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Linear acral pseudolymphomatous angiokeratoma of children (APACHE): Further evidence that APACHE is a cutaneous pseudolymphoma
Linear acral pseudolymphomatous angiokeratoma of children (APACHE): Further evidence that APACHE is a cutaneous pseudolymphoma Takahiro Kiyohara, MD,a Masanobu Kumakiri, MD,a Takeo Kawasaki, MD,a Akiteru Takeuchi, MD,b Hiroaki Kuwahara, MD,b and Takanori Ueda, MDc Fukui, Japan Acral pseudolymphomatous angiokeratoma of children (APACHE) is a recently recognized, rare clinical entity. We report a case of APACHE in a 9-year-old Japanese girl with a dark red, linear plaque on the posterior area of the right lower leg. Histopathologic findings revealed further evidence that APACHE was a cutaneous pseudolymphoma rather than a vascular neoplasm because of the presence of distinct primary and secondary lymphoid follicles, and thick-walled, long blood vessels lined with prominent plump endothelial cells similar to high endothelial venules in the paracortical area of the lymph node. In addition to previous descriptions, the patient presented with a distinct linear lesion. Vacuolar alteration of the basal cell layer and scattered eosinophilic bodies in the epidermis were observed, which suggested a lichenoid tissue reaction. We believe that APACHE might show a distinct linear pattern accompanied by a lichenoid tissue reaction. (J Am Acad Dermatol 2003;48:S15-7.)
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cral pseudolymphomatous angiokeratoma of children (APACHE) is a recently recognized, rare clinical entity that is characterized by unilateral eruptions of multiple angiomatous papules on acral sites of the hands and feet, mainly in children. Whether this disease comes under the category of cutaneous pseudolymphomas or vascular neoplasms has been discussed.1-4 In this study, we describe a girl with linear APACHE and present further evidence that APACHE is a cutaneous pseudolymphoma.
CASE REPORT A 9-year-old Japanese girl had a dark red, linear plaque on the posterior area of the right lower leg for about 5 years. The linear plaque crossed her Achilles tendon perpendicularly, not along Blaschko’s lines. At first, scattered papules had appeared, which had coalesced to a linear plaque. Medical and family histories were not relevant. A clinical examination revealed a slightly raised, linearly arranged, scaly, undulating lesion that was dark red and measured 50 ⫻ 12 mm (Fig 1). A few red papules were present around the plaque. Superficial lymphadenopathy was not observed. Results of laboratory examinations were normal, including complete blood cell count and liver function tests. Anti-HTLV-1 and anti-Borrelia burgdorferi serum antibodies were negative. Gallium scintigraphy and computed tomographic scans of the entire body showed no evidence of malignancy. Although this case showed a linear lesion, the diagnosis of lichen striatus was excluded because of the nonThis supplement is made possible through an unrestricted educational grant from Stiefel Laboratories to the American Academy of Dermatology. From the Department of Dermatology,a the Division of Plastic Surgery,b and the 1st Department of Internal Medicine,c Fukui Medical University. Reprint requests: Takahiro Kiyohara, Department of Dermatology, Fukui Medical University, 23-3 Shimoaizuki, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan. E-mail: [email protected]. Copyright © 2003 by the American Academy of Dermatology, Inc. 0190-9622/2003/$30.00 ⫹ 0 doi:10.1067/mjd.2003.127
Fig 1. A, Dark red, linear plaque on posterior area of right lower leg. B, Slightly raised, scaly, undulating lesion measuring 50 ⫻ 12 mm.
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Fig 2. Top-heavy pattern of infiltrate. (Hematoxylin-eosin stain; original magnification ⫻10.)
