Kimura's Disease

Background

This rare disease was often confused in the past with angiolymphoid hyperplasia with eosinophilia. The latter is a benign condition presenting with papules on the skin of the head and neck. Kimura's disease is a deep soft tissue and subcutaneous lesion which presents with enlarged cervical lymph nodes.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/
Immunohistochemistry/
Electron Microscopy

Differential Diagnosis

Prognosis

Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

AGE RANGE-MEDIAN 2-3rd decades

SEX (M:F)
Females

GEOGRAPHY
Asians

PATHOGENESIS CHARACTERIZATION

APOPTOSIS

Kimura's disease with unusual eosinophilic epithelioid granulomatous reaction: a finding possibly related to eosinophil apoptosis.

Hosaka N, Minato T, Yoshida S, Toki J, Yang G, Hisha H, Ikehara S.

Department of Clinical Pathology, Toyooka Hospital, Toyooka City, Hyogo, Japan.
Hum Pathol 2002 May;33(5):561-4 Abstract quote
We report and discuss a case of Kimura's disease with an unusual eosinophilic epithelioid granulomatous reaction. A 3-year-old Japanese boy with eosinophilia and a high concentration of IgE developed lymphadenopathy and multiple cervical masses.

A lymph node biopsy demonstrated the infiltration of eosinophils in the stroma, which is consistent with the findings of Kimura's disease. Interestingly, a number of apoptotic eosinophils was detected in the infiltrating eosinophils. Multiple epithelioid granulomas with central eosinophilic abscesses and necrosis were also observed. Macrophages and giant cells had phagocytosed the apoptotic eosinophils at the edge of the granulomas. In situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay showed that the TUNEL-positive eosinophils were both in the macrophages and in the central eosinophilic abscesses of the granulomas.

These findings suggest that the eosinophils had undergone an accelerated apoptosis in this case of Kimura's disease, and that the epithelioid granulomas were produced by phagocytosis of the apoptotic eosinophils by macrophages.

CLONALITY

Analysis of Clonality in Kimura's Disease

C. S. Chim, M.R.C.P.; A. Fung, B.Sc.; T. W. H. Shek, F.R.C.P.A.; R. Liang, M.D.; W. K. Ho, F.R.C.S.; Y. L. Kwong, F.R.C.Path.

Am J Surg Pathol 2002; 26(8):1083-1086 Abstract quote

Kimura's disease is a chronic inflammatory disorder of unknown etiology. A 62-year-old man presented with asymptomatic cervical lymphadenopathy associated with eosinophilia and increased serum immunoglobulin E. Excision biopsy showed Kimura's disease.

Three years later another groin lymph node appeared and showed similar pathologic features. Polymerase chain reaction for Ig heavy chain and T-cell receptor (TCR) genes on DNA extracted from the cervical lymph node showed smear patterns. However, polymerase chain reaction for TCRd gene showed a clonal rearrangement. Sequencing showed a complete VDJ rearrangement (Vd1-N-Dd2-N-Jd), confirming the presence of a clonal T cell population. The same clonal TCRd rearrangement was amplified by polymerase chain reaction from the groin lymph node biopsied 3 years later.

These results showed that the primary and recurrent lesions were biologically related. Furthermore, the presence of identical T cell clones in different sites and at different times suggested that a clonal T cell population might have contributed to the pathogenesis in this case of Kimura's disease.

EPSTEIN-BARR VIRUS

Detection of Epstein-Barr virus DNA in a patient with Kimura's disease.

Nagore E, Llorca J, Sanchez-Motilla JM, Ledesma E, Fortea JM, Aliaga A.

Department of Dermatology, Hospital General Universitario, Valencia, Spain.

Int J Dermatol 2000 Aug;39(8):618-20 Abstract quote

An 80-year-old man, with a past medical history of senile dementia, presented with a 6-month history of a solitary, gradually enlarging tumor, located on his chin.

A squamous cell carcinoma had been surgically excised 30 years previously in the same location. Physical examination revealed an erythematous, well-defined plaque of 3 cm in diameter, located on the chin (Fig. 1). The submandibular lymph nodes were enlarged. Squamous cell carcinoma and primary cutaneous lymphoma were considered. Relevant laboratory findings were as follows: white blood cell count, 5.600/microL; eosinophils, 1000/microL; gammaglobulin, 2.4 g/dL; lactate dehydrogenase, 343 IU/L; and immunoglobulin G (IgG) antibodies to Epstein-Barr virus (EBV) positive (at 1 : 128 serum dilution), with negative IgM.

Skin and lymph node biopsies were performed. Histopathologic study of the cutaneous specimen revealed a heavy lymphoid infiltrate with numerous lymphoid follicles, with prominent germinal centers involving the subcutaneous fat as well as the deep dermis and muscular fascia. Some germinal centers showed folliculolysis. The lymphoid follicles were surrounded by fibrous tissue. The interfollicular infiltrate was rich in plasma cells and eosinophils that formed scattered eosinophilic microabscesses. Thin-walled vessels were numerous and prominent, but with no epithelioid or vacuolated endothelial cells (Fig. 2). Histopathology of a lymph node biopsy specimen showed reactive lymphoid follicle hyperplasia, with prominent eosinophilic infiltrates in both follicular and interfollicular areas. Eosinophilic deposits and polykaryocytes of Warthin-Finkeldey type were seen in the germinal centers. The paracortical area showed vascular proliferation.

Polymerase chain reaction (PCR) for the detection of specific sequences of EBV from routinely processed paraffin-embedded material was carried out under the conditions and with the same set of primers as described previously in detail (Tenorio A, Echevarria JE, Casas E et al. J Virol Methods 1993; 44: 261-269). DNA samples were confirmed to be amplifiable with PCR primers specific for a conserved region of the human beta-globin gene. Every sample was tested at least twice for EBV DNA and beta-globin gene. One sample from one skin lesion of the patient, with confirmed diagnosis of Kimura's disease, and 10 samples from normal skin biopsies retrospectively collected from other patients in archival files of our department were tested. Only the patient's specimen tested positive to EBV. The amplified product of EBV was analyzed using DNA sequencing and confirmed the results obtained. The patient received radiotherapy at doses of 35 Gy. Nevertheless, the tumor enlarged to reach twofold its original size 1 month later. Due to the physical status of the patient, no further treatments were considered, but the disease remained stable over the following 3 years.

HHV-8

Polymerase chain reaction (PCR) for human herpesvirus 8 and heteroduplex PCR for clonality assessment in angiolymphoid hyperplasia with eosinophilia and Kimura's disease.

Jang KA, Ahn SJ, Choi JH, Sung KJ, Moon KC, Koh JK, Shim YH.

Department of Dermatology, Seoul Paik Hospital, Inje-University, Seoul, Korea.

