Chediak–Higashi syndrome (CHS) is a rare autosomal recessive condition marked by lysosomal dysfunction, partial albinism, neurological impairment, and marked immunodeficiency. Patients with CHS exhibit increased susceptibility to aggressive malignancies, notably lymphoproliferative disorders. This report describes a 25-year-old man with CHS, complicated by an inborn error of immunity (IEI)-associated lymphoproliferative disorder (IEI-LPD). His initial symptoms presented were severe lower back pain, weight loss, and constitutional symptoms, alongside classic phenotypic features of CHS, including hypopigmentation, neurological abnormalities, and ocular manifestations. Laboratory findings revealed leucopenia, decreased immunoglobulins (IgA, IgM), and impaired natural killer cell function, confirming severe immune dysfunction. Imaging studies identified vertebral fractures, a retroaortic mass, and splenomegaly; histopathology confirmed IEI-LPD. Treatment comprised six cycles of dose-adjusted EPOCH chemotherapy with pegfilgrastim prophylaxis, achieving an initial complete response. Nevertheless, progressive neurological deterioration, recurrent infections, and institutional limitations contributed to this patient’s eventual demise. Genetic sequencing identified a homozygous LYST mutation variant c.9464GA (p.R3155Q), classified as a variant of uncertain significance. This report underscores the diagnostic and therapeutic challenges in rare hematologic malignancies, emphasizing the importance of genetic characterization through next-generation sequencing and advocating for improved awareness, early diagnosis, and multidisciplinary management strategies for optimal outcomes in CHS-associated malignancies.
Varón et al. (Wed,) studied this question.