Histologic Findings

Oral melanocytic nevi are classified as junctional, compound, or intramucosal (intra–lamina propria) nevi, similar to their cutaneous counterparts. In junctional nevi, there is proliferation of benign melanocytes along the epithelial basement membrane. In compound nevi, the melanocytes are found both in the basal cell layer and in the superficial lamina propria. In intramucosal nevi, the melanocytes are located in the lamina propria and there is no epithelial component. Oral blue nevi are intramucosal proliferations of dendritic melanocytes containing abundant melanin granules in the lamina propria. Combined oral nevi have histologic features of both melanocytic nevi and blue nevi. Intraoral nevi may rarely present histologically with pseudoepitheliomatous hyperplasia.^[53]

Oral nevi may also be classified as congenital or acquired. Congenital nevi penetrate the connective-tissue layer in a diffuse sheetlike pattern and tend to “split” into collagen bundles.^[15]Perivascular and periappendageal involvement are likely to be congenital nevi.

Immunohistochemical studies may be performed if warranted. The Melan A, MART-1, and Fontana-Masson silver stains react the same way for oral and cutaneous pigmented lesions. Immunoreactions to S-100 protein, S-100 alpha, and S-100 beta antibodies are detected in benign oral nevi, while oral mucosal melanomas in general do not react with the beta subunit, unlike melanomas in the skin.^[54]The round cells and spindle cells of benign and malignant oral lesions express HMB-45 and S-100 antigens differently.^[55]S-100 expression is more intense and more frequent than HMB-45 expression in the small round cells of intramucosal nevi. The opposite is true in the round cells of mucosal melanomas, for which HMB-45 staining is greater.

In primary oral melanomas, minichromosome maintenance 2 is a more sensitive proliferation marker than Ki-67 and geminin.^[56]The ubiquitin protein Skp2 may be a useful marker to differentiate oral benign and malignant melanocytic lesions.^[57]High levels of this protein are expressed only in the latter.

