Kimura's disease: A case report.
Kimura's disease is a rare, idiopathic condition that usually affects young men of Asian descent. The disease is characterized by swelling and lesions in the head and neck region, with involvement of the subcutaneous soft tissue, major salivary glands, and lymph nodes. Patients almost always have eosinophilia and elevated serum immuno globulin E levels. The diagnosis is established by biopsy. Kimura's disease is usually self-limiting. Its etiology is unknown but is thought to be a manifestation of an aberrant allergic response. In this paper, we describe the case of a 30-year-old patient who was diagnosed with Kimura's disease at our institution.
Kimura's disease is a rare disorder that affects the subcutaneous tissue and lymph nodes. It is seen mostly in young men of Asian descent. Clinically, Kimura's disease can be confused with a lymphoma or infectious process, but biopsy establishes the diagnosis. We report a case of this unusual disorder at our institution in the United States.
A 30-year-old man of Asian descent presented to the Tulane Medical Center in New Orleans in September 1998 with a left submandibular mass. The patient had hypertension and end-stage renal disease. He had been on peritoneal dialysis for 4 to 5 years.
The submandibular mass had first been noticed in March 1997. Fine-needle aspiration cytology at that time had revealed a mixed population of large and small lymphocytes and some histiocytes. No tumor cells had been seen. Special staining for acid-fast organisms and fungi had been negative. These findings were consistent with a reactive process.
Computed tomography (CT) of the neck in November 1997 had revealed the presence of two masses in the left submandibular region, which measured 18 and 11 mm, respectively, at the short axis. Several smaller nodes had been seen along the spinal accessory chain. The chest x-ray was normal. The patient was treated with antibiotics, but the lymph node enlargement had persisted. In May 1998, a repeat fine-needle aspiration biopsy had shown that the lymphocytes--most small, but some large--were still present, and that there had been a slight increase in the number of eosinophils.
Magnetic resonance imaging (MRI) performed in August 1998 had shown that the patient now had three sizable masses in the submandibular region; the largest dimensions of each were 3.3, 1.9, and 1.9 cm, respectively. Compared with the findings of the CT that had been performed 9 months earlier, the patient's masses had grown significantly.
The patient had mild eosinophilia (7%) in the peripheral blood and a T4/T8 ratio of 5.28. In January 1998, he had undergone a test for human immunodeficiency virus 1 infection, which was negative.
The patient was referred to us in September 1998, and we obtained a biopsy of the left submandibular mass. The specimen consisted of two nodules; one measured 3 X 2.5 X 1 cm and the other 1.2 X 1 X 1 cm. The cut surface was tan and exhibited no areas of necrosis. Frozen-section analysis revealed an atypical follicular hyperplasia, with microabscesses and multinucleate polykaryotic cells. Flow cytometry of the lymph node tissue showed an equal proportion of T and B lymphocytes, without any detectable clonality, and was suggestive of a reactive process. Smears and culture of the lymph node tissue were negative for bacteria, mycobacteria, and fungi.
Histology of the lymph node tissue revealed the presence of florid follicular hyperplasia (figure). Many of the follicular centers exhibited necrosis with proteinaceous debris. Multinucleate polykaryocytes were prominent in the germinal centers and in the paracortex. Marked diffuse eosinophilia and eosinophilic abscess formation were seen. Throughout the paracortex, there was a diffuse sclerosis and many venules with prominent endothelial cells. There was also vascularization of the germinal centers focally. Based on these findings, a histologic diagnosis of Kimura's disease was made.
The patient was given a short course of steroid therapy, and his lymphadenopathy resolved. The patient subsequently developed focal segmental glomerulosclerosis, and he is currently being treated with renal dialysis. His lymphadenopathy has remained quiescent.
