SciELO - Scientific Electronic Library Online

vol.81 issue2"Algesiogenic" lichen aureusBasics of digital photography in Dermatology author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand




Related links


Anais Brasileiros de Dermatologia

Print version ISSN 0365-0596On-line version ISSN 1806-4841

An. Bras. Dermatol. vol.81 no.2 Rio de Janeiro Mar./Apr. 2006 



Kimura disease is not angiolymphoid hyperplasia with eosinophilia: clinical and pathological correlation with literature review and definition of diagnostic criteria*



Pedro Leonardo BriggsI

IPh.D. in Dermatology from the Universidade Federal do Rio de Janeiro - UFRJ - Rio de Janeiro (RJ), Brazil. Fellow in Dermatopathology from the New York University. Fellow in Mohs Surgery from the University of Wisconsin





Kimura disease is a rare chronic inflammatory disease that presents as a tumor-like swelling in the head and neck region and is often associated with regional cervical lymphadenopathy. Cases have been described predominantly in the oriental literature. Kimura disease has been confused with angiolymphoid hyperplasia with eosinophilia, for having common characteristics, but both conditions should be differentiated. In this article, the clinical and histopathological characteristics are revised and the criteria to differentiate the two conditions are presented.

Keywords: Angiolymphoid hyperplasia with eosinophilia; Hemangioma; Histology




Kimura disease (KD) was initially described in 1937, in the Chinese literature, by Kimm and Szeto1 as an “eosinophilic hyperplastic lymphogranuloma” and it became known as KD after its publication by Kimura et al.2 of similar cases in Japan under the title “Atypical granulation associated with hyperplastic abnormalities in the lymphoid tissue.” It is a chronic inflammatory disease involving the dermis and subcutaneous tissue characterized by one or multiple nodules or unpainful masses. It occurs predominantly as a unilateral manifestation in the head and neck and it is frequently associated with regional lymphadenopathy with or without involvement of salivary glands.3 Histopathologically, this condition is characterized by a lymphocytic inflammatory infiltrate, forming lymphoid follicles interspersed with aggregates of eosinophils and variable fibrosis in a richly vascular stroma. The pathophysiology of KD remains unknown, although allergic reaction, trauma and autoimmune process have been implicated as triggering factors.3,4

Angiolymphoid hyperplasia with subcutaneous eosinophilia (ALHE) was described in 1969, by Wells and Whimpster,5 who studied nine patients with persistent subcutaneous nodules in the head and neck. In the pathological examination, these cases presented exuberant vascular proliferation, inflammatory infiltrates containing lymphocytes, eosinophils and mast cells, but with no fibrosis. The authors considered that ALHE late stage would correspond to Kimura disease and they were followed in their observations by Reed et al.6 and Eveson et al.7 Eventually, numerous articles8-10 considered the two denominations as synonyms.

Although recent articles11,12 have established consistent criteria for differentiation between ALHE and Kimura disease, several authors still confuse the two entities.13-15

Kimura disease

KD is a rare inflammatory disorder of unknown origin. Most of patients are male and oriental young adults. The prevalence in patients of other ethnicities is considered low. The disease is characterized by a triad of unpainful subcutaneous masses in the head and neck, eosinophilia in the peripheral blood and in tissues, and marked increase in serum levels of immunoglobulin E (IgE).16,17

At physical examination, patients with KD present one or more subcutaneous masses in the head and neck, accompanied by satellite adenomegalies and/or increased volume of salivary glands, especially the parotid and submaxillary glands (Figure 1). The lesions are firm at palpation, not painful and progressively increase in size with some of them reaching a diameter between 3 and 10 cm. There is a marked predominance of male patients; the male/female ratio is 2:1; and the onset of the disease occurs mostly in the third decade of life.18,19 Kung et al.3 studied 21 patients distributed as 18 men and 3 women, and they observed that the age of onset of lesions ranged from 7 to 50 years, with a mean age of 28 years. Such patients frequently reported pruritus in the overlying skin. In this study, most of the lesions were in the regions of head and neck; seven cases also presented involvement of the parotid gland. Lesions in other areas were also described such as the inguinal area, upper limbs and chest wall.3



