Castleman disease (CD) is a rare lymphoproliferative disorder that can be 
unicentric or multicentric. Multicentric CD (MCD) is further subdivided into 
human herpesvirus type-8-associated, POEMS syndrome-associated, and idiopathic 
(iMCD). TAFRO syndrome is a newly identified disorder of unknown etiology 
characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, 
renal dysfunction, and organomegaly. The TAFRO syndrome is sometimes regarded as 
a subtype of iMCD (TAFRO-iMCD), whereas iMCD without TAFRO syndrome is 
considered "not otherwise specified" (iMCD-NOS). However, a proportion of 
patients with TAFRO syndrome have been diagnosed without lymph node biopsies 
(TAFRO syndrome without proven iMCD; TAFRO-w/op-iMCD). To clarify the clinical 
features of iMCD-NOS, TAFRO-iMCD, and TAFRO-w/op-iMCD, we retrospectively 
analyzed 220 patients extracted from the database of the Multicenter 
Collaborative Retrospective Study for Establishing the Concept of TAFRO 
Syndrome. The patients included 87 with iMCD-NOS, 63 with TAFRO-iMCD, and 19 
with TAFRO-w/op-iMCD. Patients in all three groups exhibited anemia, 
hypoalbuminemia, and elevated serum C-reactive protein and interleukin-6 levels. 
No significant differences in clinical, laboratory, and prognostic features were 
noted between the TAFRO-iMCD, and TAFRO-w/op-iMCD groups. However, the iMCD-NOS 
group exhibited polyclonal hyper-γ-globulinemia. The five-year survival rates of 
patients in the iMCD-NOS and TAFRO-involved groups were 100% and 66.5%, 
respectively (dropping markedly during the first few months in the latter). The 
iMCD-NOS and the TAFRO-iMCD samples typically showed plasma cell and mixed-type 
histologies, respectively. Thus, iMCD can be classified into two distinct 
subtypes, iMCD-NOS and TAFRO-iMCD. As such, TAFRO-iMCD and TAFRO-w/op-iMCD may 
be considered the same entity, requiring prompt diagnosis and intensive care.