Angiolymphoid Hyperplasia (Kimura Disease)
Subcutaneous Report
of
a
Case
Byung-Hoon Kim, MD; Nedunchezian Sithian, MD; Gabriel
A subcutaneous
mass
F.
Cucolo, MD
removed from the cheek showed histo-
logic features of subcutaneous angiolymphoid hyperplasia (Kimura disease) at its early stage. The condition shows a wide spectrum of pathologic changes. At its early stage, the main findings consist of active vascular proliferation with plump endothelial cells and varying degrees of lymphocytic, histiocytic, and eosinophilic infiltration. The lesion at its later stage features hyperplastic blood vessels with inconspicuous endothelial cells, well-formed lymphoid follicles, and varying degrees of lymphocytic and eosinophilic infiltration. Blood eosinophilia is frequently seen. Review of the literature and study of our own case strongly suggest that this disease is a distinct clinical and pathologic entity.
A ngiolymphoid hyperplasia (Kimura disease) is a rare lesion that interests both clinicians and pathologists. The original description of this lesion was given by Kimura et al in 1948, as quoted by Kawada et al.1 Since then there have been increasing numbers of reports on this condition under different headings, such as atypical
±\.
pyogenic granuloma,- eosinophilic folliculosis,1 angiolym¬ phoid hyperplasia,1" or angioblastic lymphoid hyper¬ plasia.7 '
The lesion is often found in the cheek and auricular
gion, appearing
as
single
or
re¬
multiple, nontender, movable be benign, and shows a slow
It is considered to growth over a period of several months to many years be¬ fore it is treated. Varying degrees of blood eosinophilia are seen in many cases. As therapeutic measures for this masses.
lesion, surgical excision, radiation, chemotherapeutic agents, and adrenocorticosteroids have been employed. Pathologic findings of a typical lesion show proliferating for publication March 6, 1975. From the departments of surgery (Drs Sithian and Cucolo) and pathology (Dr Kim), Lutheran Medical Center, Brooklyn, NY. Reprint requests to Department of Surgery, Lutheran Medical Center, Brooklyn, NY 11220 (Dr Cucolo).
Accepted
blood vessels lined by plump endothelial cells, varying de¬ grees of lymphocytic infiltration with or without lymphoid follicles, and diffuse or sparse infiltration of eosinophils. Differential diagnoses include hemangioendothelioma, Kaposi sarcoma, pyogenic granuloma, and benign lymphoepithelial lesion of the salivary gland (Mikulicz dis¬
ease).
In this
report
we
present
a case
of subcutaneous
an-
giolymphoid hyperplasia (Kimura disease) examined at its early stage. REPORT OF A CASE Clinical Findings A 10-year-old boy was admitted to the hospital on Jan 2, 1975, because of a mass growing in his left cheek over a period of three to four weeks. The mass was nontender, movable, and firm, and it measured 1.0 cm in diameter. There was no history of trauma, in¬ sect bite, or previous operations at the site of the lesion. The patient was well-developed and moderately nourished, with no abnormal findings except for the mass in the cheek. Results of a laboratory work-up, including blood chemistry studies and a complete blood cell count, were within normal limits. No blood eo¬ sinophilia was reported. A soft tissue x-ray film showed no abnor¬ mal findings in the affected area. Under general anesthesia, a transverse incision was made over the buccal aspect of the cheek. The buccinator muscles were bluntly separated, and the mass was identified in the subcutaneous tissue and was completely excised. The patient had an uneventful recovery and was discharged in good condition.
