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Angiosarcoma arising in Kaposi's sarcoma (pleomorphic Kaposi's sarcoma) in a patient with human immunodeficiency virus disease
790 Brief communications Discussion. A nonscalp hair infection by a dermatophyte is unusuaL It has been postulated that hairs in a resting state, such as those found in glabrous skin, do not provide a "suitable substrate" for fungal growth. 2 In fact, hairs that are not actively growing at the time of follicular invasion are not susceptible. 2 Cell-mediated immunity may playa role in inhibiting club or vellus hair infection. Perhaps hair infection represents a balance between the "substrate" available in actively growing scalp hairs and the inhibitory effects produced by the immune system. A less likely possibility is that human immunodeficiency virus infection directly affects the composition of hair and thus more easily permits infection. In this case, we hypothesize that a compromised immune system allowed thefungus to grow in thepresenceofa reduced "substrate." REFERENCES 1. Graham JH. Superficial fungus infections. In: Graham JR, Johnson we, Helwig EB, eels. Dermal pathology. New York: Harper & Row, 1972:137-253. 2. Kligman AM. Tinea capitis due to Microsporum audouinii and Microsporum canis. II. Dynamics of the host-parasite relationship. Arch Dermatol 1955;71:313-37.
Angiosarcoma arising in Kaposi's sarcoma (pleomorphic Kaposi's sarcoma) in a patient with human immunodeficiency virus disease Kathleen J. Smith, LTC, MC, USA,a Henry G. Skelton III, CDR, MC, USN,b William D. James, COL, MC, USA,d Terry L. Barrett, MD,c David W. Anderson, MAJ, MC, USA,a Peter Angritt, COL, MC, USA,c and the Armed Forces Retroviral Research Group lA Jolla, California. and Washington, D.C. In addition to the familiar patch, plaque, and nodular stages of Kaposi's sarcoma (KS) that are seen in patients infected with the human immunodeficiency virus (HIV), From the Walter Reed Army Institute of Research," the Armed Forces Institute of Pathology Department of Dermato!ogy,b and the AIDS Registry" of the Scripps Clinic, La Jolla; and from the Department of Dermatology,d Walter Reed Army Medical Center, Washington. The opinions or assertions contained herein are the private views of the authors and are not to be considered as official or as reflecting the views of the Department of the Army. and Department of the Navy, or the Department of Defense. Reprint requests: Henry G. Skelton III, CDR, MC, USN, Armed Forces Institute of Pathology (AFIP), Department of Dermatopathology, Washington, DC 20307.
16/4/26889
Journal of the American Academy of Dermatology
Fig. 1. Proliferation of tumor involving distal half of penis 1 month after surgical removal of foreskin.
and in older persons of Mediterranean background, other forms of KS have been classified by epidemiology, clinical pattern, and histologic pattern. Epidemiologic forms include sporadic or classic KS; endemic KS, which existed before the appearance of AIDS in eastern equtorial Africa: iatrogenic or transplantation-associated KS; and epidemic KS, associated with HIV disease. Clinical patterns of KS have been divided into localized skin involvement, with subcategories of early (or macular), nodular, and aggressive forms, and generalized involvement, with subcategories of lymphadenopathic and systemic forms. l , 2 The pleomorphic variant of KS is rare; it shows marked cytologic atypia and a high mitotic rate. Pleomorphic KS has been reported primarily in endemic KS from Africa and rarely in sporadic KS oflong duration. It has a rapidly progressive clinical course. 3•S However, a majority of clinically aggressive lesions do not show the pleomorphic pattern. 5 Pleomorphic KS is often difficult to distinguish from other pleomorphic malignant neoplasms except for the presence of focal areas of typical KS.5 Case report. A 34-year-old black man who tested positive for HIV (Walter Reed stage 5) had penile lesions and swelling of several months' duration. 6 The penile lesions were papular, and a diagnosis of condyloma with phimosis was made. After elective circumcision, no evidence of healing occurred during the next month. The distal half of the penis was covered by a firm area of granulation-like tissue (Fig. I). After histopathologic examination of the circumcision specimen, the diagnosis was pleomorphic KS with features of angiosarcoma and condylomatous changes in the epidermis with epithelial dysplasia. Evaluation for metastases revealed enlarged inguinal lymph nodes that continued to enlarge during the hospitalization. The patient refused permission for examination of the bladder and inguinal nodes. The patient elected to have a partial penectomy because of increasing pain and difficulty urinating. Approximately 3 weeks after surgery the patient had a reticular-nodular pulmonary infiltrate, but he refused further hospitalization and died 2 days later. Permission for an autopsy was not given.
