1

Case reports

In case 1, in 1979, a 23-year-old Asian man presented with recurrent swelling of his left parotid region after undergoing 2 prior excisions for the same lesion in Taiwan in 1973 and again in 1975. Pathologic diagnoses from these excisions were reportedly consistent with Mickulicz disease. Examination revealed a firm mass over the angle of his jaw without obvious facial nerve involvement and cervical lymphadenopathy ( Fig. 1 ). Laboratory values were remarkable for a peripheral eosinophilia (white blood cell 6K, 35% eosinophils). He underwent re-excision via a modified Blair incision, removing both the mass and the superficial lobe of the parotid gland. Because of prior surgical resection, dissection was tedious; however, the facial nerve and its branches were identified and preserved. Final pathology revealed a 10 × 12 cm tumor with lymphoid follicles, vascular proliferation, and eosinophilic infiltrate consistent with Kimura disease. He remains disease free over 30 years later.

Preoperative image showing severe facial disfiguration from mass effect.

In case 2, in 2010, a 30-year-old Asian man noted painless swelling in his right buccal space over a period of 4 months. He had undergone an uneventful root canal in teeth numbers 30 and 31; however, swelling continued to progress to a point that it was disfiguring. He did not have any facial paresthesias or muscle weakness. On examination, he had a nodular, rubbery, mobile, and well-demarcated mass without fluctuance or pain on palpation. The overlying skin and underlying oral mucosa were unremarkable.

A contrast-enhanced magnetic resonance imaging in axial and coronal planes showed a 5 × 2.9 × 2.1 cm mass, isodense to the masseter muscle, and located just ventral to the right masseter muscle and extending cephalad and medial into the right buccal space ( Fig. 2 ). The lesion morphology suggests insinuating soft tissue characteristics with flow void and relative T2 hyperintensity. There is no invasion into the adjacent musculature or adjacent posterior wall of the right maxillary sinus. Ipsilateral subcentimeter level 2 lymph nodes without cystic or necrotic changes were also identified. Initial FNA cytology revealed bloody aspirate only, but a second attempt at FNA cytology showed spindle cells. With these cytologic features, an accurate preoperative diagnosis could not be established. Therefore, a peroral core needle biopsy was performed, which showed spindle cells and inflammatory changes with eosinophils and granulation tissue. The differential diagnosis included hemangioma, sarcoma, neurogenic tumor, accessory parotid tumor, or other benign granulomatous lesion.

Magnetic resonance imaging showing lesion (arrow) as hyperintense signal on T1 fat-saturated axial (left) and coronal (right) images.

Because the diagnosis of a malignant tumor was not established, a relatively conservative surgical approach was planned. He underwent a transoral excision of his tumor that was located deep to the buccinator muscle and adherent to both the masseter muscle and the tendon of the temporalis muscle. The lesion was removed in a monobloc fashion. The mucosa overlying the defect was easily reapproximated. Final pathology revealed a 5-cm circumscribed lobulated mass. Histologically, the tumor was composed of nodular vascular proliferation accompanied by an inflammatory infiltrate. The inflammatory component showed reactive lymphoid proliferation with plasma cells and numerous eosinophils ( Figs. 3 and 4 ). The vascular component varied in size from small capillaries to medium-sized vessels. The performed immunohistochemical stains for CD20, CD3, CD68, CD10, CD1a, LCA, CD15, and S-100 showed a mixture of inflammatory cells including B- and T-cell lymphocytes. Three weeks postoperatively, his swelling had completely resolved; there was no external evidence of the surgical intervention, with fully normal facial appearance and function. His peripheral eosinophilia that was also present on initial blood work resolved in the postoperative period.

Histologic section with hematoxylin and eosin staining showing nodular vascular proliferation and inflammatory infiltrate. High power (inset) shows lymphoid proliferation with plasma cells and eosinophils.

A 30 year old Asian man with a right sided buccal mass lesion and intact facial nerve.

