An unusual case of pyogenic granuloma-like Kaposi sarcoma.

Kaposi sarcoma (KS) is not typically included in the differential diagnosis of lesions with clinical characteristics of pyogenic granuloma. However, cases of pyogenic granuloma-like Kaposi sarcoma have been reported in the literature. This variant is extremely rare and possesses clinical and histological findings consistent with both conditions. We report an elderly, immunocompetent man with pyogenic granuloma-like Kaposi sarcoma, which was clinically consistent with a pyogenic granuloma and possessed histological findings consistent with Kaposi sarcoma and pyogenic granuloma.

Update on oncogenesis and therapy for Kaposi sarcoma.

PURPOSE OF REVIEW: This review is an update of the recent findings on pathophysiology of Kaposi sarcoma, the role of HHV-8 in Kaposi sarcoma pathogenesis and to summarize the recent advances in the treatment of Kaposi sarcoma and the role of immunity to control the disease. RECENT FINDINGS: The causal agent of Kaposi sarcoma is HHV-8 and the mechanism by which HHV-8 drives the tumor development is unique. HHV-8 is not a classic oncogenic virus and the disease is an opportunistic tumor responding to immune restoration when it is possible. SUMMARY: Five epidemiologic types of Kaposi are recognized and HHV-8 is associated to all epidemiologic forms of Kaposi. HHV-8 is a virus favoring both angiogenesis and cellular proliferation, which are the two main histological features of Kaposi sarcoma. Although in many cases, treatment of Kaposi sarcoma is not necessary, specific chemotherapy, immunomodulation and immune stimulation are the tools for treating Kaposi sarcoma. Monochemotherapy has been shown to be as efficient as polychemotherapy and less toxic. Immune checkpoint inhibitors gave some promising results, which should be confirmed by prospective studies.

Marathon of eponyms: 11 Kaposi sarcoma.

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognized relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarizes data about Kaposi sarcoma.

Update on Kaposi sarcoma-associated herpesvirus (KSHV or HHV8) - review.

Human herpesvirus 8 (HHV8), also known as Kaposi sarcoma-associated herpesvirus (KSHV), is one of the few pathogens recognized as direct carcinogen, being involved in the pathogenesis of Kaposi sarcoma, primary effusion lymphoma and multicentric Castleman disease. KSHV is a relatively recently discovered virus, with still limited possibilities for diagnosis and treatment. Therefore, ongoing studies are trying to answer the main issues related to the management of KSHV infection and its associated diseases. This review updates the current knowledge of the KSHV infection, discussing aspects related to epidemiology, virological features, clinical manifestations, diagnosis and treatment.

Epidemiology of Kaposi sarcoma: review and description of the nonepidemic variant.

Kaposi sarcoma (KS) is a rare angioproliferative tumor whose etiology is associated with human herpesvirus 8 (HHV 8). KS lesions typically involve the skin or mucosal surfaces and are characterized by purplish, red-blue, or brown-black macules, papules, and nodules which are prone to bleeding and ulceration. Definitive diagnosis requires biopsy revealing characteristic angioproliferative features. There are four widely recognized types of KS, which are histologically indistinguishable but differ in epidemiology and prognosis. These include classic, endemic, iatrogenic, and epidemic. KS has been increasingly recognized in a new subgroup of patients: men who have sex with men (MSM) but who are HIV-seronegative human immuodeficiency virus-seronegative and have no identifiable immunodeficiency. This fifth variant of KS, termed nonepidemic KS, resembles classic KS in presentation and prognosis. In this literature review, we report the characteristics of nonepidemic KS based on all published cases and highlight the need for clinicians to recognize this new clinical variant.

Endothelial cell- and lymphocyte-based in vitro systems for understanding KSHV biology.

