|Year : 2015 | Volume
| Issue : 2 | Page : 29-33
Oral melanocytic nevi: Report of two cases with immunohistochemical elaboration of their probable origin and maturation
Dipti Dutta, Venkatesh V Kamath, Komali Rajkumar
Department of Oral and Maxillofacial Pathology, Dr. Syamala Reddy Dental College, Hospital and Research Centre, Bangalore, Karnataka, India
|Date of Web Publication||6-Jan-2016|
Dr. Venkatesh V Kamath
Department of Oral and Maxillofacial Pathology, Dr. Syamala Reddy Dental College, Hospital and Research Centre, Munnekolala, Marathahalli, Bangalore - 560 037, Karnataka
Source of Support: None, Conflict of Interest: None
Oral melanocytic nevi are localized developmental tissue malformations of nevus cells in the oral mucosa. Relatively rare in occurrence compared to their dermal counterparts, considerable debate exists in the literature related to their origin, development and maturation, and their relationship to oral melanocytes.We report two cases of oral melanocytic nevi with classical clinical presentation. The histopathology was consistent with the known patterns of oral melanocytic nevi. Special stains such as Masson Fontana, further substantiated the observation. S-100 and HMB-45 were applied to immunohistochemically elaborate the cell population. Interestingly two distinct cell populations were detected in the lesions. "Type A" cells in the center of the lesion were S-100 positive, indicating a neural origin and immaturity in development, while peripheral "type B" cells stained positive with HMB-45, indicating melanocytic origin and mature development.
Keywords: HMB-45, immunohistochemistry, oral melanocytic nevi, S-100
|How to cite this article:|
Dutta D, Kamath VV, Rajkumar K. Oral melanocytic nevi: Report of two cases with immunohistochemical elaboration of their probable origin and maturation. Indian J Dermatopathol Diagn Dermatol 2015;2:29-33
|How to cite this URL:|
Dutta D, Kamath VV, Rajkumar K. Oral melanocytic nevi: Report of two cases with immunohistochemical elaboration of their probable origin and maturation. Indian J Dermatopathol Diagn Dermatol [serial online] 2015 [cited 2019 Nov 19];2:29-33. Available from: http://www.ijdpdd.com/text.asp?2015/2/2/29/173413
| Introduction|| |
Oral melanocytic nevi are probably derived from nevus cells in the oral mucosa. The nevus cells, in turn, are derived from neural crest cells that migrate to the epithelium during development. 
Clinically, a pigmented nevus is an asymptomatic, well-circumscribed, round or oval, flat or slightly elevated spot or plaque, and of size usually ranging between 0.1 cm and 3 cm. The color varies from brown to blue, bluish gray to black. The hard palate, buccal mucosa, and gingiva are the most commonly affected intraoral sites. They can be seen in persons of all ages with the mean age group affected being 3 rd -4 th decade. Women are affected more commonly than men. ,
The stimulus for the development of oral nevi is still unknown but it results in the proliferation of melanocytes into the connective tissue. The cells are round in shape and are present in clusters with granular cytoplasm containing melanin pigment. Multinucleated cell variants are also seen. The classical interpapillary location (between the rete ridges) is significant and is thought to be related to the development of epithelium. 
Histologically, nevi are classified as intradermal/intramucosal, junctional, and compound, based on the pattern of proliferation of the nevus cells. In the intramucosal variety, there is a proliferation of nevus cells in the connective tissue with a band of tissue separating the cells from the basal layer of the epithelium. In the junctional variety, nevus cells are present in the basal layer of the epithelium. The compound nevi combine the characteristics of the first two groups.
