PATHOLOGY OF VASCULAR SKIN LESIONS - PART 8 doc

224 Sangüeza and Requena / Pathology of Vascular Skin Lesions Fig. 7. AIDS-associated Kaposi’s sarcoma involving the oral mucosa. adnexae and blood vessels, producing the so-called promontory sign (71) (Fig. 9). In other areas, the blood vessels infiltrate between collagen bundles of the dermis, giving the appearance that they are “dissecting” the stroma. In rare instances, the newly formed blood vessels form clusters that resemble small hemangiomas (71,74). The inflammatory cells present are predominantly lymphocytes and plasma cells. The presence of plasma cells around newly formed irregular blood vessels is a helpful clue in the histopathologic diagnosis of the patch stage of Kaposi’s sarcoma (71). Another characteristic feature of patch stage lesions of Kaposi’s sarcoma is the presence of scattered necrotic endothelial cells, a feature that has been emphasized at both the conventional microscopy (77) and ultrastructural level (41). Hemosiderin-laden macrophages are another feature frequently found in early lesions of Kaposi’s sarcoma. The histopathologic features just described for the patch lesions can also be seen in clinically normal areas of skin in patients who have Kaposi’s sarcoma elsewhere, which supports the notion of the diffuseness of the process from its inception (79,80). Plaque lesions of Kaposi’s sarcoma tend to involve the entire dermis and even the upper part of the subcutaneous fat. At this stage, there is an increased number of spindle cells arranged in short fascicles between collagen bundles centered around proliferating vascular channels. The spindle cells line irregularly shaped, slit-like vascular spaces that contain isolated erythrocytes. They display minimal or no atypia, with only a few to no mitotic figures. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM224 Chapter 9 / Malignant Neoplasms 225 Fig. 8. Histopathologic features of patch stage Kaposi’s sarcoma. (A) At scanning magnification, the lesions consists of increased numbers of jagged spaces at different levels of the dermis. (B) Higher magnification shows that the jagged spaces are lined by thin endothelial cells. (C) At this point it is possible to see inflammatory infiltrate with some plasma cells and extravasated eryth- rocytes. When the number of spindle cells increases, lesions of Kaposi’s sarcoma become nodular. Then the spindle cells are arranged in interwoven fascicles with erythrocytes scattered in the interstices (Fig. 10). Nuclear atypia, pleomorphism, and mitotic figures may be seen but are usually not very prominent. In rare instances, however, especially 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM225 226 Sangüeza and Requena / Pathology of Vascular Skin Lesions Fig. 9. Histopathologic features in plaque lesions of Kaposi’s sarcoma. (A) Scanning power shows involvement of the upper part of the dermis by the neoplastic process. (B) Higher magnification shows irregular vascular spaces and inflammatory infiltrate. (C) The “promontory” sign is evident around preexisting capillaries. (D) Numerous plasma cells are present in the stroma surrounding the areas of “promontory” sign. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM226 Chapter 9 / Malignant Neoplasms 227 Fig. 10. Histopathologic features in nodular lesions of Kaposi’s sarcoma. (A) Scanning magnifi- cation shows a well-circumscribed cellular nodule in the dermis. (B) Higher magnification dem- onstrates that the nodule is composed of fascicles of spindle cells. Some congestive vascular lumina are also seen. (C) Spindle cells are monomorphous, and nuclear atypia, pleomorphism, and mitotic figures are not usually prominent. