PATHOLOGY OF VASCULAR SKIN LESIONS - PART 4 pps

88 Sangüeza and Requena / Pathology of Vascular Skin Lesions disorders, but there is also an idiopathic form that presents with no other associated anomalies. Among the different diseases associated with angiokeratoma corporis diffusum, Fabry’s disease is the most common. Fabry’s disease is a rare error of the metabolism that results in a deficiency of the lysosomal enzyme hydrolase α-galactosi- dase A. It is transmitted as an X-linked recessive trait. The gene responsible for the coding of α-galactosidase A has been localized to the middle of the long arm of the X chromo- some. As an X-linked disease, Fabry’s disease exclusively affects males; females may be asymptomatic carriers and may have corneal dystrophic changes that can be detected by slit-lamp examination (18,19). As a consequence of the enzymatic defect, glycosphingolipids, predominantly trihexosylceramide, accumulate within the lysosomes of endothelial cells, fibroblasts, pericytes, and smooth muscle fibers of the dermis. There is also an accumulation of this material in other organs including ganglion cells, nerves, cornea, heart, and kidney, resulting in cardiac, renal, ocular, and neurologic abnormalities (20). Angiokeratomas of Fabry’s disease usually appear shortly before puberty. They are small, punctate, dark red papules, some of them less than 1 mm, mainly located in the lower part of abdomen, genitalia, buttocks, and thighs in a bathing-trunk distribution (Figs. 15, 16, and 17). A frequent and asymptomatic finding is the so-called cornea verticillata, which is a super- ficial corneal dystrophy. This finding is of diagnostic importance for the detection of mild cases and female carriers. Other cutaneous manifestations include dry skin, anhidrosis, hyperthermic crises (21), and acroparaesthesiae secondary to capillary changes in the nail matrix (22). In rare instances patients with Fabry’s disease may also present with concur- Fig. 13. Angiokeratomas of Fordyce involving the vulva of an elderly woman. Fig. 14. Angiokeratomas of Mibelli in the inner border of the left hand. 06/Sangüeza/73-98/F 01/14/2003, 11:47 AM88 Chapter 6 / Cutaneous Lesions with Dilations 89 Fig. 15. Angiokeratoma corporis diffusum in a patient with Fabry’s disease. Multiple small red papules involving the left flank. rent Klippel-Trenaunay-Weber syndrome (23). Patients with Fabry’s disease who are devoid of cutaneous lesions have been reported (24). Angiokeratoma corporis diffusum is not exclusive to Fabry’s disease and has also been described in association with other rare inherited lysosomal storage diseases such as fucosidosis type II (25,26), galactosidosis type II (27), Kanzaki’s disease or deficiency of α-N-acetylgalactosaminidase (28–30), aspartylglycosaminuria (31), sialidosis type II (32), adult-onset GM 1 gangliosidosis (33), and β-mannosidase deficiency (34–36). By the same token, rare cases of angiokeratoma corporis diffusum have been described in patients without metabolic anomalies (37–40). In some of these patients the angiokeratomas were multiple and presented in a zosteriform distribution (41). These angiokeratomas have been described in patients with cutaneous and cerebral hemangio- mas (42), tuberous sclerosis (43), blue rubber bleb nevus syndrome (44), and juvenile dermatomyositis (45). In a recent report, angiokeratoma corporis diffusum not associated with metabolic disease was described in a three-generation family with autosomal dominant transmis- sion. Some of the affected patients showed arteriovenous shunts with hypertrophy of the affected limb (46). H ISTOPATHOLOGIC FEATURES Histopathologically, all variants of angiokeratomas are identical under a conventional microscope. Common features of all angiokeratomas include the