AIDS-associated Kaposi's sarcoma

In less than two decades, the disease mechanisms have been elucidated and hypotheses for innovative treatment have been developed. Our understanding of the sarcoma's pathogenesis has led directly to general knowledge of the physiology and pathology of angiogenesis. Hence, it can be expected that new treatments for all cancer patients may someday emerge from clinical intervention trials for the AIDS-related disease.     

Pathogenesis of HIV-related Kaposi's sarcoma

Infection with HIV-1 is associated with a 7000-fold increase in the incidence of Kaposi's sarcoma (KS). Some studies suggest that the risk of KS in HIV infection is increased with certain sexual practices and that a sexually transmitted agent could be involved. Exposure to this agent apparently alters both the morphology and growth regulation of the KS progenitor cells. These changes include the expression of the different cytokine receptors and the acquisition of autocrine growth loops. Perturbations of multiple cytokines during HIV infection, including oncostatin-M, interleukin-1 beta, and tumor necrosis factor-alpha, alter the subsequent growth of KS. These studies suggest that control of cytokine perturbations or the underlying HIV-1 infection could result in a significant reduction in the growth rate of AIDS-related KS.     

Kaposi's sarcoma of the ocular adnexa

During the last 15 years, KS has been elevated from a position of only limited academic interest to the distinction of being the most common malignancy seen in HIV-infected patients. Ophthalmologists need to become versed in the proper diagnosis and management of this condition, as ocular involvement may be seen in up to 1 in 5 patients with KS. The possibility of occult HIV disease should be entertained in a young person with an atypical hordeolum or subconjunctival hemorrhage, as KS sometimes mimics these common lesions and represents the initial presenting sign of AIDS. The patient with ocular lesions must also be evaluated appropriately for life-threatening visceral disease. Current concepts regarding the pathogenesis of KS center on a model in which an initial event, possibly infection by human herpesvirus 8, transforms normal mesenchymal cells such that they become abnormally sensitive to the high levels of cytokines present during HIV infection. Subsequent proliferation and additional mutational events result in clinically apparent disease. Present treatments include systemic chemotherapy for widespread disease and local methods such as excision, cryotherapy, radiotherapy, and intralesional injection. However, the majority of ocular lesions may be followed up with observation only. The appropriate strategy to pursue depends on the overall clinical scenario, including the patient's general health, the extent of disease, the degree of morbidity secondary to local ocular tumors, and the size of the lesions to be treated. Future therapeutic options will be aimed at modulating specific pathogenetic factors responsible for tumor development, including host cytokines, viral replication factors, and angiogenic mediators.     

The therapeutic effect of intralesional interferon in classical Kaposi's sarcoma

Interferon alpha-2a, which has antineoplastic, antiviral, immunomodulatory, and antiangiogenic effects, was evaluated in a prospective study, treating 10 lesions of patients with classical Kaposi's sarcoma. Ten patients received injections of interferon alpha-2a intralesionally in a dose of 3 million units three times weekly for 4 weeks, and in a variable dose for 4 more weeks. Two of the patients had a complete response, and in one of these, distant lesions also responded. Seven had a partial response, and one did not respond. The treatment was generally well tolerated. The results of our study support the use of interferon in the therapy of classical Kaposi's sarcoma, although it would appear that to achieve maximum efficacy, a longer period of treatment is needed.     

Kaposi's sarcoma in women with AIDS

OBJECTIVE: To describe the presentation and incidence of Kaposi's sarcoma (KS) in a cohort of women infected with HIV and to compare their clinical characteristics with men at the same institution. DESIGN: Retrospective chart and database review. SETTING: Adult clinical AIDS program outpatient clinics at a municipal teaching hospital. RESULTS: One hundred and seven people with KS were found of whom twelve (11.2%) were women. The prevalence of KS in women was 3.6% compared with 9.9% among men (P < 0.001). Women born outside the United States were at increased risk of developing KS (P < 0.05). At initial KS presentation, no difference in HIV stage or CD4 count was found between men and women. Women presented with more advanced KS than men, with increased incidence of non-cutaneous disease (P < 0.001), lymphedema (P < 0.0001), lymph-node disease (P < 0.0001) and visceral disease (P = 0.03). Women had decreased survival after KS diagnosis compared to men, although the difference was not significant (P = 0.41). CONCLUSIONS: KS is not a rare diagnosis in HIV-infected women followed at our institution. Although the increased risk of KS in men is most likely to be related to differences in exposure, the sex-related differences in presentation and course may be due in part to delay in diagnosis. KS should be considered in the spectrum of HIV-related complications in women as well as in men.     