2

Discussion

Kim and Szeto are reported to be the first to describe this rare inflammatory lesion of the head and neck in 1937, and Kimura et al further classified the disease that is more commonly named after him in 1948. This is a benign disease usually seen in young Asian men with a peak incidence in the third decade . Rarely, these lesions have been reported in non-Asian patients. Kim-Kimura disease or Kimura disease characteristically involves the major salivary glands or lymph nodes in the neck. There are occasional reports in the literature of Kimura disease identified in less frequent locations such as the eye or epiglottis, and there are also few reports describing the diagnosis of Kimura disease in black and white men . Blood work reveals an increased level of immunoglobulin E and eosinophilia. Pathologic examination shows lymphoid hyperplasia, eosinophilic infiltration of tissue, and capillary proliferation. Lymphadenopathy is common.

The pathogenesis of Kimura disease is thought to be immunologic in nature with eosinophils playing a central role. Elevated levels of cytokines such as granulocyte macrophage colony-stimulating factor, tumor necrosis factor α , and soluble interleukin 2 receptor have been observed in tissue of patients with Kimura disease, suggesting that release of these cytokines from activated lymphocytes can in turn can activate eosinophils . Activation of eosinophils then leads to elevated levels of cytotoxins such as eosinophil cytoxic protein, which can lead to tissue destruction . This autoimmune mechanism possibly accounts for the observed efficacy of immunosuppression treatment with corticosteroids and cyclosporine .

Differential diagnosis of this lesion includes other benign entities from hemangioma, histiocytosis, and schwannoma to malignant diseases such as lymphoma and angiosarcoma. Angiolymphoid hyperplasia with eosinophilia (ALHE) shares similar histologic features with Kimura disease, however, is believed to be a more superficial, vascular lesion with the absence of lymphadenopathy, or peripheral eosinophilia . Angiolymphoid hyperplasia with eosinophila can also be seen in women more and patients often complain of pruritis .

Imaging can further help delineate Kimura disease from malignant tumors. Computed tomographic scans may show poor to moderate enhancement of the lesion. Lymphadenopathy is characteristically not cystic or necrotic in appearance, as it might be in malignancy. As seen in case 2, magnetic resonance imaging can show hyperintense signal on T2-weighted images .

The immunohistochemical findings in Kimura disease are nonspecific but might help in ruling out hematopoietic malignancies. Kimura disease shares features with ALHE, but the clinical and histologic differences might help in separation of these 2 entities. Histologically, Kimura disease has predominant lymphoid proliferation and sparse vascular component with minimal endothelial changes, whereas in ALHE, the inflammatory infiltrate shows mixture of cells and the endothelial cells are prominent and pleomorphic. In contrast to ALHE, eosinophils are always numerous in Kimura disease. The role of FNA and biopsy procedure is limited in diagnosing Kimura disease, and surgical resection is likely necessary to make the final diagnosis because the histologic features of the tumor are not very specific and can be found at least partially in many other entities including reactive processes. Moreover, small biopsy materials might not demonstrate the lobulated architecture or the whole histologic picture of this tumor.

Treatment involves complete surgical resection. Adjuvant therapy in the form of corticosteroids, cyclosporine, or cyclophosphamide has been described and may be useful in lesions that are unable to be completely excised for poor surgical candidates or after recurrence . However, duration of therapy has not been thoroughly investigated; and application and length of immunosuppressive therapy remain to be elucidated. Irradiation has also been successfully used for these lesions with over 90% local control reported in 1 study . Long-term sequelae of radiation such as xerostomia, osteonecrosis, and radiation-induced malignancy must be considered before use of this modality in the often younger aged patient.

Recurrence is well known to occur, reported in up to 60% to 80% of patients . In 1 series of 54 patients with Kimura disease, there were 12 (22%) documented recurrences; but no cases of mortality or malignant transformation . Moreover, in 5 cases, disease had been present or persistent for over 10 years, again suggesting the indolent nature of this phenomenon. Management of recurrent disease remains primarily surgical; however, control of disease after recurrence may require the addition of adjuvant chemotherapy and/or radiation.