J Cutan Pathol 2001 Aug;28(7):363-7 Abstract quote

BACKGROUND: Recently, human herpesvirus 8 (HHV-8) has been isolated from almost all cases of Kaposi's sarcoma. It has not been found in most cutaneous hemangioproliferative disorders other than Kaposi's sarcoma. Benign vascular lesions including Kimura's disease were not found to contain the HHV-8 DNA sequence. However, there has been contradictory data concerning the presence of HHV-8 in angiolymphoid hyperplasia with eosinophilia (ALHE). Clonality studies in ALHE and Kimura's disease were rare.

METHODS: We performed polymerase chain reaction (PCR)-based analysis to determine whether HHV-8 is present and heteroduplex analysis of rearranged T-cell receptor (TCR) gene for clonality assessment in paraffin-embedded skin biopsy samples of 7 ALHE and 2 Kimura's disease, taken from immunocompetent patients.

RESULTS: HHV-8 could not be identified in all the cases of ALHE and Kimura's disease. Although 2 cases (2/7) of ALHE and 2 cases (2/2) of Kimura's disease showed positive result for PCR analysis of TCR, all the cases were negative for heteroduplex-PCR.

CONCLUSIONS: We suggest that HHV-8 may not involve in a pathogenetic role in ALHE and Kimura's disease and the failure to demonstrate clonality may be consistent with the reactive nature of these diseases and lack of malignant transformation. In addition, heteroduplex-PCR can be applied to confirm doubtful cases of lymphoma in that heteroduplex-PCR is more specific than PCR as seen in our study.

INTERLEUKINS

In vivo expression of IL-4, IL-5, IL-13 and IFN-gamma mRNAs in peripheral blood mononuclear cells and effect of cyclosporin A in a patient with Kimura's disease.

Katagiri K, Itami S, Hatano Y, Yamaguchi T, Takayasu S.

Department of Dermatology, Oita Medical University, Japan.

Br J Dermatol 1997 Dec;137(6):972-7 Abstract quote

Semiquantitative reverse transcription-polymerase chain reaction was used to analyse the expression of cytokine mRNAs in freshly isolated peripheral blood mononuclear cells obtained from a patient with Kimura's disease.

The patient was treated with cyclosporin A (CsA) after incomplete tumour resection and irradiation of lesions. Levels of interleukin (IL)-4, IL-5 and IL-13 mRNA were elevated and the level of interferon (IFN)-gamma mRNA was within normal limits before treatment. The levels of IL-4, IL-5 and IL-13 mRNA, the number of eosinophils, and the serum level of IgE decreased markedly after surgery and radiation therapy. CsA treatment suppressed these values in a dose-dependent manner, but had a minimal effect on the level of IFN-gamma mRNA. The number of peripheral eosinophils decreased in association with decreases in the levels of IL-4, IL-5 and IL-13 mRNAs during CsA therapy; the serum level of IgE remained low during therapy and did not fluctuate in association with changes in cytokine levels.

These results suggest the Th2 cytokines play a part in the development of Kimura's disease and that CsA suppresses the activity of this disease.

DISEASE ASSOCIATIONS CHARACTERIZATION

Kimura's disease in a chronic hemodialysis patient.

Lee CT, Huang CC, Lam KK, Chen JB.

Division of Nephrology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

Am J Nephrol 2001 Jan-Feb;21(1):47-50 Abstract quote

Eosinophilia is not an uncommon finding in chronic dialysis patients. It is usually benign in nature although definite pathogenesis is unknown.

We have encountered a young uremic Chinese adult who developed Kimura's disease after being on maintenance hemodialysis for about 3 years. Asymptomatic eosinophilia had been noted for 1 year and 8 months prior to the development of progressively enlarged neck masses, which leads to the diagnosis of Kimura's disease. In contrast to most cases, eosinophilia was first noticed before the neck masses appeared. There is often a close correlation between Kimura's disease and glomerular disease, where renal involvement is considered as a systemic manifestation. However, we do not have strong evidence to support this relationship between terminal renal failure and Kimura's disease in this patient.

To our knowledge, our patient is the first reported case of Kimura's disease occurring in chronic hemodialysis patients. Eosinophilia persisted for nearly 2 years before the neck mass developed and recurred after the excision. Besides, our patient also demonstrated a chronic and recurrent course typical of Kimura's disease.

Steroid-sensitive anemia in a boy on dialysis--an association with Kimura disease.

Hung CC, Liao PL, Chang CT, Wu MS, Huang CC.

Department of Nephrology, Chang Gung Memorial Hospital, 5, Fu Hsing Street, Kuei-Shan Hsian, Taoyuan, Taiwan.

Pediatr Nephrol 2000 Dec;15(3-4):183-5 Abstract quote

The cause of hypereosinophilia (EO) in hemodialysis (HD) patients is multifactorial and is felt to be a benign laboratory abnormality related to dialysis or uremia. Kimura disease (KD) is an angiolymphoid proliferative disorder of unknown etiology. Many cases are associated with nephrotic syndrome in children; however, it has seldom been reported in children on dialysis.

We report here a 13-year-old boy who developed persistent EO and subsequent anemia after maintenance HD; he later developed KD. The atypical clinical manifestation of KD and its relationship to HD and erythropoietin hyposensitive anemia in this patient are discussed.

JUVENILE TEMPORAL ARTERITIS

Juvenile temporal arteritis is a manifestation of kimura disease.

Watanabe C, Koga M, Honda Y, Oh-I T.

Department of Dermatology, Tokyo Medical University, Tokyo, Japan.

Am J Dermatopathol 2002 Feb;24(1):43-9 Abstract quote
An asymptomatic nodule appeared in the right temporal region of an 81-year-old woman. Histopathologic examination confirmed significant thickening of the vascular wall, constriction of the vessel lumen, and infiltration of numerous eosinophils and lymphocytes. Giant cells were not seen. Lymphoid follicles and capillaries surrounded the large vessel. Elastica van Gieson staining revealed a laceration of the internal elastic lamina. Based on these clinical and histologic findings, the patient was diagnosed as having juvenile temporal arteritis (JTA), a disease first proposed by Lie and his colleagues in 1975. Three years later, a new eruption, again asymptomatic, appeared in the posterior region of the patient's right ear. Subsequently, she was referred to our department. Histologic examination of the new lesion confirmed the infiltration of lymphocytes and eosinophils, which was accompanied by numerous lymphoid follicles, and the proliferation of endothelial cells and capillaries from the deep dermis to the subcutaneous tissue. The patient was diagnosed as having Kimura disease, which is a persistent and recurrent illness.

We hypothesized that JTA was a partial expression of Kimura disease and investigated whether past cases of JTA could be considered Kimura disease. As a result, we found that most cases of JTA could indeed be considered Kimura disease. Furthermore, we examined the vascular changes in the routinely and elastic fiber-stained sections of three cases with Kimura disease and two cases with angiolymphoid hyperplasia with eosinophilia. The results showed occlusive vascular changes in most samples from these cases, supporting the hypothesis that JTA is an accessory lesion of Kimura disease.