The mucosal component of compound nevi and intramucosal nevi typically display a characteristic finding known as histologic maturation. In this event, superficial "type A" nevus cells with voluminous cytoplasm and large nuclei "mature" to "type B" nevus cells with less cytoplasm and smaller nuclei as the lesion extends to the deeper portions of the dermis. With further descent, "type C" nevus cells are encountered, which typically have scant cytoplasm and spindle-shaped nuclei. ,
This paper presents two cases of oral melanocytic nevi. Immunohistochemistry was used to differentiate the pattern of nevus cells and their level of maturation in the tissue.
| Case Report|| |
A 22-year-old woman was referred to the Department of Oral Pathology of the institution with the chief complaint of a pigmented lesion in the right retromolar region. The patient did not have any significant medical history. Careful intraoral examination revealed a smooth, well-circumscribed pigmented lesion in the right retromolar region. The lesion was brownish-black in color [Figure 1]. An excisional biopsy was carried out under local anesthesia and the tissue was examined histologically.
A 35-year-old man was referred with the chief complaint of a pigmented overgrowth in the left buccal mucosa [Figure 1]a. The patient did not have any significant medical history. He was a cigarette smoker. On careful intraoral examination, a brownish-black, well-circumscribed, exophytic growth near the occlusal line of left premolar-molar region was seen. The lesion measured 2 mm × 2 mm. An excisional biopsy was carried out and the tissue was examined histologically.
The hematoxylin and eosin (H&E) stained section of both the cases showed hyperplastic stratified squamous parakeratinized epithelium. The cellular fibrous connective tissue showed nests of nevus cells separated by a hyalinized band below the epithelium. No junctional activity was seen. The nevus cells were histologically bland without any evidence of dysplasia [Figure 2] and [Figure 3].
|Figure 2: H&E stained section showing proliferation of nevus cells in Miescher's pattern in case 1 Note the junctional separation and differentiation of cells in the lesion (original magnification 10×)|
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|Figure 3: H&E stained section showing proliferation of nevus cells in Unna's pattern in case 2 (original magnification ×10)|
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Cells at the periphery closer to the epithelium were large, round without dendritic processes (type A), and showed intense accumulation of melanin. The cells in the deeper layers were more uniform, round to polygonal (type B), and showed decreased melanin content. Cells in the furthest depth of the lesion were small and round with spindle-shaped nuclei (type C) with a total lack of melanin pigment.
The histological features in both the cases were suggestive of intramucosal nevus.
The sections were stained with Masson Fontana stain to support the diagnosis. S-100 and HMB-45 antibodies were used to immunohistochemically delineate the pattern and type of cells in the nevi.
Masson Fontana stain classically delineated the nevus cells from the surrounding connective tissue elements [Figure 4]. The absence of junctional activity was confirmed in these sections. Interestingly "type A" cells (those in the periphery and least mature) were predominantly stained.
|Figure 4: Masson Fontana stained section of nevus cells. The delineation from the epithelium and variable staining of cells in the body of the lesion is well-demonstrated (original magnification ×10)|
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S-100 antibody stained the cells more diffusely with staining intensity being intense in the peripheral layers and extending throughout the expanse of nevus cells with decreasing intensity in the interior regions [Figure 5].
|Figure 5: S-100 antibody staining reveals most of the cells expressing the antigen with increased intensity in the top layers near the epithelium (type A cells) (original magnification ×10)|
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HMB-45 antibody detection was limited to the peripheral cells with very little reactivity in the center and was absent in the depth of the lesion [Figure 6].
|Figure 6: HMB-45 antibody staining reveals intense expression in the type A peripheral cells with limited expression in type B cells in the body of the lesion (original magnification ×10)|
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| Discussion|| |
Proliferation of melanocytes, localized or generalized, may result in an array of pigmented lesions affecting the oral mucosa ranging from physiologic (ethnic) pigmentation, pigmentation associated with smoking to bland melanotic macules to the most aggressive melanoma.  Evaluation of a patient presenting with a new pigmented lesion must include a biopsy procedure other than thorough clinical examination and laboratory tests, so as to arrive at an accurate diagnosis, notably if focal oral pigmentation cannot be explained by local factors. An added advantage of biopsy and histological examination of the tissue is to aid in differentiation between an early melanoma that may be easily mistaken as benign melanocytic nevi. 
