Publication Date

4-2024

Download

Download Full Text (372 KB)

Abstract

Background: Phacomatosis pigmentokeratotica (PPK) is a subtype of epidermal nevus syndrome characterized by the co-existence of a sebaceous nevus and a speckled lentiginous nevus and described in approximately 30 cases in literature. PPK is now recognized as a mosaic RASopathy due a postzygotic mutation in the Ras-Raf-MEK-ERK pathway. RAS variants are also known to contribute to tumorigenesis, in some pediatric cancers, including rhabdomyosarcoma. Objective: Describe the presentation and evaluation of a child with pelvic rhabdomyosarcoma and evolving skin lesions found to have a rare mosaic-RASopathy. Design/Method: Case Report Results: The patient is a former 32-week premature female who presented to dermatology clinic at 2 months of age for birthmarks on her back and right shoulder. She was diagnosed with epidermal nevi and congenital melanocytic nevi with the possibility of having an epidermal nevus syndrome. At 4 months of age, she was hospitalized for obstructive renal failure secondary to a pelvic mass. Biopsy of the mass was diagnostic for embryonal rhabdomyosarcoma with gain of chromosomes 2, 3, 5, 8 and 11, and copy-neutral loss of heterozygosity of 11p15.5. Molecular testing revealed HRAS G13R mutation in the tumor, but not in a blood sample. Five months after her cancer diagnosis she underwent tumor resection and skin biopsy. Whole exome sequencing of the skin biopsy showed a variant of uncertain significance in PORCN gene. While receiving chemotherapy and post-treatment, her skin lesions continued to evolve with increased size and number of nevi. A single nucleotide polymorphism-based microarray was performed on blood to assess for any germline copy number variants but was negative. Due to ongoing concerns for PPK, she underwent her second and third skin biopsies. The two lesions biopsied and showed the same HRAS G13R mutation as her tumor, confirming a diagnosis of a mosaic RASopathy almost 2 years after her first dermatology visit. Conclusion: Mosaic RASopathies remain a diagnostic challenge. Tissue involvement can be varied and subtle, DNA sequencing of the blood is often negative, and phenotypes can depart from germline RASopathies, even when caused by the same mutation. With only case reports and small case series describing an association between cutaneous mosaic RASopathies and rhabdomyosarcoma, there is a need for further awareness of this association as it may impact treatment decisions. Also, despite cancer screening guidelines for germline RASopathies being well established, they are not available for mosaic cases, leading providers to question future malignancy risks in this patient population.

Disciplines

Oncology | Pediatrics

Notes

Presented at the 2024 American Society of Pediatric Hematology/Oncology (ASPHO) Conference; April 2-5, 2024; Seattle, WA.

Diagnosis of Mosaic RASopathy in a Child with Rhabdomyosarcoma

Share

COinS