Kimura disease is a rare idiopathic inflammatory disease that presents as painless nodules and masses in the head and neck region. Its presentation as a large upper limb swelling is quite unusual and could be misdiagnosed as malignancy if one is not familiar with the entity.

Case Report

A 41-year-old man presented with a history of painless swelling in the right arm that gradually increased in size over a period of 28 years. He was concerned by the disfigurement and did not complain of any local symptoms like pruritus, functional compromise, or constitutional symptoms. Clinical examination revealed a firm, soft tissue mass measuring approximately 15cm×11cm on the medial aspect of the arm and elbow, with no neurovascular deficits. The overlying skin was unremarkable.

Laboratory tests revealed a high white blood count (WBC) of 20.70×109/L (reference range 3.40–9.60×109/L) with 62.7% eosinophils and a slightly elevated erythrocyte sedimentation rate (ESR). His renal panel was unremarkable (4.7mmol/L blood urea, 78µmol/L serum creatinine, 139mmol/L sodium, 4.3 mmol/L potassium, and >60mL/min estimated glomerular filtration rate). Serum immunoglobulin E levels were not obtained.

Initial radiographs [Figure 1a and 1b] showed a large soft tissue swelling on the medial aspect of the distal arm and elbow with no internal calcification. The underlying bone had no changes. Further characterization using magnetic resonance imaging (MRI) revealed a large subcutaneous soft tissue mass in the medial epitrochlear region, which appeared iso to hyperintense on T1- and hyperintense on T2-weighted images compared to muscle signals [Figure 2]. There was no necrosis, cystic degeneration, or calcifications identified within the mass. Adjacent muscles were displaced with no altered signals, suggesting a slow growing nature of the mass that was consistent with the long clinical history. There was mild fat stranding of the overlying skin. The brachial vessels were engulfed by the mass, which demonstrated moderate heterogeneous enhancement on contrast. Multiple axillary lymph nodes were enlarged and displayed signal characteristics and enhancement similar to the mass lesion.

Based on the patient’s clinical, demographic, laboratory, and imaging features, Kimura disease was considered the most probable diagnosis. The patient opted for surgical excision in the view of cosmetic concerns and anxiety to know the exact pathology. Histopathological examination revealed large confluent lymphoid and eosinophil-rich areas with background stromal fibrosis [Figure 3]. Nodules of hyperplastic lymphoid follicles of various sizes accompanied by expanded germinal centers, numerous eosinophils, and increased vascularity were also evident. There were no anaplastic cells, Hodgkin, or Reed-Sternberg cells.

Overall, the histopathological picture was in accordance with the clinical and imaging picture of Kimura disease.

Discussion

Kimura disease is a rare benign idiopathic chronic inflammatory disease. Although its initial description was made in 1937, the disease started to be called by its present name only after Kimura and Ishikawa described its distinct pathological entity.1 The disease typically affects Asians in their second and third decades of life and has a male predominance [Table 1].2

The cause of the disease has not yet been identified. An immunological response to a self-limiting allergic reaction elicited by an unknown stimulus was proposed as substantiated by elevated peripheral blood eosinophils and serum immunoglobulin E.3 Histopathologically, the lesions are characterized by hyperplasia of lymphoid follicles, eosinophilic infiltrations and proliferation of fibrocollagenous tissue and post-capillary venules.4

The usual clinical presentation is a painless and slowly progressing subcutaneous nodules/masses, frequently affecting the head and neck region associated with regional lymphadenopathy. The duration of the swelling can range from one month to 25 years.5 In the case presented here, the patient had a history of swelling dating back to 28 years; the longest history to date in the literature. In the head and neck region, there is frequent involvement of major salivary glands, especially the parotid and periparotid regions.5,6 Other salivary glands, the lacrimal gland, oral cavity, and pharynx can also be affected. Other less common locations of the disease include the axilla, extremities, and abdomen. The masses are frequently multiple.5,6 Unilateral or bilateral lymphadenopathy is commonly seen.

On ultrasound, the lesions appeared solid and hypoechoic. The lymph nodes appeared round, well-defined, hypoechoic, and showed a preserved central fatty hilum. On Doppler, the lymph nodes showed a predominant hilar pattern of vascularity with decreased intranodal resistance.7 The subcutaneous masses are commonly ill-defined and isodense to hypodense on computed tomography (CT) scans with no necrosis or calcification.5,6,8 Diffuse atrophy of subcutaneous fat may be seen, reflecting the chronic and indolent nature of the disease.5 Contrast enhancement of the lesion can vary from mild to marked and homogeneous to heterogeneous, reflecting the varied amount of vascular proliferation and fibrotic component on histology. On follow-up, the lesions may show declining enhancement as the disease progresses, which is explained by progressive fibrosis and sclerosis.9 If the subcutaneous lesions are bilateral and multiple, all the lesions tend to show relatively uniform imaging characteristics in the same patient.5 On MRI, the lesions appeared iso to hyperintense on T1- and hyperintense on T2-weighted images. Contrast MRI showed a similar enhancement pattern as CT. The enlarged lymph nodes also often exhibit the same imaging and enhancement characteristics as the subcutaneous lesions in the same individual. Upper limb involvement of Kimura’s disease characteristically presents as a mass in the epitrochlear region adjacent to the major lymphatics and medial neurovascular bundle.10 Masses in the upper limb usually show multiple internal flow voids representing vascular structures, variable amount of subcutaneous edema, and produce mass effect over adjacent muscles and neurovascular structures without any signal changes in them.10

