eMedicine Specialties > Dermatology > Benign Neoplasms
Nevi, Melanocytic: Differential Diagnoses & Workup
Updated: Nov 20, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Atypical Mole (Dysplastic Nevus)
Malignant Melanoma
Nevi of Ota and Ito
Other Problems to Be Considered
Nevus spilus
Cockarde nevus
Workup
Laboratory Studies
- No laboratory studies are indicated in the evaluation of common acquired melanocytic nevi.
- As a rule, patients with congenital melanocytic nevi also do not require laboratory evaluation.
Imaging Studies
- Imaging is not warranted in the evaluation of most patients with acquired melanocytic nevi; however, the possibility of neurocutaneous melanosis should be considered in patients (children) with multiple congenital melanocytic nevi involving the skin overlying the spine and the posterior part of the scalp.
- Some patients with multiple congenital nevi overlying the CNS warrant radiologic imaging. Such individuals are at risk for leptomeningeal melanosis.
- Some patients with neurocutaneous melanosis have nests of melanocytes within the CNS at specific sites. These nests of cells can be detected using MRI (especially with T1-weighted images).4
- Although the nests of melanocytes are benign, these cells pose a risk for transformation to CNS melanoma, and follow-up care is indicated.
Procedures
- Simple excisional biopsy is the procedure of choice for removal and diagnosis of a melanocytic nevus. All removed melanocytic nevi should be submitted for microscopic evaluation. Because the interpretation of pigmented lesions may be challenging, many dermatologists prefer to have their specimens read by a qualified dermatopathologist.5
- Either shave biopsy or punch biopsy is typically used for cosmetic removal of banal melanocytic nevi.
- It is optimal to strive for complete excision of a given lesion, if at all possible, when melanoma is considered in the differential diagnosis.
- A complete excisional biopsy permits all available histopathological criteria to be applied to a lesion and thus enables a more precise diagnosis.
- When a partial punch or shave biopsy sample is taken from a lesion, the interpreting pathologist cannot apply important criteria, such as symmetry and circumscription (lateral demarcation), to the assessment of the lesion. If a partial biopsy specimen of a larger lesion is obtained because of clinical necessity, the fact that the specimen is partial should be clearly indicated on the requisition form.
- Partial biopsy samples can sometimes lead to misdiagnosis because of sampling error.
- Partial biopsy samples can inflate the number of procedures required for diagnosis because a partial biopsy sample that does not enable a definitive diagnosis to be made necessarily leads to subsequent reexcision of the lesion in question.
Histologic Findings
The chief histopathological differential diagnosis involves the distinction of melanoma from various forms of melanocytic nevi, including Spitz nevi. Examination via conventional microscopy remains the criterion standard for making this distinction. Genomic analysis via comparative genomic hybridization (CGH) or fluorescence in situ hybridization (FISH) is being used on a limited basis to supplement conventional histopathological interpretation. Genomic analysis permits screening of fixed tumor tissue for cytogenetic aberrations. To date, studies indicate that multiple cytogenetic flaws are typical of melanoma, whereas most melanocytic nevi are cytostructurally normal.
Most melanocytic nevi develop along the dermoepidermal junction, where normal melanocytes are positioned within the lower-most part of the epidermis. Melanocytes are also distributed in smaller numbers within the dermis; therefore, wholly dermal nevi can occur. Melanocytic nevi that are exclusively dermal include the group of lesions referred to as blue nevi.
Melanocytic nevi can be categorized on the basis of the phenotype (cytological appearance) of the melanocytes that make up the lesion. Benign neoplastic melanocytes (sometimes referred to as nevus cells) most commonly have round/ovoid nuclei, scant cytoplasm, and a predilection to form nests and syncytia. However, melanocytes are morphologically nimble cells that can assume a wide variety of appearances, including spindled, epithelioid, and dendritic forms.
