Spitzoid melanoma in children: clinicopathological study and application of immunohistochemistry as an adjunct diagnostic tool

Abstract

Introduction: The term spitzoid melanoma (SM) is reserved for a rare group of tumors with striking resemblance to Spitz nevus, often developing in children diagnosed in retrospect after the development of metastases. Objectives: To determine the biological significance of SM and to analyze the effectiveness of adjuvant diagnostic techniques. Materials and methods: A retrospective, observational study of 38 cases of SM in patients younger than 18 years. Histological type, Clark level and Breslow thickness, radial and vertical growth phase, mitotic count/mm2, ulceration, regression, vascular and perineural invasion, satellitosis, cytology and associated nevi were reviewed. An immunohistochemical analysis with HMB45 and Ki67 was performed in 10 cases. These features were correlated to patient’s stage and outcome. Results: Analysis of histological and immunohistochemical features should allow accurate diagnosis in most cases. Given the low mortality rate, no conclusions about the prognostic significance of histological parameters of the primary tumor could be established. Conclusion: We report the largest series of SM from a unique center. Although these patients may have a better prognosis than adults, some patients with SM develop metastasis and die, particularly after age 11 years. Therefore, we recommend using the same treatments as in adults.

Prognostic factors for melanoma in children and adolescents

“…These lesions were reported previously. 4 The original diagnosis was confirmed in 47 nevus and in 21 other nonmelanoma malignancies. The remaining 137 patients constituted the cohort for this study.…”

“…Two smaller subsets from this group of patients recently were reported. 4,5 Histologic prognostic parameters were reviewed in hematoxylin and eosin (H&E)-stained sections.…”

The immunohistochemical profile of Spitz nevi and conventional (non-Spitzoid) melanomas: a baseline study

“…Thus, as earlier observed, Ki-67, a cell-cycle-associated nuclear antigen, nuclear survivin, a mitotic regulator by preserving microtubule stability, 38 and topoisomerase IIa, exclusively expressed in the proliferating compartments of normal tissues and tumors, 39 are significantly increased in melanoma vs nevus. 8,[40][41][42][43] Although melanomas show higher proliferation rates (37 vs 0% in Spitz nevi) when assessed with Ki-67, few cases of Spitz nevi show scattered positive cells at the top of the lesion, whereas melanoma has nuclear labeling throughout the lesion. 41,42 The structural membrane-scaffolding protein caveolin, with additional function in the transduction of signals from the plasma membrane, showed a loss of expression in vertical growth phase melanomas when compared with nevi.…”

“…8,[40][41][42][43] Although melanomas show higher proliferation rates (37 vs 0% in Spitz nevi) when assessed with Ki-67, few cases of Spitz nevi show scattered positive cells at the top of the lesion, whereas melanoma has nuclear labeling throughout the lesion. 41,42 The structural membrane-scaffolding protein caveolin, with additional function in the transduction of signals from the plasma membrane, showed a loss of expression in vertical growth phase melanomas when compared with nevi. These results are consistent with earlier reports 9 and support the reduction of its expression and caveolae formation in oncogenically transformed cells.…”

Difficulties in the diagnosis of spitzoid melanocytic lesions

“…More adverse diagnostic features include necrosis, angiolymphatic spread and perineural invasion. Although spitzoid melanoma in children may have a better prognosis than in adults, some young patients still develop metastases and die from the disease [18].…”