IJSS Journal of Surgery

Kimura’s Disease of Face: A Clinicopathological Presentation and Review

Anji Reddy BA Rama Krishna


Kimura’s disease is an extremely unusual disorder of benign nature affecting the connective tissue, and primarily seen in young males in countries of Asian pacific region particularly in China and Japan. This is characterized by three essential components of diagnostic importance. (a) Painless benign subcutaneous masses and rarely lymph nodes most predominantly in the head and neck region and usually solitary, (b) Gross eosinophilia in the blood and also in the affected tissue, (c) Markedly elevated serum immunoglobulin E levels. We are reporting this extensive case in a male aged 28 years, and the lesion started when he was 15 years old, affecting the cheeks and submental region, right parotid gland, and associated lymph nodes. Since we operated all the three masses, we present our operative and clinical experiences along with histopathological findings. We are also reviewing the cases already reported earlier and the problems of clinical diagnosis and to differentiate from other diseases which may simulate this disease. Relative merits of all the treatment protocols and the outcome of the disease is also discussed in the light of our experience with this patient.

Keywords: Angiolymphoid hyperplasia with eosinophilia, Eosinophilic granuloma, Glomerulonephritis, Kimura’s disease, Salivary gland hypertrophy


Kimura’s disease is a rare chronic inflammatory disorder.1 Its primary symptoms are subcutaneous nodules in the head and neck region or as painless unilateral or bilateral inflammation of cervical lymph nodes.2,3 Typical clinical presentation is characterized by the triad of painless cervical lymphadenopathy or subcutaneous nodules predominantly in the head and neck region, blood, and tissue eosinophilia and markedly elevated serum immunoglobulin E (IgE) levels.4 It is an allergic or autoimmune disorder of unknown etiology which is endemic in orientals. The exact etiological factors remain unknown. Reasons like allergic reaction or an alteration of immune regulation and other theories like persistent antigenic stimulation following arthropod bites are proposed as etiological factors.

The first known report of Kimura disease was made in china in 1937.5 The common term of Kimura’s disease was coined in 1948 by Kimura et al. This disease is endemic in Asia and sporadic in the rest of the world.6

The disease typically presents as painless subcutaneous masses or lymphadenopathy of insidious onset in the head and neck region with occasional pruritis in the overlying skin.7 The clinical course of the disease is generally benign and self-limiting.

Very difficult to make a clinical diagnosis and the hematological investigations, radiological investigations like us/scanning and magnetic resonance imaging (MRI) and histopathology gives the correct picture of the disease for diagnosis and treatment.

Regarding the pathophysiology of the disease theories of allergic reactions or altered autoimmune mechanism are put forward, but there is no definite evidence so far. Persistent antigenic stimulus by arthropod bites, parasites, or candida infection have been put forward in some of the reported cases. In this patient, there is a history of honey bees sting all over the body after which he developed these lesions on the face. The relief patient has with Tab cetrizine (10 mg/day) also points toward an allergic or autoimmune mechanism. On histopathology, the disease is manifested by abnormal hyperplasia of lymphoid follicles and vascular endothelium. Presence of eosinophils in the inflammatory infiltrate, and peripheral eosinophilia suggest that Kimura’s disease may be a hypersensitivity reaction even though some cases of involvement of parotid and other salivary glands is reported, it is still not very evident whether the swelling of the parotid glands is due to actual involvement in the disease process or it is due to hyperplasia of the lymph nodes like periparotid or intraparotid lymph nodes.

It is essentially a benign condition, progressive with remissions and recurrences. Surgical excision is the mainstay of treatment. Conservative medical treatment with steroids, antihistaminics, retinoids, and cytotoxic drugs are also used with good successes even though the relief is transient. In some of the patients where there are recurrences and not amenable to surgery, radiotherapy with external irradiation was also tried. Since this disease is essentially a benign condition and not known for malignant transformation use of radiotherapy should be limited only when it is absolute.

Case Report

A 28-year-old male patient came to the surgical outpatient with a complaint of swelling of the face involving both the cheeks and submental region (Figures 1-3) present since the age of 15 years. Manual agricultural laborer, married, having two sons aged 4 and 6 years. They are two brothers in the family and the eldest died at 22 years of age due to? kidney disease.

Figure 2
Figure 2
Preoperative (Rt. Cheek)
Figure 3
Preoperative (Lt. Cheek)

He sustained honey bees sting all over the body at the age of 14 years. He developed swelling over the right side of the face after 1-year. He developed itching relieved with antihistaminics. He was operated by a local doctor. Got reduced for few months. Later he developed the swellings in both cheeks and submental region, increasing in size for the last 2-3 months. Itching is present over both cheeks which are relieved with cetrizine tablets. Complains of occasional urticarial rash and itching on the face and limbs relieved by anti-hismine tabs. He smokes 5 cigarettes/day and consumes alcohol occasionally. He takes mixed diet.

