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Melanocytic hyperplasia of the oral mucosa
Melanocytic hyperplasia of the oral mucosa Amos Buchner, DMD, MSD,” Phillip W. Merrell, DDS,b Louis S. Hansen, DDS, MS, MBA,’ and Alan S. Leider, DDS, MA,d San Francisco, Calif. SCHOOL OF DENTISTRY, UNIVERSITY OF THE PACIFIC, AND SCHOOL OF DENTISTRY, UNIVERSITY OF CALIFORNIA, SAN FRANCISCO Lesions that exhibit melanocytic hyperplasia are uncommon in the oral mucosa. They are even more rare than the various morphologic types of nevomelanocytic lesions. This article reports the clinicopathologic features of oral lesions diagnosed as lentigo simplex, junctional lentigo (“jentigo”), atypical melanocytic hyperplasia (melanoma in situ), and melanoacanthoma. The proper terminology for these lesions is also discussed. (ORAL SURC ORAL MED ORAL PATHOL 1991;71:58-62)
N
onmalignant pigmented melanocytic and nevomelanocytic lesions are important primarily because of their close histogenic relationship to melanoma. A history of a preexisting pigmented lesion at the site of primary oral melanoma may be elicited in a significant number of patients.’ In recent years our knowledge has increased in the area of nevomelanocytic lesions of the oral mucosa. Buchner and Hansen2y 3 published several comprehensive studies and analyzed the clinicopathologic features of almost 200 pigmented nevi. Little is known, however, about pigmented oral lesions that exhibit melanocytic hyperplasia, such as the lentigo simplex. These lesions are probably very rare in the oral cavity, and the literature is scarce on this topic. Furthermore, some authors use loose criteria and inappropriate terms, resulting in vagueness and confusion. The purpose of this study is twofold: (1) to report on the clinicopathologic findings in six patients with lesions exhibiting melanocytic hyperplasia and to analyze their histologic features, and (2) to discuss the proper terminology of these lesions. MATERIAL AND METHODS
The files of the Oral Pathology Diagnostic Services of the University of the Pacific, San Francisco, and Wsiting Professor, Division of Oral Pathology, School of Dentistry, University of the Pacific. bAssociate Professor, Division of Oral Pathology, School of Dentistry, University of the Pacific. CProfessor, Division of Oral Pathology, University of California, San Francisco. dProfessor and Head, Division of Oral Pathology, School of Dentistry, University of the Pacific. 7/14/22110 58
the University of California, San Francisco, served as a source of material for this study. All cases coded as lentigo, junctional nevus, melanocytic hyperplasia, and melanoacanthoma were retrieved from the files. Lip lesions involving the skin were excluded from the study. In reviewing the material we applied strict histomorphologic criteria with respect to the diagnosis of lentigo simplex. Only cases that showed a slight to moderate epithelial hyperplasia with elongation of the rete ridges, an increase in the concentration of melanocytes in the basal cell layer, and an increase in the amount of melanin in both the melanocytes and keratinocytes were considered in this category.4 Lesions exhibiting an increase in the amount of melanin in the basal layer, but without proliferation of melanocytes, were considered to represent oral melanotic macules.5 Thus we had to exclude from our study several cases that had been diagnosed in the past as lentigo but according to present criteria were consistent with the diagnosis of oral melanotic macule. We also reevaluated lesions that had been coded as junctional nevi. Cases in which the nevus cells were present in nests or theques in the lower epithelium and/or beneath the epithelium but still in contact with it were considered to be junctional nevi. However, lesions that revealed an increase in the number of melanocytes just above the basement membrane, but without the formation of nests or theques, were diagnosed as lentigo simplex.6 Lesions that exhibited typical histologic features of lentigo simplex but were also associated with small nests of melanocytes at the tips of the rete ridges (i.e., combined features of simple lentigo and junctional nevus) were diagnosed as junctional lentigo or “jentig0.“7 Lesions exhibiting epithelial hyperplasia with pro-
Benign melanocytic
Volume 71 Number
hyperplasia
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1