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM227 228 Sangüeza and Requena / Pathology of Vascular Skin Lesions in the African variant (81), a significant number of mitotic figures and atypical cells may be seen in lesions of Kaposi’s sarcoma. A rather characteristic, but probably not specific, finding is the presence of the so-called hyaline globules. Although these are most common in the plaque and nodular lesions of Kaposi’s sarcoma, they can be present at any stage of the disease. These globules are periodic acid-Schiff (PAS)-positive and diastase-resistant, consist of eosinophilic spherules measuring between 1 and 10 µm, and are located both intra- and extracellularly. Most likely these hyaline globules represent degenerated erythrocytes that are phagocytized and confined to the phagolysosomes of the neoplastic cells (82–85). These globules have been also described in other vas- cular proliferations such as angiosarcomas, pyogenic granulomas, and granulation tissue (84). In rare instances, lesions of Kaposi’s sarcoma may present clinically as bullous lesions with histopathologic features of a lymphangioma. These lesions show irregular vascular channels lined by a single layer of flattened endothelial cells devoid of erythrocytes within the dermis (86–94). The absence of hemosiderin deposits and the scarcity of spindle cells also contribute to a lymphangiomatous appearance of the lesions. Occasion- ally, the lymphangiomatous pattern can be seen focally within an otherwise stereotypical lesion of Kaposi’s sarcoma. There have been patients with classic Kaposi’s sarcoma in which some lesions showed a lymphangioma-like pattern, whereas other lesions of the same patient exhibited the typical findings associated with Kaposi’s sarcoma, with abun- dant extravasated erythrocytes and hemosiderin deposits. Chronic lymphedema (86) and/ or the use of electron beam therapy (94) on the involved extremity may be responsible for the formation of the lymphangioma-like lesions in Kaposi’s sarcoma. From a histogenetic point of view, current evidence suggests that Kaposi’s sarcoma is a proliferative process. Ultrastructural and immunohistochemical studies have shown that the spindle cell component shows endothelial differentiation (95,96). Whether this repre- sents endothelium of blood vessels or lymphatics remains to be determined (97–107). Well- formed vessels in lesions of Kaposi’s sarcoma are lined by cells that are positive for factor VIII-related antigen, but studies for this marker in neoplastic spindle cells have provided conflicting results (96,99,102–109). In contrast, Ulex europaeus I lectin has consistently been detected in the spindle cells (99,108). Rutgers et al. (97) concluded that spindle cells in Kaposi’s sarcoma are blood vascular endothelial cells, because they stain with mono- clonal antibodies OKM5, anti-E92, and HCl, which react with blood capillary endothelium, but not with lymphatic endothelium. Identical conclusions were reported by Scully et al. (109) on the basis of the immunoreactivity of spindle cells with the antibody B721. Russell Jones et al. (99,108) noted that immunoreactivity of the spindle cells varies with the stage and type of the lesions. Early patch stage lesions have the profile of a lymphatic lesion because the cells are positive for the antibody EN-4, which stain all types of endothelial cells, but are negative with the antibody PAL-E, which is specific for blood vessel endothelium. Nodular lesions of Kaposi’s sarcoma stain with EN-4 and express variable immunoreactivity with PAL-E (99,108). Beckstead et al. (101) also favored lymphatic endothelial differentiation because of the lack of HLA-DR/Ia and alkaline phosphatase and the intense staining with 5' nucleotidase. In contrast, the presence of abundant laminin and type IV collagen surrounding many of the individual spindle cells has been interpreted as evidence favoring a blood vascular endothelium rather than lymphatic endothelium differentiation (110–112). More recently, Weich et al. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM228 Chapter 9 / Malignant Neoplasms 229 (113) have suggested a close relationship between the Kaposi’s sarcoma cell and the vascular smooth muscle cell, since the tumors express mRNA for α-smooth muscle actin. Different investigators have found that the Kaposi’s sarcoma cells express the CD34 antigen, also known as the human progenitor cell antigen. This is a 105–120-kDa single- chain transmembrane glycoprotein expressed constitutively by endothelial cells of small blood, but not lymphatic, vessels in several tissues (114–118). A nonvascular origin for the spindle cells of the Kaposi’s sarcoma has also