Volume 24 Number 5, Part 1 May 1991
Briefcommunications 791
Fig. 2. Pleomorphic endothelial cells dissect collagen. (XI50.) Histopathologic examination of the circumcision specimen showed areas of mild to severe epithelial dysplasia with koilocytotic cells in the epidermis of the foreskin ofthe original excision. Extending from the papillary dermis deep into the subcutaneous tissue was a proliferation of plump, pleomorphic epithelioid to spindle-shaped cells, some with hyperchromatic nuclei and prominent nucleoli and up to 2 to 3 mitoses per high-power field. In some areas pleomorphic endothelial cells dissected through collagen, forming angulated vascular channels that contained RBCs (Fig. 2). Focal areas showed more bland cells forming a mixed pattern of KS (Fig. 3). Eosinophilic globules were also found throughout the lesion. The penectomy specimen showed similar histologic changes, with the tumor extending to the proximal surgical margin and through the urethra. In addition, there were sinusoidal structures lined by pleomorphic hyperchromatic cells, with focal piling up along the lumen. The diagnosis was angiosarcoma with features of KS.
Discussion. Angiosarcoma clinically suggestive of KS has been reported in a homosexual man suspected ofhaving acquired immune deficiency syndrome (AIDS).? Cutaneous angiosarcomas are aggressive and lead to death from local extension or metastasis in a majority ofpatients with tumors more than 5 cm in diameter. 8 In KS, however, local disease may have a protracted course. The tumors may respond to chemotherapy, radiation therapy, or immunotherapy. When widespread, KS is thought to be multicentric in origin. Patients with sporadic KS have survival rates of 10 to 15 years and may die of a secondary malignancy.9 The multicentric nature of the process, rather than a tendency towards metastasis, is associated with a poor prognosis.9 In epidemic cases, KS was found to be the sole cause of death in only 12% of the patients in one study.9 The differences between the clinical behavior of angiosarcoma and KS, and the lack of many of the cytologic features of malignancy in KS, have raised the question of whether KS is malignant. Besides rarely showing me-
Fig. 3. More bland endothelial cells form a mixed pattern of Kaposi's sarcoma. (X75.)
tastasis, KS may spontaneously regress--especially in iatrogenic KS, when immunosuppression is stopped. Attempts to grow tumor cells of KS in continuous cell cultures have been unsuceessfu1. 9 Thus KS is believed by some to represent a multicentric angioproliferative disorder in which an additional oncogenic event may be necessary to produce a fully malignant phenotype. Although the lesion we studied showed features of KS in some areas, the marked cytologic atypia, the high mitotic rate, and the growth pattern are more consistent with angiosarcoma. We therefore believe that this lesion represents a malignant tumor arising in association with KS and is similar to lesions previously diagnosed as pleomorphic KSJ For this reason we prefer the term angiosarcoma (or malignant spindle cell neoplasm if less differentiated) arising in a lesion of KS because this diagnosis is more informative for treatment and prognosis. The existence of pleomorphic KS and angiosarcoma in HIVinfected patients is not well documented, in spite of the frequency ofKS. 3, 4,9 With the increasing survival rate of HIV-infected patients with KS, there exists an increased chance that, through exposure to other co-carcinogens or
792 Brief communications by random genetic events, more lesions may express a fully malignant phenotype. REFERENCES 1. Templeton AC. Kaposi's sarcoma. Pathol Ann 1981;2:31536. 2. Reynolds WA, Winkleman RK, Soule EH. KS: a clinicopathologicstudy with particular reference to its relationship to the reticuloendothelial system. Medicine (alt), 1965;44: 419-43. 3. Cox PH, Helwig EG. Kaposi's sarcoma. Cancer 1959; 12:289-98. 4. Templeton AC. Studies in KS. Postmortem findings and disease pattern in women. Cancer 1972;30:854-67. 5. Zeigler JL, Dorfman RE. Kaposi's sarcoma: pathophysiology and conical management. New York: Marcel Dekker, 1988. 6. Redfield RR. The clinical, research, and public health applications of the WaIter Reed staging classification ofHIY infections. Third International Conferenceon AIDS. Washington DC M.11.1;8:1986. 7. Schwart RA, Kardashian JP, McNutt NS, et aI. Cutaneous angiosarcoma resembling KS in a homosexual man. Cancer 1983;51:721-6. 8. Enzinger PM, Weiss SW. Soft tissue tumors: St. Louis: CY Mosby, 1988;533-80. 9. Harawi S. Kaposi's sarcoma in: Harawi SI, O'Hara CJ, eds. Pathology and pathophysiology of AIDS and HIYrelated diseases. London: Chapman and Hall Ltd., 1989:83133.
