Spitz Nevus Workup

Updated: Sep 14, 2020
  • Author: Zoltan Trizna, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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Imaging Studies

Dermatoscopy: A starburst pattern is observed (ie, pigmented streaks symmetrically distributed at the periphery of the lesion). [14]   A 2015 multicenter study found that Spiz nevi show a multicomponent and nonspecific pattern. [15]


Other Tests

Histopathologic evaluation of a suspected Spitz nevus is indicated.

The value of including individual proliferation index and histopathological parameters (eg, Ki-67, Pi-21, fatty acid synthetase) into models of predictive probabilities is uncertain, but a panel of markers including Ki-67, HMB-45, and S100A6 can be helpful in establishing a histologic diagnosis. Ki-67 staining is usually absent in dermal nuclei of benign Spitz nevi. HMB-45 staining demonstrates a gradient, and S100A6 diffusely stains the lesion.

Analyses of mutations of BRAF, NRAS, and HRAS were promising in distinguishing Spitz nevi from melanomas, but BRAF mutations do not separate all Spitz nevi from spitzoid melanomas and other melanocytic proliferations. [16, 17, 18] TERT promoter mutations are common among spitzoid lesions with an aggressive course, but some similar lesions with more indolent behavior have been described. [19] Mutations in receptor tyrosine kinases ALK, ROS1, NTRK1, and RET have been identified, and oncogenic fusions in TRK family receptor tyrosine kinases, including NTRK3, have been found in Spitz tumors. [20]

Mass spectrometry is another promising technology in the diagnosis of Spitz tumors. [21]



Surgical excision (generally with local anesthesia) and histopathologic evaluation of the margins of the specimen is recommended. With regard to sentinel node biopsy, a series of 12 cases with atypical Spitz nevi showed nodal micrometastases in one third of the patients, suggesting a yet not understood metastatic potential.


Histologic Findings

Most Spitz nevi are predominantly compound, although junctional and intradermal lesions are also observed. The sine qua non of the diagnosis is the presence of large and/or spindle-shaped melanocytes, usually in nests. The nests are composed of an admixture of spindle cells and/or epithelioid cells, although frequently, the spindle-shaped cells predominate (see the images below).

Microphotograph (low power). Microphotograph (low power).
Microphotograph (medium power). Microphotograph (medium power).
Microphotograph (low power). Microphotograph (low power).
Microphotograph (medium power). Microphotograph (medium power).

The spindle cells are usually observed in a fascicular arrangement, and typically have a vertical orientation. These cells have abundant cytoplasm and contain a vesicular nucleus with a conspicuous nucleolus. The epithelioid cells have prominent nucleoli. Tumors composed only of epithelioid cells, those that lack dispersion at the base, those that are grossly asymmetrical, those with deep mitoses, and those in older individuals are more likely to represent malignant melanoma. [22]

Striking symmetry, sharp lateral demarcation, absent (or rare) mitoses, absence of atypical mitoses, presence of eosinophilic and periodic acid-Schiff (PAS)–positive globules (Kamino bodies) and nondisruptive (single-file like) infiltration of collagen are important features indicating the diagnosis of Spitz nevi. Single-file melanocytes may also be observed in the reticular dermis located at the base of the lesion (dispersion).

Another important feature is the maturation of cellular elements toward the dermis. Pagetoid spread of the melanocytes is usually confined to the center of the lesion; when present, it can cause confusion with melanoma.

The epidermis is hyperkeratotic and acanthotic. A cleavage artifact of fixation is commonly noticed above the nests and around superficial dermal elements. Cytological features, such as oval vesicular nuclei with a single prominent nucleolus, help to differentiate Spitz nevi from melanoma. [23]

The histologic distinction between Spitz nevi and melanomas is equivocal in many cases, and pathologists often seek a second opinion. [24]

Immunohistochemistry and comparative genomic hybridization have proved helpful. [25] As specific genes related to pathogenesis and behavior are identified, next-generation sequencing and proteomics will be used increasingly to clarify the diagnosis of atypical Spitz tumors. Proteomics may be particularly important, as gene silencing may be as important as gene loss. Spitz nevi stain diffusely with S100A6, demonstrate no deep Ki-67–positive cells, and show a gradient with HMB-45 staining. Melanomas show the opposite patterns. [26]

A rare variant is the desmoplastic Spitz nevus in which the proliferating large epithelioid and/or fusiform melanocytes are embedded in a desmoplastic stroma with thick eosinophilic collagen bundles. [27] Spitz nevi showing architectural features of Clark nevi (dysplastic nevi) were also described in a small series and have been termed Spark nevi or spastic nevi. The spindle cells were oriented parallel to the epidermis with fused rete and lamellar fibroplasia. [28]

A case of a pseudogranulomatous variant (with inflammatory infiltrate mimicking a granulomatous dermatitis) was described. [29]