PATHOLOGY OF VASCULAR SKIN LESIONS - PART 9 potx

258 Sangüeza and Requena / Pathology of Vascular Skin Lesions 7. CUTANEOUS ANGIOSARCOMA ASSOCIATED WITH LYMPHEDEMA Stewart and Treves (1) first described the development of cutaneous angiosarcoma in lymphedematous areas in 1948. Since then, this disorder has been known as Stewart- Treves syndrome. In their original report, these authors reported six patients with postmastectomy lymphedema on the ipsilateral arm in whom angiosarcomas developed several years after this procedure. A large number of additional cases rapidly appeared in the literature (2–10). In addition to lymphedema secondary to mastectomy, this type of angiosarcoma has also been described in areas of lymphedema secondary to a variety of other mechanisms, including axillary node dissection for metastatic melanoma in males (11), lymphedema of the abdominal wall following lymph node dissection for carcinoma of the penis (12), congenital lymphedema (3,4,13–16), lymphedema secondary to a filarial infection (17–22), chronic idiopathic lymphedema (3,15,18,22–27), morbid obesity with lymphedema(28), and angiosarcoma complicating elephantiasis (29). Angiosarcomas arising in areas of lymphedema have been designated lymphangiosa- rcomas on the presumption that the neoplasms originated from dilated lymphatic vessels. However, this assertion has not been definitively proved, and immunohistochemical and ultrastructural studies support a hemangiomatous differentiation. Therefore at this time the term angiosarcoma is justified for neoplasms that develop in lymphedematous areas (30). More than 90% of all angiosarcomas associated with chronic lymphedema occur following mastectomy for breast carcinoma (3). The mastectomy invariably includes removal of the axillary lymph nodes, and in some patients, but not all, there is also the antecedent of adjuvant radiotherapy to the affected area. The risk of developing angiosa- rcoma in postmastectomy patients who have a survival of 5 years or more is approxi- mately 0.5% (19). The interval between the mastectomy and the development of angiosarcoma ranges from 1 to 30 years. The arm, most often the upper inner aspect, is the most frequent site for early involvement. Less commonly, the tumor appears more distally, on the elbow or on the forearm. In rare instances, postmastectomy angiosarcoma has been reported in patients who have experienced little or no lymphedema. C LINICAL FEATURES Clinically, these lesions appear as bruise-like areas or violaceous nodules superim- posed on the brownish nonpitting edema of the affected limb (31) (Fig. 21). After the appearance of the lesions, there is a rapid increase in their number and size, and they may undergo ulceration. In advanced cases, they spread distally to the hands and proximally to the chest wall. The clinical appearance and the histologic behavior of angiosarcomas in lymphedematous extremities unassociated with mastectomy are essentially identical to those of postmastectomy angiosarcoma. H ISTOPATHOLOGIC FEATURES Angiosarcomas that originate in areas of chronic lymphedema exhibit similar histo- pathologic features to those of angiosarcoma of the scalp and face (30,32). They appear as irregular vascular spaces that form an intricate network of freely anastomosing vessels containing erythrocytes with extensive dissection of collagen. Endothelial cell nuclei are plump and hyperchromatic. Patchy lymphoid infiltrates are sometimes present around 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM258 Chapter 9 / Malignant Neoplasms 259 Fig. 21. Cutaneous angiosarcoma associated with chronic postmastectomy lymphedema (Stewart- Treves syndrome). (A) The entire upper extremity appears edematous, with multiple angiomatous nodules. (B) In addition to the nodules, there are ill-delimited angiomatous plaques. the newly formed vessels. In some cases, there is a verrucous epidermal hyperplasia, presumably caused by lymphedema and the involvement of the papillary dermis (33). From a histogenetic point of view, the relationship between chronic lymphedema and angiosarcoma is enigmatic. Stewart and Treves, in their original report (1), postulated that unknown carcinogens within lymphatic fluid, acting in a locus minoris resistentia , induced the neoplastic change, a view that was also held by other authors (2). More recently, it has been suggested that the lymphedema modifies the biochemical or immu- nologic status of the affected limb fostering, the development of angiosarcoma (5,14). The notion that areas with chronic lymphedema are “immunologically privileged sites” is supported by the observation that skin grafts survive for long periods when they are transferred to lymphedematous extremities (20,21). Immunohistochemical studies in cutaneous angiosarcomas developing in lymph- edematous extremities have documented positivity for factor VIII-related antigen (8,34), and ultrastructural examination has demonstrated the presence of pericytes and Weibel- Palade bodies in some cases (7,8,35,36). These special studies are useful in establishing a differential diagnosis between Stewart-Treves angiosarcoma and metastatic breast carcinoma in a lymphedematous arm, since both entities may show similar clinical and histopathologic features. In metastatic breast carcinoma, the neoplastic cells express 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM259 260 Sangüeza and Requena / Pathology of Vascular Skin Lesions immunoreactivity for cytokeratin owing to their epithelial nature, whereas factor VIII- related antigen is negative (37). T REATMENT Survival in angiosarcoma associated with lymphedema may be worse than in other forms of cutaneous angiosarcoma. Woodward et al. (3) reported a mean survival time of patients with angiosarcoma following mastectomy of 19 months, compared with 34 months for cutaneous angiosarcomas not related to lymphedema. Sordillo et al. (6) reported a mean survival time of 31 months. A longer survival time has been reported in patients initially treated with radical surgery, including limb disarticulation, or hindquar- ter or forequarter amputation (30). Other studies have found no significant difference in survival when cases initially treated with wide excision were compared with those treated with amputation (38). References 1. Stewart FW, Treves N. Lymphangiosarcoma in postmastectomy lymphedema. Cancer 1948;1:64–81. 2. Herrmann JB. Lymphangiosarcoma of the clinically edematous extremity. Surg Gynecol Obstet 1965;121:1107–15. 3. Woodward AH, Ivins JC, Soule EH. Lymphangiosarcoma arising in chronic lymphedematous extremi- ties. Cancer 1972;30:562–72. 4. Taswell HF, Soule HE, Coventry MB. Lymphangiosarcoma arising in chronic lymphedematous extremities. J Bone Joint Surg 1962;44A:277–94. 5. Schreiber H, Barry FM, Russell WC, Macon WL IV, Ponsky JL, Pories WJ. Stewart-Treves syndrome. A lethal complication of postmastectomy lymphedema and regional immune deficiency. Arch Surg 1979;114:82–5. 6. Sordillo PP, Chapman R, Hajdu DI, Magill GB, Golbey RB. Lymphangiosarcoma. Cancer 1981; 48:1674–9. 7. Silverberg SG, Kay S, Koss LG. Postmastectomy lymphangiosarcoma: utrastructural observations. Cancer 1971;27:100–8. 8. Kanitakis J, Bendalac A, Marchand C, et al. Stewart-Treves syndrome: a histogenetic (ultrastructural and immunohistochemical) study. J Cutan Pathol 1986;13:30–9. 9. Hultberg BM. Angiosarcoma in chronically lymphedematous extremities: two cases of Stewart-Treves syndrome. Am J Dermatopathol 1987;9:406–12. 10. Hildebrandt G, Mittag M, Gutz U, Kunze ML, Haustein UF. Cutaneous breast angiosarcoma after conserving treatment of breast cancer. Eur J Dermatol 2001;11:580–3. 11. Chen KTK, Bauer V, Flam MS. Angiosarcoma in postsurgical lymphedema. An unusual occurrence in a man. Am J Dermatopathol 1991;13:488–92. 12. Calnan J, Cowdell RH. Lymphangioendothelioma of the anterior abdominal wall: report of a case. Br J Surg 1959;46:375–9. 