Although KD pathogenesis remains unknown, it is considered nowadays an allergic disease and it seems to be a systemic immunological disorder. Eosinophilia and increased serum IgE levels make KD be considered a CD4(+) T helper 2 (Th2) allergic reaction. Th2 cells would produce interleukins (IL) IL-4, IL-5 and IL-13, which, in turn, would act in B cells favoring the production of antigen-specific IgE. Th2 cell proliferation and the overexpression of cytokines would play an essential role in the development of the disease.16,20

The histopathological changes in KD consist of a massive, nodular, diffuse and mixed inflammatory infiltrate composed mainly of lymphocytes and eosinophils, occupying all the extension of reticular dermis, subcutaneous tissue and, sometimes, the muscle fascia and the skeletal muscle (Figure 2). The inflammatory infiltrate is poorly circumscribed and contains numerous lymphoid follicles; infiltration of adjacent salivary glands may also occur.13,15 Lymphoid follicles are hyperplastic and contain prominent germination centers (Figure 3). Eosinophilic infiltration may occur occasionally with areas of necrosis (Figure 4). Although plasma cells and histiocytes are present, no epithelioid cells, multinucleated giant cells or granulomas are seen.3,10 Fibroplasia is seen in the subcutaneous tissue and around the lesion. Fibrosis can be sometimes observed as septa. Fibroplasia cellularity varies and tends to hyalinization of older lesions.13,21







The lesions are markedly of vascular type; capillaries are numerous and their endothelium is prominent and with no cytological atypias.13,21 Small arteries present hyperplasia or fibrosis of tunica intima and tunica muscularis. Large caliber arteries are rarely seen. Older lesions show more pronounced fibrosis, less active lymphoid follicles, less intense inflammatory infiltrate and a relatively less exuberant vascular component.13,15,21

Due to KD benign nature, treatment may range from observation and follow-up of mild and asymptomatic cases to conservative surgical excision, although lesions sometimes tend to recur. Other therapeutic options less commonly used include intralesional corticosteroids, cyclosporine, pentoxiphylline and radiotherapy.22-27

Angiolymphoid Hyperplasia with Eosinophilia (ALHE)

In 1969, Wells and Whimpster5 studied nine patients with persistent subcutaneous nodes in the head and neck and described them as “angiolymphoid hyperplasia with subcutaneous eosinophilia” (ALHE). Wilson-Jones and Bleehen28 described similar lesions and published them in the same year and in the same journal under the name “inflammatory angiomatous nodules with abnormal blood vessels in the scalp and ears – pseudo or atypical pyogenic granuloma”. In 1983, Enzinger and Weiss,29 in their book Soft Tissue Tumor suggested the expression “epithelioid hemangioma” for this uncommon and distinct vascular formation.

ALHE is a rare disease which manifests with the presence of dermal papules and nodules measuring 2-3 cm and a color varying between light brown and pink (Figure 5). It predominantly observed in the head and neck, especially around the external ear in young patients. There seems to be a higher incidence in females and it is more common in patients aged 20-50 years (peak incidence between 30-33 years).21,30 Although its pathogenesis remains undefined and some authors consider it an abnormal vasoproliferative reaction, recent studies11,13 tend to consider this disease as a benign vascular neoplasm or a vascular malformation secondary to a subcutaneous arteriovenous shunt which sporadically can be associated with a previous trauma. Eosinophilia in the peripheral blood is frequently absent in ALHE, as well as the levels of IgE which are normal.13



Histopathologically, ALHE is predominantly characterized by vascular proliferation and inflammatory infiltrate (Figure 6).13,15,30 The vascular component includes capillaries clustered around arterial or venous vessels, dilated and atypical, forming a lobular architecture and sometimes surrounded by a fibromixoid stroma (Figure 7).13 These capillaries have a protruded endothelium with rounded and sometimes polygonal nuclei (Figure 8). One or more cytoplasmic vacuoles can be seen in the abnormal endothelial cells. The lesion can grow entirely in a blood vessel or it can originate from the vascular wall.21







The inflammatory component is characterized by a superficial and deep, nodular and diffuse infiltrate, composed predominantly of lymphocytes, a variable number of eosinophils, plasma cells and mast cells. Lymphoid follicles are rare or are absent in most cases. The inflammatory infiltrate tends to be less conspicuous in papulous lesions than in nodular lesions.13,21