presence of dilated thin- 06/Sangüeza/73-98/F 01/14/2003, 11:47 AM89 90 Sangüeza and Requena / Pathology of Vascular Skin Lesions walled blood vessels lined by a layer of endothelial cells in the papillary dermis and a variable degree of hyperkeratosis (1). Occasionally, angiokeratomas may be seen over- lying deep vascular malformations (47). Hyperkeratosis is usually absent in Fordyce’s angiokeratomas and in angiokeratoma corporis diffusum (Fabry’s disease). Ultrastruc- Fig. 17. Angiokeratoma corporis diffusum in a patient with Fabry’s disease with small red papules on the buttocks. Fig. 16. Angiokeratoma corporis diffusum in a patient with Fabry’s disease. (A) Lesions of angiokeratoma involved the dorsum of the foot. (B) Close-up view shows that small red papules are also present in the spaces among the toes. 06/Sangüeza/73-98/F 01/14/2003, 11:47 AM90 Chapter 6 / Cutaneous Lesions with Dilations 91 tural studies have demonstrated quantitative alterations of cytoplasmic organelles within the endothelial cells (48). In patients with Fabry’s disease, there is vacuolization of the cytoplasm of the endot- helial cells of the arterioles and smooth muscle cells of the arrector pili. The presence of these vacuoles may be a clue to the specific diagnosis in sections stained with hematoxy- lin and eosin. However, in most cases the amount of glycolipid in the skin is small, making it extremely difficult, if not impossible, to identify them in routinely prepared sections. Special stains such as Sudan black B (49) and PAS (50) highlight the presence of glycolipid deposits within the vacuoles in patients with Fabry’s disease and related disorders (Fig. 18). The lipid material is double refractile, which can be demonstrated by means of polariscopic examination of unfixed, or formalin-fixed frozen sections. Depos- its of glycolipids in patients with Fabry’s disease are not restricted to the lesions of angiokeratoma but may also be seen in skin that appears to be normal (51). Electron microscopy examination of the skin in Fabry’s disease shows large, electrodense lipid deposits in endothelial cells, pericytes, fibroblasts, arrector pili muscles, and secretory, ductal, and myoepithelial cells of the eccrine glands (52). These deposits show a charac- teristic lamellar structure(53–58), not seen in other types of angiokeratomas or in lesions of angiokeratoma corporis diffusum with no enzymatic anomalies (38–45). Other ultra- structural findings in patients with Fabry’s disease consist of intersecting short, crescent- shaped, tightly packed membranes in the endothelial cells of the small cutaneous blood vessels (59) and cytoplasmic vacuoles in the epithelial cells of the eccrine glands (60). T REATMENT Small angiokeratomas may be managed by diathermy, electrodessication and curet- tage, or cryotherapy with liquid nitrogen. Good cosmetic results have been reported with laser therapy (61–67). For larger lesions the preferred treatment is surgical excision if treatment is required. Recombinant human α-galactosidase A replacement therapy has been demonstrated to be safe and efficient in reversing the chief clinical manifestations in patients with Fabry’s disease (68). References 1. Imperial R, Helwig EB. Angiokeratoma: a clinicopathological study. Arch Dermatol 1967;95:166–75. 2. Kumar MV, Thappa DM, Shanmugam S, Ratnakar C. Angiokeratoma circumscriptum of the oral cavity. Acta Derm Venereol 1988;78:472. 3. Foucar E, Mason WV. Angiokeratoma circumscriptum following damage to underlying vasculature. Arch Dermatol 1986;122:245–6. 4. Goldman L, Gibson SH, Richfield DF. Thrombotic angiokeratoma circumscriptum simulating mela- noma. Arch Dermatol 1981;117:138–9. 5. Imperial R, Helwig EB. Angiokeratoma of the scrotum (Fordyce type). J Urol 1967;98:379–87. 