LABORATORY/
RADIOLOGY CHARACTERIZATION

PET SCAN

Kimura's disease with generalized lymphadenopathy demonstrated by positron emission tomography scan.

Wang TF,
Liu SH,
Kao CH,
Chu SC,
Kao RH,
Li CC.

Division of Oncology and Hematology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan, ROC.

Intern Med. 2006 Dec;45(12):775-8. Epub 2006 Jul 18. Abstract quote

Kimura's disease is a chronic inflammatory disorder that occurs mainly in Asian patients. Most imaging studies focus on the loco-regional involvement of this disorder. Images of the whole body fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan have not been reported in the literature before. The possibility of lymphoid clonality is also discussed frequently despite its clinically benign course.

We present a patient of Kimura's disease initially assessed by whole body 18F-FDG PET study and proved by pathologic findings. 18F-FDG-PET scan showed diffusely intense uptake in the neck, axillary, pelvic and inguinal nodal regions bilaterally, as well as in the mediastinal, celiac region. The flow cytometric analysis of lymph node tissue confirmed the absence of clonality.

The image of 18F-FDG-PET in Kimura's disease can closely resemble that seen in neoplastic disorders such as lymphoma or metastatic lymphadenopathy. It should be taken into consideration as a differential diagnosis for a generalized lymphadenopathy.

CLINICAL/GROSS VARIANTS CHARACTERIZATION

Kimura disease: a clinicopathologic study of 21 cases.

Chen H, Thompson LD, Aguilera NS, Abbondanzo SL.

Department of Hematopathology, Armed Forces Institute of Pathology, Washington, DC 20306, USA.

Am J Surg Pathol. 2004 Apr;28(4):505-13. Abstract quote

Kimura disease is a rare form of chronic inflammatory disorder involving subcutaneous tissue, predominantly in the head and neck region and frequently associated with regional lymphadenopathy and/or salivary gland involvement. This condition has a predilection for males of Asian descent and may clinically simulate a neoplasm. Kimura disease is sometimes confused with angiolymphoid hyperplasia with eosinophilia, which occurs in the superficial skin of the head and neck region. Although sporadic cases have been reported in non-Asians, there is no large, comprehensive study of Kimura disease in the United States.

We report 21 cases with nodal involvement that, histologically, are consistent with Kimura disease. There were 18 males and 3 females (male/female ratio 6:1), 8 to 64 years of age (mean, 32 years), and included 7 Caucasians, 6 Blacks, 6 Asians, 1 Hispanic, and 1 Arabic. Anatomic sites of involvement included posterior auricular (n = 10), cervical (n = 6), inguinal (n = 3), and epitrochlear (n = 2) lymph nodes, with two patients having associated salivary gland involvement. Most (n = 16) cases had peripheral blood eosinophilia.

Consistent histologic features were follicular hyperplasia, eosinophilic infiltrates, and proliferation of postcapillary venules. Follow-up data on 18 patients revealed that 13 were alive without disease (3 had recurrence), mean follow-up, 10.9 years; 4 were alive with disease (2 had a recurrence), mean follow-up, 8.8 years; and 1 died with disease (12.7 years). Kimura disease has been described more often in Asians, but it does occur in non-Asians with a similar clinicopathologic presentation. It is a distinctive entity with no known etiology.

Kimura disease has characteristic histologic features that are important to recognize and can be used to differentiate it from hypersensitivity and drug reactions and infections.

Kimura's disease: a clinicopathologic study of 54 Chinese patients.

Li TJ, Chen XM, Wang SZ, Fan MW, Semba I, Kitano M.

Department of Oral Pathology, Hubei Medical University Dental School, Wuhan, People's Republic of China.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996 Nov;82(5):549-55 Abstract quote

Kimura's disease, a chronic inflammatory condition of unknown cause, is endemic in Orientals.

The present study documented 54 cases of Kimura's disease in patients from mainland China. The main clinical features of this series included young and middle-aged male predominance (male:female = 3.5:1), predilection for the head and neck regions, and a long duration. The disease presented as either single (31 cases), or multiple lesions (23 cases), and mainly involved subcutaneous tissues (29 cases), major salivary glands (21 cases), and lymph nodes (17 cases) in isolation or in combination. Histopathologically, the lesion was characterized by hyperplasia of lymphoid tissue with well-developed lymphoid follicles, marked infiltration of eosinophils, proliferation of thin-walled capillary venules, and varying degrees of fibrosis. Distinctive features of salivary glands and nodal involvement were also described.

Differences between Kimura's disease and angiolymphoid hyperplasia with eosinophilia, mostly reported in the West, were discussed to draw attention to their distinction.

Kimura's disease presenting as subcutaneous facial plaque in an African American.

Daaleman TP, Woodroof J.

Department of Family Medicine, University of Kansas Medical Center, Kansas City

Cutis 2000 Sep;66(3):201-4 Abstract quote

Kimura's disease is a benign, uncommon, chronic inflammatory condition that usually presents with painless subcutaneous nodules or plaques in the head and neck region. Although the disease is predominantly found in Asian populations, there are occasional cases reported among Caucasians and rare occurrences in African populations.

The etiology and pathogenesis of the disease are unknown and the clinical presentation can mimic several benign and malignant disease states. The accurate diagnosis of Kimura's disease is based on clinical and histopathological findings. There is no evidence of malignant transformation and occasional spontaneous resolution occurs. Various treatment modalities have been suggested in the management of this condition. Oral corticosteroids have been the mainstay of therapy, even though steroid withdrawal can result in lesion recurrence.

HEAD AND NECK

Kimura's disease of the parapharyngeal space.

Goh Hood Keng C,
Pang KP,
Teng PW.

Department of Otorhinolaryngology, Singapore General Hospital. golghk@sgh.com.sg

Ear Nose Throat J. 2006 Feb;85(2):106-8. Abstract quote

Kimura's disease is a fairly uncommon inflammatory condition of unknown etiology. It classically presents in young Asian males as tumorlike subcutaneous nodules in the head and neck with associated lymphadenopathy, peripheral eosinophilia, and an elevated serum IgE level. Kimura's disease affects the subcutaneous tissues, salivary glands, and lymph nodes; less common sites in the head and neck include the eyelid and tympanic membrane.

We report a case of Kimura's disease of the parapharyngeal space in a 42-year-old Chinese woman. To the best of our knowledge, this is the first report of Kimura's disease at this site.

HISTOLOGICAL TYPES CHARACTERIZATION

General Am J Surg Pathol 1988;12:843-854

Lymph Node
Hyperplastic lymphoid follicles
Variable intefollicular eosinophilia with proliferation of thin-walled vessels

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

Angiolymphoid hyperplasia with eosinophilia Superficial lesion with characteristic hobnail appearance of endothelial cells

Kimura's disease and angiolymphoid hyperplasia with eosinophilia: two disease entities in the same patient: case report and review of the literature.

Chong WS,
Thomas A,
Goh CL.