Blaschko linear distribution and dark red plaque appearance. Therefore, an excisional biopsy was carried out. She has been free of disease after 20 months of follow-up. A histopathologic examination revealed a dense, bandlike or nodular infiltrate immediately below the epidermis and a small nodular infiltrate in the deep reticular dermis or the subcutis (Fig 2). The architecture showed a top-heavy pattern of infiltrate. Nodular areas below the epidermis showed primary or secondary lymphoid follicles. Primary follicles were composed mainly of small lymphocytes that had bland nuclei. Secondary follicles possessed a germinal center surrounded by a mantle of small lymphocytes (Fig 3). The center was clear and composed of large lymphocytes, which had vesicular nuclei and ample cytoplasms. Tingible bodies and apoptotic, eosinophilic cells were also observed. The bandlike area showed a polymorphous infiltrate composed of small lymphocytes, histiocytes, and plasma cells. There were thick-walled, long blood vessels lined with prominent plump endothelial cells. Small nodules in the deep portion had many plasma cells. The epidermis showed irregular acanthosis, vacuolar alteration of the basal cell layer and scattered eosinophilic bodies (Fig 4). There were several small lymphocytes in the epidermis. An immunohistochemical examination showed the following: Small lymphocytes of the primary follicle, and small and large cells of the secondary follicle were positive for B-cell markers, eg, CD19 or CD20, and negative for T-cell markers, eg, CD45RO or CD5. There was a mixture of kappa-positive and lambda-positive cells, but the kappa-positive cells predominated. Small lymphocytes in the bandlike area were mainly positive for CD45RO and CD5. They were also positive for CD4 or CD8. A few CD20-positive cells were present. Scattered histiocytes were positive for CD68. Nearly all cells were positive for LCA and negative for CD10 and CD30. A clonal immunoglobulin heavy chain or T-cell receptor gene rearrangement by Southern blot analysis was not shown in the tumor tissue.
DISCUSSION APACHE is a recently recognized, rare clinical entity.1-4 The disease is characterized by unilateral eruptions of multiple angiomatous papules on acral sites of the hands and feet, mainly in children.1-3 Ramsay et al1,2 described the lesions as a vascular malformation. Two reports since Ramsay et al emphasized that the disease was a pseudolymphoma rather than a vascular neoplasm.3,4
Fig 3. Secondary follicles possessed germinal center (arrows) composed of large lymphocytes. (Hematoxylin-eosin stain; original magnification ⫻50.)
Fig 4. Vacuolar alteration of basal cell layer and scattered eosinophilic bodies (arrows). (Hematoxylin-eosin stain; original magnification ⫻100.)
Our patient revealed the following histopathologic and immunohistochemical findings: top-heavy pattern of infiltration, polymorphous cellular pattern, including mixed B and T lymphocytes, histiocytes, and plasma cells, the presence of primary and secondary lymph follicles, the presence of thick-walled, long blood vessels lined with prominent plump endothelial cells, which is similar to high endothelial venules in the paracortical area of the lymph node, and the absence of a light-chain restriction. In addition, a clonal immunoglobulin heavy chain or T-cell
J AM ACAD DERMATOL VOLUME 48, NUMBER 2
