Immunohistochemical analysis of IgA expression differentiates IgG4-related disease from plasma cell-type Castleman disease

Abstract

Plasma cell-type Castleman disease (PCD) is often encountered when differentiating IgG4-related disease (IgG4-RD). Given that serum IgA is often elevated in Castleman disease, we investigated whether IgA expression levels in histological specimens can be used to differentiate between the two diseases. Lymph node lesions obtained from 12 IgG4-RD and 11 PCD patients were analysed by immunohistochemistry with anti-IgG, -IgG4, and -IgA antibodies. In addition to all 12 cases of IgG4-RD, 8/11 cases (72.7 %) of PCD also met the diagnostic criteria of IgG4-RD (serum IgG4 ≥135 mg/dl and IgG4/IgG-positive cells ≥40 %). IgA-positive cells were sparsely and densely distributed in IgG4-RD and PCD cases, respectively. The median number of IgA-positive cells ± SD in all 12 cases of IgG4-RD was 31 ± 37 cells per three high-powered fields (3HPFs) (range 4-118 cells/3HPFs). In contrast, the median number of IgA-positive cells, which was significantly higher in all 11 cases of PCD, was 303 ± 238 cells/3HPFs (range 74-737 cells/3HPFs) (P < 0.001). In conclusion, our findings indicate that in cases where serum analysis-based data are unavailable, anti-IgA immunostaining can be used for differential diagnosis of IgG4-RD.

International, evidence-based consensus diagnostic criteria for HHV-8–negative/idiopathic multicentric Castleman disease

“…11 A discussion about the overlap between IgG4-related disease (IgG4-RD) and iMCD led to consensus that iMCD should supersede a diagnosis of IgG4-RD, even with very high IgG4 levels, which is in agreement with recommendations from 2 IgG4-RD expert 43,44 Dense immunostaining of IgA in the lymph node and low serum IgG4/IgG also support a diagnosis of iMCD over IgG4-RD. 45 Hemophagocytic lymphohistiocytosis (HLH) shares significant overlap with iMCD, but our group decided that more data are needed to determine whether HLH should be excluded or considered an associated disease.…”

Severe refractory TAFRO syndrome requiring continuous renal replacement therapy complicated with Trichosporon asahii infection in the lungs and myocardial infarction: an autopsy case report and literature review

“…We could not identify a case of TAFRO syndrome involving significantly elevated IgG4 levels (≥135 mg/dL), displaying an association with IgG4-related disease (IgG4-RD). Although IgG4-RD was denied according to the histopathological evaluation in the present case, differentiating IgG4-RD from CD is sometimes challenging [37]. Sato et al have analyzed six cases of MCD with abundant IgG4positive cells, meeting the criteria of IgG4-RD (IgG4/IgGpositive cell ratio, > 40%), and they have concluded that serum IL-6 and CRP elevation was more frequent in patients with MCD than in those with IgG4-RD [38].…”

Hemosiderin deposition in lymph nodes of patients with plasma cell-type Castleman disease

“…It is sometimes difficult to distinguish PCD from IgG4-RD, as they have similar histological features including plasma cell infiltration in the interfollicular areas; additionally, PCD patient lymph nodes can also exhibit abundant infiltration of IgG4-positive cells. 11,12 Specific characteristics have been reported as useful in differentiating PCD from IgG4-RD, including the presence of IgA-positive cells in PCD, and eosinophilic infiltration observed in IgG4-RD. 11,13 Furthermore, hemosiderin deposition appears to be useful in differentiating between the two diseases.…”

“…Keywords: hemosiderin deposition; plasma cell-type Castleman disease; IgG4-related disease; serum IL-6; serum C-reactive protein differentiate PCD from IgG4-RD. 11 Furthermore, PCD frequently presents with variable lesions infiltrated by large numbers of IgG4-positive plasma cells, accompanied by high serum IgG4 levels. 11,12 Moreover, hemosiderin deposition has regularly been observed in lymph node lesions of PCD patients.…”

“…11 Furthermore, PCD frequently presents with variable lesions infiltrated by large numbers of IgG4-positive plasma cells, accompanied by high serum IgG4 levels. 11,12 Moreover, hemosiderin deposition has regularly been observed in lymph node lesions of PCD patients. Thus, we assessed the usefulness of hemosiderin deposition in differentiating between PCD and IgG4-RD.…”