Relative frequency of solitary melanocytic lesions of the oral mucosa

Background: Solitary pigmented lesions of melanocytic origin are uncommon in the oral mucosa. These lesions include the oral and labial melanotic macule, oral melanocytic nevus, oral melanoacanthoma, oral melanoma and atypical melanocytic proliferation. The purpose of the study was twofold: to report a large series of solitary melanocytic lesions from one source, and to determine the relative frequency of these lesions. Methods: The study was based on a systematic search of the files of the Pacific Oral and Maxillofacial Pathology Laboratory, University of the Pacific, San Francisco for solitary pigmented melanocytic lesions (benign and malignant) accessed during the years 1984–2002. Results: Of the 89 430 biopsies accessed during the 19‐year period, 773 (0.83%) cases of solitary pigmented melanocytic lesions in the oral mucosa were identified. Oral and labial melanotic macules were the most common melanocytic lesions comprising 86.1% of the entire group and 0.7% of the total number of accessed biopsies. The vermilion border and gingiva were the most common sites (31.1% and 31.0% respectively). Oral melanocytic nevi comprised 11.8% of the entire melanocytic group and 0.1% of the total number of biopsies. The most common site was the palate (44%). Intramucosal nevi were the most common (64%), followed by compound nevi (16.5%) and common blue nevi (16.5%). Junctional nevi were uncommon (3.0%). Oral melanoacanthoma comprised only 0.9% of the entire melanocytic group and 0.008% of the total number of biopsies. Oral melanoma and atypical melanocytic proliferation were the least common lesions each comprising 0.6% of the entire melanocytic group and 0.006% of the total number of biopsies. The most common site for oral melanoma was the palate (60%). Conclusion: The palate was the most common location for both melanocytic nevi and oral melanoma. Thus, all melanocytic lesions in the palate should be viewed with caution and biopsy is recommended to rule out melanoma. Further studies are required to elucidate the entity of oral atypical melanocytic proliferation.     

Melanocytic nevi of the oral mucosa: a clinicopathologic study of 130 cases from northern California

This paper presents analysis of data on 130 cases of oral melanocytic nevi from the files of the University of the Pacific, San Francisco and the University of California, San Francisco. This is the largest detailed series from one geographic location published to date. Nevi of the intramucosal type are the most common (63%) followed by the common blue nevus (19%). Compound nevi are uncommon (9%) and junctional nevi are rare (5%). Combined nevi are the rarest type (4%). The data are analyzed as to the location, presence of clinical pigmentation, configuration, and size of the nevi, as well as the patient's age, gender and race. Because the malignant potential of oral nevi is still uncertain and because preexisting macular pigmentation is present in about one third of all patients with oral melanoma, it is advisable to remove all pigmented lesions suspected to be melanocytic nevi.     

Blue nevus: report of a case

Blue nevus is a benign, acquired melanocytic lesion that typically manifests as an asymptomatic, slate-blue or blue-black, smooth-surfaced macule or papule. It usually measures less than 4 mm in diameter. Intraoral melanocytic nevi are uncommon compared to those found in the skin, with the exception of the blue nevus. The blue nevus is proportionally more prevalent in oral mucosa and represents the second most common form of nevus, accounting for 16.5% to 36% of all oral nevi. The palate is the predominant location for blue nevi, accounting for 87% of all oral cases, although other lesions are found in this region as well. This paper presents a case of common blue nevus of the hard palate in a 76-year-old woman, describes the clinical and histological aspects of the nevus, and discusses the difference between benign and malignant melanocytic lesion in the palate.     

Balloon cell nevus of the oral mucosa

The balloon cell nevus is an uncommon variant of melanocytic nevi in which the majority of the proliferation consists of cells demonstrating peculiarly large clear, foamy, or finely vacuolated cytoplasm. The vacuolated cells represent altered nevus cells and upon immunoperoxidase evaluation react positively with several melanocytic markers. Complete excision results in cure. This report describes the second balloon cell nevus of the oral mucosa documented in the English-language literature.     