Pathologic Findings The specimen was a grayish-tan soft tissue measuring 1.0x0.8x0.8 cm, and was fixed in 10% buffered neutral formalde¬ hyde solution. Routine sections were stained with hematoxylin-eo¬ sin. Special stains for reticulum and elastic fibers were also obtained. Microscopic examination showed a well-circumscribed lesion surrounded by thin layers of fibrous connective tissue. Nei¬ ther lymph nodes nor salivary glands were identified in the lesion. The main pathologic findings consisted of exuberant proliferation of small blood vessels with plump endothelial cells lining their lu¬ mina and infiltration by moderate numbers of lymphocytes in the stroma. Small numbers of eosinophils and histiocytes were also
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Fig 1.—Proliferating blood vessels and surrounding lymphocytic infiltration (hematoxylin-eosin, 160). seen in scattered areas. The nuclei of the endothelial cells were round or oval, and much larger than those of ordinary capillary endothelial cells. They showed no atypical changes (Fig 1 and 2). The endothelial cells of the vessels were so numerous and plump that many vascular lumina were partially or completely obliter¬ ated (Fig 3). This made the vessels resemble the acini of the sali¬ vary gland. The blood vessels seen in the fibroadipose tissue sur¬ rounding the lesion showed only inconspicuous endothelial cells lining their lumina. No lymphoid follicles were found in this le¬ sion. The proliferating vessels did not contain any elastic fibers in their walls. Reticulum fibers were seen throughout the lesion (Fig
4).
COMMENT
As stated by Kawada et al1 and Wells and Whimster,4 also believe that angiolymphoid hyperplasia (Kimura disease) is a distinct clinical and pathologic entity. The histogenesis of this condition has not been clearly defined. Reed and Terazakis7 concluded that the newly formed blood vessels were derived from the preexisting vessels. Wells and Whimster4 and Kandil·'' emphasized that angangiolymphoid hyperplasia is a wide spectrum of histo¬ logie changes taking place at different tissue levels. Wells and Whimster4 and Reed and Terazakis7 stated that the early phase of the disease is characterized by prominent vascular proliferation with plump endothelial cells, and the later phase by progressive thickening of the vessels with inconspicuous endothelial cells, prominent lymphoid tissue with lymphoid follicles and varying degrees of fi¬ brosis. The changes described in our case appear to repre¬ sent the early phase of the disease. The early lesions were also described by Kandil,5 Mehregan and Shapiro,'1 and Pe¬ terson et al.2 The lesions described as atypical or pseudowe
Fig 2.—Blood vessels with their lumina obliterated dothelial cells (hematoxylin-eosin, 400).
by plump
en¬
Peterson et al2 and Wilson Jones opinion, believed to be the case of angiolymphoid hyperplasia at its early stage. We concur with the opinion of Wells and Whimster4 that the cases described by Kawada et al1 and other authors represent the later phase of the disease. The cases reported by Ka¬ wada et al' had durations ranging from 2 to 12 years and showed only hyperplastic blood vessels with flat endothe¬ lial cells. In spite of frequent occurrence of blood eosinophilia in association with this lesion, Mehregan and Shapiro" could find blood eosinophilia of 4% to 9% in only five out of the 14 cases they studied. They remarked that circumscribed le¬ sions might not always be associated with blood eosino¬ philia. Our case was also a well-circumscribed lesion sur¬ rounded by thin layers of fibrous connective tissue and showed no eosinophilia in the blood. The significance of eo¬ sinophilia remains to be explained. As to the sites of involvement by this disease, it seems apparent that the lesion occurs mainly in the subcutane¬ ous tissue, but sometimes extends into the overlying der¬ mis or underlying muscle. The differential diagnoses include hemangioendothelioma, pyogenic granuloma, Kaposi sarcoma, and benign lymphoepithelial lesion of the salivary gland (Mikulicz disease). In hemangioendothelio¬ ma, the degree of endothelial proliferation is far greater, at times replacing the vessels of origin, and atypical cellu¬ lar features are often present. In pyogenic granuloma the surface epidermis is usually atrophie or ulcerated and the stroma shows edema with infiltration by polymorphonuclear leukocytes, lymphocytes, and plasma cells. Endothe¬ lial proliferation is not so prominent as in the lesion under discussion. In Kaposi sarcoma, slit-like blood vessels with
pyogenic granuloma by and Bleehen1 are, in
our
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3.—Vascular lumina obliterated by many plump endothelial cells. Many cells resembling endothelial cells are visible outside blood vessels (Gomori reticulum stain, 400).