Lichen planus and hepatitis C virus M. Mokni,a M. Rybojad,a D. Puppin, Jr.,a S. Catala,a F. Venezia,b RDjian,b and P. Morela Paris, Fraru:e The frequency and the specificity of a possible clinical relation betweenlichen planus (LP) and liver disease have been reviewed recently,l-4 A multicenter case control study5 showed that increased alanine aminotransferase and aspartate aminotransferase activities and a positive test for hepatitis B virus surface antigen approximately doubled the risk of lichen planus. In addition, the same study noted that the increased risk of LP in patients with liver disorders (high transaminase activities) is still significant after adjustment for the presence of hepatitis B virus surface antigen and a history of viral hepatitis. The authors suggested that there may be an indirect relation between LP and other hepatotropic viruses that are posFrom the Departments of Dermatology' and Gastro-enterology,b Saint-Louis Hospital. Reprint requests: Pro P. Morel, Clinique Dermatologique, Hopital Saint-Louis, 75475 Paris Cedex 10, France. 16/4/27455
Journal of the American Academy of Dermatology
sibly transmitted in a similar manner to hepatitis B virus such as non-A, non-B hepatitis, cytomegalovirus, and Epstein-Barr virus. We report a patient in whom LP developed during chronic hepatitis, probably in response to the hepatitis C virus (HCV). Case report. In 1980, a 33-year-old man addicted to heroin was found to have increased transaminase levels. These levels have persisted and have intermittently increased in value. In 1989 itchy, flat-topped violaceous papules appeared on the patient's arms and rapidly spread to the trunk. A biopsy specimen confirmed the diagnosis of LP. Values from laboratory studies in 1989 were as follows: aspartate aminotransferase, 102 U/L (normal 4 to 27 U/L; alanine aminotransferase, 50 U/L (normal 4 to 27 U/L); gammaglobulinemia, 13 gm/L (normal 11 to 15 gm/L); albuminemia, 47 gm/L (normal 40 gm/L). AntiHBc and anti-HCY tests (Ortho HCY ELISA) were positive. Antinuclear, antimitochondria, and anti-smooth muscle antibody tests were negative. Serologic tests for human immunodeficiency virus types 1 and 2 were also negative. A biopsy specimen of the liver was consistent with chronic active hepatitis.
Discussion. Our patient appears to have an HCVrelated hepatitis. Chronic hepatitis B can be excluded because, except for a positive anti-HBc antibody, all markers·of HBV infection were absent. The specificity of enzyme immunoassay for antibodies against HCV has been recently questioned in patients with autoimmune chronic active hepatitis and hypergammaglobulinemia. 6 However, these conditions were absent in our patient, who had none of the autoantibodies usually found in autoimmune hepatitis. He also had normal serum globulin and IgG concentrations. The occurrence of LP in a patient with HCV hepatitis may be coincidental. To our knowledge this is the first such observation reported. We would be interested to know the incidence of LP in HCV hepatitis. This might be achieved by examining drug addicts both prospectively and retrospectively because a large percentage of them are infected with HCV. REFERENCES 1. Rebora A, Rongioletti P. Lichen planus and chronic active hepatitis. A retrospective survey. Acta Derm Venereol (Stockh) 1984;64:52-6. 2. Mobacken H, Nilsson LA, Olsson R, et al. Incidence ofliver disease in chronic lichen planus of the mouth. Acta Derm Venereol (Stockh) 1984;64:70-3. 3. Monk BE. Lichen planus and the liver [Letter]. J AM ACAD DERMATOL 1985;12:122-3. 4. Korkij W, Chuang TY, Soltani K. Liver abnormalities in patients with lichen planus. A retrospective case-control study. J AM ACAD DERMATOL 1984;11:609-15. 5. Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED). Lichen planus and liver diseases: a multicentric case-control study. Br Med J 1990;300:227-30. 6. McFarlane IG, Smith HM, Johnson PJ, et aI. Hepatitis C virus antibodies in chronic active hepatitis: pathogenic factor or false-positive result? Lancet 1990;335:754-7.
