma as the source of proliferating melanocytic activity [1, 8]. What also makes the reactive process the main factor is that some lesions regress after eliminating irritants or biopsy. Lawrence et al. in 2013 and Cvikl et al. in 2015 found the chronic contact with petroleum products, such as sodium lauryl sulfate, nitrophenol, phenolphthalein, chlorophenol, amine fluoride or phenylenediamine sulfate was associated with OM or other pigmented lesions. These components are present in mouthwashes and toothpastes, and they may act as irritants [9, 10]. Some authors have found these lesions in bruxism patients, where lesions align with the occlusal plane. Similarly, lesions have also been correlated to placement of a new dental restoration, which may cause soft tissue trauma [11, 12]. In 2007, Yarom et al. describe as etiologic factors ill-fitting removable prothesis and it was noticed in one of our cases an edentulous patient developed a diffuse pigmented lesion all over the palate and upper alveolar ridge.

Most cases of OM are be localized to an anatomic region that is continuously subjected to trauma, especially the buccal mucosa [2]. Stress-bearing areas (e.g., alveolar ridge or the palate) are second most common site. Clinically the lesion usually presents as a flat or slightly elevated black or brown macule.

OM are usually solitary and well-circumscribed, though a few authors have reported bilateral or multiple melanoacanthoma. In our study, only three cases were bilateral and all of them were in African-American females. Gingival melanoacanthoma has been reported in only 12 cases generally occurring as a solitary lesion [5].

Cutaneous melanoacanthoma is considered neoplastic, in contrast to oral melanoacanthoma. Unlike OM cutaneous lesions typically present with surface textural alterations and are not usually correlated with trauma, fast growth, or spontaneous regression [2, 13]. Furthermore, the average age of affected patients with cutaneous lesions is 55–65. It exhibits a slow growth rate and has no gender predilection. Cutaneous melanoacanthoma occurs mainly in fair-skinned adults and has a preference for the head and neck region, and many researchers consider it as a seborrheic keratosis variation [4].

OM has a strong female predilection. Cantudo-Sanagustín et al. reported in 2016 a female: male ratio of 3: 2 in solitary phenotype and 5: 3 in the multifocal phenotype. Our case series varied slightly from previous published literature with a female: male ratio of 2.6:1 [14].

The reported age of presentation varies from 6 to 77 years with a mean age of 29 years [15, 16]. Although the lesion is mostly seen among African American females patients, manifestations have also been noted among Hispanics, Asians and Caucasians. [16, 17].

OM is characterized by acanthosis, occasional spongiosis, and melanin pigmentation with several prominent dendritic melanocytes distributed diffusely in the suprabasal and spinous cell layers. A chronic lichenoid inflammatory cell infiltrate may be present in the subjacent connective. The melanocytes are immunoreactive for Melan-A, S-100, Tyrosinase and HMB-45 [18]. Other typical features of melanoacanthoma include elongated, often fusing rete ridges, focal spongiosis and increased number of eosinophils [8].

All cases in our study showed no atypical cells proliferation with no increased mitosis or any malignant features. A diagnosis of OM can be performed solely based on histological characteristics.

The main clinical and microscopical differential diagnosis for OM is melanotic macule (MM), the most commonly occurring intraoral pigmented lesion. MM is a well-circumscribed, small, black to brown macule that occurs most commonly on the lips and gingiva, followed by the palate and buccal mucosa. Patient’s age range from 4 to 98 years (mean 43.7), showing predilection for females (1.9:1). The histomorphology is characterized by increased production of melanin by basal melanocytes, which are otherwise normal in distribution and number [19]. This could explain the relation between oral MM and OM, and it could represent more of a reactive than physiologic process. Supporting this hypothesis, Horlick et al. [7] suggest that OM could be designated as mucosal MM, reactive type.

Smoker's melanosis is additional common pigmented lesion and presents as multifocal brown to black lesions. The most common site is anterior gingiva and buccal mucosa but tongue and lip mucosa can be affected.

Post-inflammatory hyperpigmentation usually develops after long-lasting of underlying inflammatory process. Lichen planus and lichenoid reactions are most commonly observed. Hyperpigmentation may persist even after the resolution of the disease [16, 19].

Oral pigmentation may be provoked by huge number of drugs. A full medical history is required when disseminated pigmentations are evident and must excluded all physiological causes. It may present as focal to multiple and diffuse black to brown or bluish areas. Drugs including antimalarials, cytotoxic agents, azathioprines and oral contraceptives. Drug induced pigmentations mostly affect the palate [19].

Multifocal hyperpigmented melanocytic lesions can be triggered by certain conditions, such as HIV, syndromes like neurofibromatosis, Peutz-Jeghers, Addison’s disease, Laugier-Hunziker, McCune-Albright syndrome. Non-melanocytic diffuse pigmentation may be due to trauma, hemochromatosis or heavy metals [16].

Rapid onset of oral pigmented lesion of unknown etiology necessitates histopathologic evaluation to rule out oral melanoma.

Oral melanoacanthoma is a benign lesion without any known risk of malignant transformation, so once diagnosed, further treatment is not necessary [20]. Clinical resolution of the lesion is often seen after incisional biopsy. If treatment is preferred, the lesion may be excised surgically with a negative margin. Argon plasma coagulation has also been utilized with promising results [21]. Cryotherapy, curettage, and the topic application of fluorouracil 5% are other treatment options described in the literature.

Conclusions

Many pigmented lesions can be clinically diagnosed based on size, shape, color, distribution or other clinical information. However, a biopsy is required for lesions such as OM, which often comes on suddenly and may spread to continuous areas. Developing a comprehensive differential diagnosis is important for a clinician who encounters these lesions in order to properly diagnose and treat the patient and allay their fears of melanoma.

Author Contributions

All authors contributed equally do conceptual study design, article review and inclusion, and manuscript preparation.

Funding

No funding was received to assist with the preparation of this manuscript.

Availability of Data and Material

Not applicable.

Code Availability

Not applicable.

Declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical Approval

Approval was granted by the University of Florida Institutional Review Board (IRB202002265) for protecting the rights and welfare of participants in this retrospective study.

Consent to Participate

A retrospective analysis was conducted, with individual patient consent waived through IRB approval process.

Consent for Publication

Not applicable.