Oral Nevi

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Background

Nevi are benign proliferations of nevus cells located either entirely within the epithelium, in both the epithelium and underlying stroma, or in the subepithelial stroma alone. They are best categorized as hamartomas rather than true neoplasms. Nevi of the oral cavity are usually called mucosal melanocytic nevi or intramucosal nevi. In 1943, Field and Ackermann may have reported the first documented case of an intraoral nevus.[1] Comerford and his coworkers were the first to propose the term intralamina propria nevus.[2] King et al adopted the less anatomically specific term, intramucosal nevus, which clinicians more easily understand.[3]

White adults have 10-40 cutaneous nevi on average, but intraoral lesions are rare.

On the basis of the histologic location of the nevus cells, cutaneous nevi can be classified into 3 categories. The first category, junctional nevus, is when nevus cells are limited to the basal cell layer of the epithelium. The second category, compound nevus, is used if the cells are in the epidermis and dermis. The third category, intradermal nevus, is when nests of nevus cells are entirely in the dermis. Oral nevi follow the same classification; however, the term intradermal is replaced by intramucosal.

Nevi may also be classified as congenital or acquired (see Histologic Findings). Oral acquired melanocytic nevi evolve through stages similar to those of nevi on the skin. Junctional nevi that are first noted in infants, children, and young adults typically mature into compound nevi. Then, during later adulthood, the lesions mature into intramucosal nevi. By far, the most common mucosal type is the intramucosal nevus, which accounts for more than one half of all reported oral nevi. Note the image below.


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Intramucosal nevus on the lower lip. This brown papule measured 0.6 cm in diameter and was only slightly raised. Melanotic macules are invariably flat....

The common blue nevus is the second most common type found in the oral cavity. The proportion of total nevi that are blue nevi is greater in the mouth than in the skin; blue nevi account for 25-36% of all oral nevi, according to different studies. Junctional and compound nevi account for only 3-6% of all oral nevi, and only a few cases of congenital nevi, cellular blue nevi, Spitz nevi, balloon cell nevi,[4] and combined nevi have been reported. With the probable exception of halo and dysplastic nevi, all of the cutaneous subtypes of nevi have been found in the oral mucosa. Note the image below.


View Image

Blue nevus on the gingiva. This 1-cm saucer-shaped tan macule on the gingiva has histologic features consistent with those of a blue nevus, which is t....

The term nevus is used in reference to many other hamartomatous or neoplastic entities that are not composed of nevus cells or melanocytes. These entities include white sponge nevus, epidermal nevus syndrome (nevus unius lateris), nevus sebaceous, blue rubber-bleb nevus syndrome,[5, 6, 7, 8] nevoid basal cell carcinoma syndrome, and widespread intramucosal nevus associated with hypertrophy of the oral mucosa and alveolar bone. This article reviews only true melanocytic nevi.

Pathophysiology

Although little doubt exists that nevus cells arise from the neural crest, whether the cells represent true melanocytes or a closely related but distinct cell type is debatable. Melanocytes of the oral epithelium are localized to primarily the tips of the rete ridges. They have a small, regular nucleus along the basal cell layer and a dendritic cytoplasm that contains melanosomes. Melanocytes transfer melanosomes to neighboring keratinocytes.

Supporting their distinction from melanocytes, nevus cells have rounded cytoplasms and lack the dendritic processes typical of melanocytes. Nevus cells have similar nuclear morphologic features, but their cytoplasm is ovoid, rounded, or spindle shaped. In addition, nevus cells have no contact inhibition and are able to form nests and clusters of cells. Normally, melanosomes are retained by nevus cells and not transferred to adjacent keratinocytes. Nevus cells also have the ability to migrate from the basal cell layer into the underlying submucosa.

Melanocytic cells derived from the neural crest migrate to the skin and oral mucous membranes during embryogenesis, and both locations are characterized by melanin production in the epithelial component. Nevus cell formation probably begins with the proliferation of melanocytes along the basal cell layer, and it is possibly associated with elongation of the rete ridges. Nevus cells either lack contact inhibition or lose it shortly after the proliferation process begins. They retain melanin pigment and form a nest or thèque. On the skin, this process usually results in the formation of a flat tan-to-brown junctional nevus measuring less than 0.5 mm in diameter.

