Melanocytic Nevus

Intradermal nevus showing benign nevi cells

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Definition

A localized, benign melanocytic proliferation of the skin.

Clinical Features

Usually acquired (clinically apparent after first year of life)
Most appear between second and sixth years
Nearly all manifest by age 20 years
Every Caucasian has variable number (average 20–30)1
Intradermal nevus:
- common adult type of nevus
Multiple lentigines in:
- Peutz–Jeghers syndrome
- centrofacial lentiginosis
- Moynahan's syndrome
- LEOPARD syndrome
- Carney's syndrome
- xeroderma pigmentosum2

Pathogenesis

Predictable evolution:
- rarely upset by dramatic event, such as:
  - spontaneous resolution
  - activation
  - malignant transformation3
- proliferative activity roughly correlates with age4
Straddle fence between malformation and neoplasia:
- cellular blue nevi and Spitz nevi:
  - morphologic and behavioral features consistent with true neoplastic process
- usual compound nevi:
  - distinctive organoid configuration (with adnexal participation) suggesting developmental abnormality5 (may represent atavistic structures)
  - exhibit clonality and loss of heterozygosity (in favor of neoplastic nature)6,7
- ordinary compound mole may have dual origin from:
  - deeper cells with features strongly suggesting differentiation toward specialized peripheral nerve structures (not necessarily schwannian related)8–12
  - supported by ultrastructural, histochemical, immunohistochemical, and experimental studies
Lentigo simplex:
- generally regarded as first phase in evolution of common nevi (‘nevi incipientes')
- therefore a precursor of junctional nevus
Percentage of nevi with junctional changes decreases as patient age increases 13

Gross Pathology

Usually in skin:
- most commonly head, neck, and trunk
Also any mucosal membrane covered by squamous epithelium
Every size, shape, and degree of pigmentation
May be more or less hairy
Junctional nevus:
- flat or slightly elevated
- nonhairy
- fawn colored
Intradermal nevus:
- papillomatous, pedunculated, or flat
- often hairy
Clusters of benign nevus cells can be seen in capsule of lymph node:

Histopathology

Classification

Variously classified
Location of melanocytes:
- best system – definite relationship to likelihood of malignant transformation

Junctional Nevus

Melanocytic proliferation restricted to basal portion of epidermis (‘junctional’ area)
Characterized by melanocytic nests (‘theques') on epidermal side of dermoepidermal junction (Fig. 1
Fig. 1: Typical junctional nevus. Two large theques of melanocytes expand the basal layer of the epidermis.
)

Lentigo Simplex

Consists of proliferation of melanocytes in epidermal basal layer
Differs from junctional nevus because melanocytes are individually arranged rather than in thèques

Intradermal Nevus

All melanocytes are in dermis
Small nests or bundles of melanocytes:
- in upper dermis
- tend to concentrate around pilosebaceous units
Degree of pigmentation and cellularity vary widely
Lower half:
- tends to be less cellular and less pigmented
- composed of spindle cells with fibrillary cytoplasm arranged in bundles16
- sometimes structures resembling tactile (Wagner–Meissner) corpuscles
- immunohistochemically different from neurofibromas,17 but may represent neural component of nevus (hard to dismiss these highly organoid structures as result of atrophy)18
- occasionally, a storiform pattern of growth, establishing link with dermal tumor known as storiform neurofibroma19
Multinucleated melanocytes:
- scattered throughout nevus, particularly upper half
- often characteristic ‘mulberry’ shape
Ultrastructurally and immunohistochemically, cells surrounded by basement membrane components20,21

Compound Nevus

Combines features of junctional and intradermal nevi (i.e. epidermal and dermal components)
Melanin deposition:
- sometimes abundant (hypermelanotic nevus)22
- generally in superficial half, particularly intraepidermal portion
Lymphocytes and other mononuclear cells:
- as with other nevi, may be at base23
- tend to be in clusters (rather than bandlike quality more common in melanoma)

