Background and Aims

X linked hyper IgM (X-HIGM) is caused by CD40LG mutations, resulting in absent CD40L on T cells. Patients typically present with low serum IgG & IgA, but normal or elevated IgM and recurrent infections.

Methods

Although not a common complication, malignancy has been reported, the US Immunodeficiency Network registry reported 4 cases of malignancy in a series of 82 X-HIGM patients.

Results

Here we present a case of X-HIGM with metastatic spindle cell carcinoma. The patient was diagnosed at the age of 1 having presented with infections and a family history of infection-related male infant death. IgM was elevated, but IgA & IgG undetectable. Immunophenotyping subsequently revealed absence of CD154 on activated T cells, and genetics confirmed CD40LG mutation. He was treated with immunoglobulin replacement, Co-trimoxazole prophylaxis and remained reasonably well into adulthood.

At the age of 46 he developed a blistering lesion on his left anterior scalp which gradually increased in size. Histology confirmed a poorly differentiated spindle cell squamous cell carcinoma. Further investigation was declined. Two years later, he presented with worsening dyspnoea and weight loss. CT of his chest revealed large biapical well-defined opacities with significant mass effect and compression of his superior vena cava. Histology confirmed a malignant spindle cell neoplasm, likely representing metastasis of his previous SCC.

Conclusions

This is the first case report of X-HIGM with metastatic spindle cell carcinoma. It is not known why these patients have a higher predisposition to malignancy but a postulated mechanism involves inadequate anti-tumour immunity in the context of absent CD40L.