m
Kirnura's disease and angiolymphoid hyperplasia with eosinophilia: Clinical and histopathologic differences Soo I1 Chun, MD, and H y e Goo Ji, MD Seoul, Korea
Background: There has been considerable controversy about the relation between Kimura's disease and angiolymphoid hyperplasia with eosinophilia (ALHE). Objective: We describe the clinical and histopathologic differences between the two diseases. Methods: We reviewed clinical findings and histopathologic changes in two cases of Kimura's disease and three cases of ALHE. Results: Kimura's disease shows typical lymphoid follicles. It is associated with lymphadenopathy and is always accompanied by peripheral eosinophilia. ALHE shows typical changes in endothelial ceils. It is characterized by superficial papules or nodules with no lymphadenopathy and is less frequently accompanied by peripheral eosinophilia. Conclusion: Kimura's disease and ALHE are separate entities. (J AM ACAD DERMATOL1992;27:954-8.) Kimura's disease and angiolymphoid hyperplasia with eosinophilia ( A L H E ) are rare disorders involving mainly the head and neck. Kimura's disease, originally reported by Kimura et al., 1 is an unusual granuloma with proliferation of lymphoid tissue. M a n y similar cases have been reported under a variety of names such as A L H E , inflammatory angiomatous nodule, pseudopyogenic granuloma, atypical pyogenic granuloma, papular angioplasia, subcutaneous angioblastic lymphoid hyperplasia with eosinophilia, nodular angioblastic hyperplasia with eosinophilia and Iymphofolliculosis, intravenous atypical vascular proliferation, histiocytoid hemangioma, and epithelioid hemangioma. 2-4 A L H E is a benign, uncommon skin disease characterized by single or multiple nodules located mainly on the head or neck of young adults. Wells and Whimster s published the first report describing a condition that resembled Kimura's disease and designated it as subcutaneous ALHE. Since then, there has been considerable controversy about the relation between Kimura's disease and A L H E , 6' 7 and recent reports From the Department of Dermatology, Yonsei UniversityCollege of Medicine. Accepted for publicationJune 8, t992. Reprint requests: Soo I1 Chun, MD, Department of Dermatology, Yonsei University College of Medicine, C.P.O. Box 8044, Seoul, Korea. 16/1/40019
954
have suggested that they are two different diseases. 8-1~Kimura's disease is apparently more prevalent in Oriental patients. 7' 8 In Korea, Kimura's disease was first reported by Kim et al. 11 in 1975. Since then, 19 cases of Kimura's disease and A L H E have been reported, which are usually considered to be identical] 2 The rare occurrence of genuine Kimura's disease in western countries probably caused the current confusion. 13-16 We describe two cases of Kimura's disease and three cases of A L H E and discuss differences between the two diseases. CASE REPORTS Kimura's disease Clinical features Case 1. A 19-year-old man had large, deep nodules in both inguinal areas. About 14 months earlier, an asymptomatic, deep nodule appeared in the left upper inguinal area; it grew slowly. Similar nodules developed below the first 2 months later and in the right upper inguinal area 4 months later. Physical examination revealed an ellipsoid, slightly hard, movable, nontender, subcutaneous mass, measuring 8 • 16 cm, in the left upper groin, and a similar mass in the right groin. A complete blood cell count (CBC) showed the following: white blood cells (WBCs) 15,490/mm 3 and eosinophil count 6080/mm 3 (39.2%). Computed tomographic scans of the inguinal area showed enlarged soft masses. A chest roentgenogram was normal. With an initial dose of triamcinolone, 32 mg daily for 2 weeks, no improvement was observed.
Volume 27 Number 6, Part 1 December 1992
Kimura's disease and A L H E
955
Fig. 1. Case 2. Subcutaneous nodule with overlying normal skin in right postauricular area and excision scar from previous operation.