Mount Elizabeth Hospital, Singapore, Singapore. wschong@nsc.sg

Int J Dermatol. 2006 Feb;45(2):139-45 Abstract quote

BACKGROUND: Much controversy has existed with regard to the relationship between Kimura's disease and angiolymphoid hyperplasia with eosinophilia. They were initially thought to represent the same disease spectrum, but it has now been widely accepted that they are two separate disease entities. To our knowledge, there have been no reports to date describing a case of both Kimura's disease and angiolymphoid hyperplasia with eosinophilia coexisting in the same patient.

METHODS: We describe a patient presenting initially with a right postauricular subcutaneous swelling and subsequently developing multiple erythematous facial papules and nodules. The medical literature is reviewed.

RESULTS: Clinical features of the right postauricular subcutaneous swelling and multiple erythematous facial papules/nodules suggest Kimura's disease in the former and angiolymphoid hyperplasia with eosinophilia in the latter. Histopathological examinations of these lesions helped to confirm the diagnosis of Kimura's disease and angiolymphoid hyperplasia with eosinophilia, respectively.

CONCLUSIONS: Kimura's disease and angiolymphoid hyperplasia with eosinophilia can coexist in the same patient. Coexistence of the two types of lesions in one patient may also be considered evidence that Kimura's disease and angiolymphoid hyperplasia with eosinophilia form a spectrum in one disease.

Involvement of regional lymph nodes and distinction from angiolymphoid hyperplasia with eosinophilia.

Kuo TT, Shih LY, Chan HL.

Chang Gung Medical College, Department of Pathology, Taipei, Taiwan, Republic of China.

Am J Surg Pathol 1988 Nov;12(11):843-54 Abstract quote

The clinicopathologic features of nine patients with Kimura's disease and 15 patients with angiolymphoid hyperplasia with eosinophilia (ALHE) were studied and compared in order to clarify the confusion between these two entities.

The common features shared by both conditions included male predominance, predilection for the head and neck regions, tendency to recur, and vascular nature of the lesion with lymphoid and eosinophilic infiltrates. However, Kimura's disease was usually seen in younger individuals for a longer duration and occurred as a deeply seated, large soft-tissue mass, without significant change of the overlying skin initially. In addition, it was often accompanied by peripheral blood eosinophilia and elevated serum IgE. In contrast, ALHE lesions were multiple small dermal papular or nodular eruptions observed in older patients and present for a shorter duration; they were less frequently accompanied by peripheral blood eosinophilia.

The main histopathological difference was the presence of "histiocytoid" or "epithelioid" blood vessels in ALHE but not in Kimura's disease. Kimura's disease was further characterized by eosinophilic folliculolysis; IgE deposits in the germinal centers; and frequent involvement of regional lymph nodes, salivary glands, and skeletal muscles. The eosinophilic infiltration, especially the formation of eosinophilic microabscesses, along with increased number of small blood vessels, perinodal eosinophilic infiltration, and eosinophilic folliculolysis characterized the nodal involvement by Kimura's disease.

Our study indicates that Kimura's disease and ALHE are two distinct clinicopathologic entities. We place particular emphasis on the involvement of regional lymph nodes in Kimura's disease. In addition, we observed Charcot-Leyden crystals and polykaryocytes in both conditions. One of the patients with Kimura's disease also had an associated nephrotic syndrome.

LYMPHOMA

Changing clinical manifestations of a T-peripheral lymphoma: from hypereosinophilic syndrome to questionable Kimura's disease resulting in parotid mass.

Beyazit Y,
Haznedaroglu IC,
Aksu S,
Kekilli M,
Uner A,
Agbaht K,
Sungur A,
Koca E,
Goker H,
Ozcebe OI.

Department of Internal Medicine, Hacettepe University Medical School, Ankara, Turkey. yavuzbeyaz@yahoo.com

Leuk Lymphoma. 2006 Feb;47(2):357-60 Abstract quote

The diagnosis of low-grade lymphoproliferative disorders during a long clinical course sometimes represents a great clinical challenge.

The idiopathic hypereosinophilic syndrome (HES) represents a pre-malignant state in some patients and close follow-up is necessary to detect early signs of malignant transformation. Kimura's disease (KD) mimicking HES is an immune mediated inflammatory disorder that usually involves the head and neck region, primarily affecting the salivary glands, adjacent muscle and regional lymph nodes. Clinically, it is very difficult to differentiate KD from salivary gland lymphoid malignancies. Lymphomas may uncommonly present as a parotid mass. One, herein, would like to present a 35-year-old patient with changing clinical presentation patterns over a period of more than 6 years of follow-up. The first clinical presentation of the patient was HES. The 'diagnosis' of KD was reached after 4 years of management with HES.

The final manifestation was parotid gland, preauricular and cutaneous manifestations of a peripheral T-cell lymphoma. This unique clinical presentation pattern of the patient may represent the distinct pathobiological progression of a clonal neoplastic lymphoproliferative disorder.

PROGNOSIS AND TREATMENT CHARACTERIZATION

Survival Excellent

Treatment Surgical removal
May utilize radiation or corticosteroids in inoperable lesions

Combined treatment of steroids and cyclosporine in Kimura disease.

Sato S,
Kawashima H,
Kuboshima S,
Watanabe K,
Kashiwagi Y,
Takekuma K,
Hoshika A.

Department of Pediatrics, Tokyo Medical University, Nishishinjuku, Tokyo, Japan. sato115@tokyo-med.ac.jp

Pediatrics. 2006 Sep;118(3):e921-3. Epub 2006 Abstract quote

Kimura disease is a rare but distinctive chronic eosinophilic inflammatory disorder that is characterized by tumor-like lesions in the soft tissue and lymph nodes of the head and neck or parotid gland. Recently, many immunopathogenetic features of underlying T lymphocytes and related cytokines have been noted in Kimura disease. However, few previous studies have investigated the serial levels of cytokines in children.

In this report we describe an 11-year-old Japanese boy with relapsing Kimura disease. Before the diagnosis of Kimura disease, the patient had a swelling on his left neck. Steroids were effective, but the tumor relapsed within a few months as the steroids were tapered. He was treated with steroids and cyclosporine. This treatment was done by measuring serial levels of serum soluble interleukin-2 receptor, interleukin-4, interleukin-5, and eosinophil cationic protein.

These results suggest the activation of T-helper cells and T-helper 2 cytokines, that after activated B cells and eosinophilic infiltration play an important role in Kimura disease, and that cyclosporine suppresses the activity of this disease.

Recurrent Kimura's disease: excellent response to cyclosporine.

Shenoy VV,
Joshi SR,
Kotwal VS,
Shedge RT,
Ramraje NN,
Lanjewar DN.

Dept. of Medicine; Grant Medical College & Sir J.J. Group of [Govt.] Hospitals, Mumbai, India

J Assoc Physicians India. 2006 Feb;54:153-5. Abstract quote

Kimura's disease is a chronic inflammatory disorder involving the skin, subcutaneous tissues and lymph nodes, predominantly in the head and neck region. Though surgery, intralesional or systemic steroids or radiation therapy have been the mainstay of treatment recurrence is a common problem.

