Analysis of DNA distribution in Kaposi's sarcoma in patients with and without the acquired immune deficiency syndrome

While Kaposi's sarcoma in patients with the acquired immune deficiency syndrome (AIDS) may present as a multicentric disease with progressive organ involvement, the classic form of Kaposi's sarcoma is an indolent tumor seldom affecting extracutaneous areas and almost never responsible for the patient's demise. An attempt was made to correlate these clinical differences with the nuclear DNA content of tumor cells in histologic sections from 15 patients (9 with AIDS and 6 without AIDS). All tumors showed a similar DNA distribution pattern, with most cells appearing diploid, indicative of a low malignant potential. These findings indicate that Kaposi's sarcoma of both AIDS and non-AIDS patients is a tumor of intrinsically low malignancy and that lack of immune surveillance is most probably responsible for its aggressive biologic behavior in many AIDS patients.     

人疱疹病毒8型KS330基因片段的检出与Kaposi肉瘤的关系

HHV-8 sequences were recently identified in 100% of the amplifiable samples from AIDS patients with Kaposi's sarcoma(KS)and in 15% of the non-KS tissue samples from AIDS patients, so there is a strong correlation of Kaposi's sarcoma with HHV-8. Serum and DNA samples from a clinically diagnosed Kaposi's sarcoma Chinese patient were tested. HHV-8 antibody was tested positive by IFA and HIV-I antibody was negative by Western blot. The KS330 PCR product was found both in peripheral blood mononuclear cells and in KS tumor cells from this Chinese patient. This supports the hypothesis that Kaposi's sarcoma results from infection of HHV-8.     

NKG2C+ NK cells are enriched in AIDS patients with advanced-stage Kaposi's sarcoma

Kaposi's sarcoma (KS) is an AIDS-defining condition in individuals with human immunodeficiency virus type 1 infection. We investigated the phenotype and function of the NKG2C+ NK cell population in individuals with AIDS and Kaposi's sarcoma. The staging of AIDS KS patients according to the AIDS Clinical Trial Group criteria revealed that patients with the S1 disease stage have a significantly higher proportion of NKG2C+ cells than those with the S0 disease stage. NKG2C+ cells from S1-stage patients are highly enriched for the expression of KIR3DL1, are depleted of NKp46, and respond poorly to major histocompatibility complex class I-positive target cells. These data demonstrate a link between NK cell phenotype and function and disease prognosis in AIDS.     

Primary Research: Short Communication: Evidence Supporting Rare AIDS-Kaposi's Sarcoma Metastasis In Keeping With Their Vascular Endothelial Evolution

BACKGROUND: It is postulated that the unusual manifestations of Kaposis's sarcoma cells in nonendothelial brain tissues and on eyeballs in advanced acquired immune deficiency syndrome (AIDS) cases are metastasized AIDS-Kaposi's sarcoma cells arising from vascular endothelial cells. METHODS: Experiments were performed to explore the above hypothesis by testing for intercellular adhesion molecule-1 (CD54 antigens) on cutaneous AIDS-Kaposi's sarcoma cells as well as on AIDS-Kaposi's sarcoma cells isolated from eyeballs as studies have illustrated that, unlike localized Kaposi's sarcoma cells of primary lesions, proliferating Kaposi's sarcoma cells in proximity to primary lesions express a negative or diminished phenotype when evaluated for identical surface antigens. Parallel CD54 antigen tests were done on vascular endothelial cells and monocytes/macrophages as endothelial cells are considered evolutionarily related to Kaposi's sarcoma cells and monocytes/macrophages are ideal CD54 antigen positive controls. RESULTS: Our data showed that only AIDS-Kaposi's sarcoma cells of the eyes did not express CD54 antigens. CONCLUSIONS: We therefore report that our findings support the postulation suggesting AIDS-Kaposi's sarcoma dissemination in advanced AIDS patients in keeping with their vascular endothelial heredity.     