The radiation therapy (300 rad/day for 6 days) resulted in a marked decrease in the size of the lesions. Systemic corticosteroids and azathioprine therapy was given and the lesions gradually disappeared. No new or recurrent lesions developed 1 year after discontinuation of the therapy. Case 2. A 35-year-old man had had a prufitic lesion in the right postauricular area for 10 months. A similar lesion had appeared at the same site 18 months earlier and had been excised. On the basis of histologic findings the lesion was diagnosed as Kimura's disease. Physical examination revealed an oval nodule in the right postauricular area (Fig. 1). Routine CBC showed WBCs to be 13,300/mm 3, and eosinophil count 950/ram 3 (13.3%). He was treated with systemic corticosteroids, intralesional corticosteroid, and azathoprine. The lesion gradually resolved and did not recur.
Histopathologicfeatures Case 1. The epidermis was normal. There was an infiltration of some mononuclear cells and many eosinophils around blood vessels throughout the dermis. In the subcutaneous fat, nodular to diffuse mononuclear cells were densely infiltrated in the edematous stroma that contained many lymphoid follicles and several focal eosinophilic abscesses (Fig. 2, A). Proliferation and marked dilatation of vessels were seen in the stroma. The endothelial ceils were swollen. Case 2. The epidermis was normal. The dermis was markedly thickened and replaced the entire subcutaneous tissue with thick hyalinized collagen bundles. There was mild mononuclear cell infiltr~ition around the blood vessels in the papillary and mid dermis, but in the reticular dermis, mononuclear ceils and many eosinophils were present. Lymphoid follicles with eosinophilic infiltration were observed (Fig. 2, B). Collagen bundles in the reticular dermis were markedly thickened and hyalinized.
Fig. 2. A. Case I. In subcutaneous fat, nodular to d/ffusecollectionsofmononuclear ceilsinfiltrated thestroma. Many lymphoid follicles and several focal eosinophilic abscesses were observed. B. Case 2. Lymphoid follicles with eosinophilic infiltration. (A and B, Hematoxylineosin stain; A, X5; B, •
Proliferation and dilatation of capillaries were observed in areas of densely infiltrated inflammatory cells in the reticular dermis. The endothelial cells were swollen.
Angiolymphoid hyperplasia with eosinophilia Clinical features (Table I) Case 1. A 41-year-old man had skin lesions on the [eft frontal and left postauricular areas for 2% years. Physical examination showed erythematous to brown papules and nodules with some scaling in the frontal and postauricular areas (Fig. 3). All lesions were excised. A complete blood cell count showed eosinophilia ( 19.3%, 1250/mm 3) and stool examination revealed Clonorchis sinensis. Results of other routine laboratory tests were normal or negative. Two years later, two papules appeared in the postauricular area. One was excised and the other was injected with corticosteroids. At 10-month follow-up, no recurrence was seen. Case 2. A 57-year-old man had multiple lesions on the right preauricular area and right cheek of 22 months' du-
956
Journal of the American Academy of Dermatology
Chun and Ji
Table I. Clinical features of three patients with angiolymphoid hyperplasia wkh eosinophilia ( A L H E ) Patient No.
