The Spectrum of Spitz Melanocytic Lesions: From Morphologic Diagnosis to Molecular Classification

Abstract

Spitz tumors represent a distinct subtype of melanocytic lesions with characteristic histopathologic features, some of which are overlapping with melanoma. More common in the pediatric and younger population, they can be clinically suspected by recognizing specific patterns on dermatoscopic examination, and several subtypes have been described. We now classify these lesions into benign Spitz nevi, intermediate lesions identified as "atypical Spitz tumors" (or Spitz melanocytoma) and malignant Spitz melanoma. More recently a large body of work has uncovered the molecular underpinning of Spitz tumors, including mutations in the HRAS gene and several gene fusions involving several protein kinases. Here we present an overarching view of our current knowledge and understanding of Spitz tumors, detailing clinical, histopathological and molecular features characteristic of these lesions.

Keywords: atypical spitz nevus; spitz; spitz nevus; spitzoid lesions; spitzoid melanoma.

Figure 1

Historical Timeline of the Evolution of Our Understanding of Spitz Tumors.

Figure 2

Common Localization of Spitz Tumors on Adults and Children.

Figure 3

Clinical examples of Spitz nevi (histologically confirmed). (A) Intradermal Spitz nevus; (B) Pigmented spindle cell nevus of Reed; (C) Compound Spitz nevus; (D) Dermoscopy of the Spitz nevus in panel (C). (E) ALK translocated Spitz nevus; (F) “Spark” nevus.

Figure 4

Representative histologic micrographs of Spitz nevi. (A) Low power overview of a compound Spitz nevus, which show symmetry and circumscription. The lesion is characterized by spindled and epithelioid cell morphology (2x). Inset: Higher power view of the same Spitz nevus with junctional nest “hanging” from the epidermis and prominent Kamino bodies (arrowhead) (20x). (B) Low power view of pigmented spindle cell nevus of Reed with the characteristic heavy pigmentation (10x). Inset: Higher power view of the same lesion demonstrating spindle cell morphology and heavy pigmentation (20x). (C) Intradermal desmoplastic Spitz nevus, showing effacement of rete ridge and an exclusively intradermal, amelanotic melanocytic proliferation. Inset: High power view showing predominantly epithelioid melanocytes distributed between thick collagen bundles.

Figure 5

Atypical Spitz lesions. (A, B) “SPARK” compound nevus, showing a relatively broad atypical melanocytic proliferation (A), with bridging of rete ridge and mild fibroplasia (B). (C–E) Atypical Spitz tumor (AST), characterized by a relatively symmetrical melanocytic proliferation with little maturation with descent (C), effacement of the epidermis (D) and relatively dense cellularity of both spindled and epithelioid melanocytes (E).

Figure 6

Spitzoid melanoma. There is a broad atypical compound spitzoid melanocytic proliferation with notable asymmetry (A), cells in pagetoid array (B), frequently single celled at the junction, alternating with irregular and confluent nests, with effacement of the epidermis (C), asymmetric pigmentation and clusters of lymphocytes (D). This lesion was classified as spitzoid melanoma and not Spitz melanoma based on the detection of a BRAF V600E mutation on NGS studies.

Figure 7

Translocated Spitz nevi. (A, B) Example of ALK fused Spitz nevus with a polypoid silhouette (A) and plexiform intersecting fascicles of fusiform melanocytes (B). (C, D) Example of ROS fused Spitz nevus with a diffuse proliferation of melanocytes (C) mostly in small nests (D).