Pegylated liposomal doxorubicin in the treatment of AIDS-related Kaposi's sarcoma

Kaposi's sarcoma is a vascular tumor of skin and viscera first described in 1872. Prior to the 1980s, this disease was rarely seen in the Western world, but was quite prevalent in Sub-Saharan African countries. Since the onset of the HIV pandemic in the 1980s, the incidence of Kaposi's sarcoma has increased markedly in Africa and continues to be a significant problem in association with AIDS in Western countries. Many therapies have been demonstrated to be effective in the treatment of HIV-related Kaposi's sarcoma, including alitretinoin gel, interferon alpha, and various forms of cytotoxic chemotherapy. Antiretroviral therapy combined with cytotoxic agents has yielded significantly greater efficacy than chemotherapy alone. However, as reviewed in this report, pegylated liposomal doxorubicin has been established as the treatment of choice for patients with AIDS-associated Kaposi's sarcoma in Western countries. Compelling preclinical and clinical evidence, reviewed herein, has demonstrated that the nanoparticle (pegylated liposome) delivery system of this formulation leads to greater tumor localization of doxorubicin and consequent improved efficacy, as well as reduced toxicity.     

Viruses, cancer and AIDS

Patients with AIDS are at risk of lymphoma and Kaposi's sarcoma. These tumours are associated with the gamma herpesviruses, Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8), although a proportion of AIDS lymphomas lacks both viruses. EBV and HHV-8 are latent in the tumour cells, with genes that play a direct role in driving cell proliferation. Human immunodeficiency virus, in contrast, while being the greatest risk factor for lymphoma and Kaposi's sarcoma, acts indirectly, mainly by causing immune suppression, as immunosuppressed transplant patients are at risk for the same types of tumour.     

Cell signaling pathways engaged by KSHV

Kaposi's sarcoma herpesvirus (KSHV) is the eighth human herpesvirus discovered in 1994 from Kaposi's sarcoma lesion of an AIDS patient. The strong molecular and epidemiological links associating KSHV with Kaposi's sarcoma and certain lymphoproliferative disorders indicate that KSHV is required for the development of these malignancies. Although KSHV is equipped to manipulate and deregulate several cellular signaling pathways, it is not yet understood how this leads to cell transformation. Profound understanding of the interplay of viral and cellular factors in KSHV-infected cells will provide valuable information on the mechanisms of viral tumorigenesis and enable development of efficient targeted therapies for virus-induced cancers. This review focuses on the cellular signaling pathways that KSHV gene products impinge on and discusses their putative contribution to tumorigenesis.     

AIDS and associated malignancies

AIDS associated malignancies (ARL) is a major complication associated with AIDS patients upon immunosuppression. Chronically immunocompromised patients have a markedly increased risk of developing lymphoproliferative disease. In the era of potent antiretrovirals therapy (ARV), the malignant complications due to HIV-1 infection have decreased in developed nations where ARV is administered, but still poses a major problem in developing countries where HIV-1 incidence is high and ARV is still not yet widely available. Even in ARV treated individuals there is a concern that the prolonged survival of many HIV-1 carriers is likely to eventually result in an increased number of malignancies diagnosed. Malignancies that were found to have high incidence in HIV-infected individuals are Kaposi's sarcoma (KS), Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). The incidence of NHL has increased nearly 200 fold in HIV-positive patients, and accounts for a greater percentage of AIDS defining illness in the US and Europe since the advent of HAART therapy. These AIDS related lymphomas are distinct from their counterparts seen in HIV-1 seronegative patients. For example nearly half of all cases of ARL are associated with the presence of a gamma herpesvirus, Epstein Barr virus (EBV) or human herpesvirus-8 (HHV-8)/ Kaposi's sarcoma associated herpesvirus (KSHV). The pathogenesis of ARLs is complex. B-cell proliferation driven by chronic antigenemia resulting in the induction of polyclonal and ultimately monoclonal lymphoproliferation may occur in the setting of severe immunosuppression.     

Ocular complications of the acquired immunodeficiency syndrome

The acquired immunodeficiency syndrome (AIDS) affects the ocular structures in several ways. Kaposi's sarcoma has been observed on the bulbar conjunctiva of the globe. Retinal complications, however, are of major concern. Cotton-wool spots are commonly seen in AIDS patients and are usually of no consequence, except that they must be distinguished from the early stages of cytomegalovirus (CMV) retinitis, seen in 20-40% of these patients. CMV causes a necrotic-type retinitis potentially leading to blindness. 9-[2-Hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine (DHPG) has been found effective in the short-term treatment of this disorder. It is planned to use AS101 in the regimen to see if a long-term cure from this disease can be affected. Care must be taken in handling ocular tissue of AIDS patients or the re-use of ophthalmic instruments touching the eye of AIDS patients since the human immunodeficiency virus has been found in these structures.     