On the basis of occasional case report of Kimura's disease responding to cyclosporine, we attempted oral cyclosporine in our patient with dramatic improvement.

Outcomes of Kimura's disease after radiotherapy or nonradiotherapeutic treatment modalities.

Chang AR,
Kim K,
Kim HJ,
Kim IH,
Park CI,
Jun YK.

Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Hospital, Republic of Korea.

Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):1233-9. Epub 2006 Jun 5 Abstract quote

PURPOSE: To evaluate the clinical outcome of Kimura's disease and to identify the optimal treatment regimen for Kimura's disease.

METHODS AND MATERIALS: Between 1984 and 2003, 14 patients with Kimura's disease were treated with radiotherapy (RT) and 9 patients were treated with local excision or systemic steroids. The radiation doses ranged from 20 to 45 Gy. Immunohistochemical studies were performed in 13 cases.

RESULTS: At RT completion, a marked response in terms of tumor size was noted in most cases. The median follow-up was 65 months. Local control was obtained in 9 (64.3%) of the 14 in the RT group and in 2 (22.2%) of the 9 in the non-RT group. No secondary malignancies were observed in the RT group.

CONCLUSION: These results supports the finding that RT is more effective against Kimura's disease. Simple or immunohistochemical features did not influence the treatment outcome.

Treatment of Kimura's disease with cyclosporine.

Wang YS,
Tay YK,
Tan E,
Poh WT.

Division of Dermatology, Department of Laboratory Medicine, Changi General Hospital, Singapore.

J Dermatolog Treat. 2005;16(4):242-4 Abstract quote

Kimura's disease is a rare, chronic inflammatory disease of unknown cause. It is characterized by painless subcutaneous swellings and lymphadenopathy, commonly affecting the head and neck region.

This is associated with peripheral blood eosinophilia and raised serum IgE. It has distinct histological features of lymphoid follicles, eosinophilic infiltrate, fibrosis and vascular proliferation. The disease usually has a benign, indolent course. Traditionally, therapeutic options have included surgery, radiotherapy and steroids but response has been less than satisfactory. Recently, cyclosporine has been reported to be effective in the treatment of Kimura's disease.

In this article, we present a middle-aged Chinese female with Kimura's disease for 20 years and her favourable response to cyclosporine.

Radiotherapy for Kimura's disease: the optimum dosage.

Hareyama M, Oouchi A, Nagakura H, Asakura K, Saito A, Satoh M, Tamakawa M, Akiba H, Sakata K, Yoshida S, Koito K, Imai K, Kataura A, Morita K.

Department of Radiology, Sapporo Medical University, School of Medicine, Japan.

Int J Radiat Oncol Biol Phys 1998 Feb 1;40(3):647-51 Abstract quote

PURPOSE: To evaluate retrospectively the optimum dosage of irradiation for Kimura's disease.

METHODS AND MATERIALS: Twenty patients with Kimura's disease were treated with radiotherapy. The sex ratio was 19 males to 1 female. The mean ages at onset, initial treatment, and radiotherapy were 26.2, 29.5, and 32.2 years, respectively. Radiotherapy was mainly applied for residual or recurrent tumors. The eosinophil count increased by more than 10% in 18 of the 20 patients. In most instances, irradiation was given through a single field with dosages ranging from 20 to 44 Gy.

RESULTS: At the completion of radiotherapy, a marked response in tumor size was noted in all cases. The minimum follow-up was 48 months. Local control was obtained in 23 of 31 lesions (74.1%). At dosages of < or =25 Gy, 26-30 Gy, and > 30 Gy, local control was obtained in 2 of 8 (25.0%), 9 of 10 (90.0%), and 12 of 13 sites (92.3%), respectively.

CONCLUSIONS: Radiotherapy is an effective treatment for Kimura's disease. This strongly suggests that no surgical procedure other than a biopsy should be carried out. The radiation field should be limited to the lesion and swelling of the adjacent lymph nodes as much as possible, with a optimum dosage of 26-30 Gy regardless of tumor size.

Successful treatment of Kimura's disease with cyclosporine.

Kaneko K, Aoki M, Hattori S, Sato M, Kawana S.

Department of Dermatology, Nippon Medical School, Tokyo, Japan.

J Am Acad Dermatol 1999 Nov;41(5 Pt 2):893-4 Abstract quote

We report the case of a 29-year-old Japanese woman presenting with recurring Kimura's disease. We began treatment with cyclosporine within 7 days, the nodular lesion had almost cleared. The cyclosporine dose was then gradually reduced and discontinued after 6 months. The patient was reassessed 18 months after the cessation of treatment and there was no evidence of recurrence of the disease.

We speculate that the effects of cyclosporine on T helper-2 cells improves Kimura's disease.