Field HJ, Ackerman AA. Non-pigmented nevus on labial mucosa. Am J Orthodontics Oral Surg. 1943. 29:180-1.
Buchner A, Merrell PW, Carpenter WM. Relative frequency of solitary melanocytic lesions of the oral mucosa. J Oral Pathol Med. 2004 Oct. 33(9):550-7. [QxMD MEDLINE Link].
Marques YM, de Lima Mde D, Raitz R, Pinto Ddos S Jr, de Sousa SO. Blue nevus: report of a case. Gen Dent. 2009 Jan-Feb. 57(1):e1-3. [QxMD MEDLINE Link].
Buchner A, Leider AS, Merrell PW, Carpenter WM. Melanocytic nevi of the oral mucosa: a clinicopathologic study of 130 cases from northern California. J Oral Pathol Med. 1990 May. 19(5):197-201. [QxMD MEDLINE Link].
Cardoso LB, Consalaro A, da Silva Santos PS, da Silva Sampieri MB, Tinoco-Araújo JE. Oral compound nevus. Dermatol Online J. 2014 Feb 18. 20(2):[QxMD MEDLINE Link].
Teh M, Sinniah R. Spindle and epithelioid cell nevus of tongue at an unusual site. Oral Surg Oral Med Oral Pathol. 1989 Jan. 67(1):68-72. [QxMD MEDLINE Link].
Nikai H, Miyauchi M, Ogawa I, Takata T, Hayashi Y, Okazaki H. Spitz nevus of the palate. Report of a case. Oral Surg Oral Med Oral Pathol. 1990 May. 69(5):603-8. [QxMD MEDLINE Link].
Seehra J, Sen P, Lloyd R, Sloan P. Intraoral Spitz naevus: a case report. Int J Oral Maxillofac Surg. 2007 Jul. 36(7):661-2. [QxMD MEDLINE Link].
Xavier RL, Vasconcelos MG, Galvão HC, Freitas Rde A, Souza EL, Pinto LP. Intra-oral Spitz naevus: a case report. Clinics (Sao Paulo). 2008 Feb. 63(1):140-2. [QxMD MEDLINE Link]. [Full Text].
Piperi EP, Tosios KI, Sklavounou A, Stich E, Koutlas IG. Junctional spitz tumor (nevus) of the upper lip. Head Neck Pathol. 2014 Sep. 8(3):354-8. [QxMD MEDLINE Link]. [Full Text].
Li CC, Harrist TJ, Noonan VL, Woo SB. Intraoral Spitz nevus: case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014 Apr. 117(4):e320-4. [QxMD MEDLINE Link].
Takeda Y. Congenital nevocellular nevus of the oral mucosa. Ann Dent. 1988 Winter. 47(2):40-2. [QxMD MEDLINE Link].
Reychler H. [Oral nevocellular nevus]. Rev Stomatol Chir Maxillofac. 1988. 89(2):97-101. [QxMD MEDLINE Link].
Ojha J, Akers JL, Akers JO, Hassanein AM, Islam NM, Cohen DM, et al. Intraoral cellular blue nevus: report of a unique histopathologic entity and review of the literature. Cutis. 2007 Sep. 80(3):189-92. [QxMD MEDLINE Link].
Allen CM, Pellegrini A. Probable congenital melanocytic nevus of the oral mucosa: case report. Pediatr Dermatol. 1995 Jun. 12(2):145-8. [QxMD MEDLINE Link].
Gilbert ML, Hanna W, Ghazarian D, Dover D, Klieb HB. Congenital melanocytic nevus of the oral mucosa: report of a rare pigmented lesion and review of the literature. Clin Pract. 2011 Mar 29. 1(1):e17. [QxMD MEDLINE Link]. [Full Text].
Ficarra G, Hansen LS, Engebretsen S, Levin LS. Combined nevi of the oral mucosa. Oral Surg Oral Med Oral Pathol. 1987 Feb. 63(2):196-201. [QxMD MEDLINE Link].
Barker GR, Sloan P. An intraoral combined blue naevus. Br J Oral Maxillofac Surg. 1988 Apr. 26(2):165-8. [QxMD MEDLINE Link].
Damm DD, White DK, Lyu PE, Puno P. Balloon cell nevus of the oral mucosa. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Jun. 105(6):755-7. [QxMD MEDLINE Link].
Ide F, Obara K, Enatsu K, Mishima K, Saito I. Balloon cell nevus of the soft palate: an immunohistochemical and ultrastructural study. Pathol Int. 2004 Nov. 54(11):872-6. [QxMD MEDLINE Link].
Gulati A, Singhal D, Lal D, Agarwal AK. Balloon cell nevus of the pharynx. Head Neck. 2004 Oct. 26(10):910-4. [QxMD MEDLINE Link].
Pinto A, Raghavendra S, Lee R, Derossi S, Alawi F. Epithelioid blue nevus of the oral mucosa: a rare histologic variant. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003 Oct. 96(4):429-36. [QxMD MEDLINE Link].
Hanna A, Rawal SY, Anderson KM, Rawal YB. The epithelioid blue nevus: A rare intraoral nevomelanocytic tumor. J Oral Maxillofac Pathol. 2011 Jan. 15(1):88-90. [QxMD MEDLINE Link]. [Full Text].
Fistarol SK, Itin PH. Plaque-type blue nevus of the oral cavity. Dermatology. 2005. 211(3):224-33. [QxMD MEDLINE Link].
