Thymic lesions in fatal infectious mononucleosis

Area of Science:

• Immunopathology
• Virology
• Histopathology

Background:

• Fatal infectious mononucleosis (FIM) is a severe condition with significant morbidity.
• X-linked lymphoproliferative syndrome (XLP) is a primary immunodeficiency with high mortality following Epstein-Barr virus (EBV) infection.
• The thymus plays a crucial role in T-cell maturation and immune system regulation.

Purpose of the Study:

• To investigate thymic histopathological changes in patients with FIM.
• To compare thymic lesions in XLP patients versus non-XLP patients with FIM.
• To explore the potential role of thymic epithelial destruction in the immunopathology of XLP.

Main Methods:

• Histopathological examination of thymic tissues from 35 FIM patients (21 XLP, 14 non-XLP).
• Classification of lesions based on lymphocyte content and Hassall's bodies (HB) status.
• Correlation of morphological findings with clinical context and EBV infection.

Main Results:

• Six distinct thymic lesion patterns were identified, characterized by lymphoproliferation, HB depletion, necrosis, multinucleated giant cells, and abundant plasma cells/macrophages.
• Normal-appearing HB were infrequent (5/35); marked depletion or absence of HB was common.
• Thymic alterations were observed in both XLP and non-XLP FIM cases, though generally less severe in sporadic FIM.

Conclusions:

• Destruction of thymic epithelium and Hassall's bodies is a prominent feature of FIM, especially in XLP.
• These thymic lesions may contribute to the progression of immune defects following EBV infection in XLP.
• The observed thymic pathology shares similarities with lesions seen in other immune deficiency disorders.