6. Agger P, Osmundsen PE. Angiokeratoma of the scrotum (Fordyce). Acta Derm Venereol 1970;50:221–4. 7. Patrizi A, Neri I, Trevisi P, Landi C, Bardazzi F. Congenital angiokeratoma of Fordyce. J Eur Acad Dermatol Venereol 1998;10:195–6. 8. Bisceglia M, Carosi I, Castelvetere M, Nurgo R. Angiocheratomi multipli dello scroto, “tipo Fordyce.” Su un cado ad insorgenza iatrogena. Pathologica 1998;90:46–50. 9. Carrasco L, Izquierdo MJ, Fariña MC, Martín L, Moreno C, Requena L. Strawberry glans penis: a rare manifestation of angiokeratomas involving the glands penis. Br J Dermatol 2000;142:1256–7. 10. Novick NL. Angiokeratoma vulvae. J Am Acad Dermatol 1985;12:561–3. 11. Clark JR, Wheelock JB. Angiokeratoma of the vulva. A case report. J Reprod Med 1988;33:473–4. 12. Cohen PR, Young AW Jr, Tovell HM. Angiokeratoma of the vulva: diagnosis and review of the litera- ture. Obstet Gynecol Surv 1989;44:339–46. 06/Sangüeza/73-98/F 01/14/2003, 11:47 AM91 92 Sangüeza and Requena / Pathology of Vascular Skin Lesions 06/Sangüeza/73-98/F 01/14/2003, 11:47 AM92 Chapter 6 / Cutaneous Lesions with Dilations 93 13. Imperial R, Helwig EB. Angiokeratomas of the vulva. Obstet Gynecol 1967;29:307–12. 14. Novick NL. Angiokeratoma vulvae. J Am Acad Dermatol 1985;12:561–3. 15. Pringle JJ. Four cases of angiokeratoma from one family. Br J Dermatol 1913; 25:40–53. 16. Haye KR, Rebello DJA. Angiokeratoma of Mibelli. Acta Derm Venereol 1961;41:56–60. 17. Dave VK, Main RA. Angiokeratoma of Mibelli with necrosis of the fingertips. Arch Dermatol 1972;106:726–8. 18. Fox MF, Dutoit DL, Warnich L, et al. Regional localization of alpha-galactosidase (GLA) to Xpter→q22, hexosaminidase B (HEXB) to 5 q13→qter and arylsulphatase B (ARSB) to 5 pter→q13. Cytogenet Cell Genet 1984;38:45–9. 19. Bishop DF, Calhoun DH, Bernstein MS, et al. Structure of the human alpha-galactosidase A gene: 5' control elements, intron/exon splice junction sequence and alternative 3' termination. Am J Hum Genet 1987;41(suppl):A208. 20. Wallace HJ. Anderson-Fabry disease. Br J Dermatol 1973;88:1–21. 21. Kang WH, Chun SI, Lee S. Generalized anhidrosis associated with Fabry’s disease. J Am Acad Dermatol 1987;17:883–7. 22. Jansen W, Lentner A, Genzel I. Capillary changes in angiokeratoma corporis diffusum Fabry. J Dermatol Sci 1994;7:68–70. 23. Germain DP. Co-occurrence and contribution of Fabry disease and Klippel-Trenaunay-Weber syn- drome to a patient with atypical skin lesions. Clin Genet 2001;60:63–7. 24. Clarke JTR, Knack J, Crawhall JC, et al. Ceramide trihexosidase (Fabry’s disease) without skin lesions. N Engl J Med 1971;284:233–5. 25. Epinette WW, Norins AL, Zeman W, Patel V. Angiokeratoma corporis diffusum with alpha-L fucosidase deficiency. Arch Dermatol 1973;107:754–7. 26. Patel V, Watanabe I, Zeman W. Deficiency of alpha-L-fucosidase. Science 1972;176:420–7. 27. Ishibashi A, Tsuboi R, Shinmei M. β-Galactosidase and neuraminidase deficiency associated with angiokeratoma corporis diffusum. Arch Dermatol 1984;120:1344–6. 28. Kanzaki T, Yokota M, Mizuno N, Matsumoto Y, Hirabayashi Y. Novel lysosomal glycoaminoacid storage disease with angiokeratoma corporis diffusum. Lancet 1989;1:875–7. 29. Kanzaki T, Wang AM, Desnick RJ. Lysosomal alpha-N-acetylgalactosaminidase deficiency: the enzy- matic defect in angiokeratoma corporis diffusum with glycopeptiduria. J Clin Invest 1991;88:707–11. 30. Chabás A, Coll MJ, Aparicio M, Rodríguez E. Mild phenotypic expression of alpha-N-acetyl- galactosaminidase deficiency in two adult siblings. J Inherit Metab Dis 1994;17:724–31. 31. Gehler J, Sewell AC, Becker C, Hartmann J, Spranger J. Clinical and biochemical delineation of aspartylglycosaminuria as observed in two members of an Italian family. Helv Paediatr Acta 1981;36:179–89. 