receptor gene rearrangement by Southern blot analysis was not shown in the tumor tissue. They strongly displayed the characteristics of a pseudolymphoma.5 Our patient was consistent with APACHE because of lymphoproliferative pattern accompanied by prominent vascular proliferation on the acral site of the extremity. Linear arrangement of the papules has been reported.3 Unlike APACHE, Kimura’s disease involves the head, and its histopathologic views reveal a deeper location of the lesion and the presence of eosinophils.5 Lymphomatoid papulosis shows large atypical cells that are positive for the CD30 antibody. Lymph follicles are not shown. Lymphadenosis benigna cutis shows a solitary nodule on the face and has an uninvolved epidermis.5 A persistent arthropod bite reaction reveals the infiltrate of numerous eosinophils. In our patient, further evidence was shown that APACHE was a cutaneous pseudolymphoma. Namely, distinct primary and secondary follicles were observed. Thick-walled, long blood vessels lined with prominent plump endothelial cells simulated high endothelial venules in the paracortical area of the lymph node. These structures were characteristic of cutaneous pseudolymphomas rather than vascular neoplasms. Our patient was unusual in some viewpoints. Clinically, a distinct linear arrangement was observed. Hara et al3 described a case of linearly arranged papules. However, our patient had a distinct linear pattern. Moreover, histopathologic findings revealed vacuolar alteration of the basal cell layer and scattered eosinophilic bodies in the epidermis. Although the former has been reported,3 the latter has not to our knowledge. Both of them suggested the presence of a lichenoid tissue reaction. Our patient’s lesion had to be differentiated from lichen striatus, which is a more common dermatosis that generally affects chil-
Kiyohara et al S17 dren. Whereas lichen striatus should run along Blaschko’s lines,5 her lesion crossed her Achilles tendon perpendicularly. The histopathology of lichen striatus shows variable lichenoid and spongiotic changes with a nonspecific lymphohistiocytic infiltrate, which is arranged around the appendages.6 However, distinct lymph follicles and thick-walled, long blood vessels are not observed.7 Therefore, this case does not correspond with lichen striatus. We believe that APACHE might show a distinct linear pattern accompanied by a lichenoid tissue reaction. REFERENCES 1. Ramsay B, Dahl MGC, Malcolm AJ, Soyer HP, Wilson Jones E. Acral pseudolymphomatous angiokeratoma of children (APACHE). Br J Dermatol 1988;119(Suppl 33):13. 2. Ramsay B, Dahl MGC, Malcolm AJ, Wilson Jones E. Acral pseudolymphomatous angiokeratoma of children. Arch Dermatol 1990;126:1524-5. 3. Hara M, Matsunaga J, Tagami H. Acral pseudolymphomatous angiokeratoma of children (APACHE): a case report and immunohistologic study. Br J Dermatol 1991;124:387-8. 4. Kaddu S, Cerroni L, Pilatti A, Soyer HP, Kerl H. Acral pseudolymphomatous angiokeratoma: a variant of the cutaneous pseudolymphomas. Am J Dermatopathol 1994;16:130-3. 5. Taieb A, Youbi A, Grosshans E, Maleville J. Lichen striatus: a Blaschko linear acquired inflammatory skin eruption. J Am Acad Dermatol 1991; 25:637-42. 6. Wood GS. Inflammatory diseases that simulate lymphomas: cutaneous pseudolymphomas. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SL, et al, editors. Dermatology in general medicine. 5th ed. New York: McGraw-Hill; 1999. p. 1259-74. 7. Gianotti R, Restano L, Grimalt R, Berti E, Alessi E, Caputo R. Lichen striatus—a chameleon: an histopathological and immunohistological study of forty-one cases. J Cutan Pathol 1995;22:18-22.
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cral pseudolymphomatous angiokeratoma of children (APACHE) is a recently recognized, rare clinical entity that is characterized by unilateral eruptions of multiple angiomatous papules on acral sites of the hands and feet, mainly in children. Whether this disease comes under the category of cutaneous pseudolymphomas or vascular neoplasms has been discussed.1-4 In this study, we describe a girl with linear APACHE and present further evidence that APACHE is a cutaneous pseudolymphoma.