Kaposi's sarcoma and human herpesvirus-8

KS is a major cause of morbidity and mortality among AIDS patients and a treatment problem in the sporadic cases that are not associated with HIV. All four forms of the disease are linked to a newly described herpesvirus, HHV-8 or KSHV, via strong epidemiologic associations and biologic plausibility as a causal agent. HHV-8 is also epidemiologically associated with body cavity-based lymphomas, which are almost unique to AIDS, and Castleman's disease. Existing radiation and chemotherapeutic treatments of KS are only partially effective and cause significant adverse effects. New preventive approaches and therapies aimed at inhibiting HHV-8 may be effective. New treatments that interfere with the molecular mechanisms that drive KS may, in the future, provide the best opportunities to control the disease.     

Kaposi's sarcoma (author's transl)

Kaposi's sarcoma of the skin and an aplastic syndrome occurred together in a 51-year-old patient. Macroscopically livid papules and nodules were observed. Histomorphologically endotheliomatous cell proliferation with signs of infiltrative growth was found. Because of the aplastic pancytopenia cytostatic treatment of the Kaposi sarcoma was contraindicated. The patient finally died of vascular failure with haemorrhagic diathesis being manifest. Syntropy of Kaposi's sarcoma with malignant haematological diseases is known. However, association with aplastic anaemia has not been observed so far. The pathogenesis of Kaposi's sarcoma is unknown.     

Kaposi's sarcoma in renal transplant recipients

One hundred and seventeen of 270 (43%) recipients of organs obtained from donors with malignancies had evidence of transmitted cancers. In 9 instances these were removed from renal allografts immediately prior to transplantation. Including these cases there were 45 recipients of organs in which a neoplasm involved the allograft, 6 others in whom adjacent structures were invaded, and another 66 patients who had distant metastases. Precautions to prevent cancer transmission include meticulous preoperative screening of donors, careful examination of all organs at the time of harvesting, biopsy of any suspicious lesions, and routine donor autopsy, if possible.     

Monoclonal origin of multicentric Kaposi's sarcoma lesions

BACKGROUND: Kaposi's sarcoma has features of both hyperplastic proliferation and neoplastic growth. Multiple lesions, in which spindle cells are prominent, often arise synchronously over widely dispersed areas. We tested the hypothesis that the spindle cells in these multicentric lesions originate from a single clone of precursor cells. METHODS: To determine whether Kaposi's sarcoma is a monoclonal disorder, we assessed the methylation patterns of the androgen-receptor gene (HUMARA) in multiple lesions from women with the acquired immunodeficiency syndrome. In polyclonal tissues, about half the copies of each HUMARA allele are methylated, whereas in cells derived from a single clone all the copies of only one allele are methylated. To minimize contamination by normal DNA, we used microdissection to isolate areas composed primarily of spindle cells, the putative tumor cells. RESULTS: Eight patients with a total of 32 tumors were studied. Of these tumors, 28 had highly unbalanced methylation patterns (i.e., predominant methylation of one HUMARA allele). In all the tumors that had unbalanced methylation from a given patient, the same allele predominated. CONCLUSIONS: These data indicate that Kaposi's sarcoma is a disseminated monoclonal cancer and that the changes that permit the clonal outgrowth of spindle cells occur before the disease spreads.     