Kaposi's sarcoma

A case of Kaposi's sarcoma in a 86-year female farmer is presented in view of the epidemiological data, currently changed biology of Kaposi's sarcoma, and its importance related to an association with acquired immunodeficiency syndrome (AIDS). In this particular case, the clinical course of the disease was very rapid with skin lesions on the upper and lower extremities and on mucous membranes of the oral cavity and epiglottis. Immunologic disorders caused afebrile pneumonia, prolonged healing of the post-traumatic wound and fracture of the shaft of the radius and ulna. Progressive cachexia and weakness have led to the loss of the waking ability and self-care.     

AIDS and associated syndromes: clinical manifestations

Numerous clinical and immunological manifestations are commonly observed in AIDS patients. Among these, Kaposi's sarcoma and major opportunistic infections appear today as clinical "markers" of the disease. Other signs and symptoms such as fever, diarrhea, lymphadenopathy and immunological abnormalities are currently recognized as "associated" disorders. One of the main problems faced by clinicians is to evaluate the significance of these "associated" abnormalities, especially when they occur in at risk populations. Much work is still needed to clarify whether they actually imply an individual predisposition to contract the disease, a minor form or some early stage of AIDS.     

AIDS-associated Kaposi's sarcoma cells in culture express vascular endothelial growth factor.

PCR cloning and cDNA sequencing have been used to identify mRNAs of two splice products of the vascular endothelial growth factor (VEGF) gene, VEGF121 and VEGF165, in cells isolated from Kaposi's sarcomas (KS) of AIDS patients (AIDS-KS). As demonstrated by Northern blot analysis, AIDS-KS cells as well as tumor cells show a high expression level of the VEGF gene as compared to primary human vascular cells like smooth muscle cells or endothelial cells. In addition to the lower expression of the gene, vascular cells express a 3.9 kb band together with a 3.2 kb band instead of a 3.9 kb and a 4.3 kb band in AIDS-KS cells. Our data suggest that the angiogenic properties of AIDS-KS cells might be mediated by the secretion of this growth factor and that this factor alone or in combination with other endothelial mitogens may be involved in endothelial proliferation associated with Kaposi's sarcoma.     

Bacillary angiomatosis

Bacillary angiomatosis is a bacterial disease which affects mainly immunosuppressed patients. It may compromise any tissue, especially the skin, presenting papules, nodules or angiomatous tumors. We studied three young men with AIDS, all of them with 1-2 papules, nodules or subcutaneous tumors suggesting telangiectatic granuloma, sarcoma and lipoma. Microscopically, they were misdiagnosed as telangiectatic granuloma, Kaposi's sarcoma and "angioma with secondary inflammation". After reviewing the histopathology, we saw them to be composed by vessels with prominent endothelium and stroma rich in leukocytoclastic polymorphonuclears. Fibrinoid deposits were observed in the neighborhood of vessels as well as minute eosinophilic granular interstitial masses corresponding to Bartonella aggregates, criteria which answer to the diagnosis of bacillary angiomatosis with HE staining. The Warthin-Starry stain was not useful; using resin embedded tissue from paraffin-embedded material, bacterial clusters, both in semithin section stained with toluidine blue and in thin sections observed under the electron microscope, were clearly seen, confirming bacillary angiomatosis diagnosis. Patients were successfully treated with surgery and either erythromycin or doxycycline. We reviewed the entity as well as its differential diagnoses with telangiectatic granuloma, Kaposi's sarcoma, Carrión's disease, and cat-scratch disease. In conclusion, we showed the presence of bacillary angiomatosis in three patients, illustrated its typical histopathological appearance with HE staining and demonstrated the causal bacteria in thick sections and with the electron microscope. It is essential to recognize bacillary angiomatosis, as it can be cured with antibiotics.     

Hepatitis B virus (HBV) DNA in leucocytes in acquired immune deficiency syndrome (AIDS)

Earlier reported findings of hepatitis B virus (HBV) DNA in white blood cells of patients with hepatoma, and in a patient with autoimmune haemolytic anaemia, led to the examination of HBV DNA in a series of twenty three patients with acquired immune deficiency syndrome (AIDS), including nine with opportunistic infections and fourteen with Kaposi's sarcoma, by Southern blot hybridization method, using 32P labelled HBV DNA specific probe obtained by nick translation of HBV DNA cloned into plasmid pBR325. Four of the patients were found to be positive for HBV DNA or HBV related DNA in their leucocytes. The HBV DNA was found free or integrated in the leucocytes of the patients.     

