Kimura Disease: CT and MR Imaging Findings

Discussion

KD is a chronic inflammatory disease characterized histologically by proliferation of folliculoid structures, which are infiltrated by eosinophils, plasma cells, lymphocytes, and mast cells and demonstrate associated vascular proliferation and stromal fibrosis.⁹ Fibrosis can be present in the early stage of the lesions and may be replaced later by hyalinization.^4,13 Many synonymous terms have been used to describe KD, including subcutaneous eosinophilic lymphoid granuloma, eosinophilic lymphoid follicular hyperplasia, and eosinophilic folliculosis of the skin.^5,14,15 Although the cause of KD still remains unknown, it may be a self-limited allergic or autoimmune response to an unknown stimulus; this hypothesis is supported by the increased eosinophil count and IgE in the peripheral blood.^13,15 It has been speculated that 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.^13,16

Clinically, KD primarily affects those of Asian descent in their second, third, and fourth decades of life with a male predilection (87%).^6,9,15 Most patients present with firm, painless, single, or multiple subcutaneous lesions in the head and neck, especially in the parotid and submandibular regions.^2,13 Associated lymphadenopathy is frequent, with a reported incidence of 42%–100%.¹⁵ Less common sites of involvement in the head and neck include the paranasal sinuses, orbits (including eyelids, conjunctiva, and lacrimal glands), epiglottis, tympanic membrane, and parapharyngeal space.¹⁷ Rarely the disease can involve non-head and neck sites such as the axilla, groin, popliteal region, and forearm.^2,18 Although the clinical course of KD is typically progressive for several years, the disease is generally benign and self-limited, though it may be complicated by renal involvement, notably nephrotic syndrome.¹⁰ Characteristically, there is accompanying peripheral blood eosinophilia (10%–70%) and an elevated serum IgE level (800–35,000 IU/mL),^2,9 which may fluctuate in the course of the disease. Several studies reported a close relationship between the lesion size and the degree of eosinophilia—that is, the bigger the lesion, the greater the eosinophilia in peripheral blood.^19,20 Serum concentrations of eosinophil cationic protein might be used as an additional parameter of disease activity.^19,21

The results of the present study are generally in accordance with those of previous studies: male predilection (86%), age distribution (mean age, 32 years; 68% occurring in the second-to-fourth decades), multiplicity (61%), parotid/periparotid predilection (69% of lesions seen in 82% of patients), and lymphadenopathy (82%). In contrast with the previous studies, our patients had bilateral disease (61%) more commonly than unilateral disease.

The diagnosis of KD may be difficult because clinicians and pathologists in Western countries are relatively unfamiliar with this rare disease, and unnecessary diagnostic tests and procedures are frequently performed to exclude other serious disorders such as tumors. In this context, although pathologic confirmation is necessary for the definite diagnosis of KD, imaging studies including CT and MR imaging can be useful for suggesting a specific diagnosis as well as delineating the extent of the disease. There have been several reports suggesting that the radiologic findings of KD of the head and neck are nonspecific and variable.^{6⇓⇓⇓⇓⇓⇓⇓⇓–15} On CT scans, either well-defined nodular masses or ill-defined plaquelike infiltrative masses in the subcutaneous tissue associated with lymphadenopathy are reported as the typical findings.^7,15 Most of the lesions are seen in the vicinity of the major salivary glands, especially the parotid gland.¹⁵ The attenuation of the masses varies from iso- to hyperattenuated.^12,14 On MR images, the masses are reported to show variable signal intensity—that is, low-to-high signal intensity on T1- and T2- weighted images.^{7,9,12⇓–14} On postcontrast CT and MR imaging, enhancement patterns vary from mild to intense and from homogeneous to heterogeneous.^7,9,13,14 Sometimes, MR images demonstrate serpentine signal-intensity-void areas, suggestive of vascular structures, within the lesions, as seen in 7 of 13 lesions in the present study. In the study on MR imaging findings of 9 cases of KD involving the upper extremity, Choi et al¹⁸ reported dotlike or tubular signal-intensity voids within the mass in all 9 cases. In the head and neck, a similar finding was described once before.⁷

The variability in the degree of enhancement on CT and MR images and the signal intensity on MR images are thought to be attributed to the different degrees of fibrosis and vascular proliferation contained in the individual lesions.^9,12,18 Abundant vascular proliferation may explain the presence of enhancement and signal-intensity-void structures on MR images.¹⁸ In the present study, most of the lesions (98%) showed ill-defined borders on CT and MR images. Compared with that in the adjacent muscle, the signal intensity of the lesions was iso- to slightly hyperintense on T1-weighted images and hyperintense on T2-weighted images. The degree of enhancement of the lesions was generally greater on postcontrast MR images than on postcontrast CT scans, reflecting the higher sensitivity of MR imaging to detect changes after contrast enhancement. Eleven of 13 lesions detected on postcontrast MR images showed marked contrast enhancement, which was noted in only 3 of 43 lesions on postcontrast CT scans. The observed difference in enhancement between CT and MR imaging may also be attributed to the different timing of these imaging studies. While postcontrast CT scans of the neck are usually acquired with a relatively short delay after contrast injection, postcontrast MR images take longer to acquire, reflecting the pattern of enhancement in which there is delayed wash-in and slow washout.

The imaging differential diagnosis for KD in the head and neck includes parotid tumors, lymphoma, metastatic tumors, malignant tumors of cutaneous or subcutaneous origin, tuberculosis, and ALHE.^9,12,14,15 The parotid tumors are usually encapsulated or pseudoencapsulated and are limited to the parotid gland, while KD is frequently associated with irregular extension into the subcutaneous tissue. Although lymphoma and metastatic lymphadenopathy may have similar presentations, the irregular margination of the lesions and the distribution of the lesions, as well as the long clinical course as seen in KD, are unusual.^12,15 Enhanced lymphadenopathy associated with tuberculosis usually demonstrates central hypoattenuation and peripheral rim enhancement, whereas enlarged lymph nodes enhance homogeneously in KD.⁹ KD can be confused clinically and histologically with ALHE, also known as epitheloid hemangioma, which is a rare but distinctive vascular tumor typically occurring in women.¹⁶ ALHE, however, usually presents as small erythematous dermal nodules in the head and neck that itch and bleed easily. There is less common association with lymphadenopathy and peripheral eosinophilia. Histologically, fibrosis is lacking in ALHE, whereas it is prominent at all stages in KD.¹⁵ Other entities that may present similarly to KD include posttransplant lymphoproliferative disorder, pseudotumor, Kuttner tumor, Castleman disease, and Sjogren syndrome.

The treatment of KD is not well-established. Although surgical excision is the preferred method of initial treatment, recurrence is common.^{7,12,16,19,20} Other therapeutic options include radiation therapy, systemic corticosteroids, cytotoxic agents, cyclosporin, and pentoxifylline, with variable responses.^16,19,20 The recurrence rate is lower when ≥2 therapies are combined.¹²