Kaposi sarcoma (KS), the most common AIDS-associated malignancy, is a multifocal tumor characterized by deregulated angiogenesis, proliferation of spindle cells, and extravasation of inflammatory cells and erythrocytes. Kaposi sarcoma-associated herpesvirus (KSHV; also human herpesvirus-8) is implicated in all clinical forms of KS. Endothelial cells (EC) harbor the KSHV genome in vivo, are permissive for virus infection in vitro, and are thought to be the precursors of KS spindle cells. Spindle cells are rare in early patch-stage KS lesions but become the predominant cell type in later plaque- and nodular-stage lesions. Alterations in endothelial/spindle cell physiology that promote proliferation and survival are thus thought to be important in disease progression and may represent potential therapeutic targets. KSHV encodes genes that stimulate cellular proliferation and migration, prevent apoptosis, and counter the host immune response. The combined effect of these genes is thought to drive the proliferation and survival of infected spindle cells and influence the lesional microenvironment. Large-scale gene expression analyses have revealed that KSHV infection also induces dramatic reprogramming of the EC transcriptome. These changes in cellular gene expression likely contribute to the development of the KS lesion. In addition to KS, KSHV is also present in B cell neoplasias including primary effusion lymphoma and multicentric Castleman disease. A combination of virus and virus-induced host factors are similarly thought to contribute to establishment and progression of these malignancies. A number of lymphocyte- and EC-based systems have been developed that afford some insight into the means by which KSHV contributes to malignant transformation of host cells. Whereas KSHV is well maintained in PEL cells cultured in vitro, explanted spindle cells rapidly lose the viral episome. Thus, endothelial cell-based systems for studying KSHV gene expression and function, as well as the effect of infection on host cell physiology, have required in vitro infection of primary or life-extended EC. This chapter includes a review of these in vitro cell culture systems, acknowledging their strengths and weaknesses and putting into perspective how each has contributed to our understanding of the complex KS lesional environment. In addition, we present a model of KS lesion progression based on findings culled from these models as well as recent clinical advances in KS chemotherapy. Thus this unifying model describes our current understanding of KS pathogenesis by drawing together multiple theories of KS progression that by themselves cannot account for the complexities of tumor development.

Kaposi Sarcoma and Cutaneous Angiosarcoma: Guidelines for Diagnosis and Treatment. / Sarcoma de Kaposi y angiosarcoma cutáneo: directrices para el diagnóstico y tratamiento.

Kaposi sarcoma is a vascular sarcoma with 4 clinical variants: classic Kaposi sarcoma, which mainly affect the extremities of elderly patients and follows a chronic, generally indolent course; African Kaposi sarcoma; immunosuppression-associated Kaposi sarcoma; and AIDS-associated Kaposi sarcoma. Type8 human herpesvirus is the etiologic agent in all 4variants. Cutaneous angiosarcoma is a cutaneous neoplasm with a very poor prognosis. It carries a high probability of local relapse and has a 10% to 15% survival rate at 5years. There are 3 main variants of cutaneous angiosarcoma: idiopathic angiosarcoma of the face and scalp; Stewart-Treves syndrome; and postradiation angiosarcoma. The only potentially curative treatment is surgery with or without radiotherapy. However, its indistinct borders and multicentric nature mean that treatment is often palliative with chemotherapy, radiotherapy, or both.

Non-HIV Associated Kaposi’s Sarcoma: A case report / Sarcoma de Kaposi no asociado a VIH: un caso clínico

Kaposi sarcoma (KS), first described in 1872, is an angioproliferative neoplasm that often presents with red-purple macules in the skin. This report is of a case ofclassic/iatrogenic form of KS in a 79-year-old male, that had a prolonged hospitalization due to surgical complications. After discharge, he presented a red-purple macule. A biopsy was made and KS was confirmed. He was HIV negative. The patient did not require any other treatment asides from the total removal of thelesion. Kaposi’s sarcoma is an uncommon disease, still very associated with HIV. This case demonstrates the importance of recognition of KS in non-HIV patients.There are four types of Kaposi’s sarcoma and the importance of its recognition in non-HIV patients. (AU)

AIDS-related Kaposi's sarcoma: prospective validation of the AIDS Clinical Trials Group staging classification. AIDS Clinical Trials Group Oncology Committee.

PURPOSE: To prospectively validate the AIDS Clinical Trials Group (ACTG) staging classification for AIDS-associated Kaposi's sarcoma (KS). PATIENTS AND METHODS: Two hundred ninety-four consecutive patients enrolled in eight ACTG therapeutic trials for AIDS-associated KS were staged prospectively according to tumor extent (T), severity of immunosuppression (I), and other systemic human immunodeficiency virus type 1 (HIV-1)-associated illness (S) and were observed for survival. Patients were classified as good risk (subscript 0) or poor risk (subscript 1) for each variable according to published ACTG criteria. Univariate and multivariate analyses were used to evaluate the associations between TIS variables and survival; additional analyses were conducted to improve the predictive value of the staging system. RESULTS: Survival was significantly shorter for patients in the poor-risk category for each of the TIS variables. Respective median survivals for patients in the good- and poor-risk categories were 27 and 15 months for T (P < .001); 40 and 13 months for I (P < .001) when I0 included CD4 counts > or = 200/microL and 22 and 16 months for S (P = .04). Multivariate analysis indicated that severity of immunosuppression gave the most predictive information but also showed that T provided significant additional predictive information in patients whose immune function was least impaired. Refined Cox models using a CD4 count of 150/microL rather than 200/microL to distinguish I0 and I1 yielded a simplified model with better fit to the observed data. CONCLUSION: The ACTG TIS classification predicts survival in patients with AIDS-associated KS; CD4 count and tumor stage provide the most predictive information. However, a lower CD4 count than the one originally proposed provides better discrimination between prognostic groups.