fuse numbers of dendritic melanocytes scattered throughout all the levels of the acanthotic epithelium were diagnosed as oral melanoacanthoma.* After applying the aforementioned strict histomorphologic criteria, only six specimens that revealed various forms of melanocytic hyperplasia remained. It is of interest to note that during the period from which the six cases were retrieved, 130 cases of pigmented nevi (ordinary and blue) were in the tissue diagnosis services of both universities. CASE CASE
REPORTS 1
A 15-year-old white girl had a flat, brown-black lesion on the right side of the lower lip (labial mucosa and vermilion border). The lesion had doubled in size during the last year and measured 1.0 X 1.0 cm. The clinical diagnosis was melanotic macule. Microscopic examination revealed elongation of the rete ridges with a substantial increase of prominent melanocytes in the basal layer. Melanin pigment was present in the basal layer and also in the underlying connective tissue, mainly within melanophages. The histopathologic diagnosis was lentigo simplex (Fig. 1). CASE
2
A 27-year-old Hispanic woman had a flat, blackish area measuring 0.5 X 0.5 cm in the lingual gingiva, between the mandibular second bicuspid and first molar. The lesion had been present for approximately 15 years and was asymptomatic. The clinical differential diagnosis included hyperpigmentation and amalgam tattoo. Microscopic examination revealed elongation of the rete ridges with an increased number of melanocytes evenly distributed along the basal layer. Large amounts of melanin were present in the basal layer and in the upper portion of the lamina propria, mainly in melanophages. The histopathologic diagnosis was lentigo simplex (Fig. 2). CASE
3
A 56-year-old Hispanic woman had a dark brown, pigmented macule, measuring 0.4 X 0.4 cm, in the posterior left part of the hard palate. The clinical diagnosis was melanotic macule. Microscopic examination revealed elongation of the rete ridges with increased number of melanocytes in the basal layer. The basal layer also exhibited prominent melanin pigment and focal collections of melanocytes at the tips of the rete ridges. The superficial connective tissue exhibited melanophages and minimal chronic inflammation. The histopathologic diagnosis was junctional lentigo (Fig. 3). CASE
Fig. 1. Case 1. Histopathologic features. Note elongation of rete ridges with increased number of normalappearing melanocytes in basal layer. (Hematoxylin-eosin stain; original magnification, X50.)
4
A 49-year-old white woman had a flat, black lesion, measuring 0.5 X 0.6 cm, on the right side of the soft palate. The clinical diagnosis was amalgam tattoo. Microscopic examination revealed flattened stratified squamous epithelium with increased concentration of melanocytes exhibiting an abundance of relatively clear cytoplasm and some irregularity in their arrangement. In some areas prominent
Fig. 2. Case 2. Histopathologic features. Elongation of rete ridges, heavily pigmented basal layer, and increase in number of basal layer melanocytes are seen. (Hematoxylineosin stain; original magnification, X.50.)
melanocytes were also present in the lower portion of the spinous cell layer. No nests of melanocytes were noticed. Abundant melanin was present in the basal layer and within underlying melanophages. A mild nonspecific chronic inflammation was also noted beneath the epithelium. The histopathologic diagnosis was atypical melanocytic hyperplasia (Fig. 4). A comment was made that because of the histologic similarities to cutaneous lentigo maligna, the lesion probably represents malignant melanoma in situ. CASE
5
A 47-year-old white man had a brownish macule, measuring 0.3 X 0.2 cm, in the midline of the vermilion border of the lower lip. The lesion had been present for several months, and the clinical diagnosis was melanotic macule. Microscopic examination revealed stratified squamous epithelium with a normal pattern of spinous cell maturation. The basal layer contained an increased number of prominent melanocytes with melanin pigment. Some of the melanocytes exhibited elongated nuclei, whereas others showed enlarged prominent nuclei occupying almost the entire cytoplasm. No melanocytes were present in the upper portion
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Fig. 3. Case3. Histopathologicfeatures.Collectionsof melanocytes at tipsof reteridges.(Hematoxylin-eosinstain; original magnification,X 100.)
Fig. 4. Case4. Histopathologicfeatures.Increasednumber of prominentmelanocytesin basalregion.(Hematoxylin-eosinstain; original magnification,X 100.)