Age (yr) Sex Duration (too) Site Lesions Itching Tenderness Lymphadenopathy Eosinophils (%) Eosinophils/mm 3
1
2
3
41 Male 30 Frontal, Lt Postauricle, Lt Papules and nodules + + 19.3 1250
57 Male 22 PreaurMe, Rt
34 Male 3 Auricle, Rt
Papules + + 6.4 430
Papules + 1,5 120
Fig. 3. Case 1. Two erythematous to brown, hard, tender scaly papulonodules on scalp. ration. Physical examinations showed erythematous papules with excoriations. Results of routine laboratory tests were normal or negative except for a peripheral eosinophilia (6.4%, 430/mm3). The lesions improved after cryotherapy, but 14 months later new papules were noted and excised. Case 3. A 34-year-old man had multiple, pruritic lesions of 3 months' duration in'the right auricular area. Physical examination revealed erythematous papules in the right auricular area. Results of routine laboratory tests were normal or negative. The patient was treated with cryotherapy. He had no recurrence during the 20-month follow-up period. Histopathologie features (Table II) Three specimens were taken in case l, two specimens in case 2, and one specimen in case 3. Case 1. The epidermis was normal to acanthotic. There was mild to moderate infiltration of mononuclear cells and a few eosinophils around the blood vessels in the papillary dermis. In the papillary and mid dermis, capillaries
and small vessels were increased and dilated. The endothelial cells protruded into the lumen, producing a cobblestone appearance. Some endothelial cells had vacuoles in their cytoplasms (Fig. 4, A) and two endothelial cells formed microvilli in the luminal portion. Some endothelial cells showed atypical hyperchromatic nuclei. Only one lymphoid nodule containing many plasma cells was seen in the reticular dermis. The stroma was fibrotic. Case 2. The epidermis contained an area of hyperkeratosis, parakeratosis, irregular acanthosis, or erosion. In the papillary and mid dermis, a moderate diffuse infiltration of mononuclear cells and some eosinophils and plasma cells were seen. Extravasation of erythrocytes was observed. Capillaries were dilated and proliferating. The endothelial cells of capillaries and small vessels had a cobblestone appearance and histiocytoid or epithelioid changes with hyperchromatic nuclei (Fig. 4, B). The stroma was somewhat edematous and increased numbers of fibroblasts were seen. Case 3. The epidermis was normal. In the papillary and mid dermis, there was a mild infiltration of mononuclear cells and some eosinophils around the vessels. Capillaries and small thickened vessels were increased in number and dilated. The endothelial cells were protruding into the lumen assuming a cobblestone appearance. Some vessel lumens were occluded with histiocytoid or epithelioid cells with atypical hyperchromatic nuclei (Fig. 4, C). DISCUSSION Kimura's disease is a chronic inflammatory disease of unknown cause that usually appears as nodules in the subcutaneous tissue of the head and neck. A L H E also involves the skin and subcutaneous tissue with a predilection for the head and neck. A L H E appears as single or multiple, smooth-topped papules without lymphadenopathyJ 1, ~2,17 Peripheral
Volume 27 Number 6, Part 1 December 1992
Kimura's disease and A L H E
957
Fig. 4. A. Case 1. Endothelial cells protruded into lumen, assuming cobblestone appearance. Some endothelial cells had vacuoles in their cytoplasms. B. Case 2. Endothelial ceils showed histiocytoid changes with hyperchromatic nuclei. C. Case 3. Some vessel lumens were occluded with atypical epithelioid endothelial ceils. (A-C, Hematoxylin-eosin stain. A and C, X100; B, • II. Histopathologic findings of three patients with angiolymphoid hyperplasia with eosinophilia (ALHE)
Table
Patient No.
Dermal involvement Cell infiltration Tissue eosinophils Lymphoid follicles Endothelial changes Proliferation Cobblestone Vacuoles Pleomorphism Histiocytoid
1
2
3
No. of biopsy
No. of biopsy
No. of biopsy
[-
Papillary, mid Mild Mild -
Entire Mild Mild
Papillary, mid Moderate Mild
Papillary, mid Moderate Mild
Papillary, mid Moderate Mild
Entire Mild Mild
+ ++ ++
+ ++ ++ +
++ + + -
++ + +
++ + _ +
++ + _ +
_
_
+
+
+
eosinophilia is often absent.ll, 12, 17Although Kimura's disease has often been considered part of the spectrum of A L H E , 7,17, ~8 recent studies suggest that Kimura's disease is a separate entityJ ~ ~9,20 In our two cases of Kimura's disease, the lesions consisted of large deep nodules with normal overly-
ing skin. They were accompanied by regional lymph node enlargement and eosinophilia. In A L H E cases the lesions were multiple erythematous to brown papules or nodules accompanied by itching or tenderness. The sites of the lesions were the ear and periauricular regions. Lympbadenopathy was not
Journal of the American Academy of Dermatology
958 Chun and Ji Table III. Clinical differences between Kimura's disease and ALHE
I Lesion Location Overlying skin Lymphadenopathy Blood eosinophils
Kimura'sdisease
ALHE
Large nodule or tumor Deep Normal skin + Mild to moderate
present, but mild to moderate eosinophilia was observed (Table III). The lesions of Kimura's disease are composed of three components: cellular, fibroc0llagenous, and vascular. 12 The conspicuous feature is the cellular component formed by distinct lymphoid follicles with surrounding fibrosisJ l, 12 The cellular areas consist mainly of lymphocytes forming follicles surrounded by an inflammatory infiltrate with many eosinophils.11, lz, 21 The vessel changes are characteristic in ALHE. 17,19 In our two cases of Kimura's disease, there was distinct lymphoid follicle formation and a moderate to dense inflammatory cell infiltrate containing numerous eosinophils in the reticular dermis or subcutis. The vascular component consisted of proliferation and swollen endothelial cells. All three cases of ALHE showed prominent vascular changes. Capillaries and small vessels were increased mostly in the papillary and mid dermis and occasionally in the reticular dermis. Endothelial cells were swollen, cobblestone-like, and showed histiocytoid or epithelioid changes. Some endothelial ceils had atypical hyperchromatic nuclei and vacuoles in their cytoplasms. Inflammatory infiltration was mild to moderate, accompanied by a few to several eosinophils. Lymphoid follicles were not observed. Therefore we believe that Kimura's disease is an inflammatory process and that ALHE is a benign tumor of endothelial cells.
REFERENCES 1. Kirnura T, Yoshimura S, Ishikawa E. Abnormal granuloma with proliferation of lymphoid tissue. Trans See Pathol Jpn 1948;37:179-80. (In Japanese) 2. Chang TL, Chen CY. Eosinophilic granuloma of lymph nodes and soft tissue: report of 21 eases. Chin Meal J 1962;81:384-7. 3. Kawada A, _AkahashiH, Anzai T. Eosiuophilie lymphofolliculosis of the skin (Kimura's disease). Nippon Hifuka Gakkai Zasshi 1966;76:117-34. 4. Dannaker C, Piacquadio D, Willoughby CB, et aI. Histio-
5. 6. 7.
8.
9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.
21.
Papule or nodule Superficial Erythema to brown Moderate to marked
eytoid hemangioma: a disease spectrum. J AM ACAD D~RMA1:OL1989;21:404-9. Wells GC, Whimster IW. Subcutaneous angiolymphoid hyperplasia with eosinophilia. Br J Dermatol 1969;81:1-15, Burrall BA, Barr R J, King DF. Cutaneous histioeytoid hemangioma. Arch Dermatol 1982;118:166-70. Waldo E, Stahl R, Sidhu GS, et al. Histiocytoid hemangioma with features of angiolymphoid hyperplasia with eosinophiha and Kaposi's sarcoma: a study by light microscopy, electron microscopy, and immunologic techniques. Am J Dermatopathol 1983;5:525-38. Kung ITM, Gibson JB, BannatynePM. Kimura's disease; a clinicopathological study of 21 cases and its distinction from angiolymphoid hyperplasia with eosinophilia. Pathology 1984;16:39-44. Googe PB, Harris NL, Mihm MC Jr. Kimura's disease and angiolymphoid hyperplasia with eosinophilia: two distinct bistopathological entities. J