Kimura’s Disease: A Diagnostic and Therapeutic Challenge

Abstract

Kimura’s disease, also known as Eosinophilic Granuloma, is a rare chronic condition seen mainly in Oriental population. It presents with subcutaneous nodules, lymphadenopathy, salivary gland hypertrophy with peripheral eosinophilia and raised serum IgE levels; rarely renal involvement may also be present. Its etiology mainly remains unknown. We present a case series of two patients. Our first case is a middle aged female which presented with a parotid swelling, mimicking a parotid neoplasm. Further investigations revealed associated intra-parotid and cervical lymphadenopathy. An excisional biopsy in the form of Superficial Parotidectomy with lymph node excision was done. Histopathological examination of the excised specimen revealed it to be a case of Kimura’s disease. Our second case, a young adult, presented with a gradually increasing post-auricular swelling. Preliminary investigations in this case pointed towards Kimura’s disease. Excision biopsy of the lesion was done. Histopathological studies confirmed the diagnosis for the same. Both the patients are under our regular follow up and remain disease-free at a follow up of 1 year and 8 months respectively.

Introduction

Kimura’s disease or eosinophilic lymphogranuloma is a rare chronic inflammatory condition which presents with multiple painless subcutaneous nodules especially in the head and neck with coexisting lymphadenopathy, salivary gland hypertrophy and peripheral eosinophilia [1, 2].

The disease is relatively more common in oriental population than western world and Indian subcontinent [3, 4]. The etiology of the disease remains largely unknown, although allergic reaction and immune system alteration have been proposed as the primary etiopathological pathways. Constant antigenic stimulation of immune system following arthropode bites and parasitic or candida infection is studied to be another cause [3].

Case-1

A 36 year old female presented with a gradually increasing swelling in front of her left pinna since last 2 years. The swelling was painless, with no history of fever, trauma, or discharge from the swelling. There was no history of facial asymmetry, rapid increase in the size of the swelling, recent weight loss or decreased appetite, similar lesions elsewhere in the body, or any other co-morbidity. On examination, a 3 cm × 2 cm swelling was noted in the left parotid region. The swelling was soft to firm in consistency, non-tender, mobile with normal overlying skin. Facial symmetry was maintained with normal facial nerve functions. Rest of the ENT examination was also within normal limits (Fig. 1).

Fig. 1.

Left parotid swelling (arrow)

The patient was advised a contrast-enhanced computed tomography which revealed multiple intra-parotid lymph nodes in the superficial lobe of left parotid gland with enlarged parotid gland but normal parotid parenchyma (Figs. 2, 3). Prominent lymph nodes along left jugular chain (level II/III/IV) were also noted.

Fig. 2.

CECT showing left parotid gland enlargement (thick arrow)

Fig. 3.

Intra-parotid lymphadenopathy (thin arrow)

Fine needle aspiration cytology was done which was suggestive of reactive lymph node.

The patient was planned for surgery (Superficial Parotidectomy with intra-parotid lymph node excision). Routine pre-anesthetic investigations were done in which an incidental finding of peripheral eosinophilia at 20.3% (normal: 1–6%) and raised serum IgE levels (890 IU) was noted.

After due consent, patient was taken up for surgery under general anaesthesia. Superfical parotidectomy was done preserving the facial nerve and its branches. Intraparotid nodes were excised along with superficial lobe of parotid gland and was sent for histopathological examination (Fig. 4).

Fig. 4.

Post superficial parotidectomy operative field, showing intra-parotid lymph node (thin arrow) and Facial nerve with its branches (thick arrow)

The intra-operative and post-operative periods went uneventful and the patient was discharged under satisfactory conditions.

The histopathological examination revealed lymphoid follicles with prominent germinal centers and lymphoid nodules with variable hyalinised vessels in parotid gland. The picture was suggestive of Kimura’s disease (Fig. 5).

Fig. 5.

a Histopathological picture showing lymphoid follicle with prominent germinal center (arrow shows eosinophilic micro abscess). b Lymphoid nodules with variable hyalinised vessels in the parotid gland (arrow shows hyalinisation within the nodule)

The patient remains asymptomatic and disease free at a follow up of 1 year.