been suggested, based on the presence of many factor XIIIa-positive spindle cells in the lesions, suggesting that the factor XIIIa-expressing dermal dendrocyte (a member of the mono- nuclear phagocytic system) may be the cell of origin for the spindle-shaped cells of Kaposi’s sarcoma (119,120). Other authors, however, believe that these factor XIIIa- positive dendritic cells represent reactive hyperplasia of dermal dendrocytes, rather than neoplastic cells (107). More recently, vascular endothelial growth factor receptor-3 (VEGFR-3) (121–124) and podoplanin (123,125), two relatively sensitive and specific markers for lymphatic endothelium, have been identified in most Kaposi’s sarcomas, supporting a lymphatic differentiation for this neoplasm. Ultrastructural studies have documented that under electron microscopy most of the spindle cells exhibit characteristics of endothelial cells, although a few of them also show features of pericytes and fibroblasts (126). The cells surrounding vascular spaces show few intercellular junctions, with gaps between them. A fragmented basal lamina encircles the luminal cells in absence of pericytes. These ultrastructural features seem to be more compatible with lymphatic than blood vascular differentiation, but it is possible that their absence may be the result of the dilation of blood vessels (41). The differential diagnosis of Kaposi’s sarcoma from pseudo-Kaposi’s sarcoma lesions is usually straightforward. In both the acroangiodermatitis and arteriovenous malforma- tion variants of pseudo-Kaposi’s sarcoma lesions, the blood vessels of the papillary dermis are involved, demonstrating a lobular proliferation of round, dilated, thick-walled capillaries, with plump endothelial cells (127). This vascular proliferation is superim- posed on a background of dermal fibrosis, erythrocyte extravasation, and abundant hemosiderin. The irregular jagged vascular channels with slit-like lumina surrounding preexisting capillaries, found in early lesions of Kaposi’s sarcoma, are not seen. Benign lymphangioendothelioma can be also mistaken for early lymphangioma-like lesions of Kaposi’s sarcoma. Similarities include thin-walled, endothelium-lined vascu- lar spaces between collagen bundles that appear to “dissect” the dermis. However, these vascular spaces of benign lymphangioendothelioma are usually arranged horizontally in the dermis and show no tendency to surround preexisting blood vessels as in Kaposi’s sarcoma. Furthermore, the absence of extravasated erythrocytes, hemosiderin, and plasma cells is also helpful. The clinical appearance of the lesion is helpful, too, because benign lymphangioendothelioma presents as a solitary lesion. Hobnail hemangioma also shares common histopathologic features with Kaposi’s sarcoma, especially at the periphery of the lesion. In these areas, there are irregular angulated vascular lumina that appear to be dissecting collagen bundles and abundant hemosiderin, raising the possibility of early lesions of Kaposi’s sarcoma. However, in the central areas of hobnail hemangioma, there are widely dilated vascular lumina with intraluminal papillary projections, prominent endothelial cells, and frequent fibrin thrombi. These features are not seen in Kaposi’s sarcoma. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM229 230 Sangüeza and Requena / Pathology of Vascular Skin Lesions Spindle cell hemangioma is frequently confused with nodules of Kaposi’s sarcoma because in both entities there are fascicles of spindle cells with slit-like vascular spaces containing erythrocytes. However, spindle cell hemangioma shows dilated blood vessels and areas of epithelioid cells, with prominent cytoplasmic vacuoles, which are not seen in nodules of Kaposi’s sarcoma. Kaposiform hemangioendothelioma bears a striking resemblance to the nodular lesions of Kaposi’s sarcoma; however, the clinical settings are different. Kaposi’s sarcoma is uncommon in infancy, and kaposiform hemangioendothelioma is a solitary neoplasm. Furthermore, histopathologically, kaposiform hemangioendothelioma shows a lobulated growth pattern and hemangioma-like areas, especially at the periphery of the lobules. The biologic