of the epithelium.The supportingconnectivetissueexhibited mild chronic inflammation.The histopathologicdiagnosiswas atypical melanocytic hyperplasia (Fig. 5). A commentwasmadethat becauseof the histologicsimilarities to cutaneouslentigomaligna,the lesionprobably representsmalignantmelanomain situ. CASE 6
A 36year-old black womanhad a slightly raised,brown pigmentedarea,measuring1.6 X 1.1 cm, in the left buccal mucosa.The duration of the lesionwasunknown,and the clinical diagnosiswas lentigo maligna melanoma.Microscopicexaminationrevealedstratified squamous epithelium with a thick spinouslayer andelongatedbulbousreteridges. Numerousclear vacuolatedcells resemblingmelanocytes were scatteredthroughout the epithelium. Many of the melanocytesexhibited dendritic processesand contained melanin.Melanin pigmentwasscarcein the keratinocytes but presentin the underlying connectivetissue,both free and within melanophages. A diffuse mononuclearinflammatory infiltrate waspresentin the subepithelialconnective tissue.The histopathologicdiagnosiswas intraoral melanoacanthoma(Fig. 6). DISCUSSION
In the skin three types of lentigo are recognized: lentigo simplex, lentigo senilis, and lentigo maligna. In the past the unmodified term lentigo was usually
understood to refer to lentigo simplex. Lentigo simplex usually arises during childhood and may occur in any portion of the skin surface or mucous membranes. There is no relation to sun exposure. The lesions are usually small (a few millimeters in diameter), round to oval, brown to black macules. Histologically, lentigo simplex reveals elongation of the rete ridges; the basal cell layer is heavily pigmented, and there is an increase in the number of basal layer melanocytes. The upper dermis may show melanin pigment in macrophages (melanophages).4, 9 The histopathology of two of our cases (Nos. 1 and 2) is consistent with that of lentigo simplex, which is found on the skin. Review of the dental literature reveals that only a few cases that were described as lentigo fulfill the aforementioned histologic criteria, especially with regard to melanocytic hyperplasia. Furthermore, lentigo simplex is confused with oral melanotic macule, which has histologic features of hyperpigmentation of the basal cell layer (without increase in the number of melanocytes and without elongation of the rete ridges). Trodahl and SpraguelO reviewed all the cases of melanocytic lesions accessioned by the Armed Forces Institute of Pathology and identified 11 cases that fulfilled the criteria of lentigo. Although they did not define their histologic criteria for lentigo, they presented a photomicrograph with an accompanying legend that described the characteristics of hyperpigmentation, downward proliferation of rete ridges, and focal proliferation of melanocytes. Watkins et al.” described five oral pigmented lesions that were diagnosed as lentigo simplex. Although their histologic criteria for lentigo included the elongation of rete ridges and the proliferation of melanocytes, their photomicrograph of lentigo is not convincing. Shapiro and Zegarelli ‘* have proposed the term labial lentigo for lesions that exhibited only hyperpigmentation of the basal cell layer but without elongation of the rete ridges and without increase in the number of melanocytes. In this regard we are in agreement with other authorss. 13,I4 who suggest that the term lentigo is inappropriate for this type of lesion; labial melanotic macule is preferred. Whereas some authors use the terms lentigo and oral melanotic macule interchangeably, we are of the opinion that, as in the skin, these are different entities, especially with regard to the proliferation of melanocytes.4* 7. 9 Case 3 exhibited combined features of lentigo simplex and junctional nevus. Some lentigines may remain unchanged into mid-adult life.15 Others may develop into junctional nevi as a result of confluence and nesting of the increased number of melanocytes. For telegraphic communication Ackerman et al.’ suggested the term “jentigo” for lesions that combine features of lentigo simplex and junctional nevus. Cook
Benign melanocytic
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and Fallowfieldr4 suggested the term incipient junctional melanocytic nevus for these lesions. Wolinsky and Silversls have shown that if numerous serial sections of lentigo simplex are performed, many of the lesions will demonstrate aggregation of melanocytes and will be diagnosed as lentiginous nevi. Cases 4 and 5 exhibited histologic features similar to those observed in cutaneous lentigo maligna. 16*l7 Kato et a1.18illustrated similar changes in the periphery of oral invasive malignant melanoma. However, applying the term lentigo maligna to intraoral lesions is somewhat problematic. Lentigo maligna of the skin occurs prodominantly on sun-exposed surfaces of elderly persons, most commonly on the face. l6 The lesion evolves slowly during the course of many years, and progression into an invasive lentigo maligna melanoma occurs only in about one third of all lesions. Usually invasion does not take place until the lentigo maligna has been in existence for 10 to 15 years and has reached the size of 4 to 6 cm.4 Thus the use of the term lentigo maligna for lesions of the oral mucosa is erroneous because they are not associated with solar (actinic) radiation. Furthermore, there is no available information on the clinical and biologic behavior of oral lesions exhibiting histologic features of cutaneous lentigo maligna (i.e., the percentage that will progress into invasive melanoma and the average time duration for this process to occur). For the time being and until more information accumulates, we suggest using the general term malignant melanoma in situ for this type of lesion. Malignant melanoma in situ, like squamous cell carcinoma in situ, is a lesion that is still biologically benign (incapable of metastasis) even though it is morphologically already malignant.4 The nature of the intraoral melanoacanthoma (case 6) is debatable at the present time. Mishima and Pinkus used the term melanoacanthoma for a benign pigmented epithelial tumor of the skin with dendritic melanocytes singly dispersed at all levels of the epidermis. Some authors4 considered this a rare form of seborrheic keratosis. Although about 20 cases of intraoral melanoacanthoma that fulfill all the histologic criteria of Mishima and Pinkus have been reported, there appear to be significant biologic differences between lesions of the skin and oral mucous membrane. The skin lesions characteristically affect elderly white persons, develop slowly over a period of years, and usually have a roughened or papillary surface. Intraoral melanoacanthomas, on the other hand, tend to affect a much younger population, occur almost exclusively in black persons, and have a flat or slightly raised surface; many patients report a rapid onset of days or weeks. Approximately half the patients with oral lesions report a history of preceding trauma, whereas patients with cutaneous melanoacanthoma do not.r9 Intraoral lesions have been
hyperplasia
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5. Case5. Histopathologic features.Prominentmelanocyteswith melaninpigment. Someof the melanocytes exhibit elongatedor large nuclei. Note that changesare confinedto lower part of epithelium. (Hematoxylin-eosin stain; original magnification,X100.)