32. Miyatake T, Atsumi T, Obayashi T, et al. Adult type neuronal storage disease with neuraminidase deficiency. Ann Neurol 1978;6:232–44. 33. Wenger DA, Sattler M, Mueller T, Myers GG, Schneimann RS, Nixon GW. Adult GM 1 gangliosidosis: clinical and biochemical studies on two patients and comparison to other patients called variant or adult GM 1 gangliosidosis. Clin Genet 1980;17:323–34. 34. Cooper A, Sarharwalla IB, Roberts MM. Human β-mannosidase deficiency. N Engl J Med 1986;315:1231. 35. Cooper A, Hatton C, Thornley M, Sardwalla IB. Human β-mannosidase deficiency: biochemical find- ings in plasma, fibroblasts, white cells and urine. J Inherit Metab Dis 1988;11:17–29. 36. Rodríguez Serna M, Botella Estrada R, Chabás A, et al. Angiokeratoma corporis diffusum associated with β-mannosidase deficiency. Arch Dermatol 1996;132:1219–22. 37. Holmes RC, Fenson AW, McKee P, Cairns RJ, Black MM. Angiokeratoma corporis diffusum in a patient with normal enzyme activities. J Am Acad Dermatol 1984;10:384–7. 38. Crovato F, Rebora A. Angiokeratoma corporis diffusum and normal enzyme activities. J Am Acad Dermatol 1985;12:885–6. 39. Marsden J, Allen R. Widespread angiokeratomas without evidence of metabolic disease. Arch Dermatol 1987;123:1125–7. Fig. 18. (Opposite page) Histopathologic features of angiokeratoma in a patient with Fabry’s disease. (A) Low-power view shows dilated vascular spaces in the papillary dermis. (B) Higher magnification demonstrates the thin walls of the vascular channels. (C) PAS stain demonstrates PAS-positive deposits within the endothelial cells. 06/Sangüeza/73-98/F 01/14/2003, 11:47 AM93 94 Sangüeza and Requena / Pathology of Vascular Skin Lesions 40. Frappaz A, Ferrier MC, Hermier C, et al. Angiokeratoma corporis diffusum avec activité enzimatique normale. Ann Dermatol Venereol 1987;114:1383–7. 41. Eizaguirre X, Landa N, Raton JA, Díaz Pérez JL. Multiple angiokeratomas with zosteriform distribution in two sisters. Int J Dermatol 1994;33:641–2. 42. Ostlere L, Hart Y, Misch KJ. Cutaneous and cerebral hemangiomas associated with eruptive angiokeratomas. Br J Dermatol 1996;135:98–101. 43. Gil Mateo MP, Miquel FJ, Velasco AM, Pitarch A, Fortea JM, Aliaga A. Widespread angiokeratomas and tuberous sclerosis. Br J Dermatol 1996;135:280–2. 44. Trattner A, Krichely D, David M. Blue rubber bleb nevus syndrome associated with diffuse angiokeratoma. Cutis 1997;59:264–6. 45. Shannon PL, Ford MJ. Angiokeratomas in juvenile dermatomyositis. Pediatr Dermatol 1999;16:488–51. 46. Calzavara-Pinton P, Colombi M, Carlino A, et al. Angiokeratoma corporis diffusum and arteriovenous fistulas with dominant transmission in the absence of metabolic disease. Arch Dermatol 1995;131:57–62. 47. Kraus MD, Lind AC, Alder SL, Dehner LP. Angiomatosis with angiokeratoma-like features in children: a light microscopic and immunophenotypic examination of four cases. Am J Dermatopathol 1999;21:350–5. 48. Gioglio L, Porta C, Moroni M, Nastasi G, Gangarossa I. Scrotal angiokeratoma (Fordyce): histopatho- logical and ultrastructural findings. Histol Histopathol 1992;7:47–55. 49. Frost P, Spaeth GL, Tanaka Y. Fabry’s disease. Glycolipid lipidosis. Arch Intern Med 1966;117:440–6. 50. Hashimoto K, Gross BG, Lever WF. Angiokeratoma corporis diffusum (Fabry). Histochemical and electron microscopic studies of the skin. J Invest Dermatol 1965;44:119–28. 51. de Groot WP. Angiokeratoma corporis diffusum Fabry. Dermatologica 1964;128:321–49. 52. Nakamura T, Kaneko H, Nishino I. Angiokeratoma corporis diffusum (Fabry disease): ultrastructural studies of the skin. Acta Derm Venereol 1981;61:37–41. 53. Hashimoto K, Lieberman P, Lamkin N Jr. Angiokeratoma corporis diffusum (Fabry’s disease): a lyso- somal disease. Arch Dermatol 1976;112:1416–23. 54. Luderschmidt C, Wolff HH. Intracytoplasmic granules with lamellae as signs of heterozygous Fabry’s disease. Am J Dermatopathol 1980;2:57–61. 