J Rheum Dis.  2015 Dec;22(6):395-400. 10.4078/jrd.2015.22.6.395.

Mikulicz's Disease with Progressively Transformed Germinal Centers-type Immunoglobulin G4-related Lymphadenopathy Mimicking Sjogren's Syndrome

• Kim HJ
• Kim JA
• Min JK

• KMID: 2222816
• DOI: http://doi.org/10.4078/jrd.2015.22.6.395

Abstract

Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease, and lymphadenopathy is frequently observed in these patients. Among the 5 subtypes of IgG4-related lymphadenopathy, progressively transformed germinal centers (PTGC)-type IgG4-related lymphadenopathy possesses a unique characteristic that differentiates it from the other 4 subtypes. Here, we report on a rare case of PTGC-type IgG4-related lymphadenopathy accompanying Mikulicz's disease. A 39-year-old female complained of a left cervical mass and bilateral upper eyelid hypertrophy. The serum level of IgG4 was elevated, and computed tomography showed enlargement of the bilateral lacrimal and submandibular glands and left cervical lymph node. Excisional biopsy of a submandibular gland and cervical lymph node was performed, and the histopathologic findings revealed Mikulicz's disease accompanied by PTGC-type IgG4-related lymphadenopathy. After treatment of the patient with oral prednisolone and azathioprine, the patient's appearance improved. To the best of our knowledge, no case of PTGC-type IgG4-related lymphadenopathy has been previously reported in Korea.

Keyword

Immunoglobulin G4-related lymphadenopathy; Progressively transformed germinal centers; Immunoglobulin G4-related disease; Mikulicz's disease

MeSH Terms

Adult
Azathioprine
Biopsy
Eyelids
Female
Germinal Center
Humans
Hypertrophy
Immunoglobulin G
Immunoglobulins*
Korea
Lymph Nodes
Lymphatic Diseases*
Prednisolone
Sjogren's Syndrome*
Submandibular Gland
Azathioprine
Immunoglobulin G
Immunoglobulins
Prednisolone

Figure

• 

  Figure 1. Comparison of radiological features before and after excisional biopsy of the left submandibular gland and left cervical lymph node and medical treatment. (A∼ C) Contrast-enhanced computed tomography images revealing enlargement of the bilateral lacrimal and submandibular glands and left cervical lymph node. (D, E) After 2 months of medical treatment, the sizes of the bilateral lacrimal glands and right submandibular gland were decreased. (E, F) The dotted circle indicates the surgically removed left submandibular gland and the lined circle indicates the surgically removed left cervical lymph node by excisional biopsy.

• 

  Figure 2. Histological and immunohistochemical features of the excisonal biopsy specimens of (A∼ D) the lymph node and (E∼ I) submandibular gland. (A) The excised lymph node shows extensive reactive follicular hyperplasia and progressively transformed germinal centers (PTGCs) (arrowheads) (H&E, ×100). The PTGCs appear as round-to-oval structures, 2 to 3 times the diameter of the other reactive follicles. These large follicles show thickened mantles with inward extensions into the germinal centers but no expansion of the interfollicular zone. (B) The germinal centersare predominantly composed of lymphocytes, centrocytes, centro-blasts, and numerous mature plasma cells and plasmacytoid cells (H&E, ×200). (C, D) The majority of immunoglobulin (Ig)G4+ plasma cells reside in the germinal centers, with a small number presenting in the interfollicular zone. This is a unique feature of PTGC-type IgG4-related lymphadenopathy, which distinguishes it from the other 4 subtypes. The IgG4+/IgG+ plasma cell ratio is 90%, and the IgG4+ plasma cells were counted as 180/high power field (C: IgG-immunostain, ×200; D: IgG4-immunostain, ×200). The features of the cervical lymph node are identical to those of the axillary lymph node specimen. (E) Acinar atrophy and destruction of the salivary gland are observed, along with marked lymphocytic infiltration with lymphoid follicles (H&E, ×40). (F) Veins occluded by inflammatory infiltrate composed of lymphocytes and plasma cells are noted, and indicate obliterative phlebitis (arrowheads) (H&E, ×200). (G) The storiform pattern of fibrosis is present, indicating dense fibrosis within which lymphocytes, plasma cells, and occasional eosinophils are embedded (H&E, ×100). Storiform fibrosis and obliterative phlebitis are usually absent in IgG4-related lymphadenopathy. (H, I) The IgG4+/IgG+ plasma cell ratio is estimated at 90% (G: IgG-immunostain, ×100; H: IgG4-immunostain, ×100).

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