Skin-Melanocytic Tumors - Dysplastic nevus

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Skin-Melanocytic Tumors

Dysplastic nevus

Last major update: November 2008 - next update November 2009

Revised: 18 September 2009

Author: Nat Pernick, M.D., PathologyOutlines.com, Inc.

Definition

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● Controversial topic, particularly for solitary lesions; better defined in dysplastic nevus syndrome (multiple dysplastic nevi and two family members with melanoma)

● Rosai believes a solitary nevus with dysplastic features should be treated as clinically benign

Terminology

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● Also called atypical nevus, nevus with architectural disorder, Clark’s nevus

● Overlaps with active nevus, nevus with architectural disorder and cytologic atypia

Epidemiology

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● Develop in teenager years and into adulthood

● Atypical nevi of scalp of adolescents resemble those in genitalia, with apparent benign behavior (J Cutan Pathol 2007;34:365)

● May be intermediate step in pathway between benign nevus and melanoma (J Clin Pathol 2005;58:453)

● Relative risk of 46x for melanoma in one study of Dutch patients with 5+ atypical nevi (J Am Acad Dermatol 2007;56:748)

● Higher risk for melanoma with more severe atypia (Mod Path 2003;16:764)

● May occasionally be associated with neurofibroma (J Cutan Pathol 2007;34:837)

Case reports

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● Agminated dysplastic nevi (Arch Dermatol. 2001;137:917)

● Melanoma arising in dysplastic nevus with intradermal sebocyte-like melanocytes (Am J Dermatopathol 2007;29:566)

● Multiple eruptive dysplastic nevi and in situ melanomas appearing shortly after completion of chemotherapy (Pediatr Dermatol 2007;24:135)

● Pointillist dysplastic nevus (Arch Dermatol. 2005;141:763) [pointillist: technique developed by neo-impressionist painters, based on the principle that juxtaposed dots of pure color, as blue and yellow, are optically mixed into the resulting hue, as green, by the viewer]

Treatment and prognosis

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● The initial diagnostic biopsy should sample the entire lesion (Australas J Dermatol 2005;46:70)

● Mildly atypical nevi are considered benign and no additional treatment is necessary

● Severely atypical nevi are excised with negative margins

● No consensus on moderate atypia, depending of the feasibility of re-excision - most physicians re-excise

Clinical description

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● Atypical due to size > 5 mm, irregular borders, variegated appearance

Clinical images

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Agminated atypical nevi on arm #1

Various images

Dermoscopy

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● Pigment patterning often disrupted with brown dots, frequently erratically placed

● Nevi often irregular in shape, asymmetric, with variable coloration and borders that vary from sharply to poorly defined

Dermoscopy

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Various images (Fig A, B) Pointilist nevus

Agminated nevi showing a “diffuse and patchy” network pattern

Micro description

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● Compound nevi with marked lentiginous proliferation of melanocytes at dermoepidermal junction extending at least 3 rete ridges beyond lateral margins of dermal component

● Nests have cytologic and architectural atypia, including irregular sizes and shapes and bridging of adjacent rete ridges, which are themselves irregular

● Papillary dermal lamellar fibroplasia with perivascular infiltrate and vascular dilation

● Usually mild/moderate cytologic atypia (nuclear hyperchromasia, prominent nucleoli, dusty melanin pigment)

● Melanocytes are spindled and parallel to surface or epithelioid

● Epidermolytic hyperkeratosis present but not specific (Am J Dermatopathol 2002;24:23)

Mild atypia:

● At high power, nuclei of melanocytes are condensed, oval/ellipsoid, hyperchromatic, indented, no/small nucleoli

● Perinuclear halo common; no/minimal pagetoid upward migration of melanocytes

● No mitotic figures in dermal component

Moderate atypia:

● At high power, nevus nuclei are variable in size and chromatin, although some have “mild atypia” plus small nucleoli

● Enlarged cytoplasm compared to melanocyte, no halo

● Few but normal mitotic figures in upper dermal part of nevus

Severe atypia:

● Usually asymmetrical but still well circumscribed in epidermis

● Usually nests of nevus cells, not individual cells

● Some central upward migration of individual nevus cells

● Crowded nests in dermis

● Enlarged nuclei, often bizarre hyperchromatic nuclei mixed with small nuclei, prominent nucleoli

● No confluent atypia as seen with melanoma; frequent mitoses in junctional component but not in deep dermal component

● Note: grading is not consistent between pathologists (Br J Dermatol 2006;155:988)

Children:

● May want to downgrade atypia since ordinary childhood nevi have large nests and large nevus cell size, as well as focal atypia

Pagetoid upward migration at periphery:

● May suggest upgrading to melanoma in situ

Mitotic figures at base of dermal component:

● Suggests invasive melanoma

Micro images

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Mild atypia Moderate atypia Severe atypia

Pointillist dysplastic nevus Lentiginous melanocytic proliferation with

with cytologic atypia papillary dermal fibrosis

Various images S100A6 staining (negative)

Dysplastic nevus

Contributed by Angel Fernandez-Flores, MD, PhD, Hospital El Bierzo and Clinica Ponferrada, Spain

Positive stains

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● Ki-67 index intermediate between benign nevi and melanoma (Appl Immunohistochem Mol Morphol 2007;15:160)

Molecular / cytogenetics

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● Usually diploid

● Often mutations in CDKN2A (Cancer 2002;94:3192)

● 24% have high risk mucosal HPV by PCR (Br J Dermatol 2005;152:909)

Videos

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● Atypical nevi introduction, Epidemiology, Incidence, Clinical appearance, Histology

Electron microscopy

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● Cases with severe dysplasia share several features with radial growth phase melanomas, including large cell size, bizarre shaped and pleomorphic nuclei, well developed Golgi, abundant and deranged mitochondria, aberrant melanosomes with deranged structures and irregular melanization

Differential Diagnoses

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● In situ melanoma arising in a compound nevus - atypia limited to epidermis, consumption of epidermis present (Am J Dermatopathol 2007;29:527), be cautious if partial excision (J Cutan Pathol 2005;32:405)

● Common nevus with some dysplastic features (Am J Dermatopathol 2000;22:391)

Additional references

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● eMedicine

End of Skin-Melanocytic Tumors > Dysplastic nevus

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