55. Strayer DS, Santa Cruz D. Intracytoplasmic granules with lamellae in Fabry’s disease. Am J Dermatopathol 1980;2:63–4. 56. Breathnach SM, Black MM, Wallace HJ. Anderson-Fabry disease. Characteristic ultrastructural fea- tures in cutaneous blood vessels in a 1-year-old boy. Br J Dermatol 1980;103:81–4. 57. Voglino A, Paradisi M, Dompe G, Onetti Muda A, Faraggiana T. Angiokeratoma corporis diffusum (Fabry’s disease) with unusual features in a female patient. Light and electron microscopic investigation. Am J Dermatopathol 1988;10:343–8. 58. Lao LM, Kumakiri M, Mima H, et al. The ultrastructural characteristics of eccrine sweat glands in a Fabry disease patient with hypohidrosis. J Dermatol Sci 1998;18:109–17. 59. Elleder M, Ledvinova J, Vosmik F, Zeman J, Stejskal D, Lageron A. An atypical ultrastructural pattern in Fabry’s disease: a study on its nature and incidence in 7 cases. Ultrastruct Pathol 1990;14:467–74. 60. Idoate MA, Pardo-Mindan FJ, Gonzalez Alamillo C. Fabry’s disease without angiokeratomas showing unusual eccrine gland vacuolation. J Pathol 1992;167:65–8. 61. Flores JT, Apfelberg DB, Maser MR et al. Angiokeratoma of Fordyce: successful treatment with the argon laser. Plast Reconstr Surg 1984;74:835–8. 62. Newton JH, McGibbon DH. The treatment of multiple angiokeratomata with the argon laser. Clin Exp Dermatol 1987;12:23–5. 63. Hobbs ER, Ratz JL. Argon laser treatment of angiokeratomas. J Dermatol Surg Oncol 1987;13:1319–20. 64. Pasyk KA, Argenta LC, Schelbert EB. Angiokeratoma circumscriptum: successful treatment with the argon laser. Ann Plast Surg 1988;20:183–90. 65. Lapins J, Emtestam L, Marcusson JA. Angiokeratomas in Fabry’s disease and Fordyce’s disease: suc- cessful treatment with Cooper vapour laser. Acta Derm Venereol 1993;73:133–5. 66. Occella C, Bleidl D, Rampini P, Schiazza L, Rampini E. Argon laser treatment of cutaneous multiple angiokeratomas. Dermatol Surg 1995;21:170–2. 67. Meyer WR, Dotters DJ. Laser treatment of recurrent vulvar angiokeratomas associated with Noonan syndrome. Obstet Gynecol 1996;87:863–5. 68. Eng CM, Guffon N, Wilcox WR, et al. Safety and efficacy of recombinant human alpha-galactosidase A-replacement therapy in Fabry’s disease. N Engl J Med 2001;345:9–16. 06/Sangüeza/73-98/F 01/14/2003, 11:47 AM94 Chapter 6 / Cutaneous Lesions with Dilations 95 5. LYMPHANGIECTASES CLINICAL FEATURES Lymphangiectases are the lymphatic counterparts of angiokeratomas resulting from the acquired permanent dilation of lymphatic capillaries. They develop in areas of the skin affected by obstruction or destruction of lymphatic drainage. Clinically, lymphangiectases localized on genital or plantar skin may mimic warts (1–4). Lymphangiectases have been described as a result of interference of lymphatic vessels secondary to surgery (5,6), scarring from scrofuloderma (7), photoaging and topical corticosteroid application (8), porphyria cutanea tarda (9), hepatic cirrhosis with ascites (10), mastectomy (11,12), and radiotherapy for breast carcinoma (13–17). In the penis and scrotum, lymphangiectases develop as a complication of a surgical procedure for a sacrococcygeal tumor (18); on the vulva and thigh they are usually secondary to Crohn’s disease (19,20), or they develop after surgery and radiotherapy for cervical carcinoma (1,21–25). Lymphangiectases of Fordyce may also appear in the genital region of elderly people without evidence of damage of the lymphatic drainage (26). Lymphangiectases have also been described as consequence of alterations in the collagen or elastic tissue, including penicillamine der- mopathy (27). Clinically, lymphangiectases appear as multiple, persistent, translucent, thick-walled white vesicles, of 2–5 mm in diameter. Some lesions may