13. Dubin HU, Creehan EP, Headington JT. Lymphangiosarcoma and congenital lymphedema of the extremity. Arch Dermatol 1974;110:608–14. 14. Laskas JJ Jr, Shelley WB, Wood MG. Lymphangiosarcoma arising in congenital lymphedema. Arch Dermatol 1975;111:86–9. 15. Mackezie DM. Lymphangiosarcoma arising in chronic congenital and idiopathic lymphedema. J Clin Pathol 1971;24:524–9. 16. Merrick T, Erlandson RA, Hajdu SI. Lymphangiosarcoma of a congenitally lymphedematous extremity. Arch Pathol 1971;91:365–71. 17. Muller R, Hajdu SI, Brenan MF. Lymphangiosarcoma associated with chronic filarial lymphedema. Cancer 1987;59:179–83. 18. Alessi E, Sala F, Berti E. Angiosarcomas in lymphedematous limbs. Am J Dermatopathol 1986;8:371–8. 19. Shirger A. Postoperative lymphedema: etiologic and diagnostic factors. Med Clin North Am 1962;46:1045–50. 20. Stark RB, Dwyer EM, DeForest M. Effect of surgical ablation of regional lymph nodes on survival of skin homographs. Ann NY Acad Sci 1960;87:140–5. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM260 Chapter 9 / Malignant Neoplasms 261 21. Lambert PB, Frank HA, Bellman S, et al. The role of the lymph trunks in the response to allogenic skin transplants. Transplantation 1965;3:62–73. 22. Sordillo EM, Sordillo PP, Hadju SI, et al. Lymphangiosarcoma after filarial infection. J Dermatol Surg Oncol 1981;7:235–9. 23. Baes H. Angiosarcoma in a chronic lymphedematous leg. Dermatologica 1967;134:331–6. 24. Sinclair SA, Sviland L, Natarajan S. Angiosarcoma arising in a chronically lymphoedematous leg. Br J Dermatol 1998;138:692–4. 25. Simonetti V, Folgaresi M, Motolese A. Angiosarcoma of the lower leg in chronic lymphoedema. Acta Derm Venereol 1999;79:251–2. 26. Azurdia RM, Guerin DM, Verbov JL. Chronic lymphoedema and angiosarcoma. Clin Exp Dermatol 1999;24:270–2. 27. Nakazono T, Kudo S, Matsuo Y, et al. Angiosarcoma associated with chronic lymphedema (Stewart- Treves syndrome) of the leg: MR imaging. Skeletal Radiol 2000;29:413–6. 28. Azam M, Saboorian H, Bieligk S, Smith T, Molberg K. Cutaneous angiosarcoma complicating morbid obesity. Arch Pathol Lab Med 2001;125:531–3. 29. Hallel-Haevy D, Yerushalmi J, Grunwald MH, Avinoach I, Halevy S. Stewart-Treves syndrome in a patient with elephantiasis. J Am Acad Dermatol 1999;41:349–50. 30. Enzinger FM, Weiss SW. Malignant vascular tumors. In: Soft Tissue Tumors, 3rd ed. St. Louis, MO, Mosby, 1995:641–77. 31. Bisceglia M, Attino V, D’Addeta C, Murgo R, Fletcher CD. Le sindrome di Stewart e Treves in fase precoce: presentazione di due casi e revisione della letteratura. Pathologica 1996;88:483–90. 32. Cooper PH. Angiosarcomas of the skin. Semin Diagn Pathol 1987;4:2–17. 33. Diaz-Cascajo C, Weyers W, Borghi S, Reichel M. Verrucous angiosarcoma of the skin: a distinct variant of cutaneous angiosarcoma. Histopathology 1998;32:556–61. 34. Capo V, Ozello L, Fenoglio CM, et al. Angiosarcomas arising in edematous extremities. Hum Pathol 1985;16:144–50. 35. McWilliam LJ, Harris M. Histogenesis of postmastectomy angiosarcoma: an ultrastructural study. Histopathology 1985;9:331–43. 36. Kindblom L-G, Stenman G, Angervall L. Morphological and cytogenetic studies of angiosarcoma in Stewart-Treves syndrome. Virchows Arch A Pathol Anat Histopathol 1991;419:439–45. 37. Hashimoto K, Hatsumoto M, Eto H, et al. Differentiation of metastatic breast carcinoma from Stewart- Treves angiosarcoma. Arch Dermatol 1985;121:742–6. 38. Grobmyer SR, Daly JM, Glotzbach RE, Grobmyer AJ. Role of surgery in the management of postmastectomy extremity angiosarcoma (Stewart-Treves syndrome). J Surg Oncol 2000;73:1182–8. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM261 262 Sangüeza and Requena / Pathology of Vascular Skin Lesions 8. RADIATION-INDUCED CUTANEOUS ANGIOSARCOMA Postirradiation cutaneous angiosarcoma is a rare condition that has been described following the use of radiotherapy for the treatment of diverse conditions. These include cutaneous hemangiomas (1,2), acne (3), hand eczema (4), X-ray depilation for scalp ringworm during childhood (5), and malignant neoplasms such as carcinoma of the cervix (6–9), endometrium (10), ovary (11), and breast (12–26), Hodgkin’s disease (27), penile squamous cell carcinoma (28), or peripheral primitive neuroectodermal tumor (29). The ensuing angiosarcoma usually manifests after a long interval, ranging from 4 to 40 years (mean 23.3 years) when radiation therapy was administered for benign con- ditions, and from 4 to 25 years (mean 12.3 years), for patients in whom radiation therapy was used for malignant tumors. These differences are probably related to the higher dosage and harder radiation in the group of patients with previous malignancy. Preexist- ing radiodermatitis of the involved area has been described in some cases (3,8,15,30,31). C LINICAL FEATURES The clinical appearance of postirradiation cutaneous angiosarcoma varies from case to case. Diffuse infiltrative plaques (Fig. 22), papulo-nodules, and ulcerated lesions have been described. All lesions occurred in the area of irradiation or its immediate vicinity, and because most of the cases appeared following radiation for breast and genitourinary malignant tumors, the chest wall and the lower abdominal wall are the sites most fre- quently involved by postirradiation angiosarcomas. Most of these patients had no evi- dence of lymphedema, suggesting that radiation is the most important etiologic factor. H ISTOPATHOLOGIC FEATURES Postirradiation angiosarcoma shows a histopathologic picture similar to that of other variants of cutaneous angiosarcoma (Fig. 23). In early lesions, neoplastic vessels infil- trate collagen bundles of the entire thickness of the dermis and often extend to the subcutaneous tissue. The endothelial cells lining these vessels show variable atypia, but at least some have large hyperchromatic nuclei and protrude into the lumina of the irregular vascular channels. Sometimes papillations lined by protuberant endothelial cells are present. As the lesions become increasingly cellular, aggregations of epithelioid neoplastic cells develop. In these aggregations, vacuoles within the cytoplasm of neo- plastic cells are seen as an expression of primitive luminal differentiation. Mitotic figures are frequently seen in the solid-appearing zones. A frequent finding is the presence of lymphoid nodules in both the superficial and deep areas of the dermis. In the advancing edges of these solid areas there are jagged vessels similar to those seen in earlier lesions infiltrating between collagen bundles of the dermis. Cutaneous angiosarcoma originating in irradiated areas of the skin should be distin- guished histopathologically from the benign vascular proliferations arising in irradiated skin (see Chapter 8, Subheading 15.), which have received different names in the litera- ture, including lymphangiectases (32), benign lymphangiomatous papules (33), lym- phangioma (34–44), atypical vascular lesions (45), benign lymphangioendothelioma (46), or benign vascular proliferations in irradiated skin (47). Histopathologically, they consist of relatively well-circumscribed vascular proliferations involving the dermis, without extension to the subcutaneous fat, and they do not involve the epidermis. Most lesions show irregular dilated vascular spaces, with a branching and anastomosing pat- tern, and a lymphatic appearance in the superficial dermis. A discontinuous single layer 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM262 Chapter 9 / Malignant Neoplasms 263 Fig. 22. (A) Angiosarcoma of the breast appeared after radiation for breast carcinoma. (B) Close-up view showing the angiomatous appearance of the plaques of angiosarcoma. of endothelial cells with spindled or flattened nuclei lines the vascular channels, and their lumina appear empty. In many areas, adjacent vascular channels show a “back-to-back” arrangement, with the two vascular lumina only separated by a thin layer of endothelial cells. Numerous small papillary projections, also lined by a single layer of endothelial cells, are seen projecting into the lumina of the dilated lymphatic vessels. The stroma of the lesions consists of fibrillary collagen and numerous spindled or stellate fibroblasts. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM263 264 Sangüeza and Requena / Pathology of Vascular Skin Lesions 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM264 Chapter 9 / Malignant Neoplasms 265 In some cases, dense nodular infiltrates of lymphocytes with germinal centers are present in the vicinity of the dilated vascular channels. Furthermore, in contrast to well-differentiated angiosarcomas, benign vascular prolif- erations in irradiated skin do not involve the subcutaneous tissue, and there is no substan- tial cytologic atypia because the nuclei of endothelial cells lining the vascular channels are monomorphous, with inconspicuous nucleoli and no mitotic figures. In contrast, angiosarcomas may present with multiple layers of atypical endothelial cells lining ir- regular vascular and anastomosing channels, the so-called piling-up phenomenon; this is not seen in atypical vascular proliferations in irradiated skin. T REATMENT In general, the prognosis for angiosarcoma originating in irradiated areas is poor (6), although there are cases of radiation-induced low-grade cutaneous angiosarcomas with multiple recurrences. However, they did not produce metastasis (11). Treatment consists of radical surgery with wide margins of noninvolved tissue. The neoplasm usually extends far beyond the clinically visible boundaries of the lesion, and metastases have already developed by the time surgery is performed. References 1. Caldwell JB, Ryan MT, Benson PM, James WD. Cutaneous angiosarcoma arising in the radiation site of a congenital hemangioma. J Am Acad Dermatol 1995;33:865–70. 2. Cabo H, Cohen ES, Casas GJ, Allevato M, Woscoff A. Cutaneous angiosarcoma arising on the radiation site of a congenital facial hemangioma. Int J Dermatol 1998;37:638–9. 3. Seo IS, Warner TFCS, Warren JS, Bennett JF. Cutaneous postirradiation sarcoma. Ultrastructural evi- dence of pluripotential mesenchymal cell derivation. Cancer 1985;56:761–7. 4. Girard C, Johnson WC, Graham JH. Cutaneous angiosarcoma. Cancer 1970;26:868–83. 5. Stone NM, Holden CA. Postirradiation angiosarcoma. Clin Exp Dermatol 1997;22:46–7. 6. Goette EK, Detlefs RL. Postirradiation angiosarcoma. J Am Acad Dermatol 1985;12:922–6. 7. Maddox JC, Evans HL. Angiosarcoma of skin and soft tissue. A study of forty-four cases. Cancer 1981;48:1907–21. 8. Krasagakis K, Hettmannsperger U, Tebbe B, Garbe C. Cutaneous metastatic angiosarcoma with a lethal outcome, following radiotherapy for a cervical carcinoma. Br J Dermatol 1995;133:610–4. 9. Kim MK, Huh SJ, Kim DY, et al. Secondary angiosarcoma following irradiation—case report and review of the literature. Radiat Med 1998;16:55–60. 10. Paik HH, Komorowski R. Hemangiosarcoma of the abdominal wall following irradiation therapy of endometrial carcinoma. Am J Clin Pathol 1976;66:810–4. 11. Chen TK, Goffman KD, Hendricks EJ. Angiosarcoma following therapeutic irradiation. Cancer 1979;44:2044–8. 12. Edeiken S, Russo DP, Knecht J, et al. Angiosarcoma after tylectomy and radiation therapy for carcinoma of the breast. Cancer 1992;70:644–7. 13. Rubin E, Maddox WA, Mazur MT. Cutaneous angiosarcoma of the breast 7 years after lumpectomy and radiation therapy. Radiology 1990;174:258–60. 14. Sessions SC, Smenk RD. Cutaneous angiosarcoma of the breast after segmental mastectomy and radia- tion therapy. Arch Surg 1992;127:1362–3. 15. Stokkel MPM, Peterse HL. Angiosarcoma of the breast after lumpectomy and radiation therapy for adenocarcinoma. Cancer 1992;69:2965–8. Fig. 23. (Opposite page) Histopathologic features of postirradiation angiosarcoma of the breast. (A) Scanning power shows dense cellular aggregates at the superficial dermis. (B) Higher magnification demonstrates that these cellular aggregates are surrounding elongated, slit-like vascular spaces. (C) Still higher magnification shows that neoplastic cells are pleomorphic, with hyperchromatic nuclei and numerous mitotic figures. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM265 266 Sangüeza and Requena / Pathology of Vascular Skin Lesions 16. Moskaluk CA, Merino MJ, Danforth DN, Medeiros LJ. Low-grade angiosarcoma of the skin of the breast: a complication of lumpectomy and radiation therapy for breast carcinoma. Hum Pathol 1992;23:710–4. 17. Bolin DJ, Lukas GM. Low-grade dermal angiosarcoma of the breast following radiotherapy. Am Surg 1996;62:668–72. 18. Autio P, Kariniemi AL. Angiosarcoma. A rare secondary malignancy after breast cancer treatment. Eur J Dermatol 1999;9:118–21. 19. Majeski J, Austin RM, Fitzgerald RH. Cutaneous angiosarcoma in an irradiated breast after breast conservation therapy for cancer: association with chronic breast lymphedema. J Surg Oncol 2000;74:208–12. 20. Cafiero EF, Gipponi M, Peressini A, et al. Radiation-associated angiosarcoma: diagnostic and therapeu- tic implications: two cases reports and review of the literature. Cancer 1996;77:2496–502. 21. Cancellieri A, Eusebi V, Mambellin V, et al. Well-differentiated angiosarcoma of the skin following radiotherapy. Pathol Res Pract 1991;187:301–6. 22. Givens SS, Ellerbroek NA, Butler JJ, et al. Angiosarcoma arising in an irradiated breast: a case report and review of the literature. Cancer 1989;64:2214–6. 23. Marchal C, Weber B, de Lafontan B. Nine breast angiosarcomas after conservative treatment for breast carcinoma: a survey from French comprehensive cancer centers. Int J Radiat Oncol Biol Phys 1999;44:113–9. 24. Otis CN, Peschel R, McKhann C et al. The rapid onset of cutaneous angiosarcoma after radiotherapy for breast cancer. Cancer 1986;57:2130–4. 25. Parham DM, Fisher C. Angiosarcomas of the breast developing post radiotherapy. Histopathology 1997;31:189–95. 26. Shaikh NA, Beaconsfield T, Walker M, et al. Postirradiation angiosarcoma of the breast: a case report. Eur J Surg Oncol 1988;14:449–51. 27. Richards PG, Bessell EM, Goolden AWG. Spinal extradural angiosarcoma occurring after treatment for Hodgkin’s disease. Clin Oncol 1983;9:165–8. 28. Prescott RJ, Mainwaring AR. Irradiation-induced penile angiosarcoma. Postgrad Med J 1990;66:576–9. 29. Coffin CM, Vietti TJ, Land VJ, et al. Cutaneous angiosarcoma as a second malignant neoplasm after peripheral primitive neuroectodermal tumor. Med Pediatr Oncol 1992;20:352–6. 30. Hodgkinson DJ, Soule EH, Woods JE. Cutaneous angiosarcoma of the head and neck. Cancer 1979;44:1106–13. 31. Calnan J, Cowdell RH. Lymphangioendothelioma of the anterior abdominal wall: report of a case. Br J Surg 1959;46:375–9. 32. Ambrojo P, Fernández-Cogolludo E, Aguilar A, et al. Cutaneous lymphangiectases after therapy for carcinoma of the cervix: a case with unusual clinical and histological features. Clin Exp Dermatol 1990;15:57–9. 33. Díaz-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. 34. Fisher I, Orkin M. Acquired lymphangioma (lymphangiectasis). Arch Dermatol 1970;101:230–4. 35. Gianelli V, Rockley PF. Acquired lymphangiectases following mastectomy and radiation therapy. Report of a case and review of the literature. Cutis 1996;58:276–8. 36. Handfield-Jones SE, Prendville WJ, Norman S. Vulval lymphangiectasia. Genitourin Med 1989;65:335–7. 37. Harwood CA, Mortimer PS. Acquired vulvar lymphangiomata mimicking genital warts. Br J Dermatol 1993;129:334–6. 38. Kennedy CTC. Lymphangiectasia of the vulva following hysterectomy and radiotherapy. Br J Dermatol 1990;123(suppl. 37):92–3. 39. Kurwa A, Waddinton E. Post mastectomy lymphangiomatosis. Br J Dermatol 1968;80:840. 40. 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. 41. Leshin B, Whitaker D, Foucar E. Lymphangioma circumscriptum following mastectomy and radiation therapy. J Am Acad Dermatol 1986;15:1117–9. 42. Plotnick H, Richfield D. Tuberous lymphangiectatic varices secondary to radical mastectomy. Arch Dermatol Syphilol 1956;74:466–8. 43. Prioleau PG, Santa Cruz DJ. Lymphangioma circumscriptum following radical mastectomy and radia- tion therapy. Cancer 1978;42:1989–91. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM266 Chapter 9 / Malignant Neoplasms 267 44. Young AW Jr, Wind RM, Tovell HM. Lymphangioma of vulva: acquired following treatment for cervical cancer. NY State J Med 1980;80:987–9. 45. Finenberg S, Rosen PP. Cutaneous angiosarcoma and atypical vascular lesions of the skin and breast after radiation therapy for breast carcinoma. Am J Clin Pathol 1994;102:757–63. 46. Rosso R, Gianelli U, Carnevali L. Acquired progressive lymphangioma of the skin following radio- therapy for breast carcinoma. J Cutan Pathol 1995;22:164–7. 47. Requena L, Kutzner H, Mentzel T, Durán R, Rodríguez-Peralto JL. Benign vascular proliferations in irradiated skin. Am J Surg Pathol 2002;26:328–37. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM267 [...]... deletion of the MEN1 gene J Invest Dermatol 199 8;110:438–40 15 Boni R, Vortmeyer AO, Pack S, et al Somatic mutations of the MEN1 tumor suppressor gene detected in sporadic angiofibromas J Invest Dermatol 199 8;110:5 39 40 16 Hoang-Xuan T, Steger JW Adult-onset angiofibroma and multiple endocrine neoplasia type I J Am Acad Dermatol 199 9;41: 890 –2 17 Sakurai A, Matsumoto K, Ikeo Y, et al Frequency of facial... difference from ordinary pure lipomas: a report of the CHAMP Study Group Am J Surg Pathol 199 7;21:441–4 14 Kaneko T, Tokushige H, Kimura N, Moriya S, Toda K The treatment of multiple angiolipomas by liposuction surgery J Dermatol Surg Oncol 199 4;20: 690 –2 10/Sangüeza/27 5-2 98 /F 2 89 01/14/2003, 4:15 PM 290 Sangüeza and Requena / Pathology of Vascular Skin Lesions 5 CUTANEOUS ANGIOLIPOLEIOMYOMA CLINICAL... with neurofibromatosis type 2 (12) and in patients with Fig 3 Multiple facial angiofibromas in a patient with tuberous sclerosis 10/Sangüeza/27 5-2 98 /F 2 79 01/14/2003, 4:15 PM 280 Sangüeza and Requena / Pathology of Vascular Skin Lesions Fig 4 Clinical appearance of a solitary angiofibroma Small, dome-shaped papule close to the nose multiple endocrine neoplasia type 1 (MEN-1) This consists of a heritable... 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Treatment of angiofibroma with the pulsed tunable dye laser J Am Acad Dermatol 199 3; 29: 790 –1 41 Boixeda P, Sanchez-Miralles E, Azaña JM, Arrazola JM, Moreno R, Ledo A CO2, argon, and pulsed dye laser treatment of angiofibromas J Dermatol Surg Oncol 199 4;20:808–12 42 Kaufman AJ, Grekin RC, Geisse JK, Frieden IJ Treatment of adenoma sebaceum with the Cooper vapor laser J Am Acad Dermatol 199 5;33:77–4... An uncommon neoplasm J Am Acad Dermatol 199 3; 29: 1043–4 9 Lawson GM, Salter DM, Hooper G Angioleiomyomas of the hand Report of 14 cases J Hand Surg [Br] 199 5;20:4 79 83 10 Baran R, Requena L, Drape JL Subungueal angioleiomyoma masquerading as a glomus tumor Br J Dermatol 2000;142:12 39 41 11 MacDonald DM, Sanderson KV Angioleiomyoma of the skin Br J Dermatol 197 4 ;91 :161–8 12 Martínez JA, Quecedo E, Fortea... Factor VIII-related antigen was negative in neoplastic cells (3) In one example of a glomangiosarcoma derived from a benign glomus tumor, immunohistochemical studies demonstrated that bcl-2, an inhibitor of apoptosis, was strongly 09/ Sangüeza/21 7-2 74/F 271 01/16/2003, 10:13 AM 272 09/ Sangüeza/21 7-2 74/F Sangüeza and Requena / Pathology of Vascular Skin Lesions 272 01/16/2003, 10:13 AM Chapter 9 / Malignant . inhibitor of apoptosis, was strongly 09/ Sangüeza/21 7-2 74/F 01/16/2003, 10:13 AM271 272 Sangüeza and Requena / Pathology of Vascular Skin Lesions 09/ Sangüeza/21 7-2 74/F 01/16/2003, 10:13 AM272 Chapter 9. Sangüeza and Requena / Pathology of Vascular Skin Lesions 16. Moskaluk CA, Merino MJ, Danforth DN, Medeiros LJ. Low-grade angiosarcoma of the skin of the breast: a complication of lumpectomy and radiation. Pathologica 199 6;88:483 90 . 32. Cooper PH. Angiosarcomas of the skin. Semin Diagn Pathol 198 7;4:2–17. 33. Diaz-Cascajo C, Weyers W, Borghi S, Reichel M. Verrucous angiosarcoma of the skin: a distinct