Fig
extravasated red blood cells are the main findings. In Ja¬ pan, prior to the report of cases by Kawada et al,1 the le¬ sions later proved to be angiolymphoid hyperplasia were erroneously diagnosed as Mikulicz disease. We believe that this erroneous diagnosis can be easily made if the le¬ sion is from an anatomic area harboring major or minor
salivary glands. In regard to the terminology of this lesion, we prefer the more inclusive term "angiolymphoid hyperplasia" to the term "angioblastic lymphoid hyperplasia" proposed by Reed and Terazakis.7 Tania
Espinosa assisted
in
preparing
the
photographs.
Fig 4.—Proliferating blood vessels (Gomori reticulum stain, 160).
surrounded
by reticulum fibers
References 1. Kawada AK, Takahash H, Anzai T: Eosinophilic folliculosis of the skin (Kimura's disease). Jap J Dermatol 76:61-72, 1966. 2. Peterson WC, Fusaro RM, Goltz RW: Atypical pyogenic granuloma: A case of benign hemangioendothelioma. Arch Dermatol 90:197-201, 1964. 3. Wilson Jones E, Bleehen SS: Inflammatory angiomatous nodules with abnormal blood vessels occuring about the ears and scalp (pseudo or atypical pyogenic granuloma). Br J Dermatol 81:804-816, 1969. 4. Wells GC, Whimster IW: Subcutaneous angiolymphoid hyperplasia with eosinophilia. Br J Dermatol 81:1-15, 1969. 5. Kandil E: Dermal angiolymphoid hyperplasia with eosinophilia versus pseudopyogenic granuloma. Br J Dermatol 83:405-408, 1970. 6. Mehregan AH, Shapiro L: Angiolymphoid hyperplasia with eosinophilia. Arch Dermatol 103:50-57, 1971. 7. Reed RJ, Terazakis N: Subcutaneous angioblastic lymphoid hyperplasia with eosinophilia (Kimura's disease). Cancer 29:489-497, 1972.
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Subcutaneous Report
of
a
Case
Byung-Hoon Kim, MD; Nedunchezian Sithian, MD; Gabriel
A subcutaneous
mass
F.
Cucolo, MD
removed from the cheek showed histo-
logic features of subcutaneous angiolymphoid hyperplasia (Kimura disease) at its early stage. The condition shows a wide spectrum of pathologic changes. At its early stage, the main findings consist of active vascular proliferation with plump endothelial cells and varying degrees of lymphocytic, histiocytic, and eosinophilic infiltration. The lesion at its later stage features hyperplastic blood vessels with inconspicuous endothelial cells, well-formed lymphoid follicles, and varying degrees of lymphocytic and eosinophilic infiltration. Blood eosinophilia is frequently seen. Review of the literature and study of our own case strongly suggest that this disease is a distinct clinical and pathologic entity.
A ngiolymphoid hyperplasia (Kimura disease) is a rare lesion that interests both clinicians and pathologists. The original description of this lesion was given by Kimura et al in 1948, as quoted by Kawada et al.1 Since then there have been increasing numbers of reports on this condition under different headings, such as atypical
±\.
pyogenic granuloma,- eosinophilic folliculosis,1 angiolym¬ phoid hyperplasia,1" or angioblastic lymphoid hyper¬ plasia.7 '
The lesion is often found in the cheek and auricular
gion, appearing
as
single
or
re¬
multiple, nontender, movable be benign, and shows a slow
It is considered to growth over a period of several months to many years be¬ fore it is treated. Varying degrees of blood eosinophilia are seen in many cases. As therapeutic measures for this masses.
lesion, surgical excision, radiation, chemotherapeutic agents, and adrenocorticosteroids have been employed. Pathologic findings of a typical lesion show proliferating for publication March 6, 1975. From the departments of surgery (Drs Sithian and Cucolo) and pathology (Dr Kim), Lutheran Medical Center, Brooklyn, NY. Reprint requests to Department of Surgery, Lutheran Medical Center, Brooklyn, NY 11220 (Dr Cucolo).