have a polypoid shape, and punction provokes the flow of a milky liquid (Fig. 19). The involved area appears to be sprinkled with lymphangiectatic vesicles with areas of normal-appearing skin among them. H ISTOPATHOLOGIC FEATURES Histopathologically, lymphangiectasias are characterized by the presence of dilated lymphatic vessels positioned within papillary dermis (Fig. 20). Sometimes lymphan- giectases rise above the level of the adjacent skin. The vessels lack contents or show a homogeneous material within their lumina, and they are lined by a thin wall with a single discontinuous layer of endothelial cells. The degree of epidermal hyperplasia in lymphangiectases is usually less marked than in angiokeratomas. The differential diag- nosis between lymphangiectases and superficial lymphatic malformations is established by the absence of a deep lymphatic component; the dilated vessels are confined to the papillary dermis, and they result from dilation of preexisting lymphatic capillaries. Fig. 19. Lymphangiectases involving the inner aspect of the thigh. Punction provoked the flow of a milky fluid. 06/Sangüeza/73-98/F 01/14/2003, 11:47 AM95 96 Sangüeza and Requena / Pathology of Vascular Skin Lesions Authentic, superficial lymphatic malformations may show lymphangiectases as part of their superficial component; however, they have a deep component with characteristic valves in their walls (23). T REATMENT Surgical excision of the superficial vesicles tends to be disappointing, and recurrences are common. Palliative results have been achieved with sclerotherapy and (28) laser therapy (29–32). References 1. Harwood CA, Mortimer PS. Acquired vulval lymphangiomata mimicking genital warts. Br J Dermatol 1993;129:334–6. 2. El Sayed F, Bazex J, Bouissou X, et al. Acquired cutaneous lymphangiectasia mimicking plantar warts. Br J Dermatol 1995;132:1014–6. 3. Darmstadt GL. Perianal lymphangioma circumscriptum mistaken for genital warts. Pediatrics 1996;98:461–3. 4. Mu XC, Tran TA, Dupree M, Carlson JA. Acquired vulvar lymphangioma mimicking genital warts. A case report and review of the literature. J Cutan Pathol 1999;26:150–4. 5. Ziv R, Schewach-Millet M, Trau H. Lymphangiectasia: a complication of thoracotomy for bronchial carcinoid. Int J Dermatol 1988;27:123. Fig. 20. Histopathologic features of lymphangiectases. (A) Low-power view shows an exophytic lesion that contains dilated vascular structures. (B) Higher magnification demonstrates that the vascular channels are lined by a thin wall of a discontinous layer of endothelial cells. 06/Sangüeza/73-98/F 01/14/2003, 11:47 AM96 Chapter 6 / Cutaneous Lesions with Dilations 97 6. Moon SE, Youn JI, Lee YS. Acquired cutaneous lymphangiectasia. Br J Dermatol 1993;129:193–5. 7. Di Leonardo M, Jacoby RA. Acquired cutaneous lymphangiectasias secondary to scarring from scrofu- loderma. J Am Acad Dermatol 1986;14:688–90. 8. Pena JM, Ford MJ. Cutaneous lymphangiectases associated with severe photoaging and topical corti- costeroid application. J Cutan Pathol 1996;23:175–81. 9. Stone MS. Central-facial papular lymphangiectases: an uncommon manifestation of porphyria. J Am Acad Dermatol 1997;36:493–5. 10. Garcia-Doval I, de la Torre C, Losada A, Ocampo C, Rodríguez T, Cruces MJ. Acquired cutaneous lymphangiectasia in a patient with cirrhotic ascites. J Eur Acad Dermatol Venereol 1999;13:109–12. 11. Plotnick H, Richfield D. Tuberous lymphangiectatic varices secondary to radical mastectomy. Arch Dermatol Syphilol 1956;74:466–8. 12. Kurwa A, Waddinton E. Post mastectomy lymphangiomatosis. Br J Dermatol 1968;80:840. 13. Prioleau PG, Santa Cruz DJ. Lymphangioma circumscriptum following radical mastectomy and radia- tion therapy. Cancer 1978;42:1989–91. 