Local examination: There are 3 swellings on the face, i.e., right cheek, left cheek and submental region. Swellings, 12 cm/10 cm oval in shape on the right cheek, circular 8 cm/8 cm on the left cheek and 6 cm/2.5 cm in the submental region. The surface is smooth overlying skin is thick and not pinchable. The swellings are firm in consistency. One submandibular lymph node is palpable on the right side. The right parotid gland appears enlarged. No facial nerve involvement. No intraoral extension. Previously operated scar on the right cheek is present. Left parotid is not enlarged no other palpable lymph nodes in the neck. He consulted several physicians and surgeons without much benefit. He is not having any other complaints.

Investigations Blood:
  • Hemoglobin - 15.1 g/dl, total white blood cells count - 10,500/cu.mm
  • Differential count: N - 45 L - 31 E - 20 M - 04
  • Erythrocyte sedimentation rate - 110/1st h
  • IgE - 6000 IU/ml
  • Absolute eosinophil count - 3528 cells/ml
  • Serum creatinine - 1.1 mg/dl.
Radioimaging: Ultrasound scanning of cheek:
  • Heterogenous Iso to hyperechoic lobulated areas in the soft tissue of bilateral pre-maxillary regions
  • Enlarged bilateral cervical lymph nodes.
  • MRI face before surgery on the right cheek.

Large irregular soft tissue mass in the subcutaneous plane of right buccal region with soft tissue extension into the infratemporal or periauricular regions associated with enlarged cervical lymph nodes and involvement of parotid gland

Schedule of surgical management:

  • Submental lesion
  • Admission: 24-04-2015; Operation: 27-04-2015; Discharge: 29-04-2015
  • Left cheek
  • Admission: 13-05-2015; Operation: 16-05-2015; Discharge: 23-05-2015
  • Right cheek
  • Admission: 15-06-2015; Operation: 18-06-2015; Discharge: 25-06-2015
Operative Procedure

Surgery was performed under general endotracheal anesthesia and the masses in the submental, left cheek and right cheek were excised in that order at intervals of 2-3 weeks Submandibular transverse incisions were made for all the surgeries. The flaps were raised carefully avoiding injury to mandibular branch of the facial nerve. The mass in all the regions consists of connective tissue with fat and extending from dermis up to the fascia covering the deep muscles. Not much of vascularity. The masses are localized even though definite borders are not present, and there is no capsule and is uniform without any nodules. After excision, the wounds were closed in layers, and the healing was good, and there was no evidence of facial nerve injury and the patient was discharged within 1-week after each operation. While operating in the submental region the deep fascia was excised along with the mass exposing the geniohyoid and mylohyoid muscles (Figures 4 and 5). While operating in the cheek masses, the masseteric fascia was also excised (Figures 6-9) and parotid glands on either side were not touched even though there is enlargement of the right parotid gland. No lymph nodal swellings are seen separately.

Figure 4
Per operative Submental swelling
Figure 5
Per operative Submental after excision of mass
Figure 6
Per operative Lt. Cheek
Figure 7
Per operative Lt. Cheek with swelling
Figure 8
Per operative Rt. Cheek0
Figure 9
Per operative after excision of mass Rt. Cheek

Similar histopathological features are seen in all the three areas where excision was done.

On gross examination, all the three specimens received at three different times revealed skin covered multiple tissue bits of sizes varying from 2 cm × 2 cm × 1 cm to largest measuring 7.5 cm × 3 cm × 2 cm. Cut section of the tissue bits revealed gray-white to yellowish solid areas (Figures 10 and 11).

Figure 10
Excision specimen Rt. Cheek
Figure 11
Per operative excision specimen Lt. Cheek

Microscopic examination revealed well-circumscribed lesion present in dermis and subcutis characterized by florid follicular hyperplasia with dense aggregates of lymphoid cells with prominent germinal centers. Several germinal centers showed description by sheets of eosinophils forming eosinophilic micro-abscess. The vascular component in the center of the germinal center is composed of vessels which are lined by attenuated endothelial cells. A diagnosis of Kimura’s disease was made with these findings (Figures 12-14).

Figure 11
Photomicrograph with eosinophilia
Figure 13
Photomicrograph Lt. Cheek mass
Figure 14
High power photomicrograph


Kimura’s disease was first described by Kimura and Szeto in 1937. The term Kimura disease was coined by Kimura et al. in 1948 describing as “an unusual granulation combined with hyperplastic changes of lymphatic tissue.”

The other synonyms of the disease are eosinophilic granuloma of the tissue, eosinophilic lympho folliculosis, and eosinophilic lymphoid granuloma.8

Most patients have a prolonged course with slow enlargement of masses. The disease usually involves subcutaneous tissue, lymph nodes (periauricular, axillary, and inguinal), parotid and submandibular glands and rarely oral mucosa.9,10 Sometimes it may be complicated by renal involvement. In case of renal involvement nephrotic syndrome is the commonest presentation,11 proteinurias may occur.

Sites affected less often include groin (15%), extremities (12%), trunk (3%).

Most of these diseases are reported in East and Southeast Asia with a small number of cases in Europe.

