Kimura’s disease has been considered as a distinct pathologic entity that was first described in 1937 by Kimm and Szeto in China as “eosinophilic hyperplastic lymphogranuloma”. Subsequently, Kimura et al. described the details of the pathological features of this disease, and this condition has since become widely referred to as Kimura’s disease (3). The majority of the cases were reported in Asia, mainly in China, Japan, and Southeast Asia, and were usually seen in young men with unilateral involvement (8). In the present study, the ratio of male to female was 5:1 and unilateral to bilateral was 4:1, which is similar to previous studies (9). We speculate that sex hormones and genetics may play an important role in the male predominance of KD just like systemic lupus erythematosus which presents with a prominent female predominance.
KD is an immune-mediated inflammatory disorder of unknown etiology. The main presentation is peripheral eosinophilia and elevated serum IgE. In our study, peripheral blood eosinophil count (87.5%) and IgE detection rate (100%) were all at a high level, both of these are of great value for auxiliary diagnosis of KD. It has been speculated that the presentation may be associated with inflammation, endocrinal disorders, autoimmune diseases, parasite infestation, viral infections, and allergies. In our study, we found 6 patients presented with focal lesions in the head and neck region accompanied by localized inflammation of the head and neck. The concurrence of these diseases might imply a causal relationship with KD. Specifically, a viral or parasitic trigger may alter T-cell immunoregulation or induce an IgE-mediated type-1 hypersensitivity, resulting in the release of eosinophilotrophic cytokines, such as interleukin 5 and interleukin 4. Future studies are needed to test this speculation.
KD follows an indolent clinical course and misdiagnosis is common. The most common clinical feature is asymptomatic unilateral soft-swelling, such as salivary glands and local lymph nodes (3). In this study, the lesions predominantly involved the salivary gland, preauricular area, and cervical lymph node. The reason may be due to the KD being more likely to involve lymph nodes, while head and neck lymph nodes are numerous . Head and neck lymph nodes first drain to the parotid, periauricular, submandibular, and other upper cervical lymph nodes, then finally into the cervical lymph nodes. KD is frequently associated with pruritus or melanin pigmentation of the overlying skin, probably due to nerve infiltration by lymphocytes and eosinophils (10). In the present study, 33.3% of the patients presented with pruritus, 20.8% had melanin pigmentation, and 12.5% had coarseness of the affected overlying skin.
Imaging examination has a high detection rate for KD involving the parotid gland and subcutaneous. It is helpful for determining the location and extent of pathological changes and lymph node involvement but has low specificity. Ultrasound examination often shows hypoechoic masses, unclear borders, irregular shape, and uneven internal echo. Consequently, KD is often misdiagnosed as maxillofacial malignant tumors (11). Shin et al. showed that ultrasound revealed a rich blood flow signal with local subcutaneous hypoechoic and internal hyperechoic features, accompanied by peripheral subcutaneous fat, adjacent lymph node enlargement, and other characteristics, suggesting a high probability of KD (12). In our study, appearance on radiological findings by different modality such as CT or MRI was variable and not well defined due to variable degrees of vascular proliferation and fibrosis. However, as suggested by Park et al., CT and MRI can be useful for diagnosing KD in the head and neck areas (13). Characteristic imaging results include multiple ill-defined enhanced masses within and around the parotid gland with associated regional lymphadenopathy.
Pathological examination is the golden standard for the diagnosis of KD. In our study, two patients failed to yield a definite diagnosis based only on Fine-needle aspiration biopsy. Moreover, the accuracy of core-needle biopsy was low (2/14, 14.3%). Therefore, we feel that patients with suspected KD should be confirmed by surgical specimens. The typical characteristics of histopathology of the 24 patients included: Lymphoid follicular hyperplasia and germinal center enlargement; eosinophilic infiltration and accumulation of eosinophilic micro-abscess; and postcapillary and venular hyperplasia, surrounded by circular collagenous fibrous deposition and different extent of fibrosis. Lymph nodes and external lesions have similar pathological manifestations.
The optimal treatment of KD is controversial due to lack of large-scale systemic clinical studies on different treatments for KD. Successful cases have been reported by applying surgery, radiotherapy, and chemotherapy (14). According to some case reports, different medications, such as cyclosporine, tacrolimus, mycophenolate mofetil, and loratadine (15-17), have been used in the treatment of KD with responses ranging from mild improvement to complete remission or even cure of the disease. As KD is benign, surgical resection does not spread lesions, but helps to reduce lumps and benefits diagnosis. Therefore, surgical excisions have been considered the golden standard of treatment for KD. However, KD typically involves subcutaneous tissue without well-defined boundaries, making it difficult to achieve a negative margin by surgical excision alone and recurrence is possible. In this study, up to 46.2% of recurrence was associated with this modality. A combination of surgery with postoperative intervention seems to be a reasonable approach for treatment of KD. Nakahara et al. reported that steroid therapy can control lesions, lymphadenopathy, and nephrotic syndrome in KD, but local recurrence occurred frequently during the period of steroid dose tapering (18), which is consistent with our findings. Radiotherapy has been used to treat recurrent or persistent lesions with better rates for local control, but the carcinogenic effects of radiotherapy along with the benign nature of the disease limits its use as the primary modality. However, Ye et al. stated that surgical resection combined with low-dose postoperative radiotherapy for treatment of KD achieved the lowest local recurrence rate (14). In this study, the recurrence rate following surgical excision combined with low-dose radiotherapy was lower than that of either surgical excision alone or surgical resection followed by oral corticosteroids. However, Chi-square test and Fisher’s exact test found this to be statistically insignificant, but this may have been caused by small number of patients. More cases are needed to confirm this conclusion.
Relapse is an important characteristic of KD. In this study, the overall recurrence rate was 46.8%. Among the 11 patients with recurrence, the ratio of male to female was 2:1, involving patients in all age groups and the most common recurrence site was in situ. The neck and parotid gland were the most likely to relapse. For relapses, the treatment as described above was still effective.