14. Leshin B, Whitaker D, Foucar E. Lymphangioma circumscriptum following mastectomy and radiation therapy. J Am Acad Dermatol 1986;15:1117–9. 15. Gianelli V, Rockley PF. Acquired lymphangiectasis following mastectomy and radiation therapy— report of a case and review of the literature. Cutis 1996;58:276–8. 16. Bouzit N, Grezard P, Communal PH, Mironneau I, Balme B, Perrot H. Lymphangiectasies cutanées acquises après traitement chirurgical et radiothérapie du cancer du sein. A propos de 2 cas. J Gynecol Obstet Biol Reprod 1999;28:384–7. 17. Diaz Cascajo C, Borghi S, Weyers W, Retzlaff H, Requena L, Metze D. Benign lymphangiomatous papules of the skin following radiotherapy: a report of five new cases and review of the literature. Histopathology 1999;35:319–27. 18. Weakley DR, Juhlin EA. Lymphagiectases and lymphangiomata. Arch Dermatol 1961;84:574–8. 19. Dap RF, van der Meijden WI. Vulvaire lymphangiectasieen bij de ziekte Crohn. Ned Tijdschr Geneeskd 2000;26:1692–5. 20. Handfield-Jones SE, Prendiville WJ, Norman S. Vulval lymphangiectasia. Genitourin Med 1989; 65:335–7. 21. Young AW Jr, Wind RM, Tovell HM. Lymphangioma of vulva: acquired following treatment for cervical cancer. NY State J Med 1980;80:987–9. 22. Kennedy CTC. Lymphangiectasia of the vulva following hysterectomy and radiotherapy. Br J Dermatol 1990;123 (suppl 37):92–3. 23. Fisher I, Orkin M. Acquired lymphangioma (lymphangiectasis): report of a case. Arch Dermatol 1970;101:230–4. 24. LaPolla J, Foucar E, Leshin B, et al. Vulvar lymphangioma circumscriptum: a rare complication of therapy for squamous cell carcinoma of the cervix. Gynecol Oncol 1985;22:363–6. 25. Ambrojo P, Fernandez Cogolludo E, Aguilar A, Sanchez Yus E, Sanchez de Paz F. Cutaneous lymphangiectases after therapy for carcinoma of the cervix: a case with unusual clinical and histological features. Clin Exp Dermatol 1990;15:57–9. 26. Cecchi R, Bartoli L, Brunetti L, Pavesi M, Giomi A. Lymphangioma circumscriptum of the vulva of late onset. Acta Derm Venereol 1995;75:79–93. 27. Goldstein JB, McNutt NS, Hambrick GW, Hsu MA. Penicillamine dermopathy with lymphangiectases. A clinical, immunohistologic, and ultrastructural study. Arch Dermatol 1989;125:92–7. 28. Ahmed DD, Waldorf JC, Randle HW. Cutaneous lymphangiectasis: treatment with sclerotherapy. Plast Reconstr Surg 1998;101:434–6. 29. Landthaler M, Hohenleutner U, Braun Falco O. Acquired lymphangioma of the vulva: palliative treat- ment by means of laser vaporization carbon dioxide. Arch Dermatol 1990;126:967–8. 30. Egan CA, Rallis TM, Zone JJ. Multiple scrotal lymphangiomas (lymphangiectases) treated by carbon dioxide laser ablation. Br J Dermatol 1998;139:561–2. 31. Novak C, Spelman L. Low energy fluence CO 2 laser treatment of lymphangiectasia. Australas J Dermatol 1998;39:277–8. 32. Loche F, Schwarze HP, Bazex J. Treatment of acquired cutaneous lymphangiectasis of the thigh and vulva with a carbon dioxide laser. Acta Derm Venereol 1999;79:335. 06/Sangüeza/73-98/F 01/14/2003, 11:47 AM97 [...]... vessel proliferation 07/Sangüeza/9 9-1 32/F 109 01/ 14/ 2003, 12:12 PM 110 Sangüeza and Requena / Pathology of Vascular Skin Lesions 21 Katta R, Bickle K, Hwang L Pyogenic granuloma arising in port-wine stain during pregnancy Br J Dermatol 2001; 144 : 644 –5 22 Kim TH, Choi EH, Ahn SK, Lee SH Vascular tumors arising in port-wine stains: two cases of pyogenic granuloma and a case of acquired tufted angioma J Dermatol... (44 49 ) can adequately manage lesions of AHE, but larger lesions show a tendency to persist (30), unless the arteriovenous shunt is excised Partial improvement of the lesions of AHE has been reported after intralesional injection of interferon- -2 a (50) or interferon- -2 b (51), as well as after oral administration of pentoxifylline (52), indomethacin (53), or isotretinoin ( 54) References 1 Wells GC, Whimster... with AIDS Report of seven cases and review of the literature J Am Acad Dermatol 1990;23 :41 –8 26 Cockerell CJ The clinical-pathologic spectrum of bacillary (epithelioid) angiomatosis Prog AIDS Pathol 1990;2:111–26 07/Sangüeza/9 9-1 32/F 115 01/ 14/ 2003, 12:12 PM 116 Sangüeza and Requena / Pathology of Vascular Skin Lesions 4 VERRUGA PERUANA Verruga peruana is the cutaneous manifestation of bartonellosis,... 