Variations Depending on Site

Palms and soles:
- nearly always junctional24
- tend to remain junctional throughout life
- most intraepidermal melanocytes concentrated in skin furrows25
Scalp:
- often prominent neural component
Vulvar skin (vulvar or genital nevi):
- tend to have larger, more irregularly shaped, and more irregular theques than elsewhere
- tend to be accompanied by lentiginous melanocytic hyperplasia
- can be misdiagnosed as malignant melanomas26

Morphologic Variations in Typical Compound or Intradermal Nevi

Marked sclerosis (desmoplastic or sclerotic nevus)27
Nodular myxoid changes28
Amyloid deposition
Elastosis
Metaplastic bone in the stroma
Folliculitis and abscess formation
Association with keratinous cysts29 and psammoma bodies
Cytoplasmic vacuolization (sometimes resulting in lipoblast-like cells)
Oncocytic changes30
Eczematous or focal acantholytic keratotic changes in overlying epidermis31,32

Diagnosis

Nevus (L. naevus, birthmark):
- can be properly applied to any circumscribed growth of skin of congenital origin
- usually used as synonym for mole (L. moles, a shapeless mass) to designate localized benign abnormality of the melanocytic system

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Melanocytic Nevus

Management

Excision:
- cold knife (not cautery) to prevent tissue distortion and peculiar staining reactions
- specific indications needed
- presence of a junctional component per se not an indication
  - most plantar and palmar nevi are junctional
  - possibility of malignant transformation too remote to warrant routine removal33,34

Definite Indications for Excision

Appearance of a pigmented lesion in an adult
Chronic mechanical irritation of a nevus
Appearance in preexisting nevus of:
- bleeding with trivial trauma 35

Incomplete Removal

May result in local recurrence:36–38
- often shows junctional activity even if not in original 39
- often nuclear enlargement and nucleolar prominence
- can be mistaken for malignant melanoma
- term pseudomelanoma proposed for this phenomenon40 (Fig. 2
  Fig. 2: Recurrent nevus following shave excision. There is an irregular proliferation of melanocytes along the dermoepidermal junction, associated with some dermal fibrosis and clusters of melanin-laden macrophages. This lesion should not be overdiagnosed as malignant melanoma.
  )

Prognosis

Junctional nevus may give rise to malignant melanoma
Intradermal nevus practically never gives rise to malignant melanoma41

References

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2 Mooi WJ, Krausz T. Biopsy pathology of melanocytic disorders. Biopsy Pathology Series 17. London: Chapman & Hall; 1992;.

3 Cochran A, Bailly C, Paul E, Dolbeau D. Nevi, other than dysplastic and spitz nevi. Semin Diagn Pathol. 1993;10:18–35.

4 Lu D, Hoch B, Dehner LP, Lind AC. Proliferative activity in melanocytic nevi from patients grouped by age. Mod Pathol. 2003;16:94a.

Laidlaw GF, Murray MF. Melanoma studies. Theory of pigmented moles. Their relation to evolution of hair follicles. Am J Pathol. 1933;9:827–838.

Addendum: Theory of pigmented moles. Am J Pathol. 1934;10:319–320.

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7 Maitra A, Gazdar AF, Moore TO, Moore AY. Loss of heterozygosity analysis of cutaneous melanoma and benign melanocytic nevi: laser capture microdissection demonstrates clonal genetic changes in acquired nevocellular nevi. Hum Pathol. 2002;33:191–197.

8 Masson P. Les naevi pigmentaires, tumeurs nerveuses. Ann Anat Pathol (Paris). 1926;3:417–453657–696.

9 Masson P. My conception of cellular nevi. Cancer. 1951;4:9–38.

10 Argenyi ZB, Rodgers J, Wick M. Expression of nerve growth factor and epidermal growth factor receptors in neural nevi with nevic corpuscles. Am J Dermatopathol. 1997;18:460–464.

