The Challenge of Melanocytic Lesions in Pediatric Patients: Clinical-Pathological Findings and the Diagnostic Value of PRAME

Abstract

Pediatric melanoma is a rare disease especially in children aged younger than 10 years old. Recent estimates report a rise of disease incidence in both adults and children. Diagnostic work-up is challenging in pediatric melanoma, as it displays a wide range of clinical presentations. Immunohistochemical biomarkers have been reported as predictors of malignancy in melanoma, however data specific to pediatric melanoma are poor. Our study aims to contribute to provide evidence of pediatric melanoma clinical features and differential diagnosis in this patient population. We describe our experience with a retrospective case series of pigmented skin lesions including malignant melanoma, atypical spitzoid tumor, and benign nevi in children and adolescents aged less than 16 years. We described the clinical and demographic characteristics of the cohort and evaluated the immunohistochemical expression of the PReferentially expressed Antigen in MElanoma (PRAME) for differential diagnosis of melanoma in children. The series displayed a similar distribution of melanoma between males and females, and the most common site of melanoma onset were the upper and lower limbs. In our cohort, PRAME was negative in most cases. Focal and slight positivity (from 1 to 5% of the neoplastic cells) was observed in four cases (two Spitz nevi and two atypical Spitz tumors). A moderate positivity in 25% of the neoplastic cells was observed in one case of atypical Spitz tumor. Immunohistochemical expression of PRAME might be useful in the differential diagnosis of malignant melanoma.

PRAME immunohistochemistry of spitzoid neoplasms

“…There was only one case considered discordant in which PRAME IHC was 0 but p16 IHC had diffuse weak to moderate p16 staining ( Previous reports revealed the use of PRAME IHC as an effective tool to distinguish benign and atypical melanocytic lesions from malignancy. [11][12][13][14][15][16]22,23,25 The results presented here are consistent with findings from those prior studies. Focusing specifically on spitzoid melanocytic neoplasms, and including much greater numbers of atypical Spitz tumors and spitzoid melanomas than any of the previous studies published to date, the results of the current study found PRAME expression to differentiate histopathologically determined spitzoid melanomas from Spitz nevi and atypical Spitz tumors.…”

“…Raghavan et al, 23 focused on the atypical/intermediate category of melanocytic lesions and observed one of two spitzoid melanomas with diffuse PRAME expression. In contrast, Umano et al 25 been no known or documented concerns raised by the patients in our health system for lesional persistence, recurrence, or progression.…”

“…9 Previous studies have also evaluated PRAME IHC expression in Spitz nevi and neoplasms. 11,12,[22][23][24][25]30 However, few studies have included cases of spitzoid melanomas, and if present, they were only rarely represented. Raghavan et al, 23 focused on the atypical/intermediate category of melanocytic lesions and observed one of two spitzoid melanomas with diffuse PRAME expression.…”

“…20,21 Among prior studies, PRAME expression in spitzoid melanocytic neoplasms, particularly spitzoid melanomas, has been incompletely characterized, with only very few cases analyzed. [22][23][24][25] Herein, we investigate the immunohistochemical expression of PRAME in a broad spectrum of histopathologically determined benign, atypical, and malignant spitzoid melanocytic neoplasms, with particular attention to the potential utility of PRAME IHC for separation of spitzoid melanomas from benign Spitz tumors.…”

Preferentially Expressed Antigen in Melanoma (PRAME) and Human Malignant Melanoma: A Retrospective Study

“…In this scenario, rising attention is being devoted to this marker, and new studies are being conducted in an attempt to increase experiences, report results, and find safer answers [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”