Epithelioid blue nevus of the oral mucosa: A rare histologic variant Andres Pinto, DMD, a Sree Raghavendra, DMD, b Richard Lee, c Scott DeRossi, DMD, a and Faizan Alawi, DDS, d Philadelphia, Pa UNIVERSITY OF PENNSYLVANIA 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. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;96:429-36) A blue nevus is a benign, acquired melanocytic lesion that typically presents as an asymptomatic, slate-blue or blue-black smooth-surfaced macule or papule and usu- ally measures less than 6 mm in diameter. 1 The vast majority of blue nevi develop on the skin; however, blue nevi have also been identified in a variety of mucosal sites, including the oral mucosa. 1-5 In the oral cavity, the blue nevus is the second most common form of nevus, accounting for 19% to 36% of all oral nevi. 2,3 The intraoral variant of blue nevus is typically identi- fied between the third and fifth decades of life, with an average patient age at diagnosis of 38 years. Females tend to be more commonly affected than males. Two thirds of all intraoral blue nevi are found on the hard palate, with the buccal mucosa being the second most common site of presentation. 2-5 Blue nevi are characterized by a variety of histologic subtypes, although most are classified as either “com- mon” or “cellular.” 5-8 The common blue nevus, which is the most frequent subtype seen in the oral cavity, 5 is characterized by an intramucosal proliferation of elon- gated, bipolar, spindle-shaped melanocytes that are of- ten grouped in short fascicles arranged parallel to the overlying epithelium. 7 The lesional melanocytes ex- hibit elongated dendritic processes that typically con- tain abundant melanin. There is usually significant fi- brosis between the fascicles of pigmented cells. Scattered melanin-laden macrophages are also seen. In contrast, a cellular blue nevus is usually characterized by an intramucosal, nodular proliferation of dendritic spindle-shaped, pigmented melanocytes, in addition to tightly-packed aggregates of larger oval-to-round me- lanocytes with pale cytoplasm and little or no mela- nin. 7,8 Fibrosis is not a typical feature of pure cellular blue nevi. However, because a number of blue nevi show microscopic features that are characteristic of both types, it is apparent that, in many cases, subtyping of these lesions may be somewhat problematic. 7 From a clinical standpoint, common blue nevi are almost always innocuous lesions and rarely, if ever, recur. In contrast, cellular blue nevi may behave ag- gressively and do exhibit an increased risk for local recurrence. 6,8 Furthermore, rare cases of malignant mela- noma have been reported to arise in cellular blue nevi. 7,8 In addition to the common and cellular variants of blue nevus, other less common histologic subtypes have also been recognized, including the recently de- scribed epithelioid blue nevus (EBN). 7,9,10 In 1996, Carney and Ferreiro 9 identified this previously unrec- ognized variant of blue nevus in patients with Carney complex. Carney complex is an autosomal-dominant, multiple neoplasia syndrome that is characterized by spotty skin pigmentation; cardiac, cutaneous and soft tissue myxomas; endocrine overactivity; and psammo- matous melanotic schwannoma. 9,10 Carney and Fer- reiro 9 described 21 cases of EBN arising in 11 patients, 5 of whom exhibited multiple lesions. In all cases, the lesions appeared as small (less than 1 cm), darkly pigmented, dome-shaped nodules on the skin. a Assistant Professor, Department of Oral Medicine. b Oral Medicine Fellow, Department of Oral Medicine. c Senior dental student, Department of Oral Medicine. d Assistant Professor, Department of Pathology. Received for publication Feb 3, 2003; returned for revision Apr 17, 2003; accepted for publication Apr 28, 2003. © 2003, Mosby, Inc. All rights reserved. 1079-2104/2003/$30.00 + 0 doi:10.1016/S1079-2104(03)00319-6 429