TAFRO Syndrome in Caucasians: A Case Report and Review of the Literature

Abstract

Background: TAFRO syndrome has been reported in Japan among human herpesvirus 8 (HHV-8)-negative/idiopathic multicentric Castleman's disease (iMCD) patients. To date, the majority of iMCD patients with TAFRO syndrome originate from Japan.

Case presentation: Herein, we report a 67-year-old HIV/HHV-8-negative Caucasian iMCD patient diagnosed with TAFRO. He presented with marked systemic inflammation, bicytopenia, terminal renal insufficiency, diffuse lymphadenopathies, and anasarca. Lymph node and bone marrow biopsies revealed atrophic germinal centers variably hyalinized and megakaryocytic hyperplasia with mild myelofibrosis. Several other biopsies performed in kidneys, liver, gastrointestinal tract, prostate, and lungs revealed unspecific chronic inflammation. The patient had a complete response to corticosteroids, tocilizumab, and rituximab. He relapsed twice following discontinuation of rituximab. When reviewing the literature, we found seven other Caucasian cases with TAFRO syndrome. There were no significant differences with those described by the Japanese cohort except for the higher frequency of kidney failure and auto-antibodies in Western patients.

Conclusion: This case illustrates that patients with TAFRO syndrome can develop non-specific inflammation in several tissue sites. Furthermore, this case and our review of the literature demonstrate that TAFRO syndrome can affect Caucasian and Japanese patients highlighting the importance of evaluating for this syndrome independently of ethnic background.

Keywords: Castleman–Kojima disease; Caucasian; TAFRO; multicentric Castleman’s disease; review of literature.

Figure 1

(A) Hematoxylin and eosin stain of a surgically removed axillary lymph node consistent with idiopathic multicentric Castleman’s disease (iMCD). Low magnification highlighting a prominent paracortex encircling atrophic secondary follicles (original magnification, ×10). (B) Hematoxylin and eosin stain focusing on an atrophic germinal center which is partially lymphocyte depleted and which is penetrated by a prominent, hyalinized blood vessel lined by plump endothelial cells with enlarged nuclei, giving the appearance of a lollipop. Note the marked vascular proliferation in the interfollicular areas (original magnification, ×40). (C) CD138 staining of sparsely scattered plasma cells in the interfollicular areas, less abundant compared to what is observed in the plasmacytic histopathological variant of iMCD (original magnification, ×10). (D) CD21 stain displaying a prominent network of follicular dendritic cells (FDCs) in an abnormal follicle with a concentric arrangement of the small lymphocytes of the mantle zone along with FDC nuclei (original magnification, ×40). (E) Hematoxylin and eosin stain of bone marrow showing megakaryocytic hyperplasia with a mixture of small hypolobated megakaryocytes and others having a multi-separated nucleus (original magnification, ×40). (F) Reticulin stain on the bone marrow trephine biopsy highlighting mild myelofibrosis (original magnification, ×40).

Figure 2

(A) Hematoxylin and eosin stain. Colon biopsy showing irregular thickening of the subepithelial basement membrane, encircling some capillaries, indicating a collagenous colitis (original magnification, ×20). (B) Hematoxylin and eosin stain. Glandular atrophy in the gastric body with foci of intestinal metaplasia and deep lymphoplasmacytic infiltrates, suggestive of an autoimune gastritis (original magnification, ×20). (C) Hematoxylin and eosin stain. Reactive periglandular chronic inflammation in the prostate (original magnification, ×10). (D) Hematoxylin and eosin stain. Rare lobular non-necrotizing epithelioid granulomas with peripheral lymphoid ring are found in addition to unspecific portal inflammation (original magnification, ×40). (E) Hematoxylin and eosin staining of a liver biopsy showing mild sinusoidal distension in the liver biopsy (original magnification, ×20). (F) Hematoxylin and eosin stain. Bronchial wall containing lymphoplasmocytic aggregates of variable densities with crush artifacts (original magnification, ×10).

Figure 3

(A) Time course of the serum CRP (mg/l) and IL-6 (pg/ml) levels, and the different immunosuppressive drugs (corticosteroids, tocilizumab, and rituximab) administered to the patient. High values of IL-6 early after tocilizumab were excluded. (B,C) PET-CT scans showing pulmonary and mediastinal lymphadenopathies before (B) and after treatment with rituximab (C).

Figure 4

Classification algorithm for TAFRO-iMCD, IPL-iMCD, and KSVH-MCD. Abbreviations: iMCD, idiopathic multicentric Castleman disease; MCD, multicentric Castleman disease; HV, hyaline vascular; IPL, idiopathic plasmacytic lymphoadenpathy; KSHV, Kaposi sarcoma-associated herpesvirus; GC, germinal center; ALP, alkaline phosphatase; HHV-8, human herpesvirus 8; PC, plasma cell; LANA, latency-associated nuclear antigen.