In addition to KD, the differential diagnoses for ALHE should include angiosarcoma, hemangioma, hemangioendothelioma and a reaction to insect bite.15

Angiosarcomas could be distinguished from ALHE for presenting nuclear atypia with hyperchromatism, mitotic activity and scarce eosinophils in the inflammatory infiltrate. Hemangiomas do not present an intrinsic inflammatory infiltrate and they rarely show enlarged and protruding endothelial cells or with an eosinophilic cytoplasm. In addition to the characteristics above, a hemangioendothelioma has a characteristic reticular growth.15,21

Reactions to insect bites or reactions to vaccines may present inflammatory characteristics in common with ALHE, but they rarely show a prominent vascular component.15

Treatment to ALHE is always a challenge.20,31 Surgical removal, including the arterial and venous segments at the base of the lesion, seems to be the most efficient alternative. Recently, a surgical technique developed by Mohs32 was used as a way to spare a larger amount of tissue and to control the margins. Other therapeutic options less commonly used include isotretinoin, interferon, pentoxifylline, imiquimod, cryotherapy and laser.33-40



For many years, the authors of medical literature in English used the expressions ALHE and KD as synonyms.13 Even today, in the last edition of Dermatology in General Medicine (Fitzpatrick et al14) there is still some doubt if the two entities represent distinct diseases. The difficulty to distinguish them is in part due to the rarity of KD in the occidental literature and to characteristics that are common to both diseases.3,13

ALHE and KD have the following histopathological characteristics13 13 in common: both may involve the dermis and subcutaneous tissue; present an inflammatory infiltrate composed by lymphocytes and eosinophils, blood vessels with endothelial cells that can be protruding and with abundant cytoplasm, and fibroplasias; have plasma cells in the inflammatory infiltrate; and spare the epithelial and non-epithelial structures in adnexal structures (Chart 1).



Despite these characteristics in common, ALHE and KD can be easily differentiated from each other (Chart 2). At low magnification, ALHE is characterized by dilated blood vessels which sometimes have bizarre and irregular shapes, in addition to enlarged and protruding endothelial cells with abundant cytoplasm. These vessels are frequently surrounded by a ring of fibroplasia containing mucin. In contrast, KD is histopathologically characterized as a small enlargement due to nodular and diffuse inflammatory infiltrate throughout the dermis and containing lymphoid follicles associated with fibroplasias, which replaces a great deal of the subcutaneous tissue.13,21

At larger magnifications, ALHE is characterized by enlarged and sometimes polygonal endothelial cells with prominent vacuoles in the cytoplasm. These vacuoles are not present in KD. Although eosinophils are present in both diseases, they may be in a small number or practically absent in ALHE, but they are always abundant in KD. Lastly, while the lymphoid follicles are absolutely necessary for the diagnosis of KD, they are present in less than 10% of cases of ALHE.13

Clinically, there are also important differences which enable differentiating KD from ALHE, particularly the larger diameter of lesions, the longer time of evolution and the erythematous or purpuric color that is typical of ALHE, thus reflecting the vascular nature of the process.4,13



ALHE is considered a vascular malformation resulting from an arteriovenous shunt. The process is predominantly vascular and other changes such as lymphoid follicles and eosinophils seem to be secondary. In contrast, KD seems to have an immunological basis reflecting the numerous lymphoid follicles and eosinophils. The idea that is still present in some works considering that ALHE and KD are part of the same disease does not have a clinical, pathological or biological support. Histopathologically, the two conditions can be distinguished at first with a low microcopic magnification and other characteristics detected with higher magnification are useful to confirm diagnosis and enable allow the differentiation.



