Pediatric melanoma and aggressive Spitz tumors: a retrospective diagnostic, exposure and outcome analysis

Abstract

Background: The diagnosis and management of pediatric melanomas is challenging given the presence of both melanomas and histologically aggressive Spitz tumors of undetermined biological significance (S-UBS) in this age group. Study objectives were to examine: factors leading to diagnostic delays, therapy side effects and patient outcomes in these diagnostic groups.

Methods: A retrospective case review was performed using The University of Michigan's pediatric oncology database over a 13-year timespan. Patients referred to our clinic for consideration of interferon therapy due to a diagnosis of a stage III melanoma or aggressive appearing S-UBS with significant lymph node involvement were included.

Results: We found two major causes of diagnosis delay: patients with amelanotic lesions misdiagnosed as having a wart and cases reviewed by non-expert pathologists upfront. The side effects from interferon therapy requiring dose adjustments included neutropenia, thrombocytopenia and mood disturbances. There was wide variability in surveillance scan utilization, therefore leading to variability in patient radiation exposure. Unlike melanoma patients, none of the S-UBS patients experienced disease progression or death.

Conclusions: This study highlights the challenges with the initial clinical diagnosis and pathological sub-categorization of the pediatric S-UBS/melanoma spectrum of skin lesions and emphasizes the role of expert pathology review upfront. Further, education at the primary care level could improve accurate and timely diagnoses. Earlier diagnosis could spare patients from more extensive interventions, metastatic spread or adverse outcomes in this patient population. This study is limited due to its retrospective, single-institution perspective.

Keywords: Melanoma; Spitz tumor; interferon.

Figure 1

Patient population data from the 30 pediatric patients included in this study from 2000–2013.

Figure 2

Box plot of time to final diagnosis (in months) when comparing lesions lacking dark pigment and initially diagnosed as a wart versus not. *, P=0.00011.

Figure 3

Number of patients experiencing Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 and 4 toxicities while receiving interferon therapy.

Figure 4

Variable comparison between patients with a confirmed diagnosis of melanoma versus atypical Spitz tumor of uncertain biological potential (A). Plot of progression-free (B, P=0.0136) and overall survival (C, P=0.0355) for the melanoma and aggressive Spitz tumors of undetermined biological significance (S-UBS) patients in this study.