IgG4-RD was first reported as a systemic disease in 2001 when patients with sclerosing pancreatitis were observed to have elevated serum IgG4 concentrations [3]. Since then, it has been recognized as an immune-mediated condition involving several organs, particularly exocrine organs such as the pancreas, salivary glands, and biliary tract [1]. Several studies have reported that intrathoracic involvement may be seen in about 10 to 50% [2, 4, 5], which commonly includes interstitial lung disease, inflammatory pseudotumors, fibrosing mediastinitis, and lymphadenopathy. The formation of a mass in the anterior mediastinum, mimicking an anterior mediastinal tumor, is very rare.
The differential diagnosis of an anterior mediastinal mass includes thymoma, germ cell tumor, and mucosa-associated lymphoid tissue (MALT) lymphoma [6]. It is not necessary to obtain the preoperative diagnosis of an anterior mediastinal tumor, given the risk of dissemination by a needle biopsy [7]. Germ cell tumors usually show heterogeneous images on chest CT, and steroid treatment is not effective. MALT lymphomas present homogeneous images and occasionally respond to steroids, but it is very rare. From the clinical findings, encapsulated thymoma was considered the most likely diagnosis.
IgG4-RD is diagnosed based on clinical and histopathological findings. Umehara H et al. proposed the following comprehensive diagnostic criteria for IgG4-RD: (1) organ involvement, (2) high serum IgG4 (> 135 mg/dl), (3) histological features such as IgG4-positive plasma cells > 10/high power field and IgG4-positive/IgG-positive cells > 40% in the affected lesion [8]. The present case meets the comprehensive diagnostic criteria for IgG4-related disease; however, Castleman’s disease sometimes satisfies these criteria [9, 10]. IgG4-RD also shares pathological characteristics with storiform fibrosis and obliterative phlebitis, so when there are few findings of storiform fibrosis or obliterative phlebitis as in this case, it is very difficult to differentiate between the two diseases only based on the pathological findings. Castleman’s disease is a polyclonal lymphoproliferative disorder, which is classified into two types: unicentric and multicentric [11]. Unicentric Castleman’s disease is characterized by localized disease confined to a single site. On the other hand, multicentric Castleman’s disease (MCD) involves lymphoid hyperplasia at multiple sites. MCD sometimes accompanied by the elevation of serum IgG4 levels and infiltration of IgG4-positive plasma cells in the affected organs. In MCD, interleukin-6 (IL-6) plays an important role, which is considered to be closely associated with its clinical presentation, with symptoms such as fever, weight loss, anemia, and elevated C-reactive protein (CRP) [12]. Differentiating between IgG4-RD and MCD by clinical characteristics alone is challenging. Sasaki T et al. reported that the pattern of organ involvement, atopic history, levels of IgA, and CRP were quite distinctive, and they suggested that the combination of involved orbits, lacrimal glands, salivary glands or pancreas, and an atopic history, IgA < = 330 mg/dL, and CRP < = 0.80 mg/dL may be useful for the differentiation of IgG4-RD from MCD [13]. Sato Y et al. reported that elevation of serum IgE was more frequently observed in lymph nodes of patients with IgG4-RD compared with those with MCD, and high levels of IL-6 and CRP may be important differential diagnostic markers for MCD apart from IgG4-RD [14]. In our case, the history of autoimmune pancreatitis and asthma, normal level of IgA (51 mg/dL at the first diagnosis of IgG4-RD) and CRP, high level of IgE (267.5 mg/dL at first diagnosis of IgG4-RD) and asymptomatic condition suggest IgG4-RD rather than MCD. His past history of multiple pulmonary nodules and mediastinal lymphadenopathy would have resulted from IgG4-RD and not Castleman’s disease.
Distinguishing IgG4-RD from MCD is important because their treatments are entirely different. IgG4-RD responds well to steroid therapy. Kamisawa et al. reported that the remission rate of patients with IgG4-related pancreatitis, receiving glucocorticoids was 98% [15]. On the other hand, MCD can be resistant to such treatment and is often treated with an anti-IL-6 agent [12]. In our case, the response to steroids might be another clue to the diagnosis of IgG4-RD.