Assessing the architecture of any melanocytic neoplasm is imperative as one of the first steps in evaluation. Most melanocytic nevi are relatively small, most are reasonably symmetrical, and most show fairly sharp lateral demarcation or circumscription. Melanomas typically show the converse of these features. Many (but not all) melanocytic nevi are arrayed as nests and fascicles of cells, and the nests and the fascicles of cells are usually relatively uniform in size and shape. In contrast, marked variation in nest size and shape should amplify concern regarding the possibility of melanoma. Lesional melanocytic in a nevus typically appear smaller, microscopically, with descent in the dermis. See the image below. This phenomenon is referred to as maturation.
Histopathologically, a congenital nevus differs from an acquired melanocytic nevus in that melanocytes are often distributed deeply within the reticular dermis, within the adventitial dermis around adnexal elements, and sometimes within the subcutis. This congenital nevus shows a folliculocentric array of melanocytes.
Conventional (ordinary or common acquired) melanocytic nevi develop as a proliferation of single melanocytes along the dermoepidermal junction. As the melanocytes proliferate, small nests of cells develop in the lower-most part of the epidermis, and the resultant lesion is termed a junctional melanocytic nevus. With continued proliferation, nests persevere along the junction, but they can also be found within the superficial dermis, a configuration termed compound melanocytic nevus. As a nevus ages, the junctional component often diminishes or entirely involutes. The resultant nevus is termed an intradermal melanocytic nevus, depicted below.
A conventional compound melanocytic nevus. Note the presence of melanocytes with small nuclei in nests along the dermoepidermal junction and the presence of similar melanocytes in nests and syncytia in the subjacent dermis.
Congenital melanocytic nevi are similar to their acquired counterparts in that junctional, compound, and intradermal patterns can be seen. Most congenital nevi extend well into the dermis, with melanocytes positioned in the interstitial dermis between collagen bundles. The depth of extension into the dermis is variable. Some large congenital nevi exhibit cells that extend into subcutaneous septa. Congenital melanocytic nevi with melanocytes confined to the upper half of the reticular dermis have been termed superficial congenital nevi. Lesions of this type are typically smaller than 2 cm in overall diameter.
Spitz nevi, shown below, are virtually always acquired melanocytic nevi, and they can exhibit a microscopic pattern that is junctional, compound, or wholly intradermal. Like all benign nevi, Spitz nevi tend to be relatively small and symmetrical and laterally demarcated, but Spitz nevi differ from conventional nevi in that nucleomegalic cells are common and predominate in some lesions. Such nucleomegalic Spitz nevus cells may be aneuploid, tetraploid, or octoploid. The explanation as to why Spitz nevi are commonly nondiploid while lacking other attributes of malignancy has not yet been forthcoming. Clearly, anomalies in ploidy alone are not sufficient for full malignant transformation.
This Spitz nevus shows large melanocytes with spindled and epithelioid cytomorphology arrayed along the junctional zone of an acanthotic and hyperkeratotic epithelium.
At higher magnification, this Spitz nevus also demonstrates large, dull-pink globules along the junctional zone. These structures are known as Kamino bodies. Kamino bodies are most commonly observed in association with Spitz nevi but are occasionally observed in melanocytic nevi of other types. Well-formed Kamino bodies are almost never (if ever) found in association with melanoma.
Overlap in the morphology of melanocytic nevi can occur. For example, occasional melanocytic nevi can display overlap between the morphology of Spitz nevus and dysplastic nevus. Overlap between blue and Spitz nevi can also be seen. Such lesions have been humorously referred to as “Sparks” (Spitz + Clarks) or “blitz” (blue + Spitz) nevi.6
When more than one type of cellular morphology occurs in a melanocytic nevus, the lesion is referred to as a combined melanocytic nevus. Conventional melanocytic nevi are commonly combined with Spitz or blue nevi.
Blue nevi, shown below, are typically largely or entirely dermal melanocytic neoplasms composed of spindled and/or dendritic melanocytes with heavy cytoplasmic pigmentation. Some blue nevi are composed of epithelioid melanocytes, especially the deeply extending variant designated deep penetrating nevus, and many exhibit considerable associated sclerosis. The designation blue is far from the truth in many, if not most, instances because melanocytic nevi with spindled and dendritic melanocytes can be tan, brown, black, gray, or even skin-colored; however, despite its inaccuracy, the designation blue nevus remains the universal standard for this category of lesions.