CASE REPORT A 9-year-old Japanese girl had a dark red, linear plaque on the posterior area of the right lower leg for about 5 years. The linear plaque crossed her Achilles tendon perpendicularly, not along Blaschko’s lines. At first, scattered papules had appeared, which had coalesced to a linear plaque. Medical and family histories were not relevant. A clinical examination revealed a slightly raised, linearly arranged, scaly, undulating lesion that was dark red and measured 50 ⫻ 12 mm (Fig 1). A few red papules were present around the plaque. Superficial lymphadenopathy was not observed. Results of laboratory examinations were normal, including complete blood cell count and liver function tests. Anti-HTLV-1 and anti-Borrelia burgdorferi serum antibodies were negative. Gallium scintigraphy and computed tomographic scans of the entire body showed no evidence of malignancy. Although this case showed a linear lesion, the diagnosis of lichen striatus was excluded because of the nonThis supplement is made possible through an unrestricted educational grant from Stiefel Laboratories to the American Academy of Dermatology. From the Department of Dermatology,a the Division of Plastic Surgery,b and the 1st Department of Internal Medicine,c Fukui Medical University. Reprint requests: Takahiro Kiyohara, Department of Dermatology, Fukui Medical University, 23-3 Shimoaizuki, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan. E-mail: [email protected]. Copyright © 2003 by the American Academy of Dermatology, Inc. 0190-9622/2003/$30.00 ⫹ 0 doi:10.1067/mjd.2003.127
Fig 1. A, Dark red, linear plaque on posterior area of right lower leg. B, Slightly raised, scaly, undulating lesion measuring 50 ⫻ 12 mm.
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Fig 2. Top-heavy pattern of infiltrate. (Hematoxylin-eosin stain; original magnification ⫻10.)
Blaschko linear distribution and dark red plaque appearance. Therefore, an excisional biopsy was carried out. She has been free of disease after 20 months of follow-up. A histopathologic examination revealed a dense, bandlike or nodular infiltrate immediately below the epidermis and a small nodular infiltrate in the deep reticular dermis or the subcutis (Fig 2). The architecture showed a top-heavy pattern of infiltrate. Nodular areas below the epidermis showed primary or secondary lymphoid follicles. Primary follicles were composed mainly of small lymphocytes that had bland nuclei. Secondary follicles possessed a germinal center surrounded by a mantle of small lymphocytes (Fig 3). The center was clear and composed of large lymphocytes, which had vesicular nuclei and ample cytoplasms. Tingible bodies and apoptotic, eosinophilic cells were also observed. The bandlike area showed a polymorphous infiltrate composed of small lymphocytes, histiocytes, and plasma cells. There were thick-walled, long blood vessels lined with prominent plump endothelial cells. Small nodules in the deep portion had many plasma cells. The epidermis showed irregular acanthosis, vacuolar alteration of the basal cell layer and scattered eosinophilic bodies (Fig 4). There were several small lymphocytes in the epidermis. An immunohistochemical examination showed the following: Small lymphocytes of the primary follicle, and small and large cells of the secondary follicle were positive for B-cell markers, eg, CD19 or CD20, and negative for T-cell markers, eg, CD45RO or CD5. There was a mixture of kappa-positive and lambda-positive cells, but the kappa-positive cells predominated. Small lymphocytes in the bandlike area were mainly positive for CD45RO and CD5. They were also positive for CD4 or CD8. A few CD20-positive cells were present. Scattered histiocytes were positive for CD68. Nearly all cells were positive for LCA and negative for CD10 and CD30. A clonal immunoglobulin heavy chain or T-cell receptor gene rearrangement by Southern blot analysis was not shown in the tumor tissue.
DISCUSSION APACHE is a recently recognized, rare clinical entity.1-4 The disease is characterized by unilateral eruptions of multiple angiomatous papules on acral sites of the hands and feet, mainly in children.1-3 Ramsay et al1,2 described the lesions as a vascular malformation. Two reports since Ramsay et al emphasized that the disease was a pseudolymphoma rather than a vascular neoplasm.3,4
Fig 3. Secondary follicles possessed germinal center (arrows) composed of large lymphocytes. (Hematoxylin-eosin stain; original magnification ⫻50.)
Fig 4. Vacuolar alteration of basal cell layer and scattered eosinophilic bodies (arrows). (Hematoxylin-eosin stain; original magnification ⫻100.)