Immunohistochemical expression of Skp2 protein in oral nevi and melanoma

Objective: The aim of this study was to analyze the immunohistochemical expression of Skp2 protein in 38 oral nevi and 11 primary oral melanomas. Study Design: Expression of this ubiquitin protein was evaluated by immunohistochemistry in 49 oral melanocytic lesions, including 38 intramucosal nevi and 11 primary oral melanomas. The labeling index (LI) was assessed considering the percentage of cells expressing nuclear positivity out of the total number of cells, counting 1000 cells per slide. Results: Skp2 protein was rarely expressed in intramucosal nevi, in contrast to oral melanomas, which showed high levels of this protein. Conclusion: These results indicate that Skp2 protein may play a role in the development and progression of oral melanomas, and it also could be useful as an immunohistochemical marker for differential diagnosis of oral benign and malignant melanocytic lesions. Key words:Oral melanoma, oral nevi, Skp2, cell cycle, immunohistochemistry.     

Spitz nevus of the palate. Report of a case

A 4-year-old Japanese girl with a nonpigmented nodule on the anterior portion of the palate since birth is described. The overall microscopic appearance of the lesion was very similar to that of Spitz nevus of the skin. Diagnosis of Spitz nevus (mixed epithelioid cell and spindle cell nevus) was made on the basis of the clinical and histologic criteria for differentiating this lesion from malignant melanomas and common compound nevi. Positive immunostaining of epithelioid and spindle cells for S-100 protein and neuron-specific enolase was also indicative of their nevocellular nature. Review of the cases of Spitz nevus from the literature revealed that the present case most probably represents the first reported instance of this type of nevus in the oral cavity.     

Nodular fasciitis and solitary fibrous tumor of the oral region: tumors of fibroblast heterogeneity

OBJECTIVE: Fibroblastic proliferations of the oral cavity are extremely varied, yet they share certain features-spindle cell morphology, collagen synthesis, and fasciculation. Nodular fasciitis is a cellular fibroblastic lesion, uncommonly located in the oral submucosa, that shows smooth muscle actin (SMA) immunoreactivity. Solitary fibrous tumor expresses a CD34 fibroblast phenotype. The aim of this study is to report instances of nodular fasciitis and solitary fibrous tumor in the orofacial region and investigate immunohistochemical markers to compare and contrast fibroblastic phenotypic heterogeneity in these tumors. STUDY DESIGN: Seven benign cellular fibrogenic tumors initially diagnosed as nodular fasciitis over a 10-year period were examined. Immunohistochemical markers, including S-100 protein, SMA, CD68, CD34, and vimentin, were used to further characterize these lesions. RESULTS: All tumors occurred in adults, and the buccal mucosa was found to be the favored site. The spindle cells in these tumors showed phenotypic heterogeneity both within and between tumors. All were vimentin-reactive and harbored small populations of CD68-positive macrophage/dendrocytes. Five tumors were SMA-positive and CD34-negative; the tumor in one case was SMA-negative and CD34-positive, and that in another was SMA-positive and CD34-positive. CONCLUSION: Although rare, nodular fasciitis and solitary fibrous tumor arise in oral submucosa, usually in the cheek. The histopathologic features and immunomarkers indicative of myofibroblastic differentiation are seen in nodular fasciitis, whereas solitary fibrous tumor is CD34-positive; however, one instance was found to be positive for both markers. All of these cases harbored subpopulations of CD68-positive cells. Immunomarkers are a valuable adjunct in differentiating nodular fasciitis from solitary fibrous tumor, yet some tumors may harbor heterogeneous fibroblast phenotypes.     

Laser treatment of congenital nevi

Congenital nevi are benign proliferations present at birth that consist of cells normally present in the skin. Many of these lesions are disfiguring and a source of psychosocial impairment. Because of location or extent of the lesion, surgical excision of the nevus may leave a defect without favorable reconstructive options. Laser ablation of such lesions has been used by several clinicians. A review of laser terminology is presented along with a review of nevus of Ota, nevus of Ito, café-au-lait macules, lentigines, and congenital melanocytic nevi. Although good results may be achieved with laser ablation of these lesions, laser treatment modalities for congenital melanocytic nevi remain controversial because of the potential for malignancy.     