behavior of Kaposi’s sarcoma depends on the epidemiologic type of the disease and the immune status of the host. There have been diverse opinions as to whether Kaposi’s sarcoma represents a reactive vascular proliferation or a true neoplastic prolif- eration. Currently, there is a consensus that Kaposi’s sarcoma does not produce metasta- sis in the manner of conventional sarcomas, but rather it develops in a multifocal fashion (128). This notion is based on the finding of changes in internal organs such as the lymph nodes, gastrointestinal tract, lung, and kidney similar to those seen in the lesions of the patch stage of Kaposi’s sarcoma in the skin. Despite the lack of metastatic potential, patients can succumb to the effects of Kaposi’s sarcoma. Immunocompetent individuals affected with the classic variant of Kaposi’s sarcoma have a mortality rate between 10 and 20% after 10 years, whereas Kaposi’s sarcoma in AIDS patients has a far more aggressive course; the overall mortality rate is 41% and death occurs within a relatively short period of time (129). T REATMENT The treatment of Kaposi’s sarcoma includes local and/or systemic therapy. The appro- priate selection of therapy in each case depends on the epidemiologic variant of the disease, the number of lesions, and the immune status of the patient. In patients with AIDS, new antiretroviral therapies, in particular the protease inhibitors, appear to be changing the clinical course of Kaposi’s sarcoma. Local therapies include liquid nitrogen cryotherapy, radiation therapy, laser therapy, and intradermal therapy with cytotoxic chemotherapy drugs or interferon. Systemic therapies include limited intervention with interferon, with or without zidovudine, and more aggressive intervention with single or multiagent chemotherapy modalities. Therapeutic options for the different clinical set- tings of Kaposi’s sarcoma have been recently reviewed by Tappero et al. (10). The most recent alternatives consist of topical treatment with alitretinoin gel (130), and the admin- istration of liposomal doxorubicin (131) or vinorelbine (132). References 1. Kaposi M. Idiopathisches multiples Pigmentsarkom der Haut. Arch Dermatol Syph 1872;4:265–73. 2. DiGiovanna JJ, Safai B. Kaposi’s sarcoma: retrospective study of 90 cases with particular emphasis on the occurrence, ethnic background, and prevalence of other diseases. Am J Med 1981;71:779–83. 3. Oettle AG. Geographical and racial differences in the frequency of Kaposi’s sarcoma as evidence of environmental or genetic causes. Acta Unio Int Cancer 1962;18:330–63. 4. Gange RW, Wilson Jones E. Kaposi’s sarcoma and immunosuppressive therapy: an appraisal. Clin Exp Dermatol 1978;3:135–46. 5. Centers for Disease Control. Follow-up on Kaposi’s sarcoma and Pneumocystis pneumonia. MMWR 1981;30:409–10. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM230 Chapter 9 / Malignant Neoplasms 231 6. Friedman-Kien L, Lauberstein L, Marmor M, et al. Kaposi’s sarcoma and Pneumocystis pneumonia among homosexual men—New York and California. MMWR 1981;30:305–8. 7. Gottlieb GJ, Ragaz A, Vogel JV, et al. A preliminary communication on extensively disseminated Kaposi’s sarcoma in young homosexual men. Am J Dermatopathol 1981;3:111–4. 8. Gottlieb GJ, Ackerman AB. Kaposi’s Sarcoma: A Text and Atlas. Philadelphia, Lea & Febiger, 1988. 9. Friedman-Kien AE, Saltzman BR. Clinical manifestations of classical, endemic African, and epidemic AIDS-associated Kaposi’s sarcoma. J Am Acad Dermatol 1990;22:1237–50. 10. Tappero JW, Conant MA, Wolfe SF, Berger TG. Kaposi’s sarcoma. Epidemiology, pathogenesis, histology, clinical spectrum, staging criteria and therapy. J Am Acad Dermatol 1993;28:371–95. 11. Chor PJ, Santa Cruz DJ. Kaposi’s sarcoma. A clinicopathologic review and differential diagnosis. J Cutan Pathol 1992;19:6–20. 12. Wabinga HR, Parkin DM, Wabwire-Mangen F, Mugerwa J. Cancer in Kampala, Uganda, in 1989-91: changes in incidence in the era of AIDS. Int J Cancer 1993;54:24–36. 13. Olweny CLM. Epidemiology and clinical features of Kaposi’s sarcoma in tropical Africa. In: Fried- man-Kien AE, Laubenstin LJ, eds. AIDS: The Epidemic of Kaposi’s Sarcoma and Opportunistic Infections. New York, Masson, 1984:35–40. 