Iwaki et al described the TAFRO syndrome, which is an atypical variant of HHV-8 negative multicentric Castleman disease. The authors are from multiple hospitals in Japan.


Key features:

(1) multicentric Castleman’s disease

(2) HHV-8 negative

(3) T = thrombocytopenia (platelet count < 100,000 per µL)

(4) A = anasarca

(5) F = fever (body temperature > 38°C (> 100.4°F)

(6) R = reticulin fibers in bone marrow biopsy

(7) O = organomegaly on imaging studies


Histologic features:

(1) atrophic germinal centers with enlarged nuclei of endothelial cells

(2) proliferation of endothelial venules in the interfollicular zone

(3) small number of mature plasma cells in the interfollicular zone

(4) no evidence of light chain restriction


Major criteria for diagnosis:

(1) 3 or more of the TAFRO features

(2) absence of hypergammaglobulinemia

(3) small volume lymphadenopathy


Minor criteria:

(1) hyperplasia or normoplasia of megakaryocytes in the bone marrow

(2) elevated serum alkaline phosphatase without marked elevation of ALT or AST



(1) SLE or other rheumatologic disorders

(2) Epstein-Barr and other infectious diseases

(3) malignancies (POEMS syndrome, malignant lymphoma, cancer, etc)


The diagnosis requires:

(1) histopathologic features

(2) all of the major criteria

(3) one or both of the minor criteria

(4) exclusion of alternative diagnoses


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