Castleman disease and TAFRO syndrome: To improve the diagnostic consciousness is the key

Table 1 Diagnostic criteria for TAFRO syndrome proposed by Masaki et al (updated in 2019)

Diagnostic criteria for TAFRO syndrome
Primary criteria
Edema: Including pleural and abdominal effusion and systemic edema
Thrombocytopenia: Platelet count ≤ 105/uL before myelosuppression
Systemic inflammation: Fever of unknown origin, body temperature exceeding 37.5°C, and/or serum CRP ≥ 2 mg/dL
Secondary criteria
Pathological manifestations of CD-like lymph nodes
Bone marrow reticular fibrosis and/or increased bone marrow megakaryocyte count
Mild organ enlargement: Including liver, spleen, and lymph node enlargement
Progressive renal dysfunction
TAFRO syndrome can be diagnosed after meeting at least two of all three main criteria and four secondary criteria, and excluding malignant tumor, autoimmune disease, infection, POEMS syndrome, liver cirrhosis, TTP/HUS, etc.

CRP: C-reactive protein; CD: Castleman disease; TTP: Thrombotic thrombocytopenic purpura; HUS: Hemolytic uremic syndrome.

Table 2 Basic clinical data of 39 patients with Castleman disease (n = 39)

	UCD (n = 18)	iMCD-NOS (n = 13)	TAFRO (n = 8)	P value
Age (yr)	41.17 ± 18.23	47.23 ± 22.09	40.50 ± 9.04	0.530
Male/female	10/8	7/6	4/4	1.000
Rural/urban	5/13a	6/7	6/2a	0.085
Time of diagnosis (median, months)	NA	12	1	0.000
Systemic manifestations
Fever	2	10	8
Splenomegaly	0	5	3
Edema/polyserous cavity effusion	0	0	8
Bronchiolitis obliterans	2	0	0
Rash	0	5	3
Paraneoplastic pemphigus	1	1	0
Abnormal renal function	0	1	7
Laboratory examination
White blood cell1
Decreased	0	2	0
Raise	1	4	3
Hemoglobin1				0.000
Decrease (n)	2
Average (g/L)	132.00 ± 19.985	99.31 ± 27.41	79.57 ± 21.08
Platelet1
Decreased	0	3	8t
Raise	2	6	0
CRP (mg/L)	NA	91.09 ± 59.14	141.55 ± 64.31	0.000
Albumin (g/L)1	39.61 ± 5.52	31.65 ± 7.39	22.79 ± 9.26	0.000
Direct anti-human ball test was positive (n, %)	NA	9/13	6/6
IL-6 (median, pg/mL) (n)	NA	47.35 (8)	12.65 (8)	0.040
VGEF (median, pg/mL) (n)	NA	NA	> 800 (5)
Ferritin > five times normal value	NA	4/13	1/8
Elevated LDH	0	2	2
Elevated ALP	1/18	3/13	6/8
ANA positive (titer > 1:40)	2/18	8/13	2/8
Elevated polyclonal immunoglobulin	0	9/13	1/8
Hemophilia syndrome	0	0	1/8
Pathological type
Hyaline vascular type	13	0	5/8
Plasma cell type	3	4	0
Mixed type	2	9	2/8
No evidence of lymph node biopsy	0	0	1/8
Treatment
Biopsy only, treatment unknown	0	5	0
Symptomatic treatment only	0	0	1
Simple surgical resection	18	0	0
Glucocorticoid alone	0	2	3
Hormones combined with chemotherapy2	0	51	2
Hormone combined with rituximab	0	0	1
Hormone combined with tozumab	0	1	1
Prognosis
Loss of contact	0	3	0
Improved	16	6	7
Relapse	0	0	1
Solid cancer occurred during the follow-up	2b	1c	0
Transformation into lymphoma	0	1d	0
Death	0	2	0

^aA statistically significant difference between the two groups.

^bTwo cases with pancreatic head cancer and thyroid.

^cOne case with pancreatic cancer.

^dOne case with non-Hodgkin lymphoma.

¹Normal reference value: white blood cell count 3.5–9.5 × 10⁹/L; hemoglobin 130–175 g/L (male), 115–150 g/L (female); platelet count 125–350 × 10⁹/L; 40–55 g/L albumin.

²Chemotherapy regimens included CP (cyclophosphamide + prednisone), COP (cyclophosphamide + ciac/vincristine + prednisone), and CHOP (cyclophosphamide + doxorubicin + vincristine + prednisone).

iMCD-NOS: Idiopathic multicentric Castleman disease-not otherwise specified; UCD: Unicentric Castleman disease; ALP: Alkaline phosphatase; ANA: Antinuclear antibody; CRP: C-reactive protein; IL-6: Interleukin 6; LDH: Lactate dehydrogenase; VGEF: Vascular endothelial growth factor.