The condition now known as Kimura's disease was first described in 1937 by Kim and Szeto in China as an "eosinophilic hyperplastic granuloma"; Kimura himself reported on the disease 1948.  This rare disease is endemic in parts of Asia. It mainly affects young Asian men (median age: 26 years; male:female ratio: [greater than]3:l), [1-3] although it has been reported in other areas and ethnic groups. [4-8]
Disease characteristics. The most common presentation of Kimura' s disease is swelling in the head and neck region. The lesion primarily involves the subcutaneous soft tissues of the postauricular region and sometimes the salivary glands and lymph nodes. [1,2,7] In rare cases, it has been reported to involve other sites, such as the oral cavity, conjunctiva, eyelid, tympanic membrane, skeletal muscle, prostate, kidney, peripheral nerves, and epiglottis. [5,6,9]
The onset of the Kimura's disease is insidious. The amount of swelling at the affected site gradually increases over a period of months or years. Peripheral blood eosinophilia is almost always present. An elevation in serum immunoglobulin E (IgE) levels has also been a consistent finding, but type I hypersensitivity is rare. Associated renal disease, characterized by proteinuria, is found in about 12% of patients. [10,11]
Diagnosis. Clinically, the differential diagnoses include inflammatory and neoplastic conditions, tuberculosis, and other infectious lymph node enlargements (e.g., toxoplasmosis); Hodgkin's disease and non-Hodgkin's lymphoma should be primary considerations.
CT and MRI can help determine the extent and progression of the disease as well as the lymph node involvement.  Fine-needle aspiration cytology is helpful in some cases. 
Although there is no one specific diagnostic feature of Kimura's disease, a definitive diagnosis can made by histologic examination of the excised lesion. The gross lesion might or might not show obvious foci of necrosis. Microscopically, the key findings are marked hyperplasia with pronounced eosinophilic infiltration. Foci of necrosis are seen with vascularization of the paracortex and deposition of hyaline material within follicles. Polykaryotic giant cells are a common feature. This combination of histologic findings is very characteristic of Kimura's disease. Immunostaining can show deposition of IgE in a reticular fashion between the follicles and on the surface of nondegranulated mast cells. 
Although the intense eosinophilia and focal necrosis are suggestive of a parasitic infection, no parasites have been identified. The polymorphous infiltrate with eosinophilia and the presence of giant cells also raise the suspicion of Hodgkin's disease. This is especially true when the diagnosis is attempted by fine-needle aspiration. The absence of Reed-Sternberg cells helps distinguish Kimura's disease from Hodgkin's disease.
Kimura's disease can also be confused with angiolymphoid hyperplasia with eosinophilia (ALHE). These two diseases have some common histologic features, such as eosinophilia and vascular proliferation. The distinction between the two is reviewed by Kuo et al.  ALHE, which is usually seen in older patients, manifests as multiple small dermal eruptions. Lymphadenopathy, salivary gland involvement, and elevated serum IgE levels are rare in ALHE. In ALHE, vascular structures are lined with endothelial cells that have an epithelioid or histiocytoid appearance, a feature that is lacking in Kimura's disease. Conversely, eosinophilic follicle lysis is a characteristic of Kimura' s disease that is not seen in ALHE. 
Etiology. The etiology of Kimura' s disease is unknown. The presence of eosinophilia and elevated serum IgE levels suggests an allergic or hypersensitivity process. No specific antigens have been identified, but current thinking holds that Kimura' s disease is an unusual allergic response in which Th2 cytokines play a part. [14,15]
Treatment. Kimura' s disease responds well to oral steroids, but relapses often occur after treatment is stopped. Radiation and surgical excision are also effective. [3,5-9,11,16] The prognosis is excellent, and the disease has no potential for malignancy.
From the Department of Pathology and Laboratory Medicine, Division of Hematopathology, Tulane University Medical Center, New Orleans.
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|Author:||Krause, John R.|
|Publication:||Ear, Nose and Throat Journal|
|Article Type:||Brief Article|
|Date:||Mar 1, 2000|
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