Fig.
Fig. 6. Case6. Histopathologicfeatures.Scatteredmelanocyteswith pigment-ladendendritic processes in upper epithelium.(Hematoxylin-eosinstain; original magnification, X 100.)
reported to regress after incisional biopsy, and spontaneous resolution has been reported after elimination of a presumed causal stimulus, including a poorly fitted prosthesis, sharp cusps and fractured teeth, and cigarettes held at the site. In contrast, there is no report of cutaneous melanoacanthoma that has resolved spontaneously.20* 21Thus it is suggested that intraoral melanoacanthoma is a reactive and reversible lesion, with a biologic behavior different from the skin lesion known under this term. Because of the reactive nature of the oral lesion, some authors have suggested the term mucosal melanotic macule, reactive type. 21We are of the opinion that replacing the term intraoral melanoacanthoma with this term will cause more confusion with regard to the present nomenclature of oral melanotic macule and lentigo and suggest that, at least for the time being, the term melanoacanthoma be retained. In summary, oral lesions exhibiting melanocytic hyperplasia represent an interesting, challenging, and confusing field of diagnostic problems for the oral pa-
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We thank Barbara Chacon and Janet Kline for processing the manuscript.
lesions of the oral mucosa: an analysis of 135 cases. Cancer 1970;25:812-23. 11. Watkins KV, Chaudhry AP, Yamane GM, Sharlock SE, Jain R. Benign focal melanotic lesions of the oral mucosa. J Oral Med 1984;39:91-6. 12. Shapiro L, Zegarelli DJ. The solitary labial lentigo: a clinicopathologic study of twenty cases. ORAL SURG ORAL MED
REFERENCES
13. Weathers DR, Corio RL, Crawford BE, Giansanti JS, Page LR. The labial melanotic macule. ORAL SURC ORAL MED
thologist. The need for more data is apparent so that eventually a clearer concept of the biology of the various types of such lesions can be elucidated.
ORAL
I. Rapini RP, Golitz LE, Greer RO, Krekorian EA, Poulson T. Primary malignant melanoma of the oral cavity: a review of 177 cases. Cancer 1985;55:1543-51. 2. Buchner A, Hansen LS. Pigmented nevi of the oral mucosa: a clinicopathologic study of 36 new casesand review of 155 cases from the literature. Part I. Clinicopathologic study of 36 new cases.ORAL SURG ORAL MED ORAL PATHOL 1987;63:566-72. 3. Buchner A, Hansen LS. Pigmented nevi of the oral mucosa: a clinicopathologic study of 36 new casesand review of 155 cases from the literature. Part II. Analysis of 191 cases. ORAL SURG ORAL
MED ORAL
PATHOL
1987;63:676-82.
Lever WF, Schaumburg-Lever G. Histopathology of the skin. Philadelnhia: JB Linnincott. 1983:480. 681-725. 5. Buchner*A, Hansen’&. Melanotic macule of the oral mucosa: a clinicopathologic study of 105 cases.ORAL SURG ORAL MED
ORAL 14.
15. 16. 17. 18.
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ORAL 6.
7.
8. 9.
10.
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1979;48:244-9.
Buchner A, Hansen LS. Pigmented nevi in the oral mucosa: a clinicopathologic study of 32 new casesand review of 75 cases from the literature. Part I. Clinicopathologic study of 32 new cases. ORAL SURG ORAL MED ORAL PATHOL 1979;48:13 l-42. Ackerman AB, Niven J, Grant-Kels JM. Differential diagnosis in dermatopathology. Philadelphia: Lea & Febiger, 1982: 138-42. Mishima Y, Pinkus H. Benign mixed tumor of melanocytes and malpighian cells. Arch Dermatol 1960;81:539-50. Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, eds. Dermatology in general medicine. New York: McGraw-Hill, 1987:925-7. Trodahl JN, Sprague WG. Benign and malignant melanocytic
19. 20. 21.