Angiosarcoma arising in Kaposi's sarcoma (pleomorphic Kaposi's sarcoma) in a patient with human immunodeficiency virus disease Kathleen J. Smith, LTC, MC, USA,a Henry G. Skelton III, CDR, MC, USN,b William D. James, COL, MC, USA,d Terry L. Barrett, MD,c David W. Anderson, MAJ, MC, USA,a Peter Angritt, COL, MC, USA,c and the Armed Forces Retroviral Research Group lA Jolla, California. and Washington, D.C. In addition to the familiar patch, plaque, and nodular stages of Kaposi's sarcoma (KS) that are seen in patients infected with the human immunodeficiency virus (HIV), From the Walter Reed Army Institute of Research," the Armed Forces Institute of Pathology Department of Dermato!ogy,b and the AIDS Registry" of the Scripps Clinic, La Jolla; and from the Department of Dermatology,d Walter Reed Army Medical Center, Washington. The opinions or assertions contained herein are the private views of the authors and are not to be considered as official or as reflecting the views of the Department of the Army. and Department of the Navy, or the Department of Defense. Reprint requests: Henry G. Skelton III, CDR, MC, USN, Armed Forces Institute of Pathology (AFIP), Department of Dermatopathology, Washington, DC 20307.
16/4/26889
Journal of the American Academy of Dermatology
Fig. 1. Proliferation of tumor involving distal half of penis 1 month after surgical removal of foreskin.
and in older persons of Mediterranean background, other forms of KS have been classified by epidemiology, clinical pattern, and histologic pattern. Epidemiologic forms include sporadic or classic KS; endemic KS, which existed before the appearance of AIDS in eastern equtorial Africa: iatrogenic or transplantation-associated KS; and epidemic KS, associated with HIV disease. Clinical patterns of KS have been divided into localized skin involvement, with subcategories of early (or macular), nodular, and aggressive forms, and generalized involvement, with subcategories of lymphadenopathic and systemic forms. l , 2 The pleomorphic variant of KS is rare; it shows marked cytologic atypia and a high mitotic rate. Pleomorphic KS has been reported primarily in endemic KS from Africa and rarely in sporadic KS oflong duration. It has a rapidly progressive clinical course. 3•S However, a majority of clinically aggressive lesions do not show the pleomorphic pattern. 5 Pleomorphic KS is often difficult to distinguish from other pleomorphic malignant neoplasms except for the presence of focal areas of typical KS.5 Case report. A 34-year-old black man who tested positive for HIV (Walter Reed stage 5) had penile lesions and swelling of several months' duration. 6 The penile lesions were papular, and a diagnosis of condyloma with phimosis was made. After elective circumcision, no evidence of healing occurred during the next month. The distal half of the penis was covered by a firm area of granulation-like tissue (Fig. I). After histopathologic examination of the circumcision specimen, the diagnosis was pleomorphic KS with features of angiosarcoma and condylomatous changes in the epidermis with epithelial dysplasia. Evaluation for metastases revealed enlarged inguinal lymph nodes that continued to enlarge during the hospitalization. The patient refused permission for examination of the bladder and inguinal nodes. The patient elected to have a partial penectomy because of increasing pain and difficulty urinating. Approximately 3 weeks after surgery the patient had a reticular-nodular pulmonary infiltrate, but he refused further hospitalization and died 2 days later. Permission for an autopsy was not given.
