TAFRO Syndrome: A Syndrome or a Subtype of Multicentric Castleman Disease?

Abstract

TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis of bone marrow/renal dysfunction, organomegaly) syndrome is a systemic inflammatory disorder of unknown etiology. It has been recognized as a subtype of idiopathic multicentric Castleman disease (iMCD), and the international diagnostic criteria for iMCD-TAFRO require a lymph node histopathology consistent with iMCD. Furthermore, TAFRO syndrome is defined as a heterogeneous clinical entity caused by underlying diseases such as malignancy, autoimmune diseases, or infections. However, the cases that led to the proposal of TAFRO syndrome lacked recognizable lymphadenopathy and were inconsistent with any other diseases, despite vigorous efforts in differential diagnosis. Irrespective of the presence or absence of Castleman disease (CD)-like histology, TAFRO syndrome exhibits homogeneous clinical, laboratory, and prognostic features, setting it apart from iMCD without TAFRO syndrome. Defining iMCD-TAFRO apart from TAFRO syndrome is deemed meaningless and confusing. MCD is a heterogeneous lymphoproliferative disorder consisting of several subtypes with different pathogenesis, clinical manifestations, and histological features. Typical MCD in Japan, characterized by the histology of plasma cell type and marked polyclonal hypergammaglobulinemia, is identical to idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL). Although IPL is classified into iMCD-NOS (not otherwise specified), it should be recognized as a distinct clinicopathological entity. Furthermore, we propose to separate TAFRO syndrome from the MCD category as a defined disorder.