Case-2

A 30 year old male presented with a swelling in the right post auricular region since 1 year. The swelling was painless and gradually increasing in size. There was no history of fever, discharge from the swelling, or other similar swellings in the body. On examination, a 2 cm × 2 cm swelling was seen in the right post auricular area. It was firm in consistency, non-tender, mobile with normal overlying skin (Fig. 6).

Fig. 6.

Right post-auricular swelling

The patient was advised an Ultrasound neck which revealed a poorly defined irregular hypoechoic lesion, possibly lymphadenopathy with loss of hila, in right post auricular area.

Fine needle aspiration cytology was done. It showed eosinophilic infiltrates, suspicious of Kimura’s disease.

On his routine investigation, peripheral blood picture showed eosinophilia and raised serum IgE levels.

Chest X ray and skin tuberculin test were done and tuberculous etiology ruled out.

Patient was taken up for excisional biopsy under local anaesthesia. Biopsy was taken from the mobile,firm lymph node in the post auricular region (Fig. 7). The surgical procedure went uneventful. The excised mass was sent for histopathological examination.

Fig. 7.

Intra-operative picture showing the lesion

The histopathological examination of the lymph node showed eosinophilic micro-abscesses, folliculolysis, perivenular sclerosis and eosinophilic infiltrates in the germinal center, with well-maintained lymph node architecture which are characteristics of Kimura’s disease (Fig. 8).

Fig. 8.

Histopathological picture of the lesion, showing eosinophilic infiltrates and micro-abscesses

The patient is under our regular follow-up and remains disease free at 8 months after surgery.

Discussion

The disease was first described in 1937 in the Chinese literature by Kimm and Szeto [1]. The histological description was given by Kimura et al. in 1948, thereby crediting the name of the disease. The condition is endemic in Oriental Asia and sporadic in rest of the world [3, 4]. It has a high male preponderance of ratio 3.5 to 7: 1 [3]. The peak age of onset is the third decade.

Kimura’s disease presents with a usual triad of one or more subcutaneous indolent nodules, peripheral eosinophilia and increased serum IgE levels [2]. The nodules are slowly progressing in size, located mainly in the head and neck, mostly painless rarely painful and pruritic [5]. Lymphadenopathies and increased volume of salivary glands may be accompanying entities. Renal involvement is seen in the form of proteinuria and Nephrotic syndrome [4].

Microscopic Presentation

In microscopy the disease shows some constant features which will be present in every case of Kimura’s disease and some frequent features which if present, are so pathognomonic and help in distinguishing from their differential diagnosis [6].

Constant features: Preserved nodal architecture, germinal center hyperplasia, eosinophilic infiltration, post capillary venule proliferation.

Frequent features: sclerosis, vascularization, proteinaceous deposits in germinal centers, micro-abscesses.

Differential diagnosis for Kimura’s disease involving parotid gland [3]:

• Mikulicz’s disease

• Infective parotitis

• Salivary gland tumours

• Sjogren’s syndrome

Differential diagnosis for lymphoid proliferation and eosinophilia [5]:

• Hodgkin’s lymphoma

• Langerhan’s cell histiocytosis

• Parasitic lymphadenitis

Apart from these there is a specific differential of special mention—‘Angiofollicular Hyperplasia with Eosinophilia’ (AHE) which was considered to be part of a spectrum of Kimura’s disease. The key difference being AHE is seen more commonly in middle aged females of western population, and presents with subcutaneous nodules with overlying skin changes. Adenopathies are typically rare and serum IgE levels are distinctly normal. Vascular proliferations ranging from hemangioendothelioma to epithelioid angiosarcoma may be present [7].

Management

Though the treatment of choice is not coded, the surgical excision of the lump is the main stay of treatment. In case preliminary investigations are inconclusive, excisional biopsy may be required for establishing the diagnosis [6]. Recurrence rates are high even after complete excision of the lesion.

In patients who do not prefer surgery, medical management with oral prednisolone, all trans retinoic acid, leukotriene receptor antagonist like montelukast, and H1 receptor blockers can be tried but with varying results [8].

Local radiation can be considered as a last resort after outweighing the risk of xerostomia.

The case 1 reported here is unique in the fact that the patient is a middle aged female (where as more than 87% of patients are males) and the disease was masquerading as a benign parotid tumour. The case 2 is a prototypical presentation of Kimura’s disease. Both the cases were negative for renal involvement and are followed till date with no symptoms or signs of recurrence.