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Cytological findings of IgG4‐related pleural effusion: a case report

Dear Editor, We report here the cytological findings of a case of an immunoglobulin G4 (IgG4)-related pleural lesion showing massive pleural effusion. IgG4 is the least common of the four subclasses of IgG (IgG1, IgG2, IgG3 and IgG4) and comprises only 3–6% of the entire IgG fraction. IgG4-related disease is a recently recognized entity characterized clinically by tumour-like enlargement of one or more exocrine glands or other extranodal sites by lymphoplasmacytic infiltrates and sclerosis, accompanied by increased IgG4-positive plasma cells in the tissues and elevated IgG4 titre in the serum. The most common manifestations of IgG4-related disease are autoimmune pancreatitis, chronic sclerosing sialoadenitis of the submandibular gland and chronic sclerosing dacryoadenitis. A 57-year-old Japanese man presented with a 2month history of dyspnoea. Chest radiograph and computed tomography demonstrated massive bilateral pleural effusions and pleural thickening. The results of a complete blood count and differential analysis were normal. Total serum protein was 7.7 g ⁄ dl, and serum protein electrophoresis demonstrated a polyclonal hypergammaglobulinaemia (30%). The serum IgG4 level (970 mg ⁄ dl; normal <135 mg ⁄ dl) and interleukin-2 (IL-2) receptor level (1710 U ⁄ ml; normal <500 U ⁄ ml) were markedly elevated. However, Creactive protein (CRP) was negative and the serum lactate dehydrogenase (LDH) level was within the normal range (189 IU ⁄ l; normal <220 IU ⁄ l). The patient responded well to steroid therapy and remained well at 12 months of follow-up. The Giemsa-stained smears obtained from the pleural effusion contained numerous small lymphocytes admixed with plasma cells, plasmacytoid cells and large immunoblasts showing plasma cell differentiation, together with a few mesothelial cells (Figure 1a–c). Binucleated plasma cells were also observed (Figure 1a). The nuclei of the small lymphocytes were usually round (Figure 1a). The immunoblasts contained one or two prominent, central, basophilic nucleoli and broad basophilic cytoplasm (Figure 1b). The smear also contained a few grape cells and eosinophils (Figure 1c). Haemophagocytic histiocytes were occasionally observed (Figure 1c). Pleural biopsy specimens demonstrated pleural thickening with prominent lymphoplasmacytic infiltration and a few eosinophils (Figure 2a). Using formalin-fixed, paraffin-embedded sections, immunohistochemical study for light chain determinant demonstrated the polytypic nature of plasma cells and their precursors. There were numerous IgG4-positive plasma cells in the lesion, comprising more than 40% of the IgG-positive plasma cells (Figures 2b,c). Polymerase chain reaction assay for the immunoglobulin heavy chain gene demonstrated only germline bands. The pathological findings of IgG4-related pleural lesion characterized by pleural thickening and prominent polyclonal lymphoplasmacytic infiltration have been well described. However, little is known about the cytological findings of pleural effusion in IgG4-related pleural lesion. The presence of numerous plasma cells and their precursors appears to result from prominent pleural infiltration of plasma cells, their precursors and small lymphocytes. Moreover, Giemsa-stained specimens demonstrated a few eosinophils, which is one of the characteristic histomorphological findings of IgG4-related disease. The laboratory findings of the present case, such as increased serum IgG4 level and IL-2 receptor level, normal serum LDH level and negativity of CRP, are characteristic. IgG4-related disease more frequently affects Asian populations. In the literature, reactive plasmacytosis in serous effusion has been reported in chronic inflammatory processes and the majority of IgG4-related Correspondence: M. Kojima, Department of Anatomic and Diagnostic Pathology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan Tel.:+81-282-87-2129; Fax:+81-282-86-5171; E-mail: k-masaru@dokkyomed.ac.jp