1. Kimm HT, Szeto C. Eosinophilic hyperplastic lymphogranuloma, comparison with Mikulicz's disease. Proc Chin Med Soc. 1937;1:329.        [ Links ]

2. Kimura T, Yoshimura S, Ishikawa E. On the unusual granulation combined with hyperplastic changes of lymphatic tissues. Trans Soc Pathol Jpn. 1948;37:179-80.        [ Links ]

3. Kung IT, Gibson JB, Bannatyne PM. Kimura's disease: a clinico-pathological study of 21 cases and its distinction from angiolymphoid hyperplasia with eosinophilia. Pathology. 1984;16:39-44.        [ Links ]

4. Kuo TT, Shih LY, Chan HL. Kimura's disease. Involvement of regional lymph nodes and distinction from angiolymphoid hyperplasia with eosinophilia. Am J Surg Pathol. 1988;12:843-54.        [ Links ]

5. Wells GC, Whimster IW. Subcutaneous angiolymphoid hyperplasia with eosinophilia. Br J Dermatol. 1969;81:1-5.        [ Links ]

6. Reed RJ, Terazakis N. Subcutaneous angioblasticlymphoid hyperplasia with eosinophilia (Kimura’s disease). Cancer. 1972;29:489-97.        [ Links ]

7. Eveson JW, Lucas RB. Angiolymphoid hyperplasia with eosinophilia. J Oral Pathol. 1979;8:103-8.         [ Links ]

8. Kim BH, Sithian N, Cucolo GF. Subcutaneous angiolymphoid hyperplasia with eosinophilia (Kimura’s disease). Report of a case. Arch Dermatol. 1975;110:1246-8.        [ Links ]

9. Rehak A, Bou-Resli M, Mousa AM. Angiolymphoid hyperplasia with eosinophilia. Dermatologica. 1980;161:157-66.        [ Links ]

10. Thompson JW, Colman M, Williamson C, Ward PH. Angiolymphoid hyperplasia with eosinophilia of the external canal. Arch Otolaryngol. 1981;107:316-9.        [ Links ]

11. Googe PB, Harris NL, Mihm MC Jr. Kimura's disease and angiolymphoid hyperplasia with eosinophilia: two distinct histopathological entities. J Cutan Pathol. 1987;14:263-71.        [ Links ]

12. Chen H, Thompson LD, Aguilera NS, Abbondanzo SL. Kimura disease: a clinicopathologic study of 21 cases. Am J Surg Pathol. 2004;28:505-13.        [ Links ]

13. Ackerman AB, Briggs PL. Differential diagnosis in dermatopathology. Vol III. Pennsylvania: Lea & Febiger; 1993. p.62-5.        [ Links ]

14. Leiferman KM, Peters MS, Gleich G. Eosinophils in cutaneous diseases. In: Fitzpatrick, Eisen, Wolff, Freedberg, and Austen. Fitzpatrick's Dermatology In General Medicine. New York: McGraw-Hill; 2003. p.959-66.        [ Links ]

15. Lever WF, Schaumburg-Lever G. Histopathology of the skin. 8th ed. Philadelphia:Lippincott; 1997. p.889-931.        [ Links ]

16. Armstrong WB, Allison G, Pena F, Kim JK. Kimura's disease: two case reports and a literature review. Ann Otol Rhinol Laryngol. 1998;107:1066-71.        [ Links ]

17. Chen H, Thompson LD, Aguilera NS, Abbondanzo SL. Kimura disease: a clinicopathologic study of 21 cases. Am J Surg Pathol. 2004;28:505-13.        [ Links ]

18. Gumbs MA, Pai NB, Saraiya RJ, Rubinstein J, Vythilingam L, Choi YJ. Kimura's disease: a case report and literature review. J Surg Oncol. 1999;70:190-3.        [ Links ]

19. Chun SI, Ji HG. Kimura’s disease and angiolymphoid hyperplasia with eosinophilia: clinical and histopathologic differences. J Am Acad Dermatol. 1992;27:954–8.        [ Links ]

20. Shetty AK, Beaty MW, McGuirt W, WoodsCR, Givner LB. Kimura’s Disease: A Diagnostic Challenge. Pediatrics. 2002;110:39.        [ Links ]

21. Urabe A, Tsuneyoshi M, Enjoji M. Epithelioid hemangioma versus Kimura’s disease. Am J Pathol. 1987;11:758-66.        [ Links ]

22. Kaneko K, Aoki M, Hattori S, Sato M, Kawana S. Successful treatment of Kimura's disease with cyclosporine. J Am Acad Dermatol. 1999;41(5 Pt 2):893-4.        [ Links ]

