伴 UNC13D 和 CD27 胚系突变的复发/难治性外周 T 细胞淋巴瘤相关噬血细胞性淋巴组织细胞增生症

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory disease characterized by familial and acquired forms.

Here, we present the case of a 26-year-old male patient with relapsed/refractory peripheral T-cell lymphoma and concurrent HLH. Whole-exon sequencing revealed germline mutations associated with HLH, including those in critical genes such as CD27 and UNC13D and other germline heterozygous variants ( NOTCH2, NOTCH3, IL2RA, TYK2, AGL, CFD , and F13A1 ).

CD107a analyses consistently demonstrated impaired degranulation of cytotoxic T-lymphocytes and natural killer (NK) cells. Examination of the patient's family pedigree revealed that his father and mother harbored UNC13D and CD27 mutations, respectively; his brother carried the same CD27 heterozygous mutation.

However, none of them manifested the disease. Despite the missense mutation of CD27 (c. 779C>T; p. Pro260Leu) lacking previous documentation in databases, comprehensive analysis suggested non-pathogenic mutations in the CD27 variant, indicating minimal impact on T- and NK-cell functions. These results ultimately supported the option of hematopoietic stem cell transplantation (HSCT) as a successful curative therapeutic approach. As of this report, the patient has remained free of lymphoma and quiescent HLH 15. 2 months post-HSCT.

This study underscores the efficacy of genetic tests in identifying significant mutations and confirming their etiologies, providing an early basis for treatment decisions and the selection of suitable transplant donors.