P044 Multiple granular cell tumours in Noonan syndrome with multiple lentigines

Abstract

A 6-year-old boy with congenital hypertrophic cardiomyopathy was found to have mutation in the PTPN11 gene, consistent with Noonan syndrome. He had short stature, mild developmental delay and distinctive facial features. On cutaneous examination he had multiple lentigines on the face and neck, and two larger pigmented macules on the lower back. He was also progressively developing multiple skin-coloured nodules on the buttocks, arms and legs, 0.5–3.5 cm diameter. Due to pain and enlargement, biopsy was taken from lesion on the thigh. Histology described within the dermis a population of plump cells infiltrating in between the collagen bundles and surrounding adnexal structures. Cells had granular cytoplasm and small eccentrically placed nuclei. Periodic acid–Schiff (PAS) and PAS–diastase staining showed the cytoplasmic granules as PAS positive, diastase resistant. Lesional cells showed no features of malignancy, including no necrosis, spindled tumour cells, vesicular nuclei with large nucleoli, increased mitoses, high nucleus-to-cytoplasm ratio, or pleomorphism. Immunohistochemistry showed positivity for S-100 and CD68 (Ki67 index approximately 1%). Based on these findings, a diagnosis of benign granular cell tumour was made. These are rare soft-tissue tumours, usually benign, believed to originate from Schwann cells. They can be multiple, and grow rapidly and appear on skin or mucosal surfaces (tongue, gastrointestinal tract). Malignant transformation and metastasis occur in < 2%. Granular cell tumours have been reported in patients with Noonan syndrome because both involve mutations in the RAS–mitogen-activated protein kinase pathway. Treatment options are limited, with surgical excision of symptomatic lesions the only definitive option. Our patient chose excision for the most uncomfortable lesions on the legs. Oral sirolimus may also be considered as a neoadjuvant to surgery because, by blocking the mammalian target of rapamycin pathway, it may decrease lesional size preoperatively.