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Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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PATHOGENESIS	CHARACTERIZATION
APOPTOSIS
Kimura's disease with unusual eosinophilic epithelioid granulomatous reaction: a finding possibly related to eosinophil apoptosis. Hosaka N, Minato T, Yoshida S, Toki J, Yang G, Hisha H, Ikehara S. Department of Clinical Pathology, Toyooka Hospital, Toyooka City, Hyogo, Japan.	Hum Pathol 2002 May;33(5):561-4 Abstract quote We report and discuss a case of Kimura's disease with an unusual eosinophilic epithelioid granulomatous reaction. A 3-year-old Japanese boy with eosinophilia and a high concentration of IgE developed lymphadenopathy and multiple cervical masses. A lymph node biopsy demonstrated the infiltration of eosinophils in the stroma, which is consistent with the findings of Kimura's disease. Interestingly, a number of apoptotic eosinophils was detected in the infiltrating eosinophils. Multiple epithelioid granulomas with central eosinophilic abscesses and necrosis were also observed. Macrophages and giant cells had phagocytosed the apoptotic eosinophils at the edge of the granulomas. In situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay showed that the TUNEL-positive eosinophils were both in the macrophages and in the central eosinophilic abscesses of the granulomas. These findings suggest that the eosinophils had undergone an accelerated apoptosis in this case of Kimura's disease, and that the epithelioid granulomas were produced by phagocytosis of the apoptotic eosinophils by macrophages.
CLONALITY
Analysis of Clonality in Kimura's Disease C. S. Chim, M.R.C.P.; A. Fung, B.Sc.; T. W. H. Shek, F.R.C.P.A.; R. Liang, M.D.; W. K. Ho, F.R.C.S.; Y. L. Kwong, F.R.C.Path.	Am J Surg Pathol 2002; 26(8):1083-1086 Abstract quote Kimura's disease is a chronic inflammatory disorder of unknown etiology. A 62-year-old man presented with asymptomatic cervical lymphadenopathy associated with eosinophilia and increased serum immunoglobulin E. Excision biopsy showed Kimura's disease. Three years later another groin lymph node appeared and showed similar pathologic features. Polymerase chain reaction for Ig heavy chain and T-cell receptor (TCR) genes on DNA extracted from the cervical lymph node showed smear patterns. However, polymerase chain reaction for TCRd gene showed a clonal rearrangement. Sequencing showed a complete VDJ rearrangement (Vd1-N-Dd2-N-Jd), confirming the presence of a clonal T cell population. The same clonal TCRd rearrangement was amplified by polymerase chain reaction from the groin lymph node biopsied 3 years later. These results showed that the primary and recurrent lesions were biologically related. Furthermore, the presence of identical T cell clones in different sites and at different times suggested that a clonal T cell population might have contributed to the pathogenesis in this case of Kimura's disease.
EPSTEIN-BARR VIRUS
Detection of Epstein-Barr virus DNA in a patient with Kimura's disease. Nagore E, Llorca J, Sanchez-Motilla JM, Ledesma E, Fortea JM, Aliaga A. Department of Dermatology, Hospital General Universitario, Valencia, Spain.	Int J Dermatol 2000 Aug;39(8):618-20 Abstract quote An 80-year-old man, with a past medical history of senile dementia, presented with a 6-month history of a solitary, gradually enlarging tumor, located on his chin. A squamous cell carcinoma had been surgically excised 30 years previously in the same location. Physical examination revealed an erythematous, well-defined plaque of 3 cm in diameter, located on the chin (Fig. 1). The submandibular lymph nodes were enlarged. Squamous cell carcinoma and primary cutaneous lymphoma were considered. Relevant laboratory findings were as follows: white blood cell count, 5.600/microL; eosinophils, 1000/microL; gammaglobulin, 2.4 g/dL; lactate dehydrogenase, 343 IU/L; and immunoglobulin G (IgG) antibodies to Epstein-Barr virus (EBV) positive (at 1 : 128 serum dilution), with negative IgM. Skin and lymph node biopsies were performed. Histopathologic study of the cutaneous specimen revealed a heavy lymphoid infiltrate with numerous lymphoid follicles, with prominent germinal centers involving the subcutaneous fat as well as the deep dermis and muscular fascia. Some germinal centers showed folliculolysis. The lymphoid follicles were surrounded by fibrous tissue. The interfollicular infiltrate was rich in plasma cells and eosinophils that formed scattered eosinophilic microabscesses. Thin-walled vessels were numerous and prominent, but with no epithelioid or vacuolated endothelial cells (Fig. 2). Histopathology of a lymph node biopsy specimen showed reactive lymphoid follicle hyperplasia, with prominent eosinophilic infiltrates in both follicular and interfollicular areas. Eosinophilic deposits and polykaryocytes of Warthin-Finkeldey type were seen in the germinal centers. The paracortical area showed vascular proliferation. Polymerase chain reaction (PCR) for the detection of specific sequences of EBV from routinely processed paraffin-embedded material was carried out under the conditions and with the same set of primers as described previously in detail (Tenorio A, Echevarria JE, Casas E et al. J Virol Methods 1993; 44: 261-269). DNA samples were confirmed to be amplifiable with PCR primers specific for a conserved region of the human beta-globin gene. Every sample was tested at least twice for EBV DNA and beta-globin gene. One sample from one skin lesion of the patient, with confirmed diagnosis of Kimura's disease, and 10 samples from normal skin biopsies retrospectively collected from other patients in archival files of our department were tested. Only the patient's specimen tested positive to EBV. The amplified product of EBV was analyzed using DNA sequencing and confirmed the results obtained. The patient received radiotherapy at doses of 35 Gy. Nevertheless, the tumor enlarged to reach twofold its original size 1 month later. Due to the physical status of the patient, no further treatments were considered, but the disease remained stable over the following 3 years.
HHV-8
Polymerase chain reaction (PCR) for human herpesvirus 8 and heteroduplex PCR for clonality assessment in angiolymphoid hyperplasia with eosinophilia and Kimura's disease. Jang KA, Ahn SJ, Choi JH, Sung KJ, Moon KC, Koh JK, Shim YH. Department of Dermatology, Seoul Paik Hospital, Inje-University, Seoul, Korea.	J Cutan Pathol 2001 Aug;28(7):363-7 Abstract quote BACKGROUND: Recently, human herpesvirus 8 (HHV-8) has been isolated from almost all cases of Kaposi's sarcoma. It has not been found in most cutaneous hemangioproliferative disorders other than Kaposi's sarcoma. Benign vascular lesions including Kimura's disease were not found to contain the HHV-8 DNA sequence. However, there has been contradictory data concerning the presence of HHV-8 in angiolymphoid hyperplasia with eosinophilia (ALHE). Clonality studies in ALHE and Kimura's disease were rare. METHODS: We performed polymerase chain reaction (PCR)-based analysis to determine whether HHV-8 is present and heteroduplex analysis of rearranged T-cell receptor (TCR) gene for clonality assessment in paraffin-embedded skin biopsy samples of 7 ALHE and 2 Kimura's disease, taken from immunocompetent patients. RESULTS: HHV-8 could not be identified in all the cases of ALHE and Kimura's disease. Although 2 cases (2/7) of ALHE and 2 cases (2/2) of Kimura's disease showed positive result for PCR analysis of TCR, all the cases were negative for heteroduplex-PCR. CONCLUSIONS: We suggest that HHV-8 may not involve in a pathogenetic role in ALHE and Kimura's disease and the failure to demonstrate clonality may be consistent with the reactive nature of these diseases and lack of malignant transformation. In addition, heteroduplex-PCR can be applied to confirm doubtful cases of lymphoma in that heteroduplex-PCR is more specific than PCR as seen in our study.
INTERLEUKINS
In vivo expression of IL-4, IL-5, IL-13 and IFN-gamma mRNAs in peripheral blood mononuclear cells and effect of cyclosporin A in a patient with Kimura's disease. Katagiri K, Itami S, Hatano Y, Yamaguchi T, Takayasu S. Department of Dermatology, Oita Medical University, Japan.	Br J Dermatol 1997 Dec;137(6):972-7 Abstract quote Semiquantitative reverse transcription-polymerase chain reaction was used to analyse the expression of cytokine mRNAs in freshly isolated peripheral blood mononuclear cells obtained from a patient with Kimura's disease. The patient was treated with cyclosporin A (CsA) after incomplete tumour resection and irradiation of lesions. Levels of interleukin (IL)-4, IL-5 and IL-13 mRNA were elevated and the level of interferon (IFN)-gamma mRNA was within normal limits before treatment. The levels of IL-4, IL-5 and IL-13 mRNA, the number of eosinophils, and the serum level of IgE decreased markedly after surgery and radiation therapy. CsA treatment suppressed these values in a dose-dependent manner, but had a minimal effect on the level of IFN-gamma mRNA. The number of peripheral eosinophils decreased in association with decreases in the levels of IL-4, IL-5 and IL-13 mRNAs during CsA therapy; the serum level of IgE remained low during therapy and did not fluctuate in association with changes in cytokine levels. These results suggest the Th2 cytokines play a part in the development of Kimura's disease and that CsA suppresses the activity of this disease.

