P06 Adenosine deaminase deficient-severe combined immunodeficiency and multicentric dermatofibrosarcoma protuberans: an emerging association.

Abstract

Adenosine deaminase deficient-severe combined immunodeficiency (ADA-SCID) is an inborn error of immunity characterised by pan-lymphopenia, failure to thrive, severe infections, autoimmunity, and non-immunological organ dysfunction secondary to accumulated cytotoxic adenine metabolites (Kohn et al. 2019). ADA-SCID has been associated with an increased risk of tumour growth, including dermatofibrosarcoma protuberans (DFSP), a locally aggressive fibroblastic neoplasm associated with PDGFB or PDGFD fusions (Gardner et al. 2024). Here, we present a 6-year-old boy with ADA-SCID (treated with family-matched haematopoietic cell transplant (HCT) at age 5 months) with a six-month history of atrophic, roughened, hyperpigmented plaques over his abdomen, back, neck and right medial thigh. Post-transplant, he maintained high donor chimerism (94% donor myeloid and B-lymphocyte; 91% donor T-lymphocyte). Five excision biopsies were performed: all showed a spindle cell lesion in the dermis, with subcutaneous extension in four specimens. Immunohistochemistry revealed diffuse CD34 positivity of the spindle cells, consistent with multicentric DFSP. The tumours demonstrated reduced cellularity and more eosinophilic cytoplasm compared with typical DFSP, findings characteristic of DFSP arising in the context of ADA-SCID. This case highlights the increased incidence and distinct histological features of DFSP in ADA-SCID. Further reporting of cases of DFSP occurring in ADA-SCID is needed to raise clinical awareness and to better define any temporal relationship to enzyme-replacement therapy, HCT or gene therapy. Careful dermatological surveillance is warranted in this patient population. Any new or abnormal skin lesions should prompt early referral, histopathological assessment, and tailored surgical management, preferably with Mohs' micrographic surgery or wide local excision.