Ajagbe O. Halo nevus: an unusual upper lip presentation in a black patient and a review of the subject. NDA J. 1994 Jan-Feb. 45(1):19-23. [QxMD MEDLINE Link].
Ide F, Mishima K, Yamada H, Saito I, Tanaka A, Kusama K. Neurotized nevi of the oral mucosa: an immunohistochemical and ultrastructural analysis of nevic corpuscles. J Oral Pathol Med. 2007 Sep. 36(8):505-10. [QxMD MEDLINE Link].
Cerrato F, Wallins JS, Webb ML, McCarty ER, Schmidt BA, Labow BI. Outcomes in pediatric atypical spitz tumors treated without sentinel lymph node biopsy. Pediatr Dermatol. 2012 Jul-Aug. 29 (4):448-53. [QxMD MEDLINE Link].
Tavares AT, Pereira A, Pimentel J, et al. Blue Nevus of the Hard Palate: The Importance of a Careful Examination in an Emergency Setting. Case Rep Dermatol Med. 2022. 2022:6329334. [QxMD MEDLINE Link]. [Full Text].
Albuquerque DM, Cunha JL, Roza AL, et al. Oral pigmented lesions: a retrospective analysis from Brazil. Med Oral Patol Oral Cir Bucal. 2021 May 1. 26 (3):e284-e291. [QxMD MEDLINE Link]. [Full Text].
Meleti M, Mooi WJ, Casparie MK, van der Waal I. Melanocytic nevi of the oral mucosa - no evidence of increased risk for oral malignant melanoma: an analysis of 119 cases. Oral Oncol. 2007 Nov. 43(10):976-81. [QxMD MEDLINE Link].
Dyer PV, Eveson JW. Recurrent compound naevus of gingiva. J Periodontol. 1993 Aug. 64(8):739-41. [QxMD MEDLINE Link].
Torres Fernández G. Pigmented lesion of the oral cavity with eight years follow-up. P R Health Sci J. 2000 Jun. 19(2):165-8. [QxMD MEDLINE Link].
Buchner A, Hansen LS. Pigmented nevi of the oral mucosa: a clinicopathologic study of 36 new cases and review of 155 cases from the literature. Part II: Analysis of 191 cases. Oral Surg Oral Med Oral Pathol. 1987 Jun. 63(6):676-82. [QxMD MEDLINE Link].
Lambertini M, Patrizi A, Fanti PA, Melotti B, Caliceti U, Magnoni C, et al. Oral melanoma and other pigmentations: when to biopsy?. J Eur Acad Dermatol Venereol. 2017 Sep 1. [QxMD MEDLINE Link].
Porrini R, Valente G, Colombo E, Cannas M, Sabbatini M. Non pigmented melanocytic nevus of the oral cavity: a case report with emphasis on the surgical excision procedures. Minerva Stomatol. 2013 Jan-Feb. 62(1-2):43-9. [QxMD MEDLINE Link].
Cohen Y, Goldenberg-Cohen N, Akrish S, Shani T, Amariglio N, Dratviman-Storobinsky O, et al. BRAF and GNAQ mutations in melanocytic tumors of the oral cavity. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Dec. 114(6):778-84. [QxMD MEDLINE Link].
Dika E, Starace M, Lambertini M, et al. Oral and nail pigmentations: a useful parallelism for the clinician. J Dtsch Dermatol Ges. 2020 Jan. 18 (1):7-14. [QxMD MEDLINE Link].
King OH Jr, Blankenship JP, King WA, Coleman SA. The frequency of pigmented nevi in the oral cavity. Report of five cases. Oral Surg Oral Med Oral Pathol. 1967 Jan. 23(1):82-90. [QxMD MEDLINE Link].
Buchner A, Hansen LS. 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. Oral Surg Oral Med Oral Pathol. 1987 May. 63(5):566-72. [QxMD MEDLINE Link].
Silva L, Martins da Cruz T M, Aparecido Gonçalves MW, et al. Oral Blue Nevus two case reports and literature review. Revista Estomatologia. 2022 Jan 17. 29 (2):
Amérigo-Góngora M, Machuca-Portillo G, Torres-Lagares D, Lesclous P, Amérigo-Navarro J, González-Cámpora R. Clinicopathological and immunohistochemical analysis of oral melanocytic nevi and review of the literature. J Stomatol Oral Maxillofac Surg. 2017 Jun. 118 (3):151-155. [QxMD MEDLINE Link].
Dhanuthai K, Theungtin N, Theungtin N, et al. Pigmented Oral Lesions: A Multicenter Study. Eur J Dent. 2022 May. 16 (2):315-319. [QxMD MEDLINE Link]. [Full Text].
Tziveleka S, Georgaki M, Pettas E, et al. Acquired Compound Melanocytic Nevus on the Palate of a Child: Report of a Case. J Oral Maxillofac Res. 2022 Jan-Mar. 13 (1):e5. [QxMD MEDLINE Link]. [Full Text].
Hicks MJ, Flaitz CM. Oral mucosal melanoma: epidemiology and pathobiology. Oral Oncol. 2000 Mar. 36(2):152-69. [QxMD MEDLINE Link].
Harada H, Morimatsu M, Kusukawa J, Kameyama T. A hamartoma-like mass on the palate? A possible discussion regarding the components of a pigmented naevus and hyperplastic salivary gland. J Laryngol Otol. 1997 Mar. 111(3):296-9. [QxMD MEDLINE Link].
