International definition of iMCD-TAFRO: future perspectives

Abstract

Since thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome was first proposed in 2010, there has been considerable progress in this area, particularly regarding its association with idiopathic multicentric Castleman disease (iMCD). TAFRO syndrome is a heterogeneous category with a constellation of symptoms that can develop in the setting of infection, rheumatologic disorder, malignancy, and iMCD. Now, iMCD with TAFRO symptoms is subtyped as iMCD-TAFRO. However, confusion between TAFRO syndrome and iMCD-TAFRO remains. In this article, we discuss the current understanding and future research agenda of TAFRO syndrome and iMCD-TAFRO from the perspective of its new validated international definition.

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

“…In the 2021 international definition of iMCD–TAFRO proposed by Nishimura et al, cases with histology consistent with iMCD are labeled definite iMCD-TAFRO. Those lacking lymph node histology are deemed probable iMCD-TAFRO, and cases with lymph node histology inconsistent with iMCD or meeting exclusion criteria are classified as TAFRO syndrome [ 6 , 7 ]. However, it is imperative in the diagnosis of TAFRO syndrome to rule out diseases listed in the exclusion criteria [ 20 , 21 ].…”

“…However, it is imperative in the diagnosis of TAFRO syndrome to rule out diseases listed in the exclusion criteria [ 20 , 21 ]. Nonetheless, in their definition, TAFRO syndrome is described as a heterogeneous clinical entity caused by underlying diseases such as malignancy, autoimmune diseases, or infection [ 6 , 7 ]. This misconception might hinder accurate diagnosis and appropriate therapeutic approaches for both TAFRO syndrome and underlying diseases.…”

“…However, the first two cases that led to the proposal of TAFRO syndrome did not exhibit lymphadenopathy and could not be diagnosed as MCD [ 5 ]. Furthermore, the introduction of the term iMCD-TAFRO, apart from TAFRO syndrome as a subtype of iMCD, has contributed to confusion regarding the concept of TAFRO syndrome [ 6 , 7 ].…”

Idiopathic Plasmacytic Lymphadenopathy Forms an Independent Subtype of Idiopathic Multicentric Castleman Disease

“…Idiopathic MCD (iMCD) is defined as a group of KSHV/HHV8-negative MCD without POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-proteins, and skin changes) [ 5 ]. Clinically, iMCD is classified into iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) [ 6 , 7 , 8 ] and iMCD-NOS (not otherwise specified). Histologically, there are two main pathological variants in iMCD: plasma cell (PC) and hypervascular (HyperV) types [ 5 , 9 , 10 ].…”

Castleman disease, TAFRO syndrome, idiopathic plasmacytic lymphadenopathy, and autoimmune disease

“…review ‘Historical and pathological overview of Castleman disease’ and ‘International definition of iMCD-TAFRO: future perspectives’, respectively. 8 , 9 Takeuchi K. discusses IPL with an original paper by Mori translated to English. 10 Koga T. and Kawakami A. et al .…”