Case report: Treatment response of NF-1-associated bladder ganglioneuroma to trametinib

Abstract

We present the clinical course of a 4-year-old girl with neurofibromatosis type 1-associated, unresectable, symptomatic urinary bladder ganglioneuroma. She was initially trialed on sirolimus without response and subsequently responded to MEK inhibitor trametinib, with improvement clinically and radiographically over 10 months. This report broadens the repertoire of therapeutic strategies for MEK inhibition in diseases related to the MAPK pathway.

Keywords: MAPK pathway; MEK inhibitor; ganglioneuroma; neurofibromatosis type 1 (NF-1); targeted therapy.

Figure 1

Clinical photo of the index patient demonstrating multiple café-au-lait macules over the trunk and a congenital melanocytic nevus at the lower trunk.

Figure 2

Histopathology of the core biopsy. (A) Intermediate power of a representative segment of the biopsy in routine stain showing loose clusters of maturing neuroblastic cells (central area) in a background of spindle Schwannian cells and some inflammatory cells, including eosinophils. (B) High power of the maturing neuroblastic cells, including ganglion cells with abundant eosinophilic and peripheral basophilic cytoplasm, round nuclei, and often with prominent nucleoli. (C) Immunostain PHOX2B, which is a neuroblastic marker, staining the nuclei of the neuroblastic cells brown. Original magnifications: (A) ×100 and (B, C) ×400. The bar below the photo indicates 100 µm.

Figure 3

Comparison of sagittal postcontrast T1-weighted images before treatment (A) with follow-up MRI (B) showed reduced thickness of the solid component of ganglioneuroma from 18.8 mm to 11.9 mm. There is also an interval reduction in the degree of enhancement of solid components. Contrasting coronal T2-weighted short-tau inversion recovery (STIR) before treatment (C) with follow-up MRI (D) showed a reduction in thickness of the solid component of ganglioneuroma from 42.6 mm to 31.0 mm. Multiple subcutaneous neurofibromata along the left lateral thigh (white arrow) also showed an interval reduction in size and extent in the follow-up MRI.