PATHOL
1971;31:87-92.
PATHOL
1976;42:
196-205.
Cook MG, Fallowfield ME. Dysplastic naevi-an alternative view. Histopathology 1990;16:29-35. Wolinsky S, Silvers DN. The small lentiginous nevus. Am J Dermatopathol 1985;7:5- 1I. Clark WH Jr, Mihm MC Jr. Lentigo maligna and lentigo maligna melanoma. Am J Path01 1969;55:39-67. McGovern VJ, Mihm MC Jr, Bailly C, et al. The classification of malignant melanoma and its histologic reporting. Cancer 1973;32:1446-57. Kato T, Takematsu H, Tomita Y, Takahashi M, Abe R. Malignant melanoma of mucous membranes. Arch Dermatol 1987;123:216-20. Goode RK, Crawford BE, Calliham MD, Neville BW. Oral melanoacanthoma: review of the literature and report of ten cases. ORAL SURG ORAL MED ORAL PATHOL 1983;56:622-8. Wright JM. Intraoral melanoacanthoma: a reactive melanocytic hyperplasia-case report. J Periodontol 1988;59:53-5. Horlick HP, Walther RR, Zegarelli DJ, Silvers DN, Eliezri YD. Mucosal melanotic macule, reactive type: a simulation of melanoma. J Am Acad Dermatol 1988; 19:786-9 1.
Reprint
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to:
Alan S. Leider, DDS, MA Division of Oral Pathology School of Dentistry University of the Pacific 2155 Webster St. San Francisco, CA 94115
N
onmalignant pigmented melanocytic and nevomelanocytic lesions are important primarily because of their close histogenic relationship to melanoma. A history of a preexisting pigmented lesion at the site of primary oral melanoma may be elicited in a significant number of patients.’ In recent years our knowledge has increased in the area of nevomelanocytic lesions of the oral mucosa. Buchner and Hansen2y 3 published several comprehensive studies and analyzed the clinicopathologic features of almost 200 pigmented nevi. Little is known, however, about pigmented oral lesions that exhibit melanocytic hyperplasia, such as the lentigo simplex. These lesions are probably very rare in the oral cavity, and the literature is scarce on this topic. Furthermore, some authors use loose criteria and inappropriate terms, resulting in vagueness and confusion. The purpose of this study is twofold: (1) to report on the clinicopathologic findings in six patients with lesions exhibiting melanocytic hyperplasia and to analyze their histologic features, and (2) to discuss the proper terminology of these lesions. MATERIAL AND METHODS
The files of the Oral Pathology Diagnostic Services of the University of the Pacific, San Francisco, and Wsiting Professor, Division of Oral Pathology, School of Dentistry, University of the Pacific. bAssociate Professor, Division of Oral Pathology, School of Dentistry, University of the Pacific. CProfessor, Division of Oral Pathology, University of California, San Francisco. dProfessor and Head, Division of Oral Pathology, School of Dentistry, University of the Pacific. 7/14/22110 58
the University of California, San Francisco, served as a source of material for this study. All cases coded as lentigo, junctional nevus, melanocytic hyperplasia, and melanoacanthoma were retrieved from the files. Lip lesions involving the skin were excluded from the study. In reviewing the material we applied strict histomorphologic criteria with respect to the diagnosis of lentigo simplex. Only cases that showed a slight to moderate epithelial hyperplasia with elongation of the rete ridges, an increase in the concentration of melanocytes in the basal cell layer, and an increase in the amount of melanin in both the melanocytes and keratinocytes were considered in this category.4 Lesions exhibiting an increase in the amount of melanin in the basal layer, but without proliferation of melanocytes, were considered to represent oral melanotic macules.5 Thus we had to exclude from our study several cases that had been diagnosed in the past as lentigo but according to present criteria were consistent with the diagnosis of oral melanotic macule. We also reevaluated lesions that had been coded as junctional nevi. Cases in which the nevus cells were present in nests or theques in the lower epithelium and/or beneath the epithelium but still in contact with it were considered to be junctional nevi. However, lesions that revealed an increase in the number of melanocytes just above the basement membrane, but without the formation of nests or theques, were diagnosed as lentigo simplex.6 Lesions that exhibited typical histologic features of lentigo simplex but were also associated with small nests of melanocytes at the tips of the rete ridges (i.e., combined features of simple lentigo and junctional nevus) were diagnosed as junctional lentigo or “jentig0.“7 Lesions exhibiting epithelial hyperplasia with pro-