Males are commonly affected by Kimura’s disease than females with a ratio of 3.5:1-9:1 and usually seen in young adults during the third decade of life with a median age being 28-32 years.

The exact cause and pathogenesis of Kimura’s disease is unclear, it may be self-limited allergic or autoimmune response triggered by unknown persistent antigenic stimulus.

It has been hypothesized that an infection or toxin may trigger an autoimmune phenomenon or lead to Type I hypersensitivity reaction. Some evidence has suggested a predominance of TH-2 cells which produce eosinophilic cytokines including interkulin (IL)-4, IL-5. Elevated GM-CSF, TNF-alpha, soluble IL-2 receptor, IL-5, IL-4, IL-13.

Histopathology of Kimura’s disease is characterized by dense fibrosis, lymphoid infiltration with reactive follicles, mixed inflammatory cell infiltrate with numerous eosinophils, all of which can develop in subcutaneous tissue, salivary glands and lymph node. Some pathologists view that Kimura’s disease has three components: cellular, fibrocollagenous and vascular.

Cellular component is formed by distinct lymphoid follicles consisting of mainly lymphocytes. The fibrocollagenous component is formed by infiltrate with numerous eosinophils, and eosinophilic micro-abscess, mast cells, and plasma cells. Vascular component consists of proliferating and swollen endothelial cells.

Salivary glands are frequently involved and regional lymph nodes are also enlarged. There is follicular hyperplasia with an increase in eosinophils, with or without fibrosis.

Few specific laboratory investigations are essential in making the correct diagnosis of Kimura’s disease. Increased serum IgE levels and tissue eosinophilia are seen in the disease and also differential leukocyte count almost always reveals peripheral eosinophilia.

Imaging studies such as ultrasound scanning, computed tomography and MRI are useful only in delineating the extent of the disease.

Differential diagnosis of Kimura’s disease include angiolymphoid hyperplasia with eosinophilia (ALHE), dermatofibrosarcoma protuberans, pyogenic granuloma, Kaposi sarcoma and follicular lymphoma.12,13

This is to be differentiated from ALHE, described by Wells et al. in 1969 by the following features.

In ALHE, the blood vessels range from well-formed mature vessels to poorly formed uncanalized vessels. And these vessels are lined by epithelioid endothelial cells with scalloped border that deepens into the lumen. But in Kimura disease the vessels are lined by attenuated endothelial cells.14

Pyogenic granulomas usually present clinically as small papule like projections, and they have predominantly neutrophils and small capillary vessels without any lymphoid cells and eosinophils.7,14

Follicular lymphoma is characterized by neoplastic lymphocytes arranged in follicles with the loss of nodal architecture and without any infiltration of eosinophilic micro-abscess.

Treatment of Kimura’s disease can be surgery, medical treatment or radiotherapy.

Surgical excision of the lesion is the mainstay of treatment even though recurrences up to 25 % are reported. Local, oral or systemic administration of corticosteroids has been advocated, but often the lesions recur after with drawl of the drug. Cetrizine (histamine H-1 receptor blocker gives good symptomatic relief. All-trans retinoic acid, pranlukast (leukotriene receptor antagonist, cytotoxic drugs are all tried with limited and temporary success. Radiotherapy is only preferred for recurrent lesions after surgical and or medical treatment. Since this is a benign lesion use of long-term corticosteroids, cytotoxic drugs or radiotherapy is to be preferred in only specific situations.15


Kimura’s disease is a rare chronic inflammatory disorder of unknown etiology.

The present case reiterates that Kimura disease may cause chronic subcutaneous masses in head and neck region and especially in young male patients.

It involves deep subcutaneous tissue and lymph nodes in head and neck region. Surgery is the mainstay of treatment. We observed very good result in this patient after excision in all the three regions. The patient and his family members are extremely happy after 3 months of follow-up eventhough we cautioned him about possible recurrences. In the right cheek also eventhough we did not operate on right parotid which was enlarged, there is considerable reduction in size when he came for follow-up on 27-07-2015 Clinically and in the MRI imaging there is increase in size of the right parotid gland along with lymph nodal involvement (Figure 15).

Figure 15
MRI face before surgery Rt. cheek

We did not touch the parotid gland while operating purposefully since we felt it may be due to only hyperplasia of lymph nodes connected with right parotid gland (periparotid and intraparotid). The follow-up picture after 5 weeks shows complete reduction in the size of the parotid, thus confirming our suspicion that the increase in size of the right parotid is due to hyperplasia of lymph nodes rather than actual involvement in disease process (Figures 16-18).

Figure 16
Post operative 3 months
Figure 17
HPost operative 5 weeks after Rt. cheek surgery
Figure 14
Post operative lt. cheek 3 months post operative

Authors' information

Ravish Patel1, Nitin Chaudhary2, Hari Menon 3

1Director and Plastic Surgeon, Department of Plastic Surgery, Alluri Sita Rama Raju Academy of Medical Sciences, Eluru, Andhra Pradesh, India 2Professor and Head, Department of Pathology, Alluri Sita Rama Raju Academy of Medical Sciences, u, Andhra Pradesh, India


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