LABORATORY/ RADIOLOGY	CHARACTERIZATION
PET SCAN
Kimura's disease with generalized lymphadenopathy demonstrated by positron emission tomography scan. Wang TF, Liu SH, Kao CH, Chu SC, Kao RH, Li CC. Division of Oncology and Hematology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan, ROC.	Intern Med. 2006 Dec;45(12):775-8. Epub 2006 Jul 18. Abstract quote Kimura's disease is a chronic inflammatory disorder that occurs mainly in Asian patients. Most imaging studies focus on the loco-regional involvement of this disorder. Images of the whole body fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan have not been reported in the literature before. The possibility of lymphoid clonality is also discussed frequently despite its clinically benign course. We present a patient of Kimura's disease initially assessed by whole body 18F-FDG PET study and proved by pathologic findings. 18F-FDG-PET scan showed diffusely intense uptake in the neck, axillary, pelvic and inguinal nodal regions bilaterally, as well as in the mediastinal, celiac region. The flow cytometric analysis of lymph node tissue confirmed the absence of clonality. The image of 18F-FDG-PET in Kimura's disease can closely resemble that seen in neoplastic disorders such as lymphoma or metastatic lymphadenopathy. It should be taken into consideration as a differential diagnosis for a generalized lymphadenopathy.

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Angiolymphoid hyperplasia with eosinophilia	Superficial lesion with characteristic hobnail appearance of endothelial cells
Kimura's disease and angiolymphoid hyperplasia with eosinophilia: two disease entities in the same patient: case report and review of the literature. Chong WS, Thomas A, Goh CL. Mount Elizabeth Hospital, Singapore, Singapore. wschong@nsc.sg	Int J Dermatol. 2006 Feb;45(2):139-45 Abstract quote BACKGROUND: Much controversy has existed with regard to the relationship between Kimura's disease and angiolymphoid hyperplasia with eosinophilia. They were initially thought to represent the same disease spectrum, but it has now been widely accepted that they are two separate disease entities. To our knowledge, there have been no reports to date describing a case of both Kimura's disease and angiolymphoid hyperplasia with eosinophilia coexisting in the same patient. METHODS: We describe a patient presenting initially with a right postauricular subcutaneous swelling and subsequently developing multiple erythematous facial papules and nodules. The medical literature is reviewed. RESULTS: Clinical features of the right postauricular subcutaneous swelling and multiple erythematous facial papules/nodules suggest Kimura's disease in the former and angiolymphoid hyperplasia with eosinophilia in the latter. Histopathological examinations of these lesions helped to confirm the diagnosis of Kimura's disease and angiolymphoid hyperplasia with eosinophilia, respectively. CONCLUSIONS: Kimura's disease and angiolymphoid hyperplasia with eosinophilia can coexist in the same patient. Coexistence of the two types of lesions in one patient may also be considered evidence that Kimura's disease and angiolymphoid hyperplasia with eosinophilia form a spectrum in one disease.
Involvement of regional lymph nodes and distinction from angiolymphoid hyperplasia with eosinophilia. Kuo TT, Shih LY, Chan HL. Chang Gung Medical College, Department of Pathology, Taipei, Taiwan, Republic of China.	Am J Surg Pathol 1988 Nov;12(11):843-54 Abstract quote The clinicopathologic features of nine patients with Kimura's disease and 15 patients with angiolymphoid hyperplasia with eosinophilia (ALHE) were studied and compared in order to clarify the confusion between these two entities. The common features shared by both conditions included male predominance, predilection for the head and neck regions, tendency to recur, and vascular nature of the lesion with lymphoid and eosinophilic infiltrates. However, Kimura's disease was usually seen in younger individuals for a longer duration and occurred as a deeply seated, large soft-tissue mass, without significant change of the overlying skin initially. In addition, it was often accompanied by peripheral blood eosinophilia and elevated serum IgE. In contrast, ALHE lesions were multiple small dermal papular or nodular eruptions observed in older patients and present for a shorter duration; they were less frequently accompanied by peripheral blood eosinophilia. The main histopathological difference was the presence of "histiocytoid" or "epithelioid" blood vessels in ALHE but not in Kimura's disease. Kimura's disease was further characterized by eosinophilic folliculolysis; IgE deposits in the germinal centers; and frequent involvement of regional lymph nodes, salivary glands, and skeletal muscles. The eosinophilic infiltration, especially the formation of eosinophilic microabscesses, along with increased number of small blood vessels, perinodal eosinophilic infiltration, and eosinophilic folliculolysis characterized the nodal involvement by Kimura's disease. Our study indicates that Kimura's disease and ALHE are two distinct clinicopathologic entities. We place particular emphasis on the involvement of regional lymph nodes in Kimura's disease. In addition, we observed Charcot-Leyden crystals and polykaryocytes in both conditions. One of the patients with Kimura's disease also had an associated nephrotic syndrome.
LYMPHOMA
Changing clinical manifestations of a T-peripheral lymphoma: from hypereosinophilic syndrome to questionable Kimura's disease resulting in parotid mass. Beyazit Y, Haznedaroglu IC, Aksu S, Kekilli M, Uner A, Agbaht K, Sungur A, Koca E, Goker H, Ozcebe OI. Department of Internal Medicine, Hacettepe University Medical School, Ankara, Turkey. yavuzbeyaz@yahoo.com	Leuk Lymphoma. 2006 Feb;47(2):357-60 Abstract quote The diagnosis of low-grade lymphoproliferative disorders during a long clinical course sometimes represents a great clinical challenge. The idiopathic hypereosinophilic syndrome (HES) represents a pre-malignant state in some patients and close follow-up is necessary to detect early signs of malignant transformation. Kimura's disease (KD) mimicking HES is an immune mediated inflammatory disorder that usually involves the head and neck region, primarily affecting the salivary glands, adjacent muscle and regional lymph nodes. Clinically, it is very difficult to differentiate KD from salivary gland lymphoid malignancies. Lymphomas may uncommonly present as a parotid mass. One, herein, would like to present a 35-year-old patient with changing clinical presentation patterns over a period of more than 6 years of follow-up. The first clinical presentation of the patient was HES. The 'diagnosis' of KD was reached after 4 years of management with HES. The final manifestation was parotid gland, preauricular and cutaneous manifestations of a peripheral T-cell lymphoma. This unique clinical presentation pattern of the patient may represent the distinct pathobiological progression of a clonal neoplastic lymphoproliferative disorder.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Survival	Excellent
