Kimura disease is a rare chronic inflammatory condition characterized by subcutaneous painless masses, lymphadenopathy, peripheral eosinophilia, and increased serum IgE levels8,9. The condition was first described by Kim and Szeto in China in 1937 under the name 'eosinophilic hyperplastic lymphogranuloma' 1. The study summarizes the clinical characteristics and radiological findings of four patients with KD associated with mass complications. KD was most frequently observed in the head and neck, which is consistent with previous studies10. Other less frequent sites include the arm11, thigh12, groin13, breast14, back5, and et al. Lee et al5 have proposed that the male-to-female ratio was 4.5:1, and the peak age at diagnosis was middle-aged (median: 41.35 years) for KD patients. At the same time, the males accounted for 75 percent of all patients in this study and the mean age at diagnosis was 43 years ranging from 13–71 years, which is similar to the findings of the above-mentioned studies in the literature.
Currently, the cause and pathogenesis of KD are not well understood. It is widely believed that various factors such as insect bites, Epstein-Barr virus, human herpesvirus, and Candida albicans may disrupt T-cell regulation or trigger an IgE-mediated type 1 hypersensitivity reaction15,16. The presence of increased levels of eosinophils and IgE in the peripheral blood of KD patients suggests that Th1 and Th2 cells, as well as T regulatory cells, may play a role in the development of KD. Ohta et al. employed flow cytometry to analyze T-cell subsets and discovered a significantly higher proportion of Th2 cells in KD patients compared to the control group17. Furthermore, this study observed elevated eosinophil counts in three-quarters of KD patients' peripheral blood samples. Meanwhile, serum IgE was also significantly raised in three patients, and serum IgE levels were not obtained from another case. Notably, to our knowledge, there are only four cases of KD with normal serum eosinophil counts or/and IgE levels reported globally18, and this study involves a fifth case with eosinophils in the normal range. Therefore, even in the absence of peripheral eosinophilia or/and elevated IgE levels, KD must be considered in differentiating painless subcutaneous masses. In addition, there are some case reports of concurrent nephropathies, such as proteinuria and nephrotic syndrome, which might be caused by glomerular IgE deposition, and endocapillary and mesangial hyperplasia19. It has been reported that proteinuria is present in 12–16% of KD cases and nephrotic proteinuria occurs in about 60–70% of KD patients, none of whom had nephrotic symptoms in this study20. Other complications include pruritus, rash, allergic rhinitis, asthma, and urticaria, which may be related to eosinophils infiltration and cytokine release 21. However, the present study has not found any cases of related symptoms.
KD is presently recognized as a benign inflammatory disorder, with a relatively favorable prognosis. The primary pathological feature of KD is subcutaneous angioblastic lymphoid hyperplasia with peripheral eosinophilia22. Although a pathologic examination is essential for a definitive diagnosis, imaging studies play a pivotal role in the early identification and comprehensive characterization of the disease's distribution. This spares patients from potentially harmful invasive diagnostic procedures or unnecessary radical surgery. Gopinathan and Tan et al7. have divided KD into two distinct morphological subtypes in conformity with variations in CT morphological features: subtype 1, characterized by nodular lesions with well-defined borders, uniform density, and homogeneous enhancement; subtype 2, characterized by diffuse swelling with indistinct borders, heterogeneous enhancement, and infiltration of surrounding subcutaneous fat. Among the three patients who underwent CT examination in this research, only one exhibited subtype 1 while the remaining patients presented with subtype 2. Takeishi et al23. classified Kimura disease into two categories based on specific MRI features shown by KD located at different sites. The first type is located in the posterior auricular region and other sites adjacent to the bone and appears on MRI as a homogeneous solid mass, the second type is located in the parotid area and has a heterogeneous interior structure on MRI. Patient 3 belongs to the first category and patient 1 to the second category in this study.
