A Rare Case of Xeroderma Pigmentosum: Nivolumab Treatment for Three Cutaneous Malignancies with Clinical and Metabolic Imaging Correlation

TL;DR

A 26-year-old man with xeroderma pigmentosum responded well to nivolumab for three skin cancers, with PET/CT imaging showing complete metabolic response.

Contribution

Demonstrates successful immunotherapy and the value of metabolic imaging in a rare genetic disorder with multiple cancers.

Findings

Nivolumab achieved complete metabolic response in metastatic melanoma and parotid gland lesions in an XP patient.

PET/CT imaging revealed unexpected hypermetabolism in a parotid gland lesion, aiding accurate staging.

XP-related DNA repair defects may increase sensitivity to PD-1 blockade, suggesting a novel therapeutic approach.

Abstract

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme ultraviolet (UV) sensitivity, predisposing patients to multiple cutaneous malignancies. We present the case of a 26-year-old male with XP diagnosed with three distinct skin cancers: superficial spreading melanoma (SSM), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Among these, the melanoma had metastasized. A computed tomography (CT) scan revealed a suspicious pulmonary nodule, prompting further metabolic characterization via positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose ([18F]FDG). The scan detected significant hypermetabolism not only in the lung lesion but also in an unsuspected right parotid gland lesion, refining disease staging and guiding treatment decisions. The patient underwent immunotherapy with nivolumab, achieving a complete metabolic response in both metastatic lesions, as confirmed by follow-up PET/CT. This case underscores the critical role of [18F]FDG PET/CT in staging and treatment monitoring for selected patients with XP, a population in which advanced imaging is rarely employed. Moreover, the patient’s remarkable response to immunotherapy suggests a potential link between XP-related DNA repair defects and increased sensitivity to PD-1 blockade. These findings highlight the importance of integrating metabolic imaging into XP management and warrant further investigation into the immunogenicity of XP-associated malignancies.

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