Eruptive Spitz nevus, a striking example of benign metastasis

Abstract

Metastasis is generally considered a characteristic of malignant tumors. Herein, we describe a patient with more than one hundred discrete Spitz nevi scattered all over her skin. Molecular analysis from three of the lesions identified a ROS1 fusion oncogene with identical genomic breakpoints, indicating that the nevi arose from a single transformed melanocyte and then disseminated throughout the integument. The demonstration of widespread distribution of a benign tumor with limited proliferative capability indicates that metastatic dissemination is not contingent on full malignant transformation. Thus, eruptive Spitz nevus is a striking example of benign metastasis, demonstrating that metastasis can occur before malignant transformation.

An Update on Molecular Genetic Aberrations in Spitz Melanocytic Proliferations: Correlation with Morphological Features and Biological Behavior

“…The last was reported in a 49-year old female, who developed over 100 similar lesions over four years. Further molecular characterization of the proliferation revealed identical TPM3-ROS1 fusions in the three analyzed lesions (48). Only five Spitz melanomas with ROS1 fusion have been described, and none of them resulted in distant metastases or death from the disease (2,47).…”

“…Genetic alterations of the ALK gene include point mutations, gene fusions, ALK locus amplification, alternative transcription, and small deletions (35) and influence cell proliferation and survival via constitutive activation of the RAS-ERK, JAK3-STAT3, and PI3K-AKT-mTOR pathways (36)(37)(38). Fusions involving the ALK gene have been discovered in diverse cutaneous neoplasms, including primary cutaneous anaplastic large cell lymphoma (39), epithelioid fibrous histiocytoma (40), acral melanomas (41,42), and Spitz melanocytic proliferations (2,(43)(44)(45)(46)(47)(48)(49)(50).…”

“…The vast majority of hitherto reported Spitz neoplasms with ROS1 fusion in the literature were classified as either Spitz nevi or atypical Spitz tumors (2,23,32,47,(65)(66)(67). Three lesions were of desmoplastic Spitz nevus phenotype (2, 32), four were pigmented spindle cell nevi or Reed nevi (2,67), and one was an eruptive Spitz nevus (48). The last was reported in a 49-year old female, who developed over 100 similar lesions over four years.…”

Recurrence of mucosal melanoma in Li-Fraumeni syndrome: A follow-up of an index case

“…An additional possible explanation includes a Spitz nevus, which underwent benign metastasis and then transformed into melanoma after radiation therapy. 5 Another possible explanation would be nevi present in the patient's lymph nodes that transformed into melanoma under the influence of radiation.…”

Mechanisms and Clinical Significance of Tumor Lymphatic Invasion

“…There is evidence that, occasionally, LVI may occur not only in malignant tumors, but also in benign lesions such as melanocytic nevus, blue nevus, Spitz nevus, clear cell hidradenoma, uterine leiomyoma, etc. [40][41][42][43][44]. This phenomenon is often referred to as "benign metastasis" (Figure 2B).…”