14. Myers BD, Kessler E, Levi J, et al. Kaposi’s sarcoma in kidney transplant recipients. Arch Intern Med 1974;133:307–11. 15. Harwood AR, Osoba D, Hofstader SL, et al. Kaposi’s sarcoma in recipients of renal transplants. Am J Med 1979;67:759–65. 16. Penn I. Kaposi’s sarcoma in organ transplant recipients. Transplantation 1979;27:8–11. 17. Klein MB, Pereira FA, Kantor I. Kaposi’s sarcoma complicating systemic lupus erythematosus treated with immunosuppression. Arch Dermatol 1974;110:602–4. 18. Kapadia SB, Krause JR. Kaposi’s sarcoma after long-term alkylating agent therapy for multiple myeloma. South Med J 1977;70:1011–3. 19. Leung F, Fam AG, Osoba D. Kaposi’s sarcoma complicating corticosteroid therapy for temporal arteritis. Am J Med 1981;71:320–2. 20. Hoshaw RA, Schwartz RA. Kaposi’s sarcoma after immunosuppressive therapy with prednisone. Arch Dermatol 1980;116:1280–2. 21. Zisbrod Z, Haimov M, Schanzer H, et al. Kaposi’s sarcoma after kidney transplantation: report of complete remission of cutaneous and visceral involvement. Transplantation 1980;30:383–4. 22. Brooks JJ. Kaposi’s sarcoma: a reversible hyperplasia. Lancet 1986;2:1309–11. 23. Beral V, Peterman TA, Berkelman RL, et al. Kaposi’s sarcoma among persons with AIDS: a sexually transmitted infection? Lancet 1990;335:123–8. 24. Couturier E, Ancelle-Park RA, de Vicenzi I, et al. Kaposi’s sarcoma as a sexually transmitted disease. Lancet 1990;335:1105. 25. Dictor M, Bendsoe N. Transmissible agent of Kaposi’s sarcoma. Lancet 1990;335:797. 26. Kitchen VS, French MAH, Dawkins RL. Transmissible agent of Kaposi’s sarcoma. Lancet 1990; 335:797–8. 27. Barry M, Vittecoq D, Liotier JY. Heterosexual transmission of the etiological agent of Kaposi’s sar- coma. Lancet 1991;337:234. 28. Eggers HJ, Weyer J. Linkeage and independence of AIDS and Kaposi’s disease: the interaction of human immunodeficiency virus and some coagents. Infection 1991;19:115–22. 29. Archibald CP, Schecter MT, Craib KJP, et al. Risk factors for Kaposi’s sarcoma in the Vancouver lymphadenopathy-AIDS study. J Acquir Immuno Defic Syndr 1990;3(suppl 1):S18–S23. 30. Jacobson LP, Muñoz A, Phair JP, et al. Incidence of Kaposi’s sarcoma in a cohort of homosexual men infected with the human immunodeficiency virus type I. J Acquir Immuno Defic Syndr 1990;3(suppl 1):S24–S31. 31. Giraldo G, Beth E, Haguenau F. Herpes-type virus particles in tissue culture of Kaposi’s sarcoma from different geographic regions. J Natl Cancer Inst 1972;49:1409–26. 32. Giradlo G, Beth E, Kourilsky FM, et al. Antibody patterns of herpesvirus in Kaposi’s sarcoma: sero- logic associations of European Kaposi’s sarcoma with cytomegalovirus. Int J Cancer 1975;15:839–48. 33. Giraldo G, Beth E, Henle W, et al. Antibody patterns to herpesviruses in Kaposi’s sarcoma. II. Serological association of American Kaposi’s sarcoma with cytomegalovirus. Int J Cancer 1978;22:126–31. 34. Giraldo G, Beth E, Huang ES. Kaposi’s sarcoma and its relationship to cytomegalovirus (CMV). III. CMV DNA and early antigens in Kaposi’s sarcoma. Int J Cancer 1980;26:23–9. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM231 232 Sangüeza and Requena / Pathology of Vascular Skin Lesions 35. Kestens L, Melbye M, Bigger RJ, et al. Endemic African Kaposi’s sarcoma is not associated with immunodeficiency. Int J Cancer 1985;36:49–54. 36. Ambinder RF, Newman C, Hayward GS, et al. Lack of association of cytomegalovirus with endemic African Kaposi’s sarcoma. J Infect Dis 1987;156:193–7. 37. Fiala M, Payme JE, Berne TV, et al. Epidemiology of cytomegalovirus infection after transplantation and immunosuppression. J Infect Dis 1975;132:421–33. 38. Drew WL, Minitz L, Miner RC. Prevalence of cytomegalovirus infection in homosexual men. J Infect Dis 1981;143:188–92. 39. Drew WL, Conant MA, Miner RC, et al. Cytomegalovirus and Kaposi’s sarcoma in young homosexual men. Lancet 1982;2:125–7. 40. Friedman-Kien AE, Laubestein LJ, Rubenstein P, et al. Disseminated Kaposi’s sarcoma in homosexual men. Ann Intern Med 1982;96:693–700. 41. McNutt NS, Fletcher V, Conant MA. Early lesions of Kaposi’s sarcoma in homosexual men: an ultrastructural comparison with other vascular proliferations in skin. Am J Pathol 1983;111:62–77. 