Nevus cells probably continue to proliferate in the basal cell layer and then protrude into the submucosa. Eventually, they separate from the epidermis. Junctional nests are lost later, and nevus cells become confined to the submucosa. As the nevus cells penetrate into the submucosa, their pigmentation diminishes; approximately 15% of intramucosal nevi are nonpigmented. Melanocytic nevi can be present at birth, they may appear shortly after birth, or they may develop during childhood and early adulthood. Most cutaneous nevi develop in patients younger than 35 years. In studies of oral nevi, 85% of lesions are found in patients younger than 40 years.

Epidemiology

Frequency

United States

Literature from the early 1950s suggested that primary melanoma of the oral mucosa was more common than intramucosal nevi.[9] At that time, oral melanomas were reported far more commonly than oral nevi. King and associates investigated this observation by performing a prospective study to determine the incidence of oral nevi.[3] In 4191 patients examined, 3 nevi were found. None of the nevi was found in white patients. The study population had a black-to-white ratio of 2.3:1, indicating that both races were well represented. One white patient had what clinically appeared to be an oral nevus, but biopsy was deferred because of the patient's comorbidities.

According to the data of King et al, the estimated incidence of oral nevi in black patients in the United States is 3 cases per 2912 patients (rate, 0.1%). This incidence is probably similar in the white population, because 1279 white patients were examined, and one probable nevus was found.

In 1979, Buchner and Hansen determined the incidence of oral nevi by reviewing accession diagnoses from a large oral pathology service.[10] They found 32 cases among 20,731 surgical specimens (rate, 0.15%); this finding again suggested that nevi are rare in the oral cavity relative to those in the skin.

One potential reason for the relative scarcity of oral nevi may be that they are too small to be easily detected (see Physical).

International

Racial differences are found in the incidences of cutaneous nevi, with whites having more lesions than Asians or blacks. No such racial differences have been found with oral nevi.

Mortality/Morbidity

Numerous references support the association between melanocytic nevi of the skin and malignant melanoma. However, no case of melanoma arising in or around an oral melanocytic nevus has been described.

Race

Oral nevi are found in persons of all races.

Sex

Age

In one large study of patients with oral nevi, the patients were aged 3-85 years. The mean age of all patients was 35 years, but male patients tended to be a few years older than the female patients.

History

Physical

Certain classic clinical features can help clinicians in making the correct diagnosis. Nevi are often mistaken for melanotic macules, amalgam tattoos, physiologic ethnic pigmentation, smoker's melanosis, or other vascular or pigmented lesions.

An important consideration is that melanotic macules and amalgam tattoos are usually flat, and 80% of nevi are elevated. Ethnic pigmentation is nearly always symmetric and rarely affects the surface topography or disturbs the normal stippling in the gingiva. Smoker's melanosis involves only the anterior gingiva and most often occurs in women who smoke and take oral contraceptives. Vascular lesions can be mistaken for melanocytic proliferations; the former usually blanche with compression, and aspiration may be helpful in differentiating a nevus from a vascular process. Malignant melanoma is frequently associated with diffuse areas of pigmentation, possible ulceration, nodularity, variegation in color, and an irregular outline.


View Image

Intramucosal nevus on the lower lip. This brown papule measured 0.6 cm in diameter and was only slightly raised. Melanotic macules are invariably flat....


View Image

Blue nevus on the gingiva. This 1-cm saucer-shaped tan macule on the gingiva has histologic features consistent with those of a blue nevus, which is t....

Causes

See Pathophysiology.

Laboratory Studies

Imaging Studies

Other Tests

Usually, compression causes a vascular lesion to blanch, and aspiration can be used as well.

Procedures

Incisional or excisional biopsy of oral lesions is often required to confirm benignancy or malignancy. The primary diagnostic procedure is excisional biopsy. Incisional biopsy may be performed in nevi larger than 1-2 cm. The incision should be made in the nodular areas, if they exist, and the incisions should start from the center, not from the periphery of the lesion.

Biopsy should be performed in all pigmented lesions that are in high-risk areas of the oral cavity, such as the palate or maxillary gingiva. In fact, biopsy and histologic examination should be performed to assess any suspicious nevi of the oral cavity. Lesions at other sites should be similarly examined if they are not clearly defined areas of physiologic melanin pigmentation or confirmed amalgam tattoos.