Benign melanocytic
Volume 71 Number
hyperplasia
59
1
fuse numbers of dendritic melanocytes scattered throughout all the levels of the acanthotic epithelium were diagnosed as oral melanoacanthoma.* After applying the aforementioned strict histomorphologic criteria, only six specimens that revealed various forms of melanocytic hyperplasia remained. It is of interest to note that during the period from which the six cases were retrieved, 130 cases of pigmented nevi (ordinary and blue) were in the tissue diagnosis services of both universities. CASE CASE
REPORTS 1
A 15-year-old white girl had a flat, brown-black lesion on the right side of the lower lip (labial mucosa and vermilion border). The lesion had doubled in size during the last year and measured 1.0 X 1.0 cm. The clinical diagnosis was melanotic macule. Microscopic examination revealed elongation of the rete ridges with a substantial increase of prominent melanocytes in the basal layer. Melanin pigment was present in the basal layer and also in the underlying connective tissue, mainly within melanophages. The histopathologic diagnosis was lentigo simplex (Fig. 1). CASE
2
A 27-year-old Hispanic woman had a flat, blackish area measuring 0.5 X 0.5 cm in the lingual gingiva, between the mandibular second bicuspid and first molar. The lesion had been present for approximately 15 years and was asymptomatic. The clinical differential diagnosis included hyperpigmentation and amalgam tattoo. Microscopic examination revealed elongation of the rete ridges with an increased number of melanocytes evenly distributed along the basal layer. Large amounts of melanin were present in the basal layer and in the upper portion of the lamina propria, mainly in melanophages. The histopathologic diagnosis was lentigo simplex (Fig. 2). CASE
3
A 56-year-old Hispanic woman had a dark brown, pigmented macule, measuring 0.4 X 0.4 cm, in the posterior left part of the hard palate. The clinical diagnosis was melanotic macule. Microscopic examination revealed elongation of the rete ridges with increased number of melanocytes in the basal layer. The basal layer also exhibited prominent melanin pigment and focal collections of melanocytes at the tips of the rete ridges. The superficial connective tissue exhibited melanophages and minimal chronic inflammation. The histopathologic diagnosis was junctional lentigo (Fig. 3). CASE
Fig. 1. Case 1. Histopathologic features. Note elongation of rete ridges with increased number of normalappearing melanocytes in basal layer. (Hematoxylin-eosin stain; original magnification, X50.)
4
A 49-year-old white woman had a flat, black lesion, measuring 0.5 X 0.6 cm, on the right side of the soft palate. The clinical diagnosis was amalgam tattoo. Microscopic examination revealed flattened stratified squamous epithelium with increased concentration of melanocytes exhibiting an abundance of relatively clear cytoplasm and some irregularity in their arrangement. In some areas prominent
Fig. 2. Case 2. Histopathologic features. Elongation of rete ridges, heavily pigmented basal layer, and increase in number of basal layer melanocytes are seen. (Hematoxylineosin stain; original magnification, X.50.)
melanocytes were also present in the lower portion of the spinous cell layer. No nests of melanocytes were noticed. Abundant melanin was present in the basal layer and within underlying melanophages. A mild nonspecific chronic inflammation was also noted beneath the epithelium. The histopathologic diagnosis was atypical melanocytic hyperplasia (Fig. 4). A comment was made that because of the histologic similarities to cutaneous lentigo maligna, the lesion probably represents malignant melanoma in situ. CASE
5
A 47-year-old white man had a brownish macule, measuring 0.3 X 0.2 cm, in the midline of the vermilion border of the lower lip. The lesion had been present for several months, and the clinical diagnosis was melanotic macule. Microscopic examination revealed stratified squamous epithelium with a normal pattern of spinous cell maturation. The basal layer contained an increased number of prominent melanocytes with melanin pigment. Some of the melanocytes exhibited elongated nuclei, whereas others showed enlarged prominent nuclei occupying almost the entire cytoplasm. No melanocytes were present in the upper portion
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Fig. 3. Case3. Histopathologicfeatures.Collectionsof melanocytes at tipsof reteridges.(Hematoxylin-eosinstain; original magnification,X 100.)
Fig. 4. Case4. Histopathologicfeatures.Increasednumber of prominentmelanocytesin basalregion.(Hematoxylin-eosinstain; original magnification,X 100.)