Our patient revealed the following histopathologic and immunohistochemical findings: top-heavy pattern of infiltration, polymorphous cellular pattern, including mixed B and T lymphocytes, histiocytes, and plasma cells, the presence of primary and secondary lymph follicles, the presence of thick-walled, long blood vessels lined with prominent plump endothelial cells, which is similar to high endothelial venules in the paracortical area of the lymph node, and the absence of a light-chain restriction. In addition, a clonal immunoglobulin heavy chain or T-cell
J AM ACAD DERMATOL VOLUME 48, NUMBER 2
receptor gene rearrangement by Southern blot analysis was not shown in the tumor tissue. They strongly displayed the characteristics of a pseudolymphoma.5 Our patient was consistent with APACHE because of lymphoproliferative pattern accompanied by prominent vascular proliferation on the acral site of the extremity. Linear arrangement of the papules has been reported.3 Unlike APACHE, Kimura’s disease involves the head, and its histopathologic views reveal a deeper location of the lesion and the presence of eosinophils.5 Lymphomatoid papulosis shows large atypical cells that are positive for the CD30 antibody. Lymph follicles are not shown. Lymphadenosis benigna cutis shows a solitary nodule on the face and has an uninvolved epidermis.5 A persistent arthropod bite reaction reveals the infiltrate of numerous eosinophils. In our patient, further evidence was shown that APACHE was a cutaneous pseudolymphoma. Namely, distinct primary and secondary follicles were observed. Thick-walled, long blood vessels lined with prominent plump endothelial cells simulated high endothelial venules in the paracortical area of the lymph node. These structures were characteristic of cutaneous pseudolymphomas rather than vascular neoplasms. Our patient was unusual in some viewpoints. Clinically, a distinct linear arrangement was observed. Hara et al3 described a case of linearly arranged papules. However, our patient had a distinct linear pattern. Moreover, histopathologic findings revealed vacuolar alteration of the basal cell layer and scattered eosinophilic bodies in the epidermis. Although the former has been reported,3 the latter has not to our knowledge. Both of them suggested the presence of a lichenoid tissue reaction. Our patient’s lesion had to be differentiated from lichen striatus, which is a more common dermatosis that generally affects chil-
Kiyohara et al S17 dren. Whereas lichen striatus should run along Blaschko’s lines,5 her lesion crossed her Achilles tendon perpendicularly. The histopathology of lichen striatus shows variable lichenoid and spongiotic changes with a nonspecific lymphohistiocytic infiltrate, which is arranged around the appendages.6 However, distinct lymph follicles and thick-walled, long blood vessels are not observed.7 Therefore, this case does not correspond with lichen striatus. We believe that APACHE might show a distinct linear pattern accompanied by a lichenoid tissue reaction. REFERENCES 1. Ramsay B, Dahl MGC, Malcolm AJ, Soyer HP, Wilson Jones E. Acral pseudolymphomatous angiokeratoma of children (APACHE). Br J Dermatol 1988;119(Suppl 33):13. 2. Ramsay B, Dahl MGC, Malcolm AJ, Wilson Jones E. Acral pseudolymphomatous angiokeratoma of children. Arch Dermatol 1990;126:1524-5. 3. Hara M, Matsunaga J, Tagami H. Acral pseudolymphomatous angiokeratoma of children (APACHE): a case report and immunohistologic study. Br J Dermatol 1991;124:387-8. 4. Kaddu S, Cerroni L, Pilatti A, Soyer HP, Kerl H. Acral pseudolymphomatous angiokeratoma: a variant of the cutaneous pseudolymphomas. Am J Dermatopathol 1994;16:130-3. 5. Taieb A, Youbi A, Grosshans E, Maleville J. Lichen striatus: a Blaschko linear acquired inflammatory skin eruption. J Am Acad Dermatol 1991; 25:637-42. 6. Wood GS. Inflammatory diseases that simulate lymphomas: cutaneous pseudolymphomas. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SL, et al, editors. Dermatology in general medicine. 5th ed. New York: McGraw-Hill; 1999. p. 1259-74. 7. Gianotti R, Restano L, Grimalt R, Berti E, Alessi E, Caputo R. Lichen striatus—a chameleon: an histopathological and immunohistological study of forty-one cases. J Cutan Pathol 1995;22:18-22.