Presence of immunoglobulin heavy chain rearrangement in so-called IgG4-related plasma cell granuloma of the eyelid.

So-called inflammatory pseudotumor (IPT) affects almost all major organs. The histological appearance of IPT varies from fibrohistiocytic proliferation to plasma cell-dominated lesions. The latter are composed of numerous plasma cells, lymphocytes, and histiocytes as well as mesenchymal cells, that is, plasma cell granuloma (PCG). Recently, Zen et al. demonstrated that some of the pulmonary PCGs represent an immunoglobulin G4 (IgG4)-related sclerosing disease. We report here a unique case of IgG4-related PCG of the eyelid. An 85-year-old man had a history of bronchial asthma for several years. He presented with a right upper eyelid mass, and under a diagnosis of squamous cell papilloma underwent tumor resection in May 2008. The surgical tissue was diagnosed as an inflammatory granulation tissue. Preoperative patient laboratory examination results were within normal limits. Serum IgG4 level was not examined. Two years later, he also presented with a left upper eyelid mass, and mass resection was performed under the diagnosis of chalazion. There was no other evidence of disease and the patient remained free of disease on examination 12 months later. Histologically, initial and recurrent lesions presented similar findings. In a lowpower field, both lesions were characterized by chronic inflammatory processes, and irregular fibrosis and/or sclerosis were not prominent (Fig. 1a). In a highpower field, these lesions demonstrated severe infiltration of mature plasma cells, plasmacytoid cells, and small lymphocytes with scattered eosinophils (Fig. 1b). Scattered Russell bodies (intracytoplasmic inclusions) were present in both lesions (Fig. 1b), but there were no centrocyte-like (CCL) cells, Dutcher bodies (intranuclear inclusions), or amyloid deposition. A few isolated small lymphocytes and mature plasma cells invaded into the Meibomian gland epithelium. However, there was no lymphoepithelial lesion (LEL) (Fig. 1b). Elastica-van Gieson staining demonstrated that there was no obliterative phlebitis or arteritis. Immunohistochemical studies were performed using the antigen retrieval method on the Histofine Histostainer (Nichirei Bioscience Inc., Tokyo, Japan) according to the manufacturer’s instructions. Staining for CD20, CD3, and CD5 showed the mixed nature of the small lymphocytes. There were no CD43 B-cells in either lesion. In situ hybridization (ISH) and immunohistochemical studies of k-chain and l-chain demonstrated polyclonality of the plasma cells and plasmacytoid cells in both lesions (Figs. 1c & 1d). There were numerous IgG-positive plasma cells with scattered IgAor IgM-positive plasma cells. However, IgG4 cells comprised more than 40% of the IgG plasma cells (Figs. 1e & 1f). There were no LELs detected even by immunostaining for cytokeratin in any of the two lesions (Fig. 1g). CD23 immunostain demonstrated no residual follicular dendritic cell network in both lesions. On ISH study, there were no Epstein-Barr virus (EBV)-encoded small RNA (EBER) cells in either lesion. By polymerase chain reaction (PCR) for immunoglobulin heavy chain (IgH) gene, a discrete band of amplified IgH gene was found for the recurrent lesion, while for the initial lesion, only germline bands were detected (Fig. 1h). IgG4 is the least common of the 4 subclasses of IgG4,