Prognostic factors and staging classification of patients with epidemic Kaposi's sarcoma.

Two hundred twelve patients with acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) were followed prospectively. Univariate and multivariate analyses were performed to determine significant predictors of survival and development of opportunistic infection (OI) from the time of diagnosis of KS. Clinical variables analyzed were age at onset, presence of systemic symptoms, prior or coexistent OI, development of OI greater than 3 months following KS diagnosis, and extent of disease. Laboratory variables analyzed were absolute number of peripheral T-helper lymphocytes (T4), helper/suppressor ratio (T4/T8), serum beta-2-microglobulin, and serum acid labile alfa interferon. Three independent variables were predictive of shorter survival: (1) prior or coexistent OI (P = .02), (2) presence of systemic symptoms (P = .001), and (3) absolute T4 count less than 300 cells/microL (P = .002). Based on survival, patients with AIDS-related KS can be divided into four groups: (1) those with no prior or coexistent OI, no systemic symptoms, T4 greater than or equal to 300 cells/microL (median survival, 31 months): (2) those with no prior or coexistent OI, no systemic symptoms, and T4 less than 300 cells/microL (median survival, 20 months); (3) those with no prior or coexistent OI and presence of systemic symptoms (median survival, 15 months); and (4) those with prior or coexistent OI (median survival, 7 months).

Case report: classic Kaposi's sarcoma.

Classic KS usually appears between ages 50 and 70 years and has a relatively benign, indolent course for 15 years or longer. Treatment usually controls the disease quite well.

Effect of the revised AIDS case definition on AIDS reporting in San Francisco: evidence of increased reporting in intravenous drug users.

To examine the effect of the revision of the US national AIDS case definition in September 1987, we compared demographic and clinical information for AIDS patients diagnosed and reported to the San Francisco Department of Public Health between 1 September 1987 and 31 October 1989. Of the 3167 patients diagnosed and reported during the study period, 584 (18%) met the revised case definition only, increasing AIDS case reporting in San Francisco by 23%. One hundred and thirty-four of these 584 patients (23%) subsequently developed diagnoses meeting the old definition. After adjusting for this proportion, the revised case definition increased reporting by 17%. The mean time between initial diagnosis with a disease meeting the revised definition and subsequent development of a disease meeting the old definition was 18.5 months. Patients who met the revised case definition only were slightly older and more likely to be Black, female, and intravenous drug users (IVDUs) than those meeting the old case definition. The majority of patients who met the revised case definition only had initial diagnoses of HIV wasting syndrome (26%), HIV encephalopathy (21%), and presumptive Pneumocystis carinii pneumonia (19%). The revised AIDS case definition has significantly increased the reporting of severe morbidity associated with HIV infection, particularly among IVDUs.

Clinical variants and staging of Kaposi's sarcoma.

Kaposi's sarcoma (KS) in the acquired immunodeficiency syndrome (AIDS) is a new and aggressive presentation of a previously rare malignancy. Variation in the clinical course of this disease and its response to treatment suggest that clinical or immunologic parameters may be important in its prognosis. A review of the clinical staging systems for epidemic (AIDS-related) KS (EKS) suggests an improved survival with lower tumor stages, the lack of prior opportunistic infections, and the absence of systemic symptoms. In addition, retrospective analysis of 16 immune parameters for their prognostic value showed that total CD4 (T4) cell numbers and the CD4:CD8 ratio correlated most closely with survival. Response to treatment with recombinant alpha-interferon did not correlate with tumor stage, but was more frequent in patients without systemic symptoms or prior opportunistic infections. Several studies suggest that treatment response is associated with a greater degree of intact T cell function. These findings point out the importance of cellular immunity in the prognosis of patients with EKS.