Cutan Pathol 1987;14:263 -71. Urabe A, Tsuneyoshi M, Enjoji M. Epithelioid hemangioma versus Kimura's disease: a comparative elinieopathologic study. Am J Surg Pathol 1987;11:758-66. Kim MY, Lee YS, Kang H J, et al. A case of Kimura's disease. Kor J Dermatol 1975;13:243-6. (In Korean) Lee HG, Kim BS, Lee AY, et al. A case of Kimura's disease with an unusual location and clinical manifestation. Ann Derrnatol 1990;2:145-8. Hamriek H J, Jennette JC, LaForce CF. Kimura's disease: a report of a pediatric case in the United States. J Allergy Clin Immunol 1984;73:361-6. Kim BH, Sithian N, Cucolo GF. Angiolymphoid hyperplasia with eosinophilia (Kimura's disease): report of a case. Arch Surg 1975;110:1246-8. Buchner A, Silverman S Jr, Wara WM, et al. Angiolymphoid hyperplasia with eosinophilia (Kimura's disease). Oral Surg 1980;49:309-13. Eisenberg E, Lowlieht R.Angiolymphoid hyperplasia with eosinophilia. J Oral Pathol 1985;14:216-23. Olsen TG, Helwig EB. Angiolymphoid hyperplasia with eosinophilia. J AM ACAD DERMATOL1985;12:781-96. Rosai J. Angiolymphoid hyperplasia with eosinophilia of the skin: its nosological position in the spectrum of histiocytoid hemangioma. Am J Dermatopatho11982;4:175-84. Chan JK, Hui PK, Ng CS, et al. Epithelioid haemangioma (angiolymphoid hyperplasia with eosinophilia) and Kimura's disease in Chinese. Histopathology 1989;15:557-74. Kuo TT, Shih LY, Chan HL. Kimura's disease: involvement of regional lymph nodes and distinction from angiolymphoidhyperplasia with eosinophilia. Am J Surg Pathol 1988;12:843-54. Hui PK, Chart JK, Ng CS, et al. Lymphadenopathy of Kimura's disease. Am J Surg Pathol 1989;13:177-86.
Kirnura's disease and angiolymphoid hyperplasia with eosinophilia: Clinical and histopathologic differences Soo I1 Chun, MD, and H y e Goo Ji, MD Seoul, Korea
Background: There has been considerable controversy about the relation between Kimura's disease and angiolymphoid hyperplasia with eosinophilia (ALHE). Objective: We describe the clinical and histopathologic differences between the two diseases. Methods: We reviewed clinical findings and histopathologic changes in two cases of Kimura's disease and three cases of ALHE. Results: Kimura's disease shows typical lymphoid follicles. It is associated with lymphadenopathy and is always accompanied by peripheral eosinophilia. ALHE shows typical changes in endothelial ceils. It is characterized by superficial papules or nodules with no lymphadenopathy and is less frequently accompanied by peripheral eosinophilia. Conclusion: Kimura's disease and ALHE are separate entities. (J AM ACAD DERMATOL1992;27:954-8.) Kimura's disease and angiolymphoid hyperplasia with eosinophilia ( A L H E ) are rare disorders involving mainly the head and neck. Kimura's disease, originally reported by Kimura et al., 1 is an unusual granuloma with proliferation of lymphoid tissue. M a n y similar cases have been reported under a variety of names such as A L H E , inflammatory angiomatous nodule, pseudopyogenic granuloma, atypical pyogenic granuloma, papular angioplasia, subcutaneous angioblastic lymphoid hyperplasia with eosinophilia, nodular angioblastic hyperplasia with eosinophilia and Iymphofolliculosis, intravenous atypical vascular proliferation, histiocytoid hemangioma, and epithelioid hemangioma. 2-4 A L H E is a benign, uncommon skin disease characterized by single or multiple nodules located mainly on the head or neck of young adults. Wells and Whimster s published the first report describing a condition that resembled Kimura's disease and designated it as subcutaneous ALHE. Since then, there has been considerable controversy about the relation between Kimura's disease and A L H E , 6' 7 and recent reports From the Department of Dermatology, Yonsei UniversityCollege of Medicine. Accepted for publicationJune 8, t992. Reprint requests: Soo I1 Chun, MD, Department of Dermatology, Yonsei University College of Medicine, C.P.O. Box 8044, Seoul, Korea. 16/1/40019