This blue nevus is composed of small dendritic melanocytes. This type of cytomorphology can be seen in so-called common blue nevi and in topographically restricted lesions such as nevus of Ito or nevus of Ota.
Some authorities have promoted the use an eponymic approach to the classification of melanocytic nevi. The merit of this proposal derives from the fact that eponymic naming avoids the semantic misdeeds of the past. For example, the benign entity formerly (and incorrectly) known as juvenile melanoma becomes a Spitz nevus in the eponymic system. Dysplastic nevi are eponymically known as Clark nevi, in memory of Wallace Clark. The designation Miescher nevus can be used to designate dome-shaped, superficial congenital nevi that are commonly expressed on the face and the upper part of the trunk, whereas the designation Unna nevus can be used to refer to acrochordonlike lesions that commonly develop near skin folds.7,8
Despite the enthusiasm for eponymic naming in some areas, the usage of such designations can impede communication with the uninitiated. The author sees no difficulty in the usage of eponyms (and uses eponyms sporadically in his own practice), as long as the exact nature of the lesion in question is clearly stated in the language of the pathology report.
Staging
Melanocytic nevi are benign lesions. No staging is required, with the possible exception of atypical benign lesions for which uncertainty exists regarding the diagnosis and melanoma cannot be entirely eliminated from the differential diagnosis.
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 Differential Diagnoses & Workup: Nevi, Melanocytic |
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References
Kelly JW, Rivers JK, MacLennan R, Harrison S, Lewis AE, Tate BJ. Sunlight: a major factor associated with the development of melanocytic nevi in Australian schoolchildren. J Am Acad Dermatol. Jan 1994;30(1):40-8. [Medline].
Harrison SL, MacLennan R, Buettner PG. Sun exposure and the incidence of melanocytic nevi in young Australian children. Cancer Epidemiol Biomarkers Prev. Sep 2008;17(9):2318-24. [Medline].
Gallagher RP, Rivers JK, Lee TK, Bajdik CD, McLean DI, Coldman AJ. Broad-spectrum sunscreen use and the development of new nevi in white children: A randomized controlled trial. JAMA. Jun 14 2000;283(22):2955-60. [Medline].
Khera S, Sarkar R, Jain RK, Saxena AK. Neurocutaneous melanosis: an atypical presentation. J Dermatol. Jul 2005;32(7):602-5. [Medline].
Tran KT, Wright NA, Cockerell CJ. Biopsy of the pigmented lesion--when and how. J Am Acad Dermatol. Nov 2008;59(5):852-71. [Medline].
Ko CJ, McNiff JM, Glusac EJ. Melanocytic nevi with features of Spitz nevi and Clark's/dysplastic nevi ("Spark's" nevi). J Cutan Pathol. Oct 2009;36(10):1063-8. [Medline].
Ackerman AB, Milde P. Naming acquired melanocytic nevi. Common and dysplastic, normal and atypical, or Unna, Miescher, Spitz, and Clark?. Am J Dermatopathol. Oct 1992;14(5):447-53. [Medline].
Ackerman AB, Magana-Garcia M. Naming acquired melanocytic nevi. Unna's, Miescher's, Spitz's Clark's. Am J Dermatopathol. Apr 1990;12(2):193-209. [Medline].
[Guideline] The Cancer Council Australia, Australian Cancer Network, Sydney and New Zealand Guidelines Group. Congenital melanocytic naevi. Clinical practice guidelines for the management of melanoma in Australia and New Zealand. National Guideline Clearinghouse. 2008.
[Guideline] Finnish Medical Society Duodecim. Skin cancer. In: EBM Guidelines. Evidence-Based Medicine. National Guideline Clearinghouse. May 2005.
[Guideline] Scottish Intercollegiate Guidelines Network. Cutaneous melanoma. National Guideline Clearinghouse. Jul 2003.
Harth Y, Friedman-Birnbaum R, Linn S. Influence of cumulative sun exposure on the prevalence of common acquired nevi. J Am Acad Dermatol. Jul 1992;27(1):21-4. [Medline].