42. Minitz L, Drew L, Miner RC, et al. Cytomegalovirus in homosexual men: an epidemiologic study. Ann Intern Med 1983;99:326–9. 43. Drew WL. Sexual transmission of CMV and its relationship to Kaposi’s sarcoma in homosexual men. Birth Defects 1984;20:121–9. 44. Quinnan GV, Masur H, Rook AH, et al. Herpesvirus infections in the acquired immune deficiency syndrome. JAMA 1984;252:72–7. 45. Civantos F, Penneys NS, Haines H. Kaposi’s sarcoma: absence of cytomegalovirus antigens. J Invest Dermatol 1982;79:79–80. 46. Hashimoto H, Muller H, Muller F, et al. In situ hybridization analysis of cytomegalovirus lytic infection in Kaposi’s sarcoma associated with AIDS. Virchows Arch A 1987;411:441–8. 47. Drew WL, Mills J, Hauer LB, et al. Declining prevalence of Kaposi’s sarcoma in homosexual AIDS patients paralleled by fall in cytomegelovirus transmission. Lancet 1988;1:66. 48. Boldogh I, Beth E, Huang ES, Kyalwazi SK, Giraldo K. Kaposi’s sarcoma. IV. Detection of CMV DNA, CMV RNA and CMNA in tumor biopsies. Int J Cancer 1981;28:469–74. 49. Siegal B, Levinton-Kriss S, Schiffer A, et al. Kaposi’s sarcoma in immunosuppression. Possibly the result of a dual viral infection. Cancer 1990;65:492–8. 50. McDougal JK, Nelson JA. Myerson D, Beckmann AM, Galloway DA. HSV, CMV and HPV in human neoplasia. J Invest Dermatol 1984;83:72S–76S. 51. Huang YQ, Li JJ, Rush MG, et al. HPV-16-related DNA sequences in Kaposi’s sarcoma. Lancet 1992;339:515–8. 52. Nickoloff BJ, Huang YQ, Li JJ, et al. Immunohistochemical detection of papillomavirus antigens in Kaposi’s sarcoma. Lancet 1992;339:548–9. 53. Chang Y, Cesarman E, Pessin MS, Lee F, Knowles DM, Moore PS. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 1994;266:1865–9. 54. Neipel F, Albraecht J-C, Fleckenstein B. Human herpes virus 8—the first human Rhadinovirus. Monogr Natl Cancer Inst 1998;23:73–7. 55. Cathomas G, Stalder A, McGandy CE, Mihatsch MJ. Distribution of human herpesvirus 8 DNA in tumorous and nontumorous tissue of patients with acquired immunodeficiency syndrome with and without Kaposi’s sarcoma. Mod Pathol 1998;11:415–20. 56. Dictor M, Rambech E, Way D, et al. Human herpesvirus 8 (Kaposi’s sarcoma-associated herpes virus) DNA in Kaposi’s sarcoma lesions, AIDS Kaposi’s sarcoma cell lines, endothelial Kaposi’s sarcoma simulators, and the skin of immunosuppressed patients. Am J Pathol 1996;148:2009–16. 57. Herman PS, Shogreen LMR, White WL. The evaluation of human herpesvirus 8 (Kaposi’s sarcoma- associated herpesvirus) in cutaneous lesions of Kaposi’s sarcoma: a study of formalin-fixed paraffin- embedded tissue. Am J Dermatopathol 1998;20:7–11. 58. Jin YT, Tsai ST, Yan JJ, et al. Detection of Kaposi’s sarcoma-associated herpesvirus-like DNA sequence in vascular lesions: a reliable diagnostic marker for Kaposi’s sarcoma. Am J Clin Pathol 1996;105:360–3. 59. Li JJ, Huang YQ, Cockerell CJ, Friedman-Kien AE. Localization of human herpes-like virus type 8 in vascular endothelial cells and perivascular spindle shaped cells of Kaposi’s sarcoma lesions by in situ hybridization. Am J Pathol 1996;148:1741–8. 60. Huang YQ, Li JJ, Kaplan MH, et al. Human herpesvirus-like nuclei acid in various forms of Kaposi’s sarcoma. Lancet 1995;345:759–61. 61. Moore PS, Chang Y. Detection of herpesvirus-like DNA sequences in Kaposi’s sarcoma in patients with and without HIV infection. N Engl J Med 1995;332:1181-5. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM232 Chapter 9 / Malignant Neoplasms 233 62. de Lellis L, Fabris M, Cassai E, et al. Herpesvirus-like DNA sequences in non-AIDS Kaposi’s sarcoma. J Infect Dis 1995;172:1605–7. 63. Dupin N, Grandadam M, Calvez V, et al. Herpesvirus-like DNA sequences in patients with Mediter- ranean Kaposi’s sarcoma. Lancet 1995;345:761–2. 64. Chang Y, Zielger J, Wabinga H. Kaposi’s sarcoma-associated herpesvirus and Kaposi’s sarcoma in Africa. Arch Intern Med 1996;156:202–4. 65. Boshoff C, Whitby D, Hatziionnou T, et al. Kaposi’s sarcoma-associated herpesvirus in HIV-negative Kaposi’s sarcoma. Lancet 1995;345:1043–4. 66. Lebbé C, Agbalika F, de Crémoux P, et al. Detection of human herpesvirus 8 and human T-cell lymphotropic virus type 1 sequences in Kaposi’s sarcoma. Arch Dermatol 1997;133:25–30. 67. Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM. Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 1995;332:1186–91. 68. Ansari MQ, Dawson DB, Nador R, et al. Primary body cavity-based AIDS-related lymphomas. Am J Clin Pathol 1996;105:221–9. 69. Soulier J, Grollet L, Oksenhendler E, et al. Kaposi’s sarcoma associated herpesvirus-like DNA sequences in multicentric Castleman’s disease. Blood 1995;86:1276–80. 70. Rady PL, Yen A, Rollefson JL, et al. Herpesvirus-like DNA sequences in non-Kaposi’s sarcoma skin lesions of transplants patients. Lancet 1995;345:1339–40. 71. Gottlieb GJ, Ackerman AB. Kaposi’s sarcoma: an extensively disseminated form in young homosexual men. Hum Pathol 1982;13:882–92. 72. Ficarra G, Berson AM, Silverman S, et al. Kaposi’s sarcoma of the oral cavity: a study of 134 patients with a review of the pathogenesis, epidemiology, clinical aspects, and treatment. Oral Surg Oral Med Oral Pathol 1988;66:543–50. 73. McKenzie R, Travis WD, Dolan SA, et al. The causes of death in patients with human immunodefi- ciency virus infection: a clinical and pathologic study with emphasis on the role of pulmonary diseases. Medicine 1991;70:326–43. 74. Francis ND, Parkin JM, Weber J, Boylston AW. Kaposi’s sarcoma in acquired immune deficiency syndrome (AIDS). J Clin Pathol 1986;39:469–74. 75. Bergfeld WF, Zemtsov A, Lang RS. Differentiation between AIDS-related and non-AIDS related Kaposi’s sarcoma. Cleve Clin J Med 1987;54:315–9. 76. Santucci M, Pimpinelli N, Moretti S, Gianotti B. Classic and immunodeficiency-associated Kaposi’s sarcoma: clinical, histologic, and immunologic correlations. Arch Pathol Lab Med 1988;12:1214–20. 77. Niedt GW, Myskowski PL, Urmacher C, Niedzwiecki D, Chapman D, Safai B. Histology of early lesions of AIDS associated Kaposi’s sarcoma. Mod Pathol 1990;3:64–70. 78. Ackerman AB. Subtle clues to diagnosis by conventional microscopy: the patch stage of Kaposi’s sarcoma. Am J Dermatopathol 1979;1:165–72. 79. Schwartz JL, Muhlbauer JE, Steiqbigel RT. Pre-Kaposi’s sarcoma. J Am Acad Dermatol 1984;11:377–80. 80. DeDobbeler G, Godfrine S, Andre J, et al. Clinically uninvolved skin in AIDS: evidence of atypical dermal vessels similar to early lesions observed in Kaposi’s sarcoma. Ultrastructural study of four patients. J Cutan Pathol 1987;14:154–7. 81. Enzinger FM, Weiss SW. Malignant vascular tumors. In: Soft Tissue Tumors, 3rd ed. St. Louis, MO, Mosby, 1995:641–77. 82. Massarelli G, Scott CA, Mura A, et al. Hyaline bodies in Kaposi’s sarcoma: an immunocytochemical and ultrastructural study. Appl Pathol 1989;7:26–33. 83. Kao GF, Johnson FB, Sulica VI. The nature of hyaline (eosinophilic) globules and vascular slits of Kaposi’s sarcoma. Am J Dermatopathol 1990;12:256–67. 84. Furunaga M, Silverberg SG. Hyaline globules in Kaposi’s sarcoma: a light microscopic and immuno- histochemical study. Mod Pathol 1991;4:187–90. 85. Aziz DC, Srolovitz HD, Brisson ML, Begin LR. Characterization of eosinophilic hyaline bodies in Kaposi’s sarcoma. Lab Invest 1995;52:4A. 86. Ronchense F, Kern AB. Lymphangioma-like tumors in Kaposi’s sarcoma. Arch Dermatol 1957;75:418–28. 87. Gange RW, Wilson Jones E. Lymphangioma-like tumors in Kaposi’s sarcoma. Br J Dermatol 1979;100:327–34. 88. Leibowitz MR, Dagliotti M, Smith E, et al. Rapidly fatal lymphangioma-like Kaposi’s sarcoma. His- topathology 1980;4:559–66. 89. Recht B, Nickoloff BJ, Wood GS. A bullous variant of Kaposi’s sarcoma in an elderly female. J Derm Surg Oncol 1986;12:1192–7. 09/Sangüeza/217-274/F 01/16/2003, 10:12 AM233 [...]