Treatment	Surgical removal May utilize radiation or corticosteroids in inoperable lesions
Combined treatment of steroids and cyclosporine in Kimura disease. Sato S, Kawashima H, Kuboshima S, Watanabe K, Kashiwagi Y, Takekuma K, Hoshika A. Department of Pediatrics, Tokyo Medical University, Nishishinjuku, Tokyo, Japan. sato115@tokyo-med.ac.jp	Pediatrics. 2006 Sep;118(3):e921-3. Epub 2006 Abstract quote Kimura disease is a rare but distinctive chronic eosinophilic inflammatory disorder that is characterized by tumor-like lesions in the soft tissue and lymph nodes of the head and neck or parotid gland. Recently, many immunopathogenetic features of underlying T lymphocytes and related cytokines have been noted in Kimura disease. However, few previous studies have investigated the serial levels of cytokines in children. In this report we describe an 11-year-old Japanese boy with relapsing Kimura disease. Before the diagnosis of Kimura disease, the patient had a swelling on his left neck. Steroids were effective, but the tumor relapsed within a few months as the steroids were tapered. He was treated with steroids and cyclosporine. This treatment was done by measuring serial levels of serum soluble interleukin-2 receptor, interleukin-4, interleukin-5, and eosinophil cationic protein. These results suggest the activation of T-helper cells and T-helper 2 cytokines, that after activated B cells and eosinophilic infiltration play an important role in Kimura disease, and that cyclosporine suppresses the activity of this disease.
Recurrent Kimura's disease: excellent response to cyclosporine. Shenoy VV, Joshi SR, Kotwal VS, Shedge RT, Ramraje NN, Lanjewar DN. Dept. of Medicine; Grant Medical College & Sir J.J. Group of [Govt.] Hospitals, Mumbai, India	J Assoc Physicians India. 2006 Feb;54:153-5. Abstract quote Kimura's disease is a chronic inflammatory disorder involving the skin, subcutaneous tissues and lymph nodes, predominantly in the head and neck region. Though surgery, intralesional or systemic steroids or radiation therapy have been the mainstay of treatment recurrence is a common problem. On the basis of occasional case report of Kimura's disease responding to cyclosporine, we attempted oral cyclosporine in our patient with dramatic improvement.
Outcomes of Kimura's disease after radiotherapy or nonradiotherapeutic treatment modalities. Chang AR, Kim K, Kim HJ, Kim IH, Park CI, Jun YK. Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Hospital, Republic of Korea.	Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):1233-9. Epub 2006 Jun 5 Abstract quote PURPOSE: To evaluate the clinical outcome of Kimura's disease and to identify the optimal treatment regimen for Kimura's disease. METHODS AND MATERIALS: Between 1984 and 2003, 14 patients with Kimura's disease were treated with radiotherapy (RT) and 9 patients were treated with local excision or systemic steroids. The radiation doses ranged from 20 to 45 Gy. Immunohistochemical studies were performed in 13 cases. RESULTS: At RT completion, a marked response in terms of tumor size was noted in most cases. The median follow-up was 65 months. Local control was obtained in 9 (64.3%) of the 14 in the RT group and in 2 (22.2%) of the 9 in the non-RT group. No secondary malignancies were observed in the RT group. CONCLUSION: These results supports the finding that RT is more effective against Kimura's disease. Simple or immunohistochemical features did not influence the treatment outcome.
Treatment of Kimura's disease with cyclosporine. Wang YS, Tay YK, Tan E, Poh WT. Division of Dermatology, Department of Laboratory Medicine, Changi General Hospital, Singapore.	J Dermatolog Treat. 2005;16(4):242-4 Abstract quote Kimura's disease is a rare, chronic inflammatory disease of unknown cause. It is characterized by painless subcutaneous swellings and lymphadenopathy, commonly affecting the head and neck region. This is associated with peripheral blood eosinophilia and raised serum IgE. It has distinct histological features of lymphoid follicles, eosinophilic infiltrate, fibrosis and vascular proliferation. The disease usually has a benign, indolent course. Traditionally, therapeutic options have included surgery, radiotherapy and steroids but response has been less than satisfactory. Recently, cyclosporine has been reported to be effective in the treatment of Kimura's disease. In this article, we present a middle-aged Chinese female with Kimura's disease for 20 years and her favourable response to cyclosporine.
Radiotherapy for Kimura's disease: the optimum dosage. Hareyama M, Oouchi A, Nagakura H, Asakura K, Saito A, Satoh M, Tamakawa M, Akiba H, Sakata K, Yoshida S, Koito K, Imai K, Kataura A, Morita K. Department of Radiology, Sapporo Medical University, School of Medicine, Japan.	Int J Radiat Oncol Biol Phys 1998 Feb 1;40(3):647-51 Abstract quote PURPOSE: To evaluate retrospectively the optimum dosage of irradiation for Kimura's disease. METHODS AND MATERIALS: Twenty patients with Kimura's disease were treated with radiotherapy. The sex ratio was 19 males to 1 female. The mean ages at onset, initial treatment, and radiotherapy were 26.2, 29.5, and 32.2 years, respectively. Radiotherapy was mainly applied for residual or recurrent tumors. The eosinophil count increased by more than 10% in 18 of the 20 patients. In most instances, irradiation was given through a single field with dosages ranging from 20 to 44 Gy. RESULTS: At the completion of radiotherapy, a marked response in tumor size was noted in all cases. The minimum follow-up was 48 months. Local control was obtained in 23 of 31 lesions (74.1%). At dosages of < or =25 Gy, 26-30 Gy, and > 30 Gy, local control was obtained in 2 of 8 (25.0%), 9 of 10 (90.0%), and 12 of 13 sites (92.3%), respectively. CONCLUSIONS: Radiotherapy is an effective treatment for Kimura's disease. This strongly suggests that no surgical procedure other than a biopsy should be carried out. The radiation field should be limited to the lesion and swelling of the adjacent lymph nodes as much as possible, with a optimum dosage of 26-30 Gy regardless of tumor size.
Successful treatment of Kimura's disease with cyclosporine. Kaneko K, Aoki M, Hattori S, Sato M, Kawana S. Department of Dermatology, Nippon Medical School, Tokyo, Japan.	J Am Acad Dermatol 1999 Nov;41(5 Pt 2):893-4 Abstract quote We report the case of a 29-year-old Japanese woman presenting with recurring Kimura's disease. We began treatment with cyclosporine within 7 days, the nodular lesion had almost cleared. The cyclosporine dose was then gradually reduced and discontinued after 6 months. The patient was reassessed 18 months after the cessation of treatment and there was no evidence of recurrence of the disease. We speculate that the effects of cyclosporine on T helper-2 cells improves Kimura's disease.

Epidemiology
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EPIDEMIOLOGY	CHARACTERIZATION
AGE RANGE-MEDIAN	2-3rd decades
SEX (M:F)	Females
GEOGRAPHY	Asians

HISTOLOGICAL TYPES	CHARACTERIZATION
General	Am J Surg Pathol 1988;12:843-854
Lymph Node	Hyperplastic lymphoid follicles Variable intefollicular eosinophilia with proliferation of thin-walled vessels