Accepted
blood vessels lined by plump endothelial cells, varying de¬ grees of lymphocytic infiltration with or without lymphoid follicles, and diffuse or sparse infiltration of eosinophils. Differential diagnoses include hemangioendothelioma, Kaposi sarcoma, pyogenic granuloma, and benign lymphoepithelial lesion of the salivary gland (Mikulicz dis¬
ease).
In this
report
we
present
a case
of subcutaneous
an-
giolymphoid hyperplasia (Kimura disease) examined at its early stage. REPORT OF A CASE Clinical Findings A 10-year-old boy was admitted to the hospital on Jan 2, 1975, because of a mass growing in his left cheek over a period of three to four weeks. The mass was nontender, movable, and firm, and it measured 1.0 cm in diameter. There was no history of trauma, in¬ sect bite, or previous operations at the site of the lesion. The patient was well-developed and moderately nourished, with no abnormal findings except for the mass in the cheek. Results of a laboratory work-up, including blood chemistry studies and a complete blood cell count, were within normal limits. No blood eo¬ sinophilia was reported. A soft tissue x-ray film showed no abnor¬ mal findings in the affected area. Under general anesthesia, a transverse incision was made over the buccal aspect of the cheek. The buccinator muscles were bluntly separated, and the mass was identified in the subcutaneous tissue and was completely excised. The patient had an uneventful recovery and was discharged in good condition.
Pathologic Findings The specimen was a grayish-tan soft tissue measuring 1.0x0.8x0.8 cm, and was fixed in 10% buffered neutral formalde¬ hyde solution. Routine sections were stained with hematoxylin-eo¬ sin. Special stains for reticulum and elastic fibers were also obtained. Microscopic examination showed a well-circumscribed lesion surrounded by thin layers of fibrous connective tissue. Nei¬ ther lymph nodes nor salivary glands were identified in the lesion. The main pathologic findings consisted of exuberant proliferation of small blood vessels with plump endothelial cells lining their lu¬ mina and infiltration by moderate numbers of lymphocytes in the stroma. Small numbers of eosinophils and histiocytes were also
Downloaded From: http://archsurg.jamanetwork.com/ by a New York University User on 05/18/2015
Fig 1.—Proliferating blood vessels and surrounding lymphocytic infiltration (hematoxylin-eosin, 160). seen in scattered areas. The nuclei of the endothelial cells were round or oval, and much larger than those of ordinary capillary endothelial cells. They showed no atypical changes (Fig 1 and 2). The endothelial cells of the vessels were so numerous and plump that many vascular lumina were partially or completely obliter¬ ated (Fig 3). This made the vessels resemble the acini of the sali¬ vary gland. The blood vessels seen in the fibroadipose tissue sur¬ rounding the lesion showed only inconspicuous endothelial cells lining their lumina. No lymphoid follicles were found in this le¬ sion. The proliferating vessels did not contain any elastic fibers in their walls. Reticulum fibers were seen throughout the lesion (Fig
4).
COMMENT
As stated by Kawada et al1 and Wells and Whimster,4 also believe that angiolymphoid hyperplasia (Kimura disease) is a distinct clinical and pathologic entity. The histogenesis of this condition has not been clearly defined. Reed and Terazakis7 concluded that the newly formed blood vessels were derived from the preexisting vessels. Wells and Whimster4 and Kandil·'' emphasized that angangiolymphoid hyperplasia is a wide spectrum of histo¬ logie changes taking place at different tissue levels. Wells and Whimster4 and Reed and Terazakis7 stated that the early phase of the disease is characterized by prominent vascular proliferation with plump endothelial cells, and the later phase by progressive thickening of the vessels with inconspicuous endothelial cells, prominent lymphoid tissue with lymphoid follicles and varying degrees of fi¬ brosis. The changes described in our case appear to repre¬ sent the early phase of the disease. The early lesions were also described by Kandil,5 Mehregan and Shapiro,'1 and Pe¬ terson et al.2 The lesions described as atypical or pseudowe
Fig 2.—Blood vessels with their lumina obliterated dothelial cells (hematoxylin-eosin, 400).
