Classic Kaposi's Sarcoma Research Articles

Kaposi's Sarcoma and HIV-Tat: Challenges to Antiangiogenesis Research

Kaposi's sarcoma (KS) is characterized by an abnormal growth of blood vessels. KS was found mainly in older men of Mediterranean or African origin (classic KS) or in patients after organ transplantation (iatrogenic KS). However, in the early 1980s, an aggressive epidemic form, linked to AIDS, was noticed and was one of the first clues to the existence of HIV-1 pandemy. The link between KS occurrence and HIV has raised multiple hypotheses. The drastic reduction of KS after the introduction of HAART, suggests HIV as a powerful co-factor for KS progression. We and others have contributed to the elucidation of KS cell nature and the possible involvement of extracellular HIV Tat. Tat is proangiogenic and is a true promoter of KS lesions acting as a VEGFR2 ligand both on KS and endothelial cells, in addition Tat is able to bind and activate chemokine receptors on monocytes and granulocytes causing a pro-inflammatory status. Evaluation of the effects of extracellular Tat on KS cells by microarray analysis after 24 h of incubation shows an interesting clustering of gene products involved in signal transduction, especially GTP-ase, Kinase and cAMP activity, confirming that Tat acts extracellularly by ways that are probably unrelated to its nuclear activity. KS occurrence is reduced by HAART but still present and in Africa is one of the most frequent oncologic disease. To find suitable drugs with low toxic impact on KS patients, we have tested several drugs and gene therapy approaches in in vivo models. from 2005 International Meeting of The Institute of Human Virology Baltimore, USA, 29 August – 2 September 2005

Transcripts of the human herpesvirus 8 genome in skin lesions and peripheral blood mononuclear cells of a patient with classic Kaposi's sarcoma.

We report a 75-year-old Japanese woman with classic Kaposi's sarcoma. PCR amplified human herpesvirus 8 (HHV-8) DNA sequences from her skin lesions and peripheral blood mononuclear cells (PBMC), but not her plasma, saliva or urine. An antibody test against HHV-8 lytic antigens was positive. Immunohistochemical staining detected latent antigen. There was no evidence of HHV-8 infection in her husband, sister or daughter. Genes coding for HHV-8-encoded viral interleukin-6, viral macrophage inflammatory protein I, viral G protein-coupled receptor, viral cyclin D and viral Bcl-2 were expressed to the same degree in both her skin lesion and PBMC. Latency-associated T0.7 mRNA and HHV-8-encoded viral tegument protein genes were expressed in her PBMC at levels lower than in the skin lesions. Based on the gene expression profile, we concluded that lytic HHV-8 infection was present in her skin lesions and PBMC.

Infection With Kaposi’s Sarcoma–Associated Herpesvirus Among Families of Patients With Classic Kaposi’s Sarcoma

Classic Kaposi's sarcoma (CKS) primarily affects elderly Mediterranean or Eastern European men. Incidence rates of CKS in Israel are among the world's highest. In practically all cases, antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV) can be detected. A relatively high seroprevalence rate of KSHV in Israel generally correlates with the incidence of CKS. A sexual mode of virus transmission is recognized among homosexual men, whereas the precise transmission routes in the heterosexual population and those with CKS are still unclear. To better assess the transmission routes of KSHV in Israeli patients with CKS and their first-degree relatives as compared with a control group. Serum was collected from all study participants and tested for KSHV antibodies by means of latent and lytic immunofluorescence assays. An open reading frame 65 (ORF65) Western blot assay was applied as a confirmatory tool. Three dermatological departments in Israel. Sixty-four Jewish patients with CKS, 143 of their first-degree relatives, and 186 hospital-based control subjects. Seropositivity to KSHV was detected in 62 (96.9%) of the patients with CKS, in 56 (39.2%) of their first-degree relatives, and in only 21 (11.3%) of the hospital controls (P<.001). The specific relationship with the index patient (spouse, offspring, or sibling) had no significant effect on the prevalence of serpositivity in the family members. Our serologic evidence of familial clustering of KSHV infection suggests a predominantly nonsexual horizontal transmission route of the virus.