Richtig E, Jung E, Asback K, Trapp M, Hofmann-Wellenhof R. Knowledge and perception of melanocytic nevi and sunburn in young children. Pediatr Dermatol. Sep-Oct 2009;26(5):519-23. [Medline].
Barnhill RL, Argenyi ZB, From L, et al. Atypical Spitz nevi/tumors: lack of consensus for diagnosis, discrimination from melanoma, and prediction of outcome. Hum Pathol. May 1999;30(5):513-20. [Medline].
Casso EM, Grin-Jorgensen CM, Grant-Kels JM. Spitz nevi. J Am Acad Dermatol. Dec 1992;27(6 Pt 1):901-13. [Medline].
Cesinaro AM, Foroni M, Sighinolfi P, Migaldi M, Trentini GP. Spitz nevus is relatively frequent in adults: a clinico-pathologic study of 247 cases related to patient's age. Am J Dermatopathol. Dec 2005;27(6):469-75. [Medline].
DeDavid M, Orlow SJ, Provost N, et al. A study of large congenital melanocytic nevi and associated malignant melanomas: review of cases in the New York University Registry and the world literature. J Am Acad Dermatol. Mar 1997;36(3 Pt 1):409-16. [Medline].
Ferrara G, Argenziano G, Soyer HP, et al. The spectrum of Spitz nevi: a clinicopathologic study of 83 cases. Arch Dermatol. Nov 2005;141(11):1381-7. [Medline].
Florell SR, Meyer LJ, Boucher KM, et al. Nevus distribution in a Utah melanoma kindred with a temperature-sensitive CDKN2A mutation. J Invest Dermatol. Dec 2005;125(6):1310-2. [Medline].
Gallagher RP, McLean DI. The epidemiology of acquired melanocytic nevi. A brief review. Dermatol Clin. Jul 1995;13(3):595-603. [Medline].
Harrison SL, Buettner PG, MacLennan R. Body-site distribution of melanocytic nevi in young Australian children. Arch Dermatol. Jan 1999;135(1):47-52. [Medline].
James MR, Roth RB, Shi MM, et al. BRAF polymorphisms and risk of melanocytic neoplasia. J Invest Dermatol. Dec 2005;125(6):1252-8. [Medline].
Kincannon J, Boutzale C. The physiology of pigmented nevi. Pediatrics. Oct 1999;104(4 Pt 2):1042-5. [Medline].
Lazova R, McNiff JM, Glusac EJ. Under the microscope. Surgeons, pathologists, and melanocytic nevi. Clin Plast Surg. Jul 2000;27(3):323-9, vii. [Medline].
Mooi WJ. Cutaneous melanocytic naevus versus melanoma: pitfalls, surprises, dilemmas. Eur J Surg Oncol. Dec 1999;25(6):622-7. [Medline].
Murali R, McCarthy SW, Scolyer RA. Blue nevi and related lesions: a review highlighting atypical and newly described variants, distinguishing features and diagnostic pitfalls. Adv Anat Pathol. Nov 2009;16(6):365-82. [Medline].
Sagebiel RW. Pigmented lesion pathology: the specimen and its report. A personal and probably biased approach. Pathology (Phila). 1994;2(2):281-98. [Medline].
Shea CR, Prieto VG. Recent developments in the pathology of melanocytic neoplasia. Dermatol Clin. Jul 1999;17(3):615-30, ix. [Medline].
Zaal LH, Mooi WJ, Klip H, van der Horst CM. Risk of malignant transformation of congenital melanocytic nevi: a retrospective nationwide study from The Netherlands. Plast Reconstr Surg. Dec 2005;116(7):1902-9. [Medline].
Further Reading
Keywords
nevi, nevus, melanocytic nevi, nevocellular nevus, melanocytic nevus, Spitz nevus, atypical nevus, mole, dysplastic nevus, nevus spilus, congenital nevus, blue nevus, Spitz nevus, Spitz's nevi, Spitz's nevus, Clark nevus, Unna nevus, Miescher nevus, Clark nevi, Unna nevi, Miescher nevi, Clark's nevus, Unna's nevus, Miescher's nevus, Clark's nevi, Unna's nevi, Miescher's nevi, atypical mole, dysplastic nevi, dysplastic nevus