Geography of AIDS-associated Kaposi's sarcoma in Europe

BACKGROUND: Classical Kaposi's sarcoma (KS) is about four times more common in southern Europeans than in northern Europeans. OBJECTIVE: To describe the epidemiology of AIDS-associated KS (AIDS-KS) in Europe and to determine whether it occurs with increased frequency in southern Europe. METHODS: Analysis of the 'European non-aggregate AIDS data set', as of September 1995. Countries with a cumulative total of > or = 50 KS cases as the presenting manifestation of AIDS were included. Homosexual men were excluded from south versus non-south comparisons because of possible confounding effects due to their route of HIV transmission. RESULTS: KS was the presenting manifestation of AIDS for 13.3% (16,367 out of 122,679) of men and 2% (491 out of 24,826) of women. In all countries, the risk for KS was higher in individuals who acquired HIV infection via sexual rather than parenteral transmission. Among AIDS patients, there is little difference by sex in the risk of KS in injecting drug users (IDU) or transfusion recipients. The percentage with KS increased with age among homosexual and bisexual men, from 10% in the age group 15-19 years to 23% in the age group 30-39 years. In all countries, the percentage with KS declined over time. The risk of KS was not significantly higher in southern Europe. The percentage with KS in southern Europe was slightly lower than in northern Europe (P > 0.1) in male IDU (1.8% versus 2.1%), and only slightly higher (P > 0.1) in female IDU (1.5% versus 1.1%), in male transfusion recipients (3.5% versus 3.0%), in female transfusion recipients (2.4% versus 2.3%), and in both heterosexual men (7.5% versus 6.2%) and women (2.0% versus 1.6%) excluding those originating from countries where heterosexual HIV transmission is frequent. CONCLUSIONS: The strong geographic predilection described for classical KS in southern Europe was not seen for AIDS-KS. If KS is caused by a viral infection in an immunodeficient host, our findings suggest the geographical variations in classical KS are not due to variation in prevalence of the causative virus but may be due to geographical variations in the prevalence of a form of mild immunodeficiency.     

Laryngeal Kaposi's sarcoma in patients with AIDS

Over a period of 10 years 17 human immunodeficiency virus(HIV)-infected patients with laryngeal Kaposi's sarcoma were seen and treated at University College London Hospitals. All patients had advanced HIV disease. Their presentation was with symptoms of upper airway obstruction in the majority of cases and the diagnosis was made by fibreoptic examination of the larynx. Biopsy was associated with brisk haemorrhage in one patient, who required a temporary tracheostomy, and was not performed in the other 16 cases. The commonest site of laryngeal involvement was the supraglottis in 11 patients, with glottic lesions noted in eight patients: subglottic lesions were seen in only three. Treatment of laryngeal Kaposi's sarcoma was, in general, conservative, five patients received low dose radiotherapy to the larynx and 10 were treated with systemic chemotherapy for disseminated Kaposi's sarcoma. Laryngeal Kaposi's sarcoma did not contribute to patient mortality.     

Evidence for multiclonality in multicentric Kaposi's sarcoma

Kaposi's sarcoma (KS) develops in a variety of clinical states and is the most common tumor seen in patients with HIV-1 infection. KS develops as a multifocal mucocutaneous disease with subsequent spread to visceral organs, and it has been argued to be a benign proliferation caused by its multifocality at initial presentation, lack of aneuploidy, and spontaneous regression upon withdrawal of immunosuppressive agents in iatrogenically induced disease. We wished to determine whether KS lesions are clonal, indicative of a true neoplasm. Also, we tested whether multifocal KS lesions are clonally related, derived from a common progenitor cell or of independent cellular origin. We studied the X-chromosome inactivation pattern of the human androgen receptor gene in tumor biopsies of women with KS. This procedure tests for the clonality of a tissue specimen, a hallmark of neoplasia. Each specimen was microdissected to minimize normal cell contamination. Of 12 evaluable cases, 10 were HIV-seropositive and 2 were HIV-seronegative. Twenty-four biopsies from the 12 patients were examined. Five cases were consistent with individual KS lesions being clonal. In two cases, multiple KS specimens derived from the individual patients had different androgen receptor alleles inactivated, proving unequivocally that these KS lesions arose independently from distinct transformed cells. In seven cases, only a polyclonal pattern of inactivation was observed, whereas two others had tumor areas of both clonal and polyclonal inactivation patterns. These findings suggest that KS can be a clonal neoplasm, and in some of the cases multiple KS lesions in a given patient can arise from independent cellular origins and acquire clonal characteristics. The polyclonal inactivation pattern observed in other KS lesions may represent a premalignant stage or false negative results.