Association of Clinical Progression in Classic Kaposi’s Sarcoma With Reduction of Peripheral B Lymphocytes and Partial Increase in Serum Immune Activation Markers

To evaluate various immunologic markers in the peripheral blood of patients with early and advanced classic Kaposi's sarcoma (CKS). Cross-sectional study. A major referral center for skin and venereal diseases. Sixty-eight patients with histologically confirmed CKS staged according to a modified version of the Mitsuyasu-Groopman classification in stage I-II (cutaneous involvement only) and stage IV (skin and systemic involvement). Concentrations of neopterin and beta2-microglobulin, titer of anti-human herpesvirus 8 antibodies, number of natural killer cells, and numbers of total lymphocytes, B lymphocytes, T lymphocytes, and their subsets in peripheral blood. The median values of beta2-microglobulin and neopterin were elevated in patients with CKS in stage IV (median, 3.679 microg/mL [312.72 nmol/L] and 14.0 nmol/L, respectively) compared with patients in stage I-II (median, 2.406 microg/mL [204.51 nmol/L] and 6.5 nmol/L, respectively). A statistically significant reduction in total lymphocyte and B-lymphocyte counts was observed in patients with advanced-stage CKS (1679/microL and 79/microL, respectively) compared with patients in earlier stages of the disease (2142/microL and 224/microL, respectively). The human herpesvirus 8 antibody titer, determined by latent immunofluorescent assay, decreased from stage I-II to stage IV, although not at a statistically significant level (P = .14). The evolution of CKS from the early stages of the disease to the more advanced may be associated with a partial activation of the immune system and a gradual decrease in the number of total and B lymphocytes.

Herpèsvirus humain 8. Aspects virologiques, cliniques et épidémiologiques

HHV-8 belongs to the herpesviridae family, to the gammaherpesvirinae sub-family and to the rhadinovirus genus. While several viral homologues exist in different types of non human primates, HHV-8 is the only rhadinovirus known in human. The HHV-8 genome comprises a unique long region of 140 kb, containing nearly 90 genes, with, at both extremities, terminal repeated regions that comprise identical repeated sequences in variable number. Among these genes, some encode proteins necessary for the viral replication and the assembly of new particles (structural proteins, DNA polymerase, glycoproteins), others in contrast, encode homologues of cellular protein involved in the regulation of the cell cycle, apoptotic cell death mechanisms and cellular proliferation. HHV-8 has indeed several genes which have been hijacked from the host during a long parallel evolution. These viral genes, divergent homologues of the original cellular genes, play a crucial role in the tumorigenesis mediated by HHV-8 but also in mechanisms leading to escape the anti viral immune response. HHV-8 is considered as the etiological agent of the four clinico-epidemiologic forms of Kaposi's sarcoma (classic, endemic, post-transplant and epidemic/HIV associated). This human oncogenic herpesvirus is also associated with primary effusion lymphoma and some cases of multicentric Castleman disease as well as other rare lymphomas. HHV-8 is not a ubiquitous virus. It is principally endemic in areas of high endemicity for classic or endemic Kaposi's sarcoma including the Mediterranean zone, and mostly East and Central Africa. In the latter areas, HHV-8 seroprevalence can reach 80% among the adult population. While in the HHV-8 highly endemic male homosexual population (mainly in the USA and Europe), this herpesvirus is transmitted during repeated sexual contacts, HHV- 8 transmission occurs mainly from mother to child and between siblings in the general population of endemic areas (Africa). Saliva seems to play a major role in the viral transmission, being a possible reservoir for HHV-8. Molecular epidemiological studies of the K1 gene (one of the most variable genomic region) have revealed the presence of different molecular subtypes which appear, at least some of them, mostly linked to the geographical origin of the samples rather than to the associated disease.