Volume 24 Number 5, Part 1 May 1991
Briefcommunications 791
Fig. 2. Pleomorphic endothelial cells dissect collagen. (XI50.) Histopathologic examination of the circumcision specimen showed areas of mild to severe epithelial dysplasia with koilocytotic cells in the epidermis of the foreskin ofthe original excision. Extending from the papillary dermis deep into the subcutaneous tissue was a proliferation of plump, pleomorphic epithelioid to spindle-shaped cells, some with hyperchromatic nuclei and prominent nucleoli and up to 2 to 3 mitoses per high-power field. In some areas pleomorphic endothelial cells dissected through collagen, forming angulated vascular channels that contained RBCs (Fig. 2). Focal areas showed more bland cells forming a mixed pattern of KS (Fig. 3). Eosinophilic globules were also found throughout the lesion. The penectomy specimen showed similar histologic changes, with the tumor extending to the proximal surgical margin and through the urethra. In addition, there were sinusoidal structures lined by pleomorphic hyperchromatic cells, with focal piling up along the lumen. The diagnosis was angiosarcoma with features of KS.
Discussion. Angiosarcoma clinically suggestive of KS has been reported in a homosexual man suspected ofhaving acquired immune deficiency syndrome (AIDS).? Cutaneous angiosarcomas are aggressive and lead to death from local extension or metastasis in a majority ofpatients with tumors more than 5 cm in diameter. 8 In KS, however, local disease may have a protracted course. The tumors may respond to chemotherapy, radiation therapy, or immunotherapy. When widespread, KS is thought to be multicentric in origin. Patients with sporadic KS have survival rates of 10 to 15 years and may die of a secondary malignancy.9 The multicentric nature of the process, rather than a tendency towards metastasis, is associated with a poor prognosis.9 In epidemic cases, KS was found to be the sole cause of death in only 12% of the patients in one study.9 The differences between the clinical behavior of angiosarcoma and KS, and the lack of many of the cytologic features of malignancy in KS, have raised the question of whether KS is malignant. Besides rarely showing me-
Fig. 3. More bland endothelial cells form a mixed pattern of Kaposi's sarcoma. (X75.)
tastasis, KS may spontaneously regress--especially in iatrogenic KS, when immunosuppression is stopped. Attempts to grow tumor cells of KS in continuous cell cultures have been unsuceessfu1. 9 Thus KS is believed by some to represent a multicentric angioproliferative disorder in which an additional oncogenic event may be necessary to produce a fully malignant phenotype. Although the lesion we studied showed features of KS in some areas, the marked cytologic atypia, the high mitotic rate, and the growth pattern are more consistent with angiosarcoma. We therefore believe that this lesion represents a malignant tumor arising in association with KS and is similar to lesions previously diagnosed as pleomorphic KSJ For this reason we prefer the term angiosarcoma (or malignant spindle cell neoplasm if less differentiated) arising in a lesion of KS because this diagnosis is more informative for treatment and prognosis. The existence of pleomorphic KS and angiosarcoma in HIVinfected patients is not well documented, in spite of the frequency ofKS. 3, 4,9 With the increasing survival rate of HIV-infected patients with KS, there exists an increased chance that, through exposure to other co-carcinogens or
792 Brief communications by random genetic events, more lesions may express a fully malignant phenotype. REFERENCES 1. Templeton AC. Kaposi's sarcoma. Pathol Ann 1981;2:31536. 2. Reynolds WA, Winkleman RK, Soule EH. KS: a clinicopathologicstudy with particular reference to its relationship to the reticuloendothelial system. Medicine (alt), 1965;44: 419-43. 3. Cox PH, Helwig EG. Kaposi's sarcoma. Cancer 1959; 12:289-98. 4. Templeton AC. Studies in KS. Postmortem findings and disease pattern in women. Cancer 1972;30:854-67. 5. Zeigler JL, Dorfman RE. Kaposi's sarcoma: pathophysiology and conical management. New York: Marcel Dekker, 1988. 6. Redfield RR. The clinical, research, and public health applications of the WaIter Reed staging classification ofHIY infections. Third International Conferenceon AIDS. Washington DC M.11.1;8:1986. 7. Schwart RA, Kardashian JP, McNutt NS, et aI. Cutaneous angiosarcoma resembling KS in a homosexual man. Cancer 1983;51:721-6. 8. Enzinger PM, Weiss SW. Soft tissue tumors: St. Louis: CY Mosby, 1988;533-80. 9. Harawi S. Kaposi's sarcoma in: Harawi SI, O'Hara CJ, eds. Pathology and pathophysiology of AIDS and HIYrelated diseases. London: Chapman and Hall Ltd., 1989:83133.