... DNA sequences of HHV -8 were detected in an example of retiform 09/Sangüeza/21 7-2 74/F 245 01/16/2003, 10:12 AM 246 Sangüeza and Requena / Pathology of Vascular Skin Lesions Fig 15 Clinical features of retiform hemangioendothelioma (A) Multiple violaceous nodules grouped in a plaque (B) Close-up view shows the angiomatous appearance of some of the nodules hemangioendothelioma in a 73-year-old woman with... Over- 09/Sangüeza/21 7-2 74/F 253 01/16/2003, 10:12 AM 254 09/Sangüeza/21 7-2 74/F Sangüeza and Requena / Pathology of Vascular Skin Lesions 254 01/16/2003, 10:12 AM Chapter 9 / Malignant Neoplasms 255 expression of basic fibroblastic growth factor (41), angiopoietin-2, Tie-1 and Tie-2 mRNA receptors of the endothelium (42), and Ets-1 protooncogene and metalloproteinase genes such as collagenase-1 (MMP-1)... angioendothelioma of the skin Br J Dermatol 1964;76:21–39 3 Rosai J, Sumner HW, Major MC, Kostianovsky M, Perez Mesa C Angiosarcoma of the skin A clinicopathologic and fine structural study Hum Pathol 1976;7 :8 3-1 09 4 Cooper PH Angiosarcomas of the skin Semin Diagn Pathol 1 987 ;4:2–17 5 Maddox JC, Evans HL Angiosarcoma of skin and soft tissue A study of forty-four cases Cancer 1 981 ; 48: 1907–21 6 Holden... angiosarcoma involving the nose The lesion consists of an illdefined bruise-like area that simulates a hematoma 09/Sangüeza/21 7-2 74/F 251 01/16/2003, 10:12 AM 252 Sangüeza and Requena / Pathology of Vascular Skin Lesions Fig 18 Early stage of angiosarcoma involving the scalp The lesion appears as an ill-circumscribed area of erythema strong evidence of a link to HHV -8 , there seems to be is no association with... Requena / Pathology of Vascular Skin Lesions lymph node metastases, and one of these patients later died of widespread pulmonary metastases ( 18) References 1 Dabska M Malignant endovascular papillary angioendothelioma of the skin in childhood Clinicopathologic study of 6 cases Cancer 1969;24:503–10 2 de Dulanto F, Armijo Moreno M Malignant endovascular papillary hemangioendothelioma of the skin Acta... Kaposi’s sarcoma Science 1 989 ;243:1736–7 120 Nickoloff BJ, Griffiths CEM The spindle-shaped cells in cutaneous Kaposi’s sarcoma Am J Pathol 1 989 ;135:793 80 0 121 Lymboussaki A, Partanen TA, Olofsson B, et al Expression of vascular endothelium growth factor C receptor VEGFR-3 in lymphatic endothelium of the skin and in vascular tumors Am J Pathol 19 98; 153:395–403 122 Jussila L, Valtola R, Partanen TA, et al... Weiss LM Absence of Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in malignant vascular tumors of the serous membranes Mod Pathol 1996;9:1143–6 17 Li N, Anderson WK, Bhawan J Further confirmation of the association of human herpesvirus 8 with Kaposi’s sarcoma J Cutan Pathol 1 988 ;25:413–9 18 Lasota J, Miettinen M Absence of Kaposi’s sarcoma-associated virus (human herpesvirus -8 ) sequences in... hemangioendothelioma A distinctive form of low-grade angiosarcoma delineated in a series of 15 cases Am J Surg Pathol 1994; 18: 115–25 2 Fukunaga M, Endo Y, Masui F, Yoshikawa T, Ishikawa E, Ushigome S Retiform haemangioendothelioma Virchows Arch 1996;4 28: 301–4 09/Sangüeza/21 7-2 74/F 247 01/16/2003, 10:12 AM 2 48 Sangüeza and Requena / Pathology of Vascular Skin Lesions Fig 16 (C) These elongated vascular channels are lined... Vascular endothelial growth factor receptor-3 (VEGFR-3): a marker of vascular tumors with presumed lymphatic differentiation, including Kaposi’s sarcoma, kaposiform and Dabska-type hemangioendotheliomas, and a subset of angiosarcomas Mod Pathol 2000;13: 180 –5 09/Sangüeza/21 7-2 74/F 249 01/16/2003, 10:12 AM 250 Sangüeza and Requena / Pathology of Vascular Skin Lesions 5 COMPOSITE HEMANGIOENDOTHELIOMA CLINICAL... endothelial growth factor receptor-3 (VEGFR-3): a marker of vascular tumors with presumed lymphatic differentiation, including Kaposi’s sarcoma, kaposiform and Dabska-type hemangioendotheliomas, and a subset of angiosarcomas Mod Pathol 2000;13: 180 –5 16 Fukunaga M Endovascular papillary angioendothelioma (Dabska tumor) Pathol Int 19 98; 48: 840–1 17 Calonje E, Fletcher CDM, Wilson-Jones E, Rosai J Retiform hemangioendothelioma . anterior chest of an adult man. 09/Sangüeza/21 7-2 74/F 01/16/2003, 10:12 AM237 2 38 Sangüeza and Requena / Pathology of Vascular Skin Lesions 09/Sangüeza/21 7-2 74/F 01/16/2003, 10:12 AM2 38 Chapter 9. formalin-fixed paraffin- embedded tissue. Am J Dermatopathol 19 98; 20:7–11. 58. Jin YT, Tsai ST, Yan JJ, et al. Detection of Kaposi’s sarcoma-associated herpesvirus-like DNA sequence in vascular lesions: . AIDS-related Kaposi’s sarcoma: results of a phase II study. J Clin Oncol 2000; 18: 1550–7. 09/Sangüeza/21 7-2 74/F 01/16/2003, 10:12 AM235 236 Sangüeza and Requena / Pathology of Vascular Skin Lesions 2.