Kimura's disease

Kimura disease is a rare form of chronic inflammatory disorder involving subcutaneous tissue, predominantly in the head and neck region and frequently associated with regional lymphadenopathy and/or salivary gland involvement. This condition has a predilection for males of Asian descent and may clinically simulate a neoplasm. Kimura disease is sometimes confused with angiolymphoid hyperplasia with eosinophilia, which occurs in the superficial skin of the head and neck region. Although sporadic cases have been reported in non-Asians, there is no large, comprehensive study of Kimura disease in the United States. We report 21 cases with nodal involvement that, histologically, are consistent with Kimura disease. There were 18 males and 3 females (male/female ratio 6:1), 8 to 64 years of age (mean, 32 years), and included 7 Caucasians, 6 Blacks, 6 Asians, 1 Hispanic, and 1 Arabic. Anatomic sites of involvement included posterior auricular (n = 10), cervical (n = 6), inguinal (n = 3), and epitrochlear (n = 2) lymph nodes, with two patients having associated salivary gland involvement. Most (n = 16) cases had peripheral blood eosinophilia. Consistent histologic features were follicular hyperplasia, eosinophilic infiltrates, and proliferation of postcapillary venules. Follow-up data on 18 patients revealed that 13 were alive without disease (3 had recurrence), mean follow-up, 10.9 years; 4 were alive with disease (2 had a recurrence), mean follow-up, 8.8 years; and 1 died with disease (12.7 years). Kimura disease has been described more often in Asians, but it does occur in non-Asians with a similar clinicopathologic presentation. It is a distinctive entity with no known etiology. Kimura disease has characteristic histologic features that are important to recognize and can be used to differentiate it from hypersensitivity and drug reactions and infections.

Juvenile temporal arteritis

An asymptomatic nodule appeared in the right temporal region of an 81-year-old woman. Histopathologic examination confirmed significant thickening of the vascular wall, constriction of the vessel lumen, and infiltration of numerous eosinophils and lymphocytes. Giant cells were not seen. Lymphoid follicles and capillaries surrounded the large vessel. Elastica van Gieson staining revealed a laceration of the internal elastic lamina. Based on these clinical and histologic findings, the patient was diagnosed as having juvenile temporal arteritis (JTA), a disease first proposed by Lie and his colleagues in 1975. Three years later, a new eruption, again asymptomatic, appeared in the posterior region of the patient's right ear. Subsequently, she was referred to our department. Histologic examination of the new lesion confirmed the infiltration of lymphocytes and eosinophils, which was accompanied by numerous lymphoid follicles, and the proliferation of endothelial cells and capillaries from the deep dermis to the subcutaneous tissue. The patient was diagnosed as having Kimura disease, which is a persistent and recurrent illness. We hypothesized that JTA was a partial expression of Kimura disease and investigated whether past cases of JTA could be considered Kimura disease. As a result, we found that most cases of JTA could indeed be considered Kimura disease. Furthermore, we examined the vascular changes in the routinely and elastic fiber-stained sections of three cases with Kimura disease and two cases with angiolymphoid hyperplasia with eosinophilia. The results showed occlusive vascular changes in most samples from these cases, supporting the hypothesis that JTA is an accessory lesion of Kimura disease.

Kimura's Disease

Kimura's disease is a rare chronic inflammatory condition of uncertain etiology which has an affinity for the Asian population. It primarily involves the head and neck region, presenting as deep subcutaneous masses and is often accompanied by regional lymphadenopathy and salivary gland involvement. Peripheral blood eosinophilia and elevated serum immunoglobulin E (IgE) levels are characteristic features and the microscopic picture reveals lymphoid proliferation with eosinophilic infiltration. For years, Kimura's disease was believed to be identical to or part of the same disease spectrum as angiolymphoid hyperplasia with eosinophilia (ALHE). Recent reports, however, have confirmed that the two are, in fact, separate entities. We report a case of Kimura's disease in a 22-year-old Indian male who presented with a subcutaneous mass, parotid enlargement and lymphadenopathy. The clinical presentation was suggestive of Kimura's disease and microscopic examination following biopsy of the lesion allowed us to make a definitive diagnosis.