Review of linear epidermal nevus with oral mucosal involvement – series of five new cases

Introduction:  Linear epidermal nevi are sporadic hamartomatous alterations of the epidermis and superficial dermis that clinically appear as verrucous papules and plaques distributed in a linear pattern following Blaschko's lines. Their extent varies from unilateral involvement (nevus unius lateris) to extensive bilateral involvement (ichthyosis hystrix). Oral mucosal lesions have rarely been described.
Aims:  We review the literature, focusing on the rare intraoral manifestations of linear epidermal nevus.
Case series:  We present a series of five new cases with oral mucosal involvement. Four cases had associated cutaneous lesions and one case had oral lesions exclusively. Histopathologic evaluation of lesional tissue in four cases showed hyperkeratosis, acanthosis, epithelial hyperplasia, and papillomatosis. Dental abnormalities, consisting of enamel hypoplasia and congenitally missing teeth, were noted in one patient adjacent to the oral lesions.     

Oral melanocytic lesions: differences in expression of HMB-45 and S-100 antigens in round and spindle cells of malignant and benign lesions

Immunohistochemistry and melanin bleaching were used to assess the expression of antigens identified by anti-S-100 and anti-HMB-45 antibodies on melanomas and intramucosal and blue nevi from the oral mucosa of 18 patients. Both antibodies reacted with cells in all three types of lesions, but there were differences in the expression of these antigens between the round and spindle cells within the lesions. In melanomas composed of round cells, the intensity and distribution of staining with HMB-45 was greater than with S-100. The opposite was true in melanomas composed of spindle-shaped cells, and one spindle-cell melanoma was HMB-45-ncgativc. The round cells of intramucosal nevi expressed S-100 more intensely and more frequently than HMB-45. The spindle-shaped cells of blue nevi strongly expressed both S-100 and HMB-45. Whereas intradermal nevi from the skin do not express HMB-45. intramucosal nevi consistently express this antigen in the lesion and overlying mucosa. Oral melanomas composed of round and spindle-shaped cells show differences in their expression of S-100 and HMB-45 antigens, making the use of both antibodies complementary in the diagnosis of undifferentiated tumors.     

Epithelioid blue nevus of the oral mucosa: a rare histologic variant

Epithelioid blue nevus (EBN) is an extremely rare histologic variant of blue nevus that has only recently been identified. Unlike other variants of blue nevus, which primarily are composed of pigmented, spindle-shaped melanocytes, EBN is characterized by large, well-defined, heavily-pigmented polygonal or epithelioid-shaped melanocytes intermixed with less densely pigmented epithelioid- and fusiform-shaped melanocytes. Furthermore, in contrast to other benign melanocytic proliferations, the lesional cells in EBN exhibit little or no maturation as they extend deeper into the underlying tissue. Blue nevi are the second most common form of nevus in the oral cavity. However, to our knowledge, the epithelioid variant has not been previously identified in the mouth. Only 6 examples of EBN have been identified in the skin of the head and neck. We now report the first documented case of EBN involving the oral mucosa. A brief review of the clinical and histopathologic features of EBN is also presented.     

Expression of fatty acid synthase (FASN) in oral nevi and melanoma

Oral Diseases (2011) 17 , 808–812 Objective: The aim of this study was to determine the expression of fatty acid synthase (FASN) in oral nevi and melanomas, comparing the results with correspondent cutaneous lesions. Materials and Methods: Expression of FASN was evaluated by immunohistochemistry in 51 oral melanocytic lesions, including 38 intramucosal nevi and 13 primary oral melanomas, in 10 cutaneous nevi and in 14 melanomas. Results: Fatty acid synthase was strongly expressed only in melanomas, either of the oral mucosa or cutaneous. On the other hand, most oral and cutaneous nevi were negative, with a few oral cases showing focal and weak expression. Conclusion: Fatty acid synthase is expressed in malignant melanocytes, and it can be a helpful marker to distinguish oral melanomas from oral melanocytic nevi.     