11 Kroumpouzos G, Cohen LM. Intradermal melanocytic nevus with prominent schwannian differentiation. Am J Dermatopathol. 2002;24:39–42.

12 Misago N. The relationship between melanocytes and peripheral nerve sheath cells (part 1): melanocytic nevus (excluding so-called “blue nevus”) with peripheral nerve sheath differentiation. Am J Dermatopathol. 2000;22:217–229.

13 Stegmaier OC, Montgomery H. Histopathologic studies of pigmented nevi in children. J Invest Dermatol. 1953;20:51–64.

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15 Ridolfi RL, Rosen PP, Thaler H. Nevus cell aggregates associated with lymph nodes. Estimated frequency and clinical significance. Cancer. 1977;39:164–171.

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17 Gray MH, Smiller BR, McNutt NS, Hsu A. Neurofibromas and neurotized melanocytic nevi are immunohistochemically distinct neoplasms. Am J Dermatopathol. 1990;12:234–241.

18 Paesschen MAV, Goovaerts G, Buyssens N. A study of the so-called neurotization of nevi. Am J Dermatopathol. 1990;12:242–248.

19 Bednár B. Storiform neurofibroma in the core of naevocellular naevi. J Pathol. 1970;101:199–201.

20 Schaumburg-Lever G, Lever I, Fehrenbacher B, Moller H, Bischof B, Kaiserling E, et al. Melanocytes in nevi and melanomas synthesize basement membrane and basement membrane-like material: an immunohistochemical and electron microscopic study including immunoelectron microscopy. J Cutan Pathol. 2000;27:67–75.

21 Yaar M, Woodley DT, Gilchrest BA. Human nevocellular nevus cells are surrounded by basement membrane components. Immunohistologic studies of human nevus cells and melanocytes in vivo and in vitro. Lab Invest. 1988;58:157–162.

22 Cohen LM, Bennion SC, Johnson TW, Golitz LE. Hypermelanotic nevus: clinical, histopathologic, and ultrastructural features in 316 cases. Am J Dermatopathol. 1997;19:23–30.

23 Benz G, Holzel D, Schmoeckel C. Inflammatory cellular infiltrates in melanocytic nevi. Am J Dermatopathol. 1991;13:538–542.

24 Fallowfield ME, Collina G, Cook MG. Melanocytic lesions of the palm and sole. Histopathology. 1994;24:463–467.

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26 Clark WH, Hood AF, Tucker MA, Jampel RM. Atypical melanocytic nevi of the genital type with a discussion of reciprocal parenchymal-stromal interactions in the biology of neoplasia. Hum Pathol. 1998;29:S1–S24.

27 Harris GR, Shea CR, Horenstein MG, Reed JA, Burchette JL, Prieto VG. Desmoplastic (sclerotic) nevus: an underrecognized entity that resembles dermatofibroma and desmoplastic melanoma. Am J Surg Pathol. 1999;23:786–794.

28 Mehregan DR, Mehregan DA, Mehregan AH. Nodular myxoid change in melanocytic nevi: a report of two cases. Am J Dermatopathol. 1997;18:400–402.

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31 Conlin PA, Rapini RP. Epidermolytic hyperkeratosis associated with melanocytic nevi: a report of 53 cases. Am J Dermatopathol. 2002;24:23–25.

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36 Estrada JA, Pierard-Franchimont C, Pierard GE. Histogenesis of recurrent nevus. Am J Dermatopathol. 1990;12:370–372.

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39 Cox AJ, Walton RG. The induction of junctional changes in pigmented nevi. Arch Pathol. 1965;79:428–434.

40 Kornberg R, Ackerman AB. Pseudomelanoma. Recurrent melanocytic nevus following partial surgical removal. Arch Dermatol. 1975;111:1588–1590.

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Last updated: 20 Mar 2006