If the initial biopsy reveals benign melanotic macules, the lesions should be closely monitored, and biopsy should be repeated if they recur or enlarge. See the image below.


View Image

This biopsy-proven intramucosal nevus on the gingiva is unusual because it is not raised and has an irregular outline.

Histologic Findings

As previously described in Background, oral nevi are classified as junctional, compound, or intramucosal (intralamina propria nevus) nevi, according to the location of the nevus cell nests.

Nevi may also be classified as congenital or acquired. However, congenital nevi in the mouth are difficult to diagnose. Lesions larger than 1.25 cm and/or those that penetrate deep into the connective tissue layer and involve muscle, split collagen bundles, and/or salivary gland tissue are likely to be congenital nevi. Nevi with a definite history of being present at birth also fit into this category, but few examples have been reported. Whether oral congenital nevi have an increased risk of a malignant transformation is unknown.

Oral nevi are composed of 4 main types of nevus cells. Type A cells are found in the superficial portion of the nevus and are larger, rounded cells that often contain melanin. These cells are epithelioid and contain abundant pink cytoplasm and a large round or oval nucleus. Type B cells are smaller and resemble lymphocytes and are usually found in the mid portion of nevi. Type C cells resemble fibroblasts and are primarily found in the lower portions of the lesions. Type D cells are nevus giant cells that are multinucleated, and these cells are often scattered throughout the lesion. In oral nevi, type A and B cells are more common than type C cells. In nonpigmented nevi, type A cells are often absent.

Medical Care

Regular and thorough oral examinations should be performed; the goal is to find and remove all suspicious pigmented lesions.

Surgical Care

Incisional or excisional biopsy of oral lesions is often required to confirm benignancy or malignancy (see Procedures).

Consultations

Deterrence/Prevention

Complications

Prognosis

Author

Donald Cohen, DMD, MS, Professor of Oral and Maxillofacial Pathology, Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry

Disclosure: Merck & Co Grant/research funds Consulting

Coauthor(s)

Indraneel Bhattacharyya, DDS, MSD, Associate Professor, Department of Oral and Maxillofacial Diagnostic Sciences, Director of Oral & Maxillofacial Pathology Residency Program, University of Florida, College of Dentistry

Disclosure: Nothing to disclose.

Specialty Editors

Michelle Pelle, MD, Clinical Assistant Professor, Division of Dermatology, Department of Medicine, University of California, San Diego, School of Medicine

Disclosure: Nothing to disclose.

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

Disclosure: Nothing to disclose.

Drore Eisen, MD, DDS, Consulting Staff, Department of Dermatology, Dermatology Research Associates of Cincinnati

Disclosure: Nothing to disclose.

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Ackerman Academy of Dermatopathology, New York

Disclosure: Nothing to disclose.

References

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Intramucosal nevus on the lower lip. This brown papule measured 0.6 cm in diameter and was only slightly raised. Melanotic macules are invariably flat.

Blue nevus on the gingiva. This 1-cm saucer-shaped tan macule on the gingiva has histologic features consistent with those of a blue nevus, which is the second most common type of oral nevus. This location is atypical because most blue nevi occur on the palate.

Intramucosal nevus on the lower lip. This brown papule measured 0.6 cm in diameter and was only slightly raised. Melanotic macules are invariably flat.

Blue nevus on the gingiva. This 1-cm saucer-shaped tan macule on the gingiva has histologic features consistent with those of a blue nevus, which is the second most common type of oral nevus. This location is atypical because most blue nevi occur on the palate.

This biopsy-proven intramucosal nevus on the gingiva is unusual because it is not raised and has an irregular outline.

This biopsy-proven intramucosal nevus on the gingiva is unusual because it is not raised and has an irregular outline.

Intramucosal nevus on the lower lip. This brown papule measured 0.6 cm in diameter and was only slightly raised. Melanotic macules are invariably flat.

Blue nevus on the gingiva. This 1-cm saucer-shaped tan macule on the gingiva has histologic features consistent with those of a blue nevus, which is the second most common type of oral nevus. This location is atypical because most blue nevi occur on the palate.