07/Sangüeza/9 9-1 32/F 116 01/ 14/ 2003, 12:12 PM Chapter 7 / Cutaneous Vascular Hyperplasias 117 Fig 9 Clinical aspects of verruga peruana (A) Multiple lesions with angiomatous appearance on the face of a Peruvian girl (B) The same patient had similar lesions on the anterior chest and abdomen 07/Sangüeza/9 9-1 32/F 117 01/ 14/ 2003, 12:12 PM 118 Sangüeza and Requena / Pathology of Vascular Skin Lesions Fig...98 06/Sangüeza/7 3-9 8/F Sangüeza and Requena / Pathology of Vascular Skin Lesions 98 01/ 14/ 2003, 11 :47 AM Chapter 7 / Cutaneous Vascular Hyperplasias 7 99 Cutaneous Vascular Hyperplasias CONTENTS ANGIOLYMPHOID HYPERPLASIA WITH EOSINOPHILIA PYOGENIC GRANULOMA BACILLARY ANGIOMATOSIS VERRUGA PERUANA INTRAVASCULAR PAPILLARY ENDOTHELIAL HYPERPLASIA (MASSON’S PSEUDO-ANGIOSARCOMA) PSEUDO-KAPOSI’S SARCOMA... the skin and scapula: a case report with electron microscopy and immunohistochemistry Cancer 1983;51:1656–62 35 Burgdorf WHC, Mukai K, Rosai J Immunohistochemical identification of factor VIII related antigen in endothelial cells of cutaneous lesions of alleged vascular nature Am J Clin Pathol 1981;75:167–71 07/Sangüeza/9 9-1 32/F 103 01/ 14/ 2003, 12:12 PM 1 04 Sangüeza and Requena / Pathology of Vascular. .. the gingiva, lips (Fig 3), mucosa of the nose, fingers, and face (1,9, 14) , but examples of PG have been described in all parts of the skin and mucous membranes including the vulva (15), scrotum (16), penis (17), and glans penis (18) In a epidemiologic study of 325 cases (9), cutaneous lesions accounted for 86% of the lesions, with mucosal lesions representing only 12% of the cases Overall, male patients... strong expression of phosphorylated mitogen-activated protein kinase (61) in PG lesions 07/Sangüeza/9 9-1 32/F 107 01/ 14/ 2003, 12:12 PM 108 Sangüeza and Requena / Pathology of Vascular Skin Lesions Fig 5 Histopathologic features of PG (A) Low power shows a polypoid lesion with eroded surface (B) Higher magnification demonstrates capillary blood vessels surrounded by inflammatory infiltrate of neutrophils... Kimura’s disease: a clinico-pathological study of 21 cases and its distinction from angiolymphoid hyperplasia with eosinophilia Pathology 19 84; 16:39 44 6 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 7 Rosai J Angiolymphoid hyperplasia with eosinophilia of the skin Its nosological... Lenti E Intravascular lobular capillary haemangioma of the lip Histopathology 1996;29:382 4 47 Song MG, Kim HJ, Lee ES Intravenous pyogenic granuloma Int J Dermatol 2001 ;40 :57–9 48 Qian LH, Hui YZ Intravenous pyogenic granuloma: immunohistochemical considerations—a case report Vasc Surg 2001;35:315–9 07/Sangüeza/9 9-1 32/F 110 01/ 14/ 2003, 12:12 PM Chapter 7 / Cutaneous Vascular Hyperplasias 111 49 Hagiwara . 1989 ;44 :339 46 . 06/Sangüeza/7 3-9 8/F 01/ 14/ 2003, 11 :47 AM91 92 Sangüeza and Requena / Pathology of Vascular Skin Lesions 06/Sangüeza/7 3-9 8/F 01/ 14/ 2003, 11 :47 AM92 Chapter 6 / Cutaneous Lesions. 1999;79:335. 06/Sangüeza/7 3-9 8/F 01/ 14/ 2003, 11 :47 AM97 98 Sangüeza and Requena / Pathology of Vascular Skin Lesions 06/Sangüeza/7 3-9 8/F 01/ 14/ 2003, 11 :47 AM98 Chapter 7 / Cutaneous Vascular Hyperplasias. cells of cutaneous lesions of alleged vascular nature. Am J Clin Pathol 1981;75:167–71. 07/Sangüeza/9 9-1 32/F 01/ 14/ 2003, 12:12 PM103 1 04 Sangüeza and Requena / Pathology of Vascular Skin Lesions 36.