Kimuraʼs Disease

Rare case of Kimura disease of the upper lip: A case report

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.

Angiolymphoid hyperplasia with eosinophilia (ALHE) and Kimura disease were previously considered the same entities and are now considered a distinct disorder clinically and histologically. ALHE is a benign vasoproliferative disorder with unclear etiology. The clinical presentation of ALHE includes the involvement of skin and vascular structures sparing lymph nodes. It predominantly involves the head and neck region, extremities, and rarely orbit, oral mucosa, bones, and colon. On the other hand, Kimura disease is a rare benign chronic inflammatory disorder of unknown etiology that predominantly involves subcutaneous lymphoid masses and regional lymph nodes of the head and neck region. Both disorders are classified under hypereosinophilia (HE); however, Kimura disease is more associated with peripheral eosinophilia. It is tough to differentiate both the disorders clinically from each other and also from other HE syndromes including eosinophilic granulomatosis with polyangiitis and systemic HE syndromes. However, tissue diagnosis is the key to differentiation. Here, we describe a female at her 50s without any prior comorbidities, presented to our OPD with atypical multiple symmetrical soft tissue swellings which were of diagnostic dilemmas. She showed features of both ALHE and Kimura disease in investigations. As there is no specific recommendation for treatment, she was started with oral glucocorticoid and weekly methotrexate showing a good response in follow-up visit.

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.

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.

Kimura Disease of the Orbit and Ocular Adnexa

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare reactive angio-proliferative lesion. ALHE was initially classified as the late stage of Kimura’s disease (KD), although studies later showed that they were two separate clinical entities. Diagnosing ALHE remains a clinical challenge. Here, we report a case of ALHE in a young man and review current literature with an emphasis on how to distinguish ALHE particularly from KD. A 26-year-old man presented with a subcutaneous nodule in right infra-auricular area. Recurrence had occurred after three surgical excisions. Neither enlargement of salivary glands nor lymph nodes were found. Hematological examinations and renal function were normal. The mass was removed surgically. Microscopic examination showed proliferation of vascular channels with accompanying mixed inflammatory infiltrate consisting of lymphocytes, plasma cells, and eosinophils. Based on clinical data and histopathological examination, the patient was diagnosed with ALHE. Several clinical features differ between ALHE and KD, such as gender predilection, hypereosinophilia, IgE levels, and renal involvement. However, clinical features can overlap, so definitive diagnosis relies on histopathological examination. The most important hallmark of ALHE is vascular proliferation with epithelioid endothelial cells. Distinguishing ALHE from KD is important due to the lack of systemic manifestations in ALHE. However, ALHE can be easily mistaken for other diseases due to its rarity. Careful microscopic examination is very important to distinguish ALHE from KD and other mimicking lesions.