Wijs RW, Meleti M, Bloemena E, van der Waal I. [A non-pigmented naevus as an uncommon gingival swelling]. Ned Tijdschr Tandheelkd. 2012 Jun. 119(6):283-4. [QxMD MEDLINE Link].
Biesbrock AR, Aguirre A. Multiple focal pigmented lesions in the maxillary tuberosity and hard palate: a unique display of intraoral junctional nevi. J Periodontol. 1992 Aug. 63(8):718-21. [QxMD MEDLINE Link].
Lai WS, Hsu CH, Lee JC, Chu YH. Extensive blue nevus of the pharynx. Indian J Dermatol Venereol Leprol. 2012 May-Jun. 78(3):376-7. [QxMD MEDLINE Link].
Kauzman A, Rei N, Avon SL. The blue nevus: a rare lesion of the oral cavity. Gen Dent. 2014 Sep-Oct. 62(5):e22-6. [QxMD MEDLINE Link].
Kauzman A, Pavone M, Blanas N, Bradley G. Pigmented lesions of the oral cavity: review, differential diagnosis, and case presentations. J Can Dent Assoc. 2004 Nov. 70(10):682-3. [QxMD MEDLINE Link].
Müller S. Melanin-associated pigmented lesions of the oral mucosa: presentation, differential diagnosis, and treatment. Dermatol Ther. 2010 May-Jun. 23(3):220-9. [QxMD MEDLINE Link].
Hansen LS, Buchner A. Changing concepts of the junctional nevus and melanoma: review of the literature and report of case. J Oral Surg. 1981 Dec. 39(12):961-5. [QxMD MEDLINE Link].
Suzuki T, Kumamoto H, Nagasaka H, Kawamura H, Ooya K. Intramucosal naevus with pseudoepitheliomatous hyperplasia in the gingiva: a case report. Int J Oral Maxillofac Surg. 2002 Jun. 31(3):330-3. [QxMD MEDLINE Link].
Fujita S, Takahashi H, Tsuda N, Okabe H. Immunohistochemical localization of S-100 protein and its subunits in melanotic lesions in the oral mucosa and skin. J Oral Pathol Med. 1991 Oct. 20(9):429-32. [QxMD MEDLINE Link].
Gazit D, Daniels TE. Oral melanocytic lesions: differences in expression of HMB-45 and S-100 antigens in round and spindle cells of malignant and benign lesions. J Oral Pathol Med. 1994 Feb. 23(2):60-4. [QxMD MEDLINE Link].
de Andrade BA, León JE, Carlos R, Delgado-Azañero W, Mosqueda-Taylor A, de Almeida OP. Expression of minichromosome maintenance 2, Ki-67, and geminin in oral nevi and melanoma. Ann Diagn Pathol. 2013 Feb. 17(1):32-6. [QxMD MEDLINE Link].
Benevenuto-de-Andrade BA, León JE, Carlos R, Delgado-Azañero W, Mosqueda-Taylor A, Paes-de-Almeida O. Immunohistochemical expression of Skp2 protein in oral nevi and melanoma. Med Oral Patol Oral Cir Bucal. 2013 May 1. 18(3):e388-91. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

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.

of 3

Author

Kara Melissa Torres Culala, MD Training Officer, Dermatology Department, Tondo Medical Center; Faculty, Dermatology Department, Jose R Reyes Memorial Medical Center, Philippines

Kara Melissa Torres Culala, MD is a member of the following medical societies: Philippine Dermatological Society

Disclosure: Nothing to disclose.

Coauthor(s)

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Drore Eisen, MD, DDS Consulting Staff, Dermatology of Southwest Ohio

Drore Eisen, MD, DDS is a member of the following medical societies: American Academy of Dermatology, American Academy of Oral Medicine, American Dental Association

Disclosure: Nothing to disclose.

Chief Editor

Acknowledgements

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

Indraneel Bhattacharyya, DDS, MSD is a member of the following medical societies: American Academy of Oral and Maxillofacial Pathology, American Association for Dental Research, American Dental Association, International Association for Dental Research, and International Association of Oral Pathologists

Disclosure: Nothing to disclose.

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

Donald Cohen, DMD, MS is a member of the following medical societies: American Academy of Oral and Maxillofacial Pathology

Disclosure: Nothing to disclose.

Oral Nevi Workup

Histologic Findings

References

Tables

Contributor Information and Disclosures

What would you like to print?