Differential diagnosis on imaging would include tuberculosis, lymphoma, metastatic adenopathy, primary parotid tumors, angiolymphoid hyperplasia with eosinophilia (ALHE), and cat-scratch disease [Table 2].7,10,11 In cases of upper limb disease, as in our case, soft tissue sarcomas can also be considered as differential. In tuberculosis, the lymph nodes show central necrosis and tendency to matting, the features that are not seen in Kimura’s disease. Lymphomatous enlargement of the nodes is often bilateral with eccentric cortical hypertrophy and no changes in the underlying subcutaneous fat. Primary parotid tumors are well defined and encapsulated, unlike Kimura’s disease. Metastatic lymph nodes may show internal necrosis and evidence of primary elsewhere. On ultrasound the metastatic nodes show loss of central fatty hilum and predominant capsular vascularity in contrast to Kimura’s disease.7 Cat-scratch disease can mimic Kimura’s disease on imaging as it can produce lymph node enlargement in the medial epitrochlear region and axilla with surrounding subcutaneous fat stranding. However, in the cat-scratch disease there is a history of exposure to cat, positive serology, and lymph nodes often show central necrosis. ALHE is a distinct entity where there is no sex preference, nodules are more superficial and smaller, and lymphadenopathy is uncommon. Histopathologically, the lesions of ALHE do not show elements of fibrosis and sclerosis, which are uniformly seen in all cases of Kimura’s disease regardless of its stage.

Management of Kimura’s disease is controversial and options are between surgical resection and various conservative treatments such as systemic steroids, cytotoxic drugs, and radiotherapy.12 Surgical excision is treatment of choice for single and well-defined lesion with advantage of precise histopathological confirmation. Conservative treatments are opted for recurrences and systemic involvement. Though considered benign, Kimura’s disease has a recurrence rate of 25–75% after surgical excision.13 The chance of recurrence is lower when two or more conservative treatments are combined.11

Complications of Kimura’s disease include nephrotic syndrome and proteinuria.14 Other minor allergic complications, such as asthma, urticaria, dermatitis, and rhinitis, are also reported.5 Malignant transformation is not known to occur.

Conclusion

Because of its rare occurrence and non-specific imaging findings, Kimura’s disease can be missed especially in non-endemic regions. Correlation with clinical history, laboratory parameters, and imaging appearances can aid in precise diagnosis, spare the patients from multiple invasive diagnostic procedures, and alleviate their anxiety.

Disclosure

The authors declared no conflicts of interest.

references

1. Kimura T, Yoshimura S, Ishikawa E. Unusual granulation combined with hyperplastic changes of lymphatic tissue (in Japanese). Trans Soc Pathol Jpn 1948;37:179-180.
2. Takagi K, Harada T, Ishikawa E. Kimura’s disease eosinophilic: lymphfolliculoid granuloma. Nihon Rinsho. 1993 Mar; 51(3):785-788.
3. Shetty AK, Beaty MW, McGuirt WF Jr, Woods CR, Givner LB. Kimura’s disease: a diagnostic challenge. Pediatrics 2002 Sep;110(3):e39.
4. Chen H, Thompson LD, Aguilera NS, Abbondanzo SL. Kimura disease: a clinicopathologic study of 21 cases. Am J SurgPathol. 2004 Apr; 28(4):505-513.
5. Zhang R, Ban XH, Mo YX, Lv MM, Duan XH, Shen J, et al. Kimura’s disease: the CT and MRI characteristics in fifteen cases. Eur J Radiol. 2011 Nov; 80(2):489-497.
6. Park SW, Kim HJ, Sung KJ, Lee JH, Park IS. Kimura disease: CT and MR imaging findings. AJNR Am J Neuroradiol. 2012 Apr; 33(4):784-788.
7. Ahuja A, Ying M, Mok JS, Anil CM. Gray scale and power Doppler sonography in cases of Kimura disease. AJNR Am J Neuroradiol. 2001 Mar; 22(3):513-517.
8. Gopinathan A, Tan TY. Kimura’s disease: imaging patterns on computed tomography. Clin Radiol 2009 Oct;64(10):994-999.
9. Lim WE, Tan NG, Tan KP. Radiological features in a patient with Kimura’sdisease. Singapore Med J. 1997 Mar; 38(3):125-128.
10. Choi JA, Lee GK, Kong KY, Hong SH, Suh JS, Ahn JM, et al. Imaging findings of Kimura’s disease in the soft tissue of the upper extremity. AJR Am J Roentgenol 2005 Jan;184(1):193-199.
11. Hiwatashi A, Hasuo K, Shiina T, Ohga S, Hishiki Y, Fujii K, et al. Kimura’s disease with bilateral auricular masses. AJNR Am J Neuroradiol 1999 Nov-Dec;20(10):1976-1978.
12. Takeishi M, Makino Y, Nishioka H, Miyawaki T, Kurihara K. Kimura disease: diagnostic imaging findings and surgical treatment. J Craniofac Surg. 2007 Sep; 18(5):1062-1067.
13. Park JS, Jin W, Ryu KN, Won KY. Bilateral asymmetric superficial soft tissue masses with extensive involvement of both upper extremities: demonstration of Kimura’s disease by US and MRI (2008: 12b). Eur Radiol 2009 Mar;19(3):781-786.
14. Rajpoot DK, Pahl M, Clark J. Nephrotic syndrome associated with Kimura disease. Pediatr Nephrol 2000 Jun;14(6):486-488.