Kimura disease is a rare, chronic inflammatory disorder of unknown etiology, presenting as subcutaneous nodules in the head and neck region with peripheral eosinophilia and elevated serum immunoglobulin E (IgE) levels. Initially identified as eosinophilic hyperplastic lymphogranuloma in East Asia in the 1930s, it frequently involves regional lymphadenopathy.[1,2] While isolated ocular involvement is rare,[2] especially in adolescent females, it is usually observed in young Asian males.[1,2] An 18-year-old female presented with a recurrent, painless swelling in the right lower eyelid for 1 year. The swelling was insidious, gradually progressive, and not associated with redness, discharge, or visual symptoms. She had undergone two previous excisions for similar lesions, followed by three recurrences, the latest 6 weeks before presentation. There was no history of trauma, insect bite, fever, or systemic illness. Examination revealed a firm, nontender 25 mm × 7 mm swelling over the lateral two-thirds of the right lower eyelid, with an overlying surgical scar [Figures 1 and 2]. Ocular findings were normal, and there was no regional lymphadenopathy.Figure 1: Clinical photograph of the right eye showing swelling at the lateral aspect of the lower lid. The black arrow indicates the site of the swelling, with overlying skin displaying a scar from previous surgeryFigure 2: Clinical photograph showing swelling at the lateral aspect of right lower lid. The black arrow indicates the site of the swellingA provisional diagnosis of lymphoma was made. Peripheral blood analysis showed an elevated absolute eosinophil count (450/μL; normal 40–400/μL), eosinophils 7.6%, and markedly increased serum IgE (1552 IU/mL; normal <100 IU/mL). Excision biopsy under general anesthesia revealed a poorly delineated, gritty lesion. Histopathology showed lymphoid follicles with germinal centers, dense eosinophilic infiltrates, microabscesses, and fibrosis without vascular proliferation. No epithelioid vascular cells, glomeruloid features, fungal hyphae, or spores were seen – all favoring Kimura disease [Figures 3 and 4].[1] The patient was prescribed oral cetirizine (10 mg daily) postoperatively.Figure 3: Histopathology of the excision biopsy specimen. Follicular hyperplasia with eosinophilic microabscess and fibrosis H and E, ×400Figure 4: Histopathology of the excision biopsy specimen follicular hyperplasia with dense inflammation, H and E, ×100Kimura disease was first described in East Asia in the 1930s and formally named by Kimura et al. in 1948. It is characterized histologically by reactive lymphoid hyperplasia, eosinophilic infiltration, and the growth of thin-walled blood vessels.[1] The differential diagnosis includes angiolymphoid hyperplasia with eosinophilia (ALHE),[1,2] parasitic infections, Langerhans cell histiocytosis, and lymphoproliferative disorders.[3] ALHE may mimic Kimura disease but typically shows prominent epithelioid endothelial cells and lacks lymphoid follicles. Peripheral eosinophilia and elevated IgE are more commonly associated with Kimura disease.[1] Surgical excision is the mainstay of management, though recurrences occur in 25%.[3] Systemic steroids and immunosuppressants such as cyclosporine or tacrolimus may help prevent relapse.[1,2] Cetirizine, a second-generation antihistamine, has been shown to reduce lesion size and promote remission in Kimura disease.[3] Our patient received systemic cetirizine postoperatively, but response could not be assessed as she was lost to follow-up. Despite two prior surgeries, the recurrence raised suspicion of a rare diagnosis. The combination of characteristic histopathology, peripheral eosinophilia, and elevated IgE confirmed Kimura disease. What is known Kimura disease is a benign, chronic inflammatory condition primarily affecting Asian males, often with lymphadenopathy involving the head and neck regions. What is new This report highlights an exceedingly rare presentation of isolated eyelid Kimura disease in an adolescent female, without orbital or nodal extension, expanding its clinical spectrum. Data availability statement The data supporting the findings of this study will be made available on reasonable request. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, benign slow-growing lesion primarily found in the head and neck region, with onset between the third and fourth decades, and a female predominance in the nonOriental population. Kimura's disease, occurring primarily in young Oriental males, is a similar lesion with peripheral blood eosinophilia, regional lymphadenopathy, and occasional nephrotic syndrome. Orbital ALHE is rare, previously reported in only nine patients. Orbital ALHE is a solitary lesion, with an older age of onset, between the fourth and eighth decades, than ALHE elsewhere. There is a male predominance, in contradistinction to ALHE elsewhere in nonOrientals. Orbital ALHE demonstrates the same histology as other locations, with exuberant capillary proliferation and an inflammatory infiltrate of eosinophils, lymphocytes, plasma cells, and mast cells. The maturity of the lesion, not necessarily the duration, determines the presence of lymphoid follicles and germinal centers. A distinctive endothelial cell lines and even extends into the vascular lumens. Peripheral blood eosinophilia occasionally occurs, and a few cases have been reported in conjunction with asthma. Therapeutic regimens for ALHE include excision, carbon dioxide and argon laser, irradiation, steroids, electrodesiccation, and cytotoxic agents. Orbital lesions have been treated successfully with excision, or biopsy with debulking, or steroids.

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.

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.

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

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign clinical entity characterized by the presence of a variable number of papules, plaques or nodules of the dermis and subcutaneous tissues. ALHE shows a predilection for the head and neck area. Orbital involvement is unusual. A 20-year-old male presented with a 4-month history of swelling of the upper lid of right eye. Magnetic resonance imaging orbit revealed altered signal density seen in supero-medial aspect of right eyeball with adjacent inflammatory changes. The patient underwent anterior orbitotomy and excision biopsy of the mass under general anesthesia. Histopathology of the mass showed vascular proliferation and chronic inflammation accompanied by infiltration of eosinophils, which confirmed the diagnosis of ALHE. The patient recovered both functionally and cosmetically and had no signs of recurrence after 6 months. Angiolymphoid hyperplasia with eosinophilia with orbital involvement in males is a rare clinical entity, and further work is required to accurately describe its incidence, etiology and presentation. ALHE can be diagnosed and differentiated from Kimura's disease (KD) on histopathological grounds. The presence of vascular hyperplasia with plump of endothelial cells protruding into the lumen is the most important discriminator in establishing the diagnosis of ALHE. Such distinction is crucial for the patient because ALHE is not associated with any of the systemic manifestations present in KD.

Kimura's disease and angiolymphoid hyperplasia with eosinophilia: Clinical and histopathologic differences