A pigmented nevus forms a rare cause of focal oral pigmentation and is a tissue malformation resulting from excessive proliferation of nevus cells. Three theories exist to explain the development of the oral nevi: (1) Abtropfung Theory: This is the classical and the most widely accepted theory which states that nevus cells migrate from epidermis to dermis and proliferate during the development of melanocytic tumors; (2) Dual Origin Theory: This theory attributes a dual origin to the nevus cells. Nevus cells located in the basal layer of the epithelium and juxta-epithelial region of the submucosa are thought to originate from melanocytes while nevus cells deep in the dermis or submucosa are thought to be derived from nerve cells, specifically Schwann cells. (3) Hochstringerung Theory: This theory states that melanocytes derived from the neural crest migrate upwards from the dermis to the epidermis. Interestingly, this theory reverses the traditional belief of epidermal origin of nevus cells and is largely supported by immunohistochemical observations.
Macroscopically, nevi may proliferate in two patterns. In Unna's nevi, nevus cells grow in a papillary or round pattern, giving an exophytic emergence. In Meischer's nevi, there is diffuse infiltration of the cells into the sub-epithelial region giving an endophytic outlook.
The nevus cell per se shares features histologically and immunohistochemically of both the melanocytes and neural structures, though lacking in the classic dendritic processes. The origin of nevus cells in oral melanocytic nevi is still under confusion. What is definite is the fact that cell populations have differing levels of maturation.
The staining pattern exhibited in our two cases is consistent with those reported in literature. The specificity of HMB-45 antibody in the peripheral cells (type A) with definitive lack of expression in the depths of the lesion points to the melanocytic origin of these cells. The ubiquitous S-100 antibody, known to stain cells of neural origin including melanocytes stained more cellular areas including the center and depth of the lesion, pointing to presence of neurological structure origin. The inference seems to be that the highly differentiated melanocytes lose their melanocytic expression in the process of maturation and express the more embryological stable neurological differentiation in the depths of the lesion. While this may be argued as dedifferentiation, we prefer to label it as "change in differentiation." The retention and expression of neurological features is a more stable feature and unlikely to be affected by stimuli that brought about the change in the first instance. The lack of cellular differentiation of the nevus cells vis-à-vis their parent melanocytes also supports the above observation.
While classical theories of origin have propagated the migration of melanocytes from the basal layer of the epithelium to the underlying connective tissue, the histological presentation of the intramucosal nevi seems interesting. The lack of connectivity to the basal layer and the definitive band of connective tissue that separates the proliferating nevus cells from the epithelium do not support the concept of epithelial migration of melanocytes. "Hochstringerung theory" of dermal proliferation seems more plausible in view of the histological presentations. Melanocytes derived from the neural crest are normal components of the basal layer of the epithelium and juxta-epithelial layers of the subjacent connective tissue. It is plausible that stimuli causing proliferation of these cells lead to a mass of nevus cells that migrate in the region and tend to push toward the epithelium, probably because of a common embryological link. Restricted proliferation incites a connective tissue response that results in a morphological and immunological alteration of the cells leading to localization of the proliferating nevus cells and the formation of an intramucosal nevus. A more aggressive clone of nevus cells moves toward the epithelium leading to junctional activity and the formation of a junctional nevus. A combination of both the patterns predictably forms a compound nevus. 
The origin and pattern of maturation of the nevus cells has been discussed previously. In a previous immunohistochemical study done using S-100, MIT, and Melan-A antibodies in 12 cases of oral melanocytic nevi, a strong affinity of the antibodies to type A cells and a decreased affinity for the type B cells at the edge of the lesion was noted. The authors postulated that the subpopulation of cells is a feature of maturation of the lesion and a form of adaptation to the environment. 
In another study of 29 cases of oral melanocytic nevi, three-fourths of the cells were found to be of type A while types B and C constituted the rest.  Few multinucleated giant cells were observed, a feature that was not present in our cases.
Oral melanocytic nevi present an excellent instance of tissue interactions and embryological influence. Clinically very few cases are known to undergo malignant transformation and lesions more likely behave like a hamartoma. Nevertheless, frequent follow-up after detection and excision at sites of irritation are advisable.
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Conflicts of interest
There are no conflicts of interest.
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