Previous reports on the imaging manifestations of KD are somewhat non-specific and variable. On pre-contrast CT and MRI scans, KD tends to manifest as either well-defined nodular masses or ill-defined plaque-like infiltrative masses in the subcutaneous tissue, with or without accompanied by lymphadenopathy7. The majority of lesions are situated near the major salivary glands, especially the parotid gland, and may be accompanied by diffuse atrophy of subcutaneous fat, which is considered a relatively characteristic feature. The density of the involved enlarged lymph nodes is homogeneous on CT, and areas of hypodense cystic necrosis and foci of calcification are rarely seen13. It has been suggested that varying degrees of subcutaneous fat atrophy and lesion enhancement indicate different stages of this inflammatory disease spectrum. The more pronounced the subcutaneous fat atrophy, the worse the focal enhancement of KD, reflecting the chronicity of the disease6, which was confirmed by Lin et al24. in a follow-up of the same patients suffering from KD, where gradual fibrosis and sclerosis around the microvessels behind the lesion capillaries increased as time progressed, resulting in decreased lesion enhancement. Three patients (3/4) with KD in this study showed diffuse subcutaneous fat atrophy, and only one case did not show this symptom, which may be related to the short clinical course of the disease at 1 month and early inflammation. Patient 4 had slight enhancement, probably due to chronic inflammation, and this patient was found to have a painless mass in the left preauricular and retro-auricular for almost 180 months, which was consistent with previous studies. The diversity of signal intensities on MR images of KD lesions is due to histologically varying degrees of vascular and fibrotic components. Abundant vascular proliferation may explain the marked enhancement and flow-through effect, whereas extensive fibrosis may contribute to the linear low attenuation pattern after enhancement on MR images21,24. In the present study, the lesion features of patient 3 on MR images indicated that a vascular component was present.
KD needs to be distinguished from various inflammatory and neoplastic diseases, including parotid tumors, lymphomas, tuberculous lymphadenopathy, and Angio lymphoid hyperplasia with eosinophilia (ALHE)21,25,26. Parotid tumors are typically encapsulated or pseudo-encapsulated and are confined to the parotid gland. In contrast, KD often extends irregularly into the subcutaneous tissue region21. Hodgkin's lymphoma typically manifests as painless lymph node enlargement. The initial masses are commonly found in the neck region like KD. However, lymphomas are usually not associated with peripheral soft tissue or fatty changes and have a short clinical course, often accompanied by the fusion of lymph nodes in the affected region27. Lymphoma has a high signality on DWI, and its ADC value is much lower than KD25. In contrast, tuberculous lymphadenopathy often manifests as symptoms including mild fever, fatigue, night sweats alongside elevated erythrocyte sedimentation rate. Unlike KD, Tuberculous lymphadenopathy is usually necrotic with central low density, peripheral rim enhancement, and a tendency for matting13. KD and ALHE have similar histopathologic and clinical features, both are prevalent in the head and neck and present clinically as subcutaneous masses with lymphoid infiltrates, eosinophils, and angioplasia. However, the prevalence of ALHE is highest among women in the middle-age group, exhibiting no significant ethnic disparities, and lacking any association with renal impairment. Histopathologically, it is the absence of fibrosis in ALHE, whereas KD has significant fibrosis at all stages, thus serving as the key to differential diagnosis 18,25. The treatment options for KD include surgical excision or conservative therapies, such as systemic or intralesional corticosteroids, cytotoxic therapy, or radiotherapy, while the optimal treatment is still controversial28. The preferred treatment for this condition has been suggested to be complete surgical excision, with or without corticosteroid therapy. However, in cases where the lesion is large, ill-defined, and systemically involved, achieving complete removal through surgery can often be challenging and recurrence rates tend to be high. Oral corticosteroids are effective in the treatment of Kimura disease, but patients are more likely to relapse once they stop taking the drug (about 45%)5,28,29. To achieve stratified patient management and effectively control recurrence in high-risk patients, Li et al5. proposed a treatment algorithm. When the lesion size is ≥ 3 cm, the symptom duration is ≥ 3 years, the peripheral blood eosinophilia is ≥ 20%, or the serum IgE is ≥ 10000 IU/ml, the combination of adjuvant therapy with surgical resection is preferred. In recent years, a novel treatment utilizing antibodies has surfaced, patients successfully treated with mepolizumab, dupilumab, and benalizumab have been reported in some literature30–32.
Despite the four valuable cases presented herein, this study has several limitations. Firstly, a small and single-center retrospective study population was included, although this sample size was larger than that of many previous case reports that included only one patient. Secondly, patients were excluded based on keyword searches in the electronic medical records, which may have introduced selection bias. Finally, not all patients underwent brain MR, as CT is not sensitive to detecting small early lesions, and patients with KD may have been overlooked and underestimated.
In summary, younger men with a painless subcutaneous head and neck mass, peripheral blood eosinophilia, and elevated serum IgE levels should be highly considered for the diagnosis of KD. CT or MRI can demonstrate the distribution, morphology, and enhancement pattern of the lesion. These imaging techniques serve as valuable tools for diagnosing KD and assessing the inflammatory state of the disease. Nevertheless, a definitive diagnosis should be confirmed through pathological biopsy. In terms of treatment, surgery intervention, conservative treatment, or antibodies can be used to treat KD, which requires prolonged follow-up of patients due to its tendency to recur.