The clinicopathologic features of nine patients with Kimura's disease and 15 patients with angiolymphoid hyperplasia with eosinophilia (ALHE) were studied and compared in order to clarify the confusion between these two entities. The common features shared by both conditions included male predominance, predilection for the head and neck regions, tendency to recur, and vascular nature of the lesion with lymphoid and eosinophilic infiltrates. However, Kimura's disease was usually seen in younger individuals for a longer duration and occurred as a deeply seated, large soft-tissue mass, without significant change of the overlying skin initially. In addition, it was often accompanied by peripheral blood eosinophilia and elevated serum IgE. In contrast, ALHE lesions were multiple small dermal papular or nodular eruptions observed in older patients and present for a shorter duration; they were less frequently accompanied by peripheral blood eosinophilia. The main histopathological difference was the presence of "histiocytoid" or "epithelioid" blood vessels in ALHE but not in Kimura's disease. Kimura's disease was further characterized by eosinophilic folliculolysis; IgE deposits in the germinal centers; and frequent involvement of regional lymph nodes, salivary glands, and skeletal muscles. The eosinophilic infiltration, especially the formation of eosinophilic microabscesses, along with increased number of small blood vessels, perinodal eosinophilic infiltration, and eosinophilic folliculolysis characterized the nodal involvement by Kimura's disease. Our study indicates that Kimura's disease and ALHE are two distinct clinicopathologic entities. We place particular emphasis on the involvement of regional lymph nodes in Kimura's disease. In addition, we observed Charcot-Leyden crystals and polykaryocytes in both conditions. One of the patients with Kimura's disease also had an associated nephrotic syndrome.

Microcirculatory systems, which can be divided into several segments, have crucial physiological functions. We investigated whether monoclonal antibody against alpha-smooth muscle actin (alpha SMA) was useful for the identification of microcirculatory segments, according to the structure of their periendothelial cells, in two pathological cutaneous conditions. We examined skin specimens from patients with Kimura's disease and with angiolymphoid hyperplasia with eosinophilia, since little information is available on microvascular segments in these conditions. Immunostaining for alpha SMA revealed the morphological characteristics of the periendothelial cells clearly enough to identify five segments in the proliferative microvessels of Kimura's disease and angiolymphoid hyperplasia with eosinophilia. In Kimura's disease, postcapillary venules were predominant, while each vascular segment in angiolymphoid hyperplasia with eosinophilia was uniform. Vessels without periendothelial cells were detected to a greater extent in angiolymphoid hyperplasia with eosinophilia than in Kimura's disease. The antibody against alpha SMA appeared to be useful in the observation of periendothelial cells for the identification of vascular segments in pathological cutaneous conditions.

Unusual presentation of Kimura's disease involving the parotid gland in an Indian male: a case report and review of literature

Kimura's Disease (KD) is a rare chronic inflammatory disorder presenting as multiple painless solitary subcutaneous nodules, predominantly in the head and neck region and frequently associated with regional lymphadenopathy and/or salivary gland involvement. Because of painless nature and indolent course, there is usually a delay in the patient's presentation. KD may radiologically mimic other chronic inflammatory conditions like tuberculosis, vascular malformations and neoplasms. Clinical correlation and histological evaluation along with elevated peripheral eosinophil and serum IgE level are considered important for confirmatory diagnosis. We report a case of painless swelling over right submandibular region extending to the right superficial parotid. The haematological reports were within normal limits. Ultrasound (USG), Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiogram (MRA) favoured a diagnosis of venous malformation. However, histopathological examination of excised lesion confirmed a diagnosis of KD. This case proves the possibility of the KD even in the absence of peripheral eosinophilia and/ or elevated serum IgE level, and may mimic venous malformation on imaging studies. Therefore, KD must find a place in the differentials of solitary painless neck swelling even in the absence of peripheral eosinophilia and/or elevated IgE level.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular neoplasm mainly affecting middle-aged women. Lesions typically affect the head and neck region. ALHE is considered a distinct disease entity different from Kimura's disease, a benign reactive lymphoid proliferation that is predominantly seen in young Asian men although it can affect all ethnic groups. In contrast to ALHE, Kimura's disease is typically associated with peripheral blood eosinophilia, increased serum IgE and lymphadenopathy. Several case reports suggest an overlap between ALHE and Kimura's disease. We review the current literature and discuss whether AHLE and Kimura's disease might represent two extreme variants of the same disease entity.

Much controversy has existed with regard to the relationship between Kimura's disease and angiolymphoid hyperplasia with eosinophilia. They were initially thought to represent the same disease spectrum, but it has now been widely accepted that they are two separate disease entities. To our knowledge, there have been no reports to date describing a case of both Kimura's disease and angiolymphoid hyperplasia with eosinophilia coexisting in the same patient. We describe a patient presenting initially with a right postauricular subcutaneous swelling and subsequently developing multiple erythematous facial papules and nodules. The medical literature is reviewed. Clinical features of the right postauricular subcutaneous swelling and multiple erythematous facial papules/nodules suggest Kimura's disease in the former and angiolymphoid hyperplasia with eosinophilia in the latter. Histopathological examinations of these lesions helped to confirm the diagnosis of Kimura's disease and angiolymphoid hyperplasia with eosinophilia, respectively. Kimura's disease and angiolymphoid hyperplasia with eosinophilia can coexist in the same patient. Coexistence of the two types of lesions in one patient may also be considered evidence that Kimura's disease and angiolymphoid hyperplasia with eosinophilia form a spectrum in one disease.