by plump
en¬
Peterson et al2 and Wilson Jones opinion, believed to be the case of angiolymphoid hyperplasia at its early stage. We concur with the opinion of Wells and Whimster4 that the cases described by Kawada et al1 and other authors represent the later phase of the disease. The cases reported by Ka¬ wada et al' had durations ranging from 2 to 12 years and showed only hyperplastic blood vessels with flat endothe¬ lial cells. In spite of frequent occurrence of blood eosinophilia in association with this lesion, Mehregan and Shapiro" could find blood eosinophilia of 4% to 9% in only five out of the 14 cases they studied. They remarked that circumscribed le¬ sions might not always be associated with blood eosino¬ philia. Our case was also a well-circumscribed lesion sur¬ rounded by thin layers of fibrous connective tissue and showed no eosinophilia in the blood. The significance of eo¬ sinophilia remains to be explained. As to the sites of involvement by this disease, it seems apparent that the lesion occurs mainly in the subcutane¬ ous tissue, but sometimes extends into the overlying der¬ mis or underlying muscle. The differential diagnoses include hemangioendothelioma, pyogenic granuloma, Kaposi sarcoma, and benign lymphoepithelial lesion of the salivary gland (Mikulicz disease). In hemangioendothelio¬ ma, the degree of endothelial proliferation is far greater, at times replacing the vessels of origin, and atypical cellu¬ lar features are often present. In pyogenic granuloma the surface epidermis is usually atrophie or ulcerated and the stroma shows edema with infiltration by polymorphonuclear leukocytes, lymphocytes, and plasma cells. Endothe¬ lial proliferation is not so prominent as in the lesion under discussion. In Kaposi sarcoma, slit-like blood vessels with
pyogenic granuloma by and Bleehen1 are, in
our
Downloaded From: http://archsurg.jamanetwork.com/ by a New York University User on 05/18/2015
3.—Vascular lumina obliterated by many plump endothelial cells. Many cells resembling endothelial cells are visible outside blood vessels (Gomori reticulum stain, 400).
Fig
extravasated red blood cells are the main findings. In Ja¬ pan, prior to the report of cases by Kawada et al,1 the le¬ sions later proved to be angiolymphoid hyperplasia were erroneously diagnosed as Mikulicz disease. We believe that this erroneous diagnosis can be easily made if the le¬ sion is from an anatomic area harboring major or minor
salivary glands. In regard to the terminology of this lesion, we prefer the more inclusive term "angiolymphoid hyperplasia" to the term "angioblastic lymphoid hyperplasia" proposed by Reed and Terazakis.7 Tania
Espinosa assisted
in
preparing
the
photographs.
Fig 4.—Proliferating blood vessels (Gomori reticulum stain, 160).
surrounded
by reticulum fibers
References 1. Kawada AK, Takahash H, Anzai T: Eosinophilic folliculosis of the skin (Kimura's disease). Jap J Dermatol 76:61-72, 1966. 2. Peterson WC, Fusaro RM, Goltz RW: Atypical pyogenic granuloma: A case of benign hemangioendothelioma. Arch Dermatol 90:197-201, 1964. 3. Wilson Jones E, Bleehen SS: Inflammatory angiomatous nodules with abnormal blood vessels occuring about the ears and scalp (pseudo or atypical pyogenic granuloma). Br J Dermatol 81:804-816, 1969. 4. Wells GC, Whimster IW: Subcutaneous angiolymphoid hyperplasia with eosinophilia. Br J Dermatol 81:1-15, 1969. 5. Kandil E: Dermal angiolymphoid hyperplasia with eosinophilia versus pseudopyogenic granuloma. Br J Dermatol 83:405-408, 1970. 6. Mehregan AH, Shapiro L: Angiolymphoid hyperplasia with eosinophilia. Arch Dermatol 103:50-57, 1971. 7. Reed RJ, Terazakis N: Subcutaneous angioblastic lymphoid hyperplasia with eosinophilia (Kimura's disease). Cancer 29:489-497, 1972.
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