Flow cytometric DNA analysis of vascular soft tissue tumors, including African endemic-type Kaposi's sarcoma.

Vascular tumors of the soft tissue display a wide spectrum of histologic features and biologic behavior. Flow cytometric DNA analysis was performed on 40 vascular tumors, including nine African endemic-type Kaposi's sarcomas, nine angiosarcomas, seven hemangiopericytomas, six glomus tumors, and nine capillary hemangiomas. Six of the nine angiosarcoma cases (67%) and one of the seven hemangiopericytomas cases (14%) were aneuploid. All benign vascular tumors and Kaposi's sarcomas were diploid. Clinically, five of the six angiosarcoma patients with aneuploidy died within 2 to 28 months, while the remaining patient, who had the smallest tumor (2 x 1 cm), survived more than 4 years after the initial diagnosis was made. All three angiosarcoma patients with diploidy died within 10 to 14 months. One hemangiopericytoma patient with aneuploidy died within 1 month. No cases of benign tumor recurred. These results suggest that most vascular tumors, which generally follow a benign clinical course, were diploid and that the majority of those with a poor outcome were aneuploid. However, flow cytometrically assessed DNA ploidy has no prognostic value in angiosarcomas or hemangiopericytomas.

Immunological profile of endemic and epidemic Kaposi's sarcoma patients in Dar-es-Salaam, Tanzania.

Kaposi's sarcoma (KS) presents in four clinicopathological types namely classical/sporadic (CKS), endemic African (EKS), iatrogenic (IKS) and that associated with AIDS (AKS). Recently a putative herpes virus (HHV-8) was described and shown to be present in all four types of KS. The immunological status of patients with EKS has been conflicting. In this study total leucocyte counts, total lymphocyte counts and lymphocyte subsets of patients with EKS and AKS were determined by flow cytometry and compared to those of healthy HIV-1 seronegative controls. Results show that 50% of EKS lesions were of nodular type. Patients with EKS had significantly lower levels of CD4+ T- lymphocytes and CD4:CD8 ratio but significantly higher CD8+ T-lymphocytes compared to controls. Patients with AKS had significantly lower levels of CD4+ T-lymphocytes and also CD4:CD8 ratios but significantly higher percentage of CD8+ T-lymphocytes when compared with EKS patients. These findings indicate that in both forms of KS there is a certain degree of immunological disturbance which is more conspicuous in AKS because of HIV infection and suggests that HIV-1 acts synergistically with the aetiological agent (HHV-8) to cause a more aggressive type of KS.

Bcl-2 and p53 immunoprofile in Kaposi's sarcoma.

Seventy three cases of Kaposi's sarcoma (KS) from the 3 histological subtypes (patch, plaque and nodular) were assessed for bcl-2 and p53 protein expression. The aim was to determine the level of expression of these proteins in KS and in the different subtypes. Commercially available antibodies to bcl-2 and p53 were applied after both microwave and pressure cooking antigen retrieval. Bcl-2 immunoexpression increased from the patch stage (36%) to the plaque stage (45%) to the nodular stage (70.83%). Better immunostaining for bcl-2 was obtained after pressure cooking. p53 on the other hand, was not expressed in the patch or plaque stages, but 54.16% of cases in the nodular stage were immunopositive. These results show a progression of immunoexpression of both bcl-2 and p53 from the early histological stages to the late tumor stage, implying that these proteins are upregulated late in the evolution of KS.

Distribution of basement membrane-associated heparan sulfate proteoglycan in idiopathic and AIDS-associated Kaposi's sarcoma.

In the present study we analyzed the immunohistochemical distribution of different major basement membrane (BM) components with special emphasis on the BM-associated heparan sulfate proteoglycan (HSPG) in early and late stages of Kaposi's sarcoma (KS), both of idiopathic and AIDS-associated origin. In early KS all BM components tested were found surrounding the small clefts of tumour vessels. Heparan sulfate proteoglycan showed the weakest and often fragmented pattern of staining. In the late, nodular sarcomatous form of KS individual tumour cells were surrounded by a BM composed of collagen IV, laminin and fibronectin, while heparan sulfate proteoglycan was not detectable in most cases. Neither between idiopathic and AIDS-associated KS nor between cutaneous and visceral lesions were significant differences in the staining pattern. Our findings of a rather selective expression of various BM-components and the known distribution in normal blood and lymphatic capillaries raises the hypothesis that KS-cells may be derived from cells of lymphaticovenous differentiation.