954
have suggested that they are two different diseases. 8-1~Kimura's disease is apparently more prevalent in Oriental patients. 7' 8 In Korea, Kimura's disease was first reported by Kim et al. 11 in 1975. Since then, 19 cases of Kimura's disease and A L H E have been reported, which are usually considered to be identical] 2 The rare occurrence of genuine Kimura's disease in western countries probably caused the current confusion. 13-16 We describe two cases of Kimura's disease and three cases of A L H E and discuss differences between the two diseases. CASE REPORTS Kimura's disease Clinical features Case 1. A 19-year-old man had large, deep nodules in both inguinal areas. About 14 months earlier, an asymptomatic, deep nodule appeared in the left upper inguinal area; it grew slowly. Similar nodules developed below the first 2 months later and in the right upper inguinal area 4 months later. Physical examination revealed an ellipsoid, slightly hard, movable, nontender, subcutaneous mass, measuring 8 • 16 cm, in the left upper groin, and a similar mass in the right groin. A complete blood cell count (CBC) showed the following: white blood cells (WBCs) 15,490/mm 3 and eosinophil count 6080/mm 3 (39.2%). Computed tomographic scans of the inguinal area showed enlarged soft masses. A chest roentgenogram was normal. With an initial dose of triamcinolone, 32 mg daily for 2 weeks, no improvement was observed.
Volume 27 Number 6, Part 1 December 1992
Kimura's disease and A L H E
955
Fig. 1. Case 2. Subcutaneous nodule with overlying normal skin in right postauricular area and excision scar from previous operation.
The radiation therapy (300 rad/day for 6 days) resulted in a marked decrease in the size of the lesions. Systemic corticosteroids and azathioprine therapy was given and the lesions gradually disappeared. No new or recurrent lesions developed 1 year after discontinuation of the therapy. Case 2. A 35-year-old man had had a prufitic lesion in the right postauricular area for 10 months. A similar lesion had appeared at the same site 18 months earlier and had been excised. On the basis of histologic findings the lesion was diagnosed as Kimura's disease. Physical examination revealed an oval nodule in the right postauricular area (Fig. 1). Routine CBC showed WBCs to be 13,300/mm 3, and eosinophil count 950/ram 3 (13.3%). He was treated with systemic corticosteroids, intralesional corticosteroid, and azathoprine. The lesion gradually resolved and did not recur.
Histopathologicfeatures Case 1. The epidermis was normal. There was an infiltration of some mononuclear cells and many eosinophils around blood vessels throughout the dermis. In the subcutaneous fat, nodular to diffuse mononuclear cells were densely infiltrated in the edematous stroma that contained many lymphoid follicles and several focal eosinophilic abscesses (Fig. 2, A). Proliferation and marked dilatation of vessels were seen in the stroma. The endothelial ceils were swollen. Case 2. The epidermis was normal. The dermis was markedly thickened and replaced the entire subcutaneous tissue with thick hyalinized collagen bundles. There was mild mononuclear cell infiltr~ition around the blood vessels in the papillary and mid dermis, but in the reticular dermis, mononuclear ceils and many eosinophils were present. Lymphoid follicles with eosinophilic infiltration were observed (Fig. 2, B). Collagen bundles in the reticular dermis were markedly thickened and hyalinized.
Fig. 2. A. Case I. In subcutaneous fat, nodular to d/ffusecollectionsofmononuclear ceilsinfiltrated thestroma. Many lymphoid follicles and several focal eosinophilic abscesses were observed. B. Case 2. Lymphoid follicles with eosinophilic infiltration. (A and B, Hematoxylineosin stain; A, X5; B, •
Proliferation and dilatation of capillaries were observed in areas of densely infiltrated inflammatory cells in the reticular dermis. The endothelial cells were swollen.