Selection de resumes interessant les acquisitions nouvelles en pathologie tumorale des tissus mous au cours des annees 88 et 89: description de 2 nouvelles entites. La tumeur fibrohistiocytaire plexiforme et le myofibroblastome palissadique, distinction entre haemangiome epithelioide et maladie de KIMURA et interet de l'anticorps anti EMA comme outil diagnostique courant dans le cadre des tumeurs des tissus mous

To investigate the clinicopathologic features, immunophenotypes and differential diagnosis of Kimura's disease (KD) and epithelioid hemangioma (EH). Nine cases of KD and three cases of EH were evaluated by light microscopy and immunohistochemistry. In this series, KD occurred predominantly in males, whereas EH had a female predilection. Both KD and EH arose most frequently in the head and neck region. However, KD usually presented as multiple subcutaneous nodules or swellings and was accompanied by lymphadenopathy in some cases. On the other hand, EH appeared only as a small skin nodule or red plaque. Histologically, both lesions may involve the dermis or subcutis. All the 9 KD cases displayed florid hyperplasia of lymphoid tissue, of which, 7 cases exhibited formation of lymphoid follicles and active germinal centers. Proliferation of post-capillary venules were seen between follicles. They were lined by plump or attenuated endothelial cells. Large number of eosinophils aggregated around the vessels or adjacent to the follicles, formation of microabscesses were observed in 3 cases. All the 3 EH cases showed prominent proliferation of vessels (capillary-sized in 2 cases and small to medium-sized in 1 case). The vessels were lined by epithelioid endothelial cells with abundant eosinophilic cytoplasm. The endothelial cells also proliferated within the lumen in 1 case and grew in sheets or cords adjacent to the vessel walls in 2 cases. Some endothelial cells contained intracytoplasmic vacuoles, suggesting formation of primitive vessels. Associated inflammatory component was noted in 2 cases. Lymphoid follicles however were not present and eosinophil infiltration was not as prominent as in KD. Immunohistochemical study in KD revealed B cells in the lymphoid follicles and mostly T cells in the interfollicular regions. In EH, the epithelioid endothelial cells showed strong reactivity to CD31 and factor VIII-related antigen. KD and EH are two distinctive entities. The former represents a lymphoid hyperplasia and the latter represents a benign vascular tumor. Recognition of the clinical characteristics and morphologic features of KD and EH is very important in making this distinction.

A case of juvenile temporal arteritis, which is a rare vascular lesion in children and young adults, associated with Kimura's disease in a healthy 23-year-old asymptomatic man is described. The patient presented with a painless 2.5 cm nodule with eosinophilia and normal erythrocyte sedimentation rate. Histologically, the left superficial artery showed marked intimal thickening with moderate eosinophilic infiltrates, constriction of the vascular lumen, focal disruptions of the internal elastic lamina and media, moderate eosinophilic infiltrates in the adventia, and absence of giant cells. The subcutaneous tissue surrounding the artery was characterized by lymphofollicular hyperplasia, marked eosinophilic infiltrates in the intra- and extra-follicles with abscess, capillary proliferations, lymphocytic, plasma cell and mast cell infiltrates, and fibrosis in the interfollicular region. Immunohistochemically, reticular, positive IgE staining was observed in the germinal centers. Clinically and histologically, the lesion was consistent with juvenile temporal arteritis associated with Kimura's disease. The findings indicate that both entities are closely related and juvenile temporal arteritis may be secondary to Kimura's disease.

Recently, human herpesvirus 8 (HHV-8) has been isolated from almost all cases of Kaposi's sarcoma. It has not been found in most cutaneous hemangioproliferative disorders other than Kaposi's sarcoma. Benign vascular lesions including Kimura's disease were not found to contain the HHV-8 DNA sequence. However, there has been contradictory data concerning the presence of HHV-8 in angiolymphoid hyperplasia with eosinophilia (ALHE). Clonality studies in ALHE and Kimura's disease were rare. We performed polymerase chain reaction (PCR)-based analysis to determine whether HHV-8 is present and heteroduplex analysis of rearranged T-cell receptor (TCR) gene for clonality assessment in paraffin-embedded skin biopsy samples of 7 ALHE and 2 Kimura's disease, taken from immunocompetent patients. HHV-8 could not be identified in all the cases of ALHE and Kimura's disease. Although 2 cases (2/7) of ALHE and 2 cases (2/2) of Kimura's disease showed positive result for PCR analysis of TCR, all the cases were negative for heteroduplex-PCR. We suggest that HHV-8 may not involve in a pathogenetic role in ALHE and Kimura's disease and the failure to demonstrate clonality may be consistent with the reactive nature of these diseases and lack of malignant transformation. In addition, heteroduplex-PCR can be applied to confirm doubtful cases of lymphoma in that heteroduplex-PCR is more specific than PCR as seen in our study.