of the epithelium.The supportingconnectivetissueexhibited mild chronic inflammation.The histopathologicdiagnosiswas atypical melanocytic hyperplasia (Fig. 5). A commentwasmadethat becauseof the histologicsimilarities to cutaneouslentigomaligna,the lesionprobably representsmalignantmelanomain situ. CASE 6
A 36year-old black womanhad a slightly raised,brown pigmentedarea,measuring1.6 X 1.1 cm, in the left buccal mucosa.The duration of the lesionwasunknown,and the clinical diagnosiswas lentigo maligna melanoma.Microscopicexaminationrevealedstratified squamous epithelium with a thick spinouslayer andelongatedbulbousreteridges. Numerousclear vacuolatedcells resemblingmelanocytes were scatteredthroughout the epithelium. Many of the melanocytesexhibited dendritic processesand contained melanin.Melanin pigmentwasscarcein the keratinocytes but presentin the underlying connectivetissue,both free and within melanophages. A diffuse mononuclearinflammatory infiltrate waspresentin the subepithelialconnective tissue.The histopathologicdiagnosiswas intraoral melanoacanthoma(Fig. 6). DISCUSSION
In the skin three types of lentigo are recognized: lentigo simplex, lentigo senilis, and lentigo maligna. In the past the unmodified term lentigo was usually
understood to refer to lentigo simplex. Lentigo simplex usually arises during childhood and may occur in any portion of the skin surface or mucous membranes. There is no relation to sun exposure. The lesions are usually small (a few millimeters in diameter), round to oval, brown to black macules. Histologically, lentigo simplex reveals elongation of the rete ridges; the basal cell layer is heavily pigmented, and there is an increase in the number of basal layer melanocytes. The upper dermis may show melanin pigment in macrophages (melanophages).4, 9 The histopathology of two of our cases (Nos. 1 and 2) is consistent with that of lentigo simplex, which is found on the skin. Review of the dental literature reveals that only a few cases that were described as lentigo fulfill the aforementioned histologic criteria, especially with regard to melanocytic hyperplasia. Furthermore, lentigo simplex is confused with oral melanotic macule, which has histologic features of hyperpigmentation of the basal cell layer (without increase in the number of melanocytes and without elongation of the rete ridges). Trodahl and SpraguelO reviewed all the cases of melanocytic lesions accessioned by the Armed Forces Institute of Pathology and identified 11 cases that fulfilled the criteria of lentigo. Although they did not define their histologic criteria for lentigo, they presented a photomicrograph with an accompanying legend that described the characteristics of hyperpigmentation, downward proliferation of rete ridges, and focal proliferation of melanocytes. Watkins et al.” described five oral pigmented lesions that were diagnosed as lentigo simplex. Although their histologic criteria for lentigo included the elongation of rete ridges and the proliferation of melanocytes, their photomicrograph of lentigo is not convincing. Shapiro and Zegarelli ‘* have proposed the term labial lentigo for lesions that exhibited only hyperpigmentation of the basal cell layer but without elongation of the rete ridges and without increase in the number of melanocytes. In this regard we are in agreement with other authorss. 13,I4 who suggest that the term lentigo is inappropriate for this type of lesion; labial melanotic macule is preferred. Whereas some authors use the terms lentigo and oral melanotic macule interchangeably, we are of the opinion that, as in the skin, these are different entities, especially with regard to the proliferation of melanocytes.4* 7. 9 Case 3 exhibited combined features of lentigo simplex and junctional nevus. Some lentigines may remain unchanged into mid-adult life.15 Others may develop into junctional nevi as a result of confluence and nesting of the increased number of melanocytes. For telegraphic communication Ackerman et al.’ suggested the term “jentigo” for lesions that combine features of lentigo simplex and junctional nevus. Cook
Benign melanocytic
Volume 71 Number 1
and Fallowfieldr4 suggested the term incipient junctional melanocytic nevus for these lesions. Wolinsky and Silversls have shown that if numerous serial sections of lentigo simplex are performed, many of the lesions will demonstrate aggregation of melanocytes and will be diagnosed as lentiginous nevi. Cases 4 and 5 exhibited histologic features similar to those observed in cutaneous lentigo maligna. 16*l7 Kato et a1.18illustrated similar changes in the periphery of oral invasive malignant melanoma. However, applying the term lentigo maligna to intraoral lesions is somewhat problematic. Lentigo maligna of the skin occurs prodominantly on sun-exposed surfaces of elderly persons, most commonly on the face. l6 The lesion evolves slowly during the course of many years, and progression into an invasive lentigo maligna melanoma occurs only in about one third of all lesions. Usually invasion does not take place until the lentigo maligna has been in existence for 10 to 15 years and has reached the size of 4 to 6 cm.4 Thus the use of the term lentigo maligna for lesions of the oral mucosa is erroneous because they are not associated with solar (actinic) radiation. Furthermore, there is no available information on the clinical and biologic behavior of oral lesions exhibiting histologic features of cutaneous lentigo maligna (i.e., the percentage that will progress into invasive melanoma and the average time duration for this process to occur). For the time being and until more information accumulates, we suggest using the general term malignant melanoma in situ for this type of lesion. Malignant melanoma in situ, like squamous cell carcinoma in situ, is a lesion that is still biologically benign (incapable of metastasis) even though it is morphologically already malignant.4 The nature of the intraoral melanoacanthoma (case 6) is debatable at the present time. Mishima and Pinkus used the term melanoacanthoma for a benign pigmented epithelial tumor of the skin with dendritic melanocytes singly dispersed at all levels of the epidermis. Some authors4 considered this a rare form of seborrheic keratosis. Although about 20 cases of intraoral melanoacanthoma that fulfill all the histologic criteria of Mishima and Pinkus have been reported, there appear to be significant biologic differences between lesions of the skin and oral mucous membrane. The skin lesions characteristically affect elderly white persons, develop slowly over a period of years, and usually have a roughened or papillary surface. Intraoral melanoacanthomas, on the other hand, tend to affect a much younger population, occur almost exclusively in black persons, and have a flat or slightly raised surface; many patients report a rapid onset of days or weeks. Approximately half the patients with oral lesions report a history of preceding trauma, whereas patients with cutaneous melanoacanthoma do not.r9 Intraoral lesions have been
hyperplasia
61
5. Case5. Histopathologic features.Prominentmelanocyteswith melaninpigment. Someof the melanocytes exhibit elongatedor large nuclei. Note that changesare confinedto lower part of epithelium. (Hematoxylin-eosin stain; original magnification,X100.)