Angiolymphoid hyperplasia with eosinophilia Clinical features (Table I) Case 1. A 41-year-old man had skin lesions on the [eft frontal and left postauricular areas for 2% years. Physical examination showed erythematous to brown papules and nodules with some scaling in the frontal and postauricular areas (Fig. 3). All lesions were excised. A complete blood cell count showed eosinophilia ( 19.3%, 1250/mm 3) and stool examination revealed Clonorchis sinensis. Results of other routine laboratory tests were normal or negative. Two years later, two papules appeared in the postauricular area. One was excised and the other was injected with corticosteroids. At 10-month follow-up, no recurrence was seen. Case 2. A 57-year-old man had multiple lesions on the right preauricular area and right cheek of 22 months' du-
956
Journal of the American Academy of Dermatology
Chun and Ji
Table I. Clinical features of three patients with angiolymphoid hyperplasia wkh eosinophilia ( A L H E ) Patient No.
Age (yr) Sex Duration (too) Site Lesions Itching Tenderness Lymphadenopathy Eosinophils (%) Eosinophils/mm 3
1
2
3
41 Male 30 Frontal, Lt Postauricle, Lt Papules and nodules + + 19.3 1250
57 Male 22 PreaurMe, Rt
34 Male 3 Auricle, Rt
Papules + + 6.4 430
Papules + 1,5 120
Fig. 3. Case 1. Two erythematous to brown, hard, tender scaly papulonodules on scalp. ration. Physical examinations showed erythematous papules with excoriations. Results of routine laboratory tests were normal or negative except for a peripheral eosinophilia (6.4%, 430/mm3). The lesions improved after cryotherapy, but 14 months later new papules were noted and excised. Case 3. A 34-year-old man had multiple, pruritic lesions of 3 months' duration in'the right auricular area. Physical examination revealed erythematous papules in the right auricular area. Results of routine laboratory tests were normal or negative. The patient was treated with cryotherapy. He had no recurrence during the 20-month follow-up period. Histopathologie features (Table II) Three specimens were taken in case l, two specimens in case 2, and one specimen in case 3. Case 1. The epidermis was normal to acanthotic. There was mild to moderate infiltration of mononuclear cells and a few eosinophils around the blood vessels in the papillary dermis. In the papillary and mid dermis, capillaries
and small vessels were increased and dilated. The endothelial cells protruded into the lumen, producing a cobblestone appearance. Some endothelial cells had vacuoles in their cytoplasms (Fig. 4, A) and two endothelial cells formed microvilli in the luminal portion. Some endothelial cells showed atypical hyperchromatic nuclei. Only one lymphoid nodule containing many plasma cells was seen in the reticular dermis. The stroma was fibrotic. Case 2. The epidermis contained an area of hyperkeratosis, parakeratosis, irregular acanthosis, or erosion. In the papillary and mid dermis, a moderate diffuse infiltration of mononuclear cells and some eosinophils and plasma cells were seen. Extravasation of erythrocytes was observed. Capillaries were dilated and proliferating. The endothelial cells of capillaries and small vessels had a cobblestone appearance and histiocytoid or epithelioid changes with hyperchromatic nuclei (Fig. 4, B). The stroma was somewhat edematous and increased numbers of fibroblasts were seen. Case 3. The epidermis was normal. In the papillary and mid dermis, there was a mild infiltration of mononuclear cells and some eosinophils around the vessels. Capillaries and small thickened vessels were increased in number and dilated. The endothelial cells were protruding into the lumen assuming a cobblestone appearance. Some vessel lumens were occluded with histiocytoid or epithelioid cells with atypical hyperchromatic nuclei (Fig. 4, C). DISCUSSION Kimura's disease is a chronic inflammatory disease of unknown cause that usually appears as nodules in the subcutaneous tissue of the head and neck. A L H E also involves the skin and subcutaneous tissue with a predilection for the head and neck. A L H E appears as single or multiple, smooth-topped papules without lymphadenopathyJ 1, ~2,17 Peripheral
Volume 27 Number 6, Part 1 December 1992
Kimura's disease and A L H E
957
Fig. 4. A. Case 1. Endothelial cells protruded into lumen, assuming cobblestone appearance. Some endothelial cells had vacuoles in their cytoplasms. B. Case 2. Endothelial ceils showed histiocytoid changes with hyperchromatic nuclei. C. Case 3. Some vessel lumens were occluded with atypical epithelioid endothelial ceils. (A-C, Hematoxylin-eosin stain. A and C, X100; B, • II. Histopathologic findings of three patients with angiolymphoid hyperplasia with eosinophilia (ALHE)
Table
Patient No.
