Continuing medical education
Spitz nevi and other Spitzoid lesions: Part I. Background and diagnoses

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Spitz nevi are melanocytic proliferations that are characterized by spindled and/or epithelioid nevomelanocytes. First interpreted as juvenile melanoma, these lesions were later characterized as benign and were observed to affect all age groups. Today, contrasting opinions persist regarding the fundamental benignancy versus malignancy within the spectrum of Spitz tumors. Beyond clinical outcome, this controversy has also been fueled by complex and sometimes convoluted classification schemes based on pathologic characteristics. More recently, immunophenotypic and molecular analyses have begun to clarify the etiologic nature of these tumors. Recent evidence suggests that histopathologic features that suggest more aggressiveness in Spitz tumors relate to mitoses and inflammation.

Section snippets

Brief history

Key points

  1. The landmark publication on Spitz nevi occurred when Sophie Spitz described pediatric lesions that had features of melanoma

  2. Recent opinion has been trending toward emphasizing the benign nature of Spitz nevi

  3. Refinement of clinical and histologic subtypes within the Spitz family of lesions has led to a highly complex classification of Spitz tumors

Although cases of perplexing melanocytic lesions have been reported in children as early as a century ago,1, 2 the landmark publication for Spitz lesions

Clinical features

Key points

  1. Younger age is associated with more likely benign behaving Spitz nevus

Table I offers a comparison of various clinical features suggestive of typical Spitz nevi versus ASTs. Greater attributes from the latter group calls for closer scrutiny to rule out melanoma.

Histopathology

Key points

  1. Classic Spitz nevi feature neat organizational attributes, such as symmetry, maturation, distinct margins, small size, and more often show epidermal hyperplasia, Kamino bodies, and junctional clefting

  2. Ulceration, significant Breslow thickness, an increased number of mitotic figures, and deep and atypical mitotic figures may be associated with metastatic behavior

  3. Most histopathologic criteria remain poorly predictive in cases that overlap between atypical Spitz tumors and melanoma

The available

Additional tests

Key points

  1. In common Spitz nevus compared to melanoma, Ki-67 is stained in fewer cells, HMB-45 exhibits differential staining at certain lesion depths, and S100-A6 is stained strongly and diffusely

  2. Cytogenetic techniques reveal amplifications in chromosome 11p in a minority of Spitz nevi

  3. Most Spitz nevi exhibit a distinct mutation profile from common nevi and melanoma, featuring more HRAS rather than BRAF or NRAS mutations

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    Supported by a grant from the American Medical Association (Dr Luo), the National Institutes of Health (K24 CA149202-01 to Dr Tsao), the American Cancer Society (RSG MGO-112970 to Dr Tsao) and generous donors to the MGH Millennium Melanoma Fund.

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