Immunohistochemical localization of S-100 protein and its subunits in melanotic lesions in the oral mucosa and skin

Immunohistochemical localization of S-100 protein, S-100 alpha and beta subunits was examined in 23 pigmented nevi, 20 malignant melanomas and 8 metastatic melanomas originating from the oral mucosa and skin. Primary oral mucosal melanomas demonstrated no beta subunit immunoreactivity while one metastatic lesion from oral melanoma that showed only a small number of melanoma cells reacted with the beta subunit. In contrast, most cutaneous melanomas and their metastatic lesions showed immunoreaction with the S-100 beta subunit. As for pigmented nevi, immunoreactions with the three antibodies were frequently detected regardless of the site. The differences in the expression of S-100 protein beta subunit between cutaneous and mucosal melanomas may be related to differences in inductive interactions between the melanoma cells and the connective tissues and skin and mucosa.     

Oral Kaposi's sarcoma: a 10-year retrospective histopathologic study

Microscopic diagnosis of early Kaposi's sarcoma continues to be a challenge to the pathologist, as does the identification of bacillary angiomatosis (BA) which may have a similar appearance. 120 oral Kaposi's sarcoma (KS) biopsies submitted to the UCSF-'oral pathology service from 1981–1991 were reviewed in order to describe the clinical-pathologic spectrum of these lesions and to search for unrecognized cases of BA. Also, histopathologic features of oral KS were compared to 30 oral pyogenic granulomas. and immunohistochemical stains for endothelium-associated CD34 antigen were done. The diagnosis of KS was confirmed in all biopsies and no cases of BA were found. Histologically, the KS specimens exhibited numerous features that separated them from pyogenic granulomas, and could themselves be divided into two clinical-pathologic subtypes: small, well-delineated macular lesions (31), which were characterized by inconspicuous patches of spindle cells containing ill-defined vascular spaces; and larger, infiltrative nodular lesions (89), which were characterized by spindle cells lining vascular slits and bizarre-shaped vessels, Extravasated RBCs were evident in almost all KS lesions; hemosiderin deposits and hyaline globules were seen in half of each of the small and large lesions. Nuclear atypia was minimal and mitotic activity was slight. Lymphocytes in small lesions added to the difficulty of microscopic interpretation of these incipient lesions. CD34 was expressed on all spindle cells lining vascular spaces in larger lesions and on spindle cells of small, subtle lesions. We conclude that within the spectrum of lesions that are diagnosed as oral KS. two clinical-pathologic types can be identified: macular small spindle-cell lesions and nodular infiltrative vascular lesions. KS expression of CD34 antigen is a characteristic that may be useful in the diagnosis of small, well-delineated oral lesions that lack classic KS features.     

Pigmented nevi of the oral mucosa: a clinicopathologic study of 36 new cases and review of 155 cases from the literature. Part I: A clinicopathologic study of 36 new cases

Pigmented nevi are uncommon oral lesions. This study adds data on 36 new cases. The most common type of nevus was the intramucosal type (20 cases), followed by the common blue nevus (11 cases). Only three cases were of the compound type and only two were of the junctional type. The hard palate was the most frequent location for the blue nevus, whereas the buccal mucosa was the most frequent site for the intramucosal nevus. One nevus (intramucosal type) was located on the tongue, and to our knowledge, this is the first reported example of pigmented nevus at this site. The individual data on the 36 cases are presented and compared with a previous study on oral nevi from the University of California at San Francisco. The previously unpublished clinical details on the 32 nevi from the previous study are also presented.     

Central giant cell granulomas of the jaws: phenotype and proliferation-associated markers