Fig.
Fig. 6. Case6. Histopathologicfeatures.Scatteredmelanocyteswith pigment-ladendendritic processes in upper epithelium.(Hematoxylin-eosinstain; original magnification, X 100.)
reported to regress after incisional biopsy, and spontaneous resolution has been reported after elimination of a presumed causal stimulus, including a poorly fitted prosthesis, sharp cusps and fractured teeth, and cigarettes held at the site. In contrast, there is no report of cutaneous melanoacanthoma that has resolved spontaneously.20* 21Thus it is suggested that intraoral melanoacanthoma is a reactive and reversible lesion, with a biologic behavior different from the skin lesion known under this term. Because of the reactive nature of the oral lesion, some authors have suggested the term mucosal melanotic macule, reactive type. 21We are of the opinion that replacing the term intraoral melanoacanthoma with this term will cause more confusion with regard to the present nomenclature of oral melanotic macule and lentigo and suggest that, at least for the time being, the term melanoacanthoma be retained. In summary, oral lesions exhibiting melanocytic hyperplasia represent an interesting, challenging, and confusing field of diagnostic problems for the oral pa-
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Buchner et al.
ORAL SURG ORAL
MED ORAL
PATHOI.
January I 99 1
We thank Barbara Chacon and Janet Kline for processing the manuscript.
lesions of the oral mucosa: an analysis of 135 cases. Cancer 1970;25:812-23. 11. Watkins KV, Chaudhry AP, Yamane GM, Sharlock SE, Jain R. Benign focal melanotic lesions of the oral mucosa. J Oral Med 1984;39:91-6. 12. Shapiro L, Zegarelli DJ. The solitary labial lentigo: a clinicopathologic study of twenty cases. ORAL SURG ORAL MED
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Lever WF, Schaumburg-Lever G. Histopathology of the skin. Philadelnhia: JB Linnincott. 1983:480. 681-725. 5. Buchner*A, Hansen’&. Melanotic macule of the oral mucosa: a clinicopathologic study of 105 cases.ORAL SURG ORAL MED
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Cook MG, Fallowfield ME. Dysplastic naevi-an alternative view. Histopathology 1990;16:29-35. Wolinsky S, Silvers DN. The small lentiginous nevus. Am J Dermatopathol 1985;7:5- 1I. Clark WH Jr, Mihm MC Jr. Lentigo maligna and lentigo maligna melanoma. Am J Path01 1969;55:39-67. McGovern VJ, Mihm MC Jr, Bailly C, et al. The classification of malignant melanoma and its histologic reporting. Cancer 1973;32:1446-57. Kato T, Takematsu H, Tomita Y, Takahashi M, Abe R. Malignant melanoma of mucous membranes. Arch Dermatol 1987;123:216-20. Goode RK, Crawford BE, Calliham MD, Neville BW. Oral melanoacanthoma: review of the literature and report of ten cases. ORAL SURG ORAL MED ORAL PATHOL 1983;56:622-8. Wright JM. Intraoral melanoacanthoma: a reactive melanocytic hyperplasia-case report. J Periodontol 1988;59:53-5. Horlick HP, Walther RR, Zegarelli DJ, Silvers DN, Eliezri YD. Mucosal melanotic macule, reactive type: a simulation of melanoma. J Am Acad Dermatol 1988; 19:786-9 1.
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