23. Hongcharu W, Baldassano M, Taylor CR. Kimura’s disease with oral ulcers: response to pentoxifylline. J Am Acad Dermatol. 2000;43:905-7.        [ Links ]

24. Itami J, Arimizu N, Miyoshi T, Ogata H, Miura K. Radiation therapy in Kimura’s disease. Acta Oncol. 1989;28:511-4.        [ Links ]

25. Pasyk KA, Elsenety EN, Schelbert EB. Angiolymphoid hyperplasia with eosinophilia-acquired port-wine-stain-like lesions: attempt at treatment with the argon laser. Head Neck Surg. 1988;10:269-79.        [ Links ]

26. Katagiri K, Itami S, Hatano Y, Yamaguchi T, Takayasu S. In vivo expression of IL-4, IL-5, IL-13 and IFN-gamma mRNAs in peripheral blood mononuclear cells and effect of cyclosporin A in a patient with Kimura's disease. Br J Dermatol. 1997;137:972-7.        [ Links ]

27. Abrahamson TG, Davis DA. Angiolymphoid hyperplasia with eosinophilia responsive to pulsed dye laser. J Am Acad Dermatol. 2003;49:S195-6.        [ Links ]

28. Wilson-Jones E, Bleehen SS. Inflammatory angiomatous nodules with abnormal blood vessels occurring about the ears and scalp (pseudo or atypical pyogenic granulomas). Br J Dermatol. 1969;81:804-16.        [ Links ]

29. Enzinger FM, Weiss SW. Soft tissue tumors. St. Louis: CV Mosby; 1983. p.391-7.        [ Links ]

30. Tabata H, Ishikawa O, Ohnishi K, Ishikawa H. Kimura’s disease with marked proliferation of HLA-DR+ CD4+ T cells in the skin, lymph node, and peripheral blood. Dermatology. 1992;184:145-8.        [ Links ]

31. Mehregan AH, Shapiro L. Angiolymphoid hyperplasia with eosinophilia. Arch Dermatol. 1971; 103: 50-7.        [ Links ]

32. Miller CJ, Iofreda MD, Ammirati CT. Mohs Micrographic Surgery for Angiolymphoid. Hyperplasia with Eosinophilia. Dermatol Surg. 2004;30:1169-73.        [ Links ]

33. Cooper SM, Dawber RP, Millard P. Angiolymphoid hyperplasia with eosinophilia treated by cryosurgery. J Eur Acad Dermatol Venereol. 2001;15:489–90.        [ Links ]

34. Papadavid E, Krausz T, Chu AC, Walker NP. Angiolymphoid hyperplasia with eosinophilia successfully treated with the flash-lamp pulsed-dye laser. Br J Dermatol. 2000;142:192-4.        [ Links ]

35. Rohrer TE, Allan AE. Angiolymphoid hyperplasia with eosinophilia successfully treated with a long-pulsed tunable dye laser. Dermatol Surg. 2000;26:211-4.        [ Links ]

36. Nomura K, Sasaki C, Murai T, Mitsuhashi Y, Sato S. Angiolymphoid hyperplasia with eosinophilia: successful treatment with indomethacin farnesil. Br J Dermatol. 1996;134:189–90.        [ Links ]

37. Oh CW, Kim KH. Is angiolymphoid hyperplasia with eosinophilia a benign vascular tumor? A case improved with oral isotretinoin. Dermatology. 1998;197:189–91.        [ Links ]

38. Person J. Angiolymphoid hyperplasia with eosinophilia may respond to pentoxifylline. J Am Acad Dermatol. 1994;31:117–8.        [ Links ]

39. Rampini P, Semino M, Drago F, Rampini E. Angiolymphoid hyperplasia with eosinophilia: successful treatment with interferon alpha 2b. Dermatology 2001;202:343.        [ Links ]

40. Shenefelt PD, Rinker M, Caradonna S. A case of angiolymphoid hyperplasia with eosinophilia treated with intralesional interferon alfa-2a. Arch Dermatol. 2000;136:837–9.        [ Links ]



Pedro Leonardo Briggs
Rua Voluntários da Pátria, 445/1207
22270-000 - Rio de Janeiro – RJ

Conflict of interest: None



* Work done at New York University, NYU Medical Center - New York, NY, EUA.

Creative Commons License All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License