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Diagnosis and Discussion: Case 1137

Final Diagnosis

RET fusion positive Compound Spitz nevus with mild atypia.

Discussion

Spitz neoplasms are melanocytic lesions with spindled or epithelioid melanocytes. The classification of spitz lesions is on a spectrum, ranging from benign spitz nevi to malignant spitzoid melanoma. Spitz nevi represent less than 1% of all childhood melanocytic lesions and mostly appear within the first two decades of life (1). Clinically, spitz nevi are symmetric with well demarcated borders and smooth topography. Additionally, they appear red to pink due to limited melanin content and increased vascularity, though approximately 10% have been found to be pigmented. They are typically less than 6 mm in diameter and are generally seen in the head and neck regions (~37%) and lower extremities (~28%) (2). Histologically, these lesions are a proliferation of maturing spindled and/or epithelioid melanocytes. They can be seen in junctional, compound or dermal forms and are symmetric with sharply demarcated borders. Additional features seen are epidermal hyperplasia, Kamino bodies (eosinophilic globules at the dermal-epidermal junction), and junctional clefting (2).

RET fusion has been identified in 3-4% of Spitz tumors. Ret proto-oncogene, located on the q arm of chromosome 10, encodes for a tyrosine kinase protein with has roles in cell proliferation, migration, and differentiation (3). Activation of the RET kinase domain can lead to activation of MAPK, PI3K/AKT, and PLCg1 pathways, regulating growth and differentiation (4). These tumors generally show a plaque-like silhouette and a monotonous epithelioid cytology with expansile and dyscohesive nesting (5). Prognosis of the atypical spitz tumors and spitzoid melanoma with RET fusion typically have a favorable outcome with no reported metastasis or deaths (3).

References

  1. Brown A, Sawyer JD, Neumeister MW. Spitz Nevus: Review and Update. Clin Plast Surg. 2021 Oct;48(4):677-686. doi: 10.1016/j.cps.2021.06.002. Epub 2021 Aug 18. PMID: 34503728.
  2. Luo S, Sepehr A, Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses. J Am Acad Dermatol. 2011 Dec;65(6):1073-84. doi: 10.1016/j.jaad.2011.04.040. PMID: 22082838; PMCID: PMC3217183.
  3. Daruish M, Ambrogio F, Colagrande A, Marzullo A, Alaggio R, Trilli I, Ingravallo G, Cazzato G. Kinase Fusions in Spitz Melanocytic Tumors: The Past, the Present, and the Future. Dermatopathology (Basel). 2024 Feb 14;11(1):112-123. doi: 10.3390/dermatopathology11010010. PMID: 38390852; PMCID: PMC10885070.
  4. Saade R, Al-Rohil RN. Genomic Alterations in Melanocytic Tumors: A Review of Spitz Tumors, Blue Nevi, Deep Penetrating Melanocytomas and Pigmented Epithelioid Melanocytomas. Applied Sciences. 2024; 14(5):1863. https://doi.org/10.3390/app14051863
  5. Kim D, Compres EV, Zhang B, Khan AU, Sunshine JC, Quan VL, Gerami P. A Series of RET Fusion Spitz Neoplasms With Plaque-Like Silhouette and Dyscohesive Nesting of Epithelioid Melanocytes. Am J Dermatopathol. 2021 Apr 1;43(4):243-251. doi: 10.1097/DAD.0000000000001780. PMID: 33742998