Dermal involvement Cell infiltration Tissue eosinophils Lymphoid follicles Endothelial changes Proliferation Cobblestone Vacuoles Pleomorphism Histiocytoid
1
2
3
No. of biopsy
No. of biopsy
No. of biopsy
[-
Papillary, mid Mild Mild -
Entire Mild Mild
Papillary, mid Moderate Mild
Papillary, mid Moderate Mild
Papillary, mid Moderate Mild
Entire Mild Mild
+ ++ ++
+ ++ ++ +
++ + + -
++ + +
++ + _ +
++ + _ +
_
_
+
+
+
eosinophilia is often absent.ll, 12, 17Although Kimura's disease has often been considered part of the spectrum of A L H E , 7,17, ~8 recent studies suggest that Kimura's disease is a separate entityJ ~ ~9,20 In our two cases of Kimura's disease, the lesions consisted of large deep nodules with normal overly-
ing skin. They were accompanied by regional lymph node enlargement and eosinophilia. In A L H E cases the lesions were multiple erythematous to brown papules or nodules accompanied by itching or tenderness. The sites of the lesions were the ear and periauricular regions. Lympbadenopathy was not
Journal of the American Academy of Dermatology
958 Chun and Ji Table III. Clinical differences between Kimura's disease and ALHE
I Lesion Location Overlying skin Lymphadenopathy Blood eosinophils
Kimura'sdisease
ALHE
Large nodule or tumor Deep Normal skin + Mild to moderate
present, but mild to moderate eosinophilia was observed (Table III). The lesions of Kimura's disease are composed of three components: cellular, fibroc0llagenous, and vascular. 12 The conspicuous feature is the cellular component formed by distinct lymphoid follicles with surrounding fibrosisJ l, 12 The cellular areas consist mainly of lymphocytes forming follicles surrounded by an inflammatory infiltrate with many eosinophils.11, lz, 21 The vessel changes are characteristic in ALHE. 17,19 In our two cases of Kimura's disease, there was distinct lymphoid follicle formation and a moderate to dense inflammatory cell infiltrate containing numerous eosinophils in the reticular dermis or subcutis. The vascular component consisted of proliferation and swollen endothelial cells. All three cases of ALHE showed prominent vascular changes. Capillaries and small vessels were increased mostly in the papillary and mid dermis and occasionally in the reticular dermis. Endothelial cells were swollen, cobblestone-like, and showed histiocytoid or epithelioid changes. Some endothelial ceils had atypical hyperchromatic nuclei and vacuoles in their cytoplasms. Inflammatory infiltration was mild to moderate, accompanied by a few to several eosinophils. Lymphoid follicles were not observed. Therefore we believe that Kimura's disease is an inflammatory process and that ALHE is a benign tumor of endothelial cells.
REFERENCES 1. Kirnura T, Yoshimura S, Ishikawa E. Abnormal granuloma with proliferation of lymphoid tissue. Trans See Pathol Jpn 1948;37:179-80. (In Japanese) 2. Chang TL, Chen CY. Eosinophilic granuloma of lymph nodes and soft tissue: report of 21 eases. Chin Meal J 1962;81:384-7. 3. Kawada A, _AkahashiH, Anzai T. Eosiuophilie lymphofolliculosis of the skin (Kimura's disease). Nippon Hifuka Gakkai Zasshi 1966;76:117-34. 4. Dannaker C, Piacquadio D, Willoughby CB, et aI. Histio-
5. 6. 7.
8.
9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.
21.
Papule or nodule Superficial Erythema to brown Moderate to marked
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