Central giant cell granulomas (CGCGs) are jaw tumors of unknown origin that often exhibit an aggressive, though unpredictable, clinical course. The purpose of this study was to determine the immunoprofile of the mononuclear cells that seem to be responsible for the biologic behavior of these tumors. Numbers of cells in cell cycle were also determined and compared in clinically aggressive and non-aggressive CGCGs. Sixteen aggressive and 12 non-aggressive CGCGs were immunohistochemically stained with antibodies to CD34, CD6S. factor XHIa, ct-smooth muscle actin. prolyl 4-hydroxylase, Ki-67. and p53 protein. Cell populations and numbers of cells in cell cycle were determined through microscopic quantitative assessment. CD34-positive ceils were limited to support vessels. CD68-positive mononuclear cells constituted a small population of cells in ail tumors. With two exceptions, factor XIIIa-positive cells were rarely seen. Alpha-smooth muscle actin staining was present in approximately half the tumors, and occasionally large numbers of positive cells were seen. Most mononuclear cells were positive for fibroblast-associated antigen. No phenotypic differences were detected between aggressive and non-aggressive tumors. P53 protein did not appear to be overexpressed in CGCGs. Ki-67 staining showed that only mononuclear cells were in cell cycle, and that there were no differences between aggressive and non-aggressive tumors. We conclude that CGCGs are primarily fibroblastic (and myofibroblastic) tumors in which macrophages appear to play a secondary role. Tumor cells show no differentiation toward endothelial cells or macrophage-related dendrocytes (factor XIIIa). Cellular phenotypes and numbers of cells in cell cycle are similar in both aggressive and non-aggressive tumors.     

Comparison of CD34 expression in fibrous reactive hyperplasia and healthy oral mucosa

ObjectivesFibrous reactive hyperplasia (FRH) is a common fibrous lesion in the oral cavity. The disease characteristics of FRH, including the expression patterns of CD34, which is a well-known fibroblast marker, have not been investigated in detail. Therefore, in this study, we aimed to investigate the characteristics of FRH compared to those of the healthy mucosa, based on CD34 expression profiles.MethodsCD34 expression was analyzed at the protein and mRNA levels using immunohistochemistry, quantitative polymerase chain reaction, and in situ hybridization (ISH).ResultsCD34 was not expressed in the lamina propria of the oral mucosa, but was commonly observed in submucosal fibroblasts. CD34-positive fibroblasts were commonly observed in FRH. A total of 17 out of 19 cases (89.5%) were CD34-positive. Furthermore, we identified a significant difference in the ratio of CD34-positive cells between the healthy and FRH tissues. Quantitative polymerase chain reaction showed that CD34 mRNA was expressed in all cases of FRH, and CD34 mRNA expression in FRH samples was found to be localized to spindle-shaped fibroblasts, as determined by ISH. A positive correlation was also found between the CD34 mRNA levels and the proportion of the CD34-positive cells.ConclusionsThese findings suggest that the increase in collagen synthesis in CD34-positive fibroblasts in the submucosa leads to the development of FRH. To our knowledge, this is the first report confirming the mRNA expression patterns of CD34 in FRH.     

Combined nevi of the oral mucosa

Pigmented nevi are uncommon oral lesions. We report the clinical and microscopic features of three cases of combined nevus, characterized by the association of an intramucosal nevus and a common blue nevus. Two cases were clinically suspected to be melanoma. The lesions were located on the maxillary gingiva, the mandibular gingiva, and the mucosa of the left posterior portion of the hard palate. Combined nevi of the skin vary considerably in histologic appearance. The microscopic findings demonstrated by oral combined nevi also appear to exhibit substantial histologic variation. The oral combined nevus should be differentiated from malignant melanoma by histopathologic means for, as in the skin, it appears to be clinically benign.     

Congenital nevus: the Indiana University's approach to treatment

The article will review the different treatment modalities for congenital nevi and the senior author's approach to these lesions. The management of congenital melanocytic nevus presents a diagnostic dilemma. Treatment must weigh the risk of malignancy, psychological distress to parents and child, and potential morbidities of excision. Excision of every nevus is neither applicable nor practical. Most plastic surgeons would agree that a large nevus mandates excision because of the risk of malignancy. However, debates occur regarding treatment of small and medium size nevi. Opinions differ regarding the types of reconstruction, malignant potential, and psychological impact of leaving a lesion untreated.     

Pigmented nevi of the oral mucosa: a clinicopathologic study of 32 new cases and review of 75 cases from the literature. Part I. A clinicopathologic study of 32 new cases.

Pigmented nevi are much less common in the oral cavity than they are in the skin. The present study adds thirty-two new cases to the literature. The most common type of nevus was found to be the intramucosal, followed in decreasing order by the common blue nevus, compound nevus, and junctional nevus. The clinical and histologic features of the nevi are analyzed and discussed.