Lichen planus and hepatitis C virus M. Mokni,a M. Rybojad,a D. Puppin, Jr.,a S. Catala,a F. Venezia,b RDjian,b and P. Morela Paris, Fraru:e The frequency and the specificity of a possible clinical relation betweenlichen planus (LP) and liver disease have been reviewed recently,l-4 A multicenter case control study5 showed that increased alanine aminotransferase and aspartate aminotransferase activities and a positive test for hepatitis B virus surface antigen approximately doubled the risk of lichen planus. In addition, the same study noted that the increased risk of LP in patients with liver disorders (high transaminase activities) is still significant after adjustment for the presence of hepatitis B virus surface antigen and a history of viral hepatitis. The authors suggested that there may be an indirect relation between LP and other hepatotropic viruses that are posFrom the Departments of Dermatology' and Gastro-enterology,b Saint-Louis Hospital. Reprint requests: Pro P. Morel, Clinique Dermatologique, Hopital Saint-Louis, 75475 Paris Cedex 10, France. 16/4/27455
Journal of the American Academy of Dermatology
sibly transmitted in a similar manner to hepatitis B virus such as non-A, non-B hepatitis, cytomegalovirus, and Epstein-Barr virus. We report a patient in whom LP developed during chronic hepatitis, probably in response to the hepatitis C virus (HCV). Case report. In 1980, a 33-year-old man addicted to heroin was found to have increased transaminase levels. These levels have persisted and have intermittently increased in value. In 1989 itchy, flat-topped violaceous papules appeared on the patient's arms and rapidly spread to the trunk. A biopsy specimen confirmed the diagnosis of LP. Values from laboratory studies in 1989 were as follows: aspartate aminotransferase, 102 U/L (normal 4 to 27 U/L; alanine aminotransferase, 50 U/L (normal 4 to 27 U/L); gammaglobulinemia, 13 gm/L (normal 11 to 15 gm/L); albuminemia, 47 gm/L (normal 40 gm/L). AntiHBc and anti-HCY tests (Ortho HCY ELISA) were positive. Antinuclear, antimitochondria, and anti-smooth muscle antibody tests were negative. Serologic tests for human immunodeficiency virus types 1 and 2 were also negative. A biopsy specimen of the liver was consistent with chronic active hepatitis.
Discussion. Our patient appears to have an HCVrelated hepatitis. Chronic hepatitis B can be excluded because, except for a positive anti-HBc antibody, all markers·of HBV infection were absent. The specificity of enzyme immunoassay for antibodies against HCV has been recently questioned in patients with autoimmune chronic active hepatitis and hypergammaglobulinemia. 6 However, these conditions were absent in our patient, who had none of the autoantibodies usually found in autoimmune hepatitis. He also had normal serum globulin and IgG concentrations. The occurrence of LP in a patient with HCV hepatitis may be coincidental. To our knowledge this is the first such observation reported. We would be interested to know the incidence of LP in HCV hepatitis. This might be achieved by examining drug addicts both prospectively and retrospectively because a large percentage of them are infected with HCV. REFERENCES 1. Rebora A, Rongioletti P. Lichen planus and chronic active hepatitis. A retrospective survey. Acta Derm Venereol (Stockh) 1984;64:52-6. 2. Mobacken H, Nilsson LA, Olsson R, et al. Incidence ofliver disease in chronic lichen planus of the mouth. Acta Derm Venereol (Stockh) 1984;64:70-3. 3. Monk BE. Lichen planus and the liver [Letter]. J AM ACAD DERMATOL 1985;12:122-3. 4. Korkij W, Chuang TY, Soltani K. Liver abnormalities in patients with lichen planus. A retrospective case-control study. J AM ACAD DERMATOL 1984;11:609-15. 5. Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED). Lichen planus and liver diseases: a multicentric case-control study. Br Med J 1990;300:227-30. 6. McFarlane IG, Smith HM, Johnson PJ, et aI. Hepatitis C virus antibodies in chronic active hepatitis: pathogenic factor or false-positive result? Lancet 1990;335:754-7.