Extracutaneous manifestations of Kaposi's sarcoma: a systemic lymphoblastoma

Kaposi's sarcoma may affect any system of the body. Serious difficulties occur only when the heart, lungs or gastrointestinal tract are affected. Usually, involvement in other viscera causes no clinical symptoms.This neoplasm is thought to be a low-grade lymphoblastoma. This idea of relationship is based on clinical and histologic association of Kaposi's sarcoma with the lymphoblastomas more commonly than would be anticipated from the rarity of the conditions under consideration. This concept is strengthened by the occasional seeming mutation of Kaposi's sarcoma into a lymphoblastoma. The associated reticuloendothelial hyperplasia in Kaposi's sarcoma is another link in the evidence of relationship.     

Kaposi's sarcoma and human chorionic gonadotropin: mechanisms,moieties and mysteries

Kaposi's Sarcoma (KS) is a highly angiogenic neoplasm associated with infection by the human gamma-herpesvirus, HHV-8 or Kaposi's sarcoma herpes virus (KSHV). When in 1872 the Hungarian scientist Moritz Kaposi described the sarcoma, which was later named after him, he was dealing with a rare dermatologic disease. Today, KS is a more common pathology due to its high incidence in AIDS, in immuno-suppressed transplantation patients and, in its endemic form, in Africa. The introduction of highly active antiretroviral therapy (HAART) has led to a drastic reduction of KS incidence in HIV-infected patients, but in some cases KS resists the treatment. KS is more common in men than in women. The observation of spontaneous remissions during pregnancy stimulated investigations into the potential anti-KS activity of the pregnancy hormone human chorionic gonadotropin (hCG). The variable effect in clinical trials using urinary preparations of the hormone (u-hCG) has led to the hypothesis that contaminating moieties present in these preparations may account for the anti-KS effect observed in vitro. While the discrepancy between laboratory tests and clinical trials remains a mystery, little is known about potential anti-KS mechanisms of the hormone itself and/or other active moieties present in u-hCG.     

Simultaneous cytomegalovirus infection and Kaposi's sarcoma of the thyroid diagnosed by fine needle aspiration in an AIDS patient. A case report and first cytologic description of the two entities occurring together

BACKGROUND: Cytomegalovirus (CMV) infection and Kaposi's sarcoma (KS) are common in AIDS patients but rarely involve the thyroid, and coexistence of these two entities in that organ has not yet been described before. CASE: A 41-year-old female AIDS patient presented with a 2 x 1-cm, well-demarcated, rubbery mass in the right side of the thyroid. On fine needle aspiration (FNA), spindle cells were retrieved singly or in small, loose clusters; they had bland, fusiform to cigar-shaped nuclei; inconspicuous nucleoli; delicate cytoplasmic vacuoles; cytoplasmic hyaline drops; and hemosiderin granules. A single endothelial cell showed an enlarged nucleus with a basophilic intranuclear inclusion and periinclusional halo. CONCLUSION: This is the first reported case of an AIDS patient with KS and CMV infection simultaneously involving the thyroid diagnosed by FNA.     

Kaposi's sarcoma of the thyroid gland in an HIV-negative woman: a case report

BACKGROUND: Kaposi's sarcoma (KS) is a neoplastic disease that affects primarily the skin, but visceral involvement is not uncommon. Most of the cases are seen in AIDS patients and transplant recipients; however, rare HIV-negative cases have also been reported. Involvement of the thyroid is exceedingly rare, with only a fw cases reported, all of them associated with AIDS. CASE: A 45-year-old, black, Haitian woman presented with a slowly enlarging left side of the thyroid. Computed tomography showed multiple thyroid nodules, and there was no uptake of iodine on the nuclear scan. Fine needle aspiration of the lesion was performed. The smears were composed of spindle and plasmacytoid cells, which raised the possibility of medullary carcinoma. The patient underwent left hemithyroidectomy. Histologic examination showed KS in the thyroid. CONCLUSION: We present the first case of KS of the thyroid in a HIV-negative patient. Familiarity with the cytologic features can be useful in making the diagnosis.