Epidemiology and clinical characteristics of classic Kaposi's sarcoma, seroprevalence, and variants of human herpesvirus 8 in South America: A critical review of an old disease

To review the current South American literature on classic Kaposi's sarcoma (KS) and human herpesvirus 8 (HHV-8), and point the way for studies that still need to be performed. The authors performed an exhaustive search in LILACS, SCIELO and PUBMED databases for classic KS and HHV-8 in South America. The relevant material was evaluated and reviewed. More than 250 cases have been reported with three big case series (Argentina, Colombia and Peru). The classic KS form seen in Colombia resembles the type of disease seen among African communities; the same unusual presentation with confluent exophytic nodules or eroded lesions has been noticed in Peru. Low rates of HHV-8 antibodies have been found in blood donors from Chile, Argentina and Brazil (3%, 4%, 2.8-7.4%, respectively); whereas high rates of HHV-8 antibodies have been found in Amerindians from Brazil and Ecuador. Five specimens from Argentina were subtyped: (three classic KS and two AIDS KS); the identified strains fell into subtypes A and C. AIDS-related KS specimens from Brazil and Venezuela were subtyped: (43 and nine respectively); analysis grouped them predominantly into subgroups A, B and C. A new HHV-8 subtype E was found endemic in Brazilian and Ecuadorian Amerindians. In French Guiana ten endemic KS and six AIDS-related KS specimens were subtyped; analysis grouped them predominantly into subgroups A, B and C. Classic KS in South America has a very similar clinical presentation but not the same as the classic KS variety described in the Mediterranean. Initial seroprevalence studies performed in the general population and in blood donors showed low seroprevalence of HHV-8, whereas high seroprevalence rates were seen in Amerindian population. The existing serological assays, nonetheless, need to be further refined, and new assays need to be developed. Finally, the key to understanding the precise molecular epidemiology and phylogenetic distribution of HHV-8 in South America would be to perform more subtyping of classic KS cases.

Kaposi’s sarcoma in Morocco: a pathological study with immunostaining for human herpesvirus-8 LNA-1

The Maghreb region is considered to be an endemic area for classical Kaposi's sarcoma (KS) but the few published reports have focused on clinical descriptions. We report here the clinical, virological and pathological features of 26 KS cases, including 17 classic forms, eight epidemic forms and one case of post-transplant KS. Evidence of human herpesvirus (HHV)-8 infection was detected by serology, immunohistochemistry and polymerase chain reaction. Antibodies directed against HHV-8 latent nuclear antigen (LNA-1/ORF73) were present in sera from all 26 KS cases and the ORF26 HHV-8 gene fragment was amplified from the tumour DNA of all patients. KS lesions that met the classical criteria for KS (spindle cells, positive endothelial markers) and were immunostained with the anti-LNA-1 marker, demonstrated typical granular intranuclear labelling of the spindle cells in all but one case of KS, in which very few spindle cells were present. Furthermore, whereas LNA-1 staining was largely confined to spindle cells in the late nodular stage, it was also observed in endothelial cells forming the walls of slit-like vessels in early patch-stage lesions. This study confirms that Morocco is an endemic area for classical KS, which remains the most frequent type of KS in this country, and emphasises the value of the LNA-1 marker for the early diagnosis of KS lesions.

Epidemiological and clinical characteristics of classic Kaposi's sarcoma in Peru

Classic Kaposi sarcoma (KS) occurs predominantly among the elderly, with predominance among Jews, Italians, and Greeks. Classic KS has been seen relatively frequently in Peru. Our purpose was to outline the epidemiological and clinical profile of classic KS in Peru. Epidemiological and clinical features of all classic KS cases diagnosed between 1969 and 2003 at Hospital Nacional Cayetano Heredia (HNCH) and between 1946 and 2004 at Instituto Nacional de Enfermedades Neoplasicas (INEN) were reviewed and studied retrospectively. An overall incidence of 2.54 per 10,000 attended patients was obtained at the INEN during the 48-year period (mean, 2.39; standard deviation: 1.99; 95% confidence interval, 2.92-1.86). Twenty-one cases were discovered at HNCH and 106 cases at INEN. A male/female ratio of 2.62:1 was found. Mean age at diagnosis was 68.5 years. Lower limbs were involved in 109 patients (85.8%); the trunk was involved in 11 patients (8.6%). Nodules were the most common type of lesion (85.8%); less commonly found were plaques (27.5%), macules (12.5%), papules (12.5%), and ulcers (8.6%). Sixty-two patients had no symptoms (48.8%). Pain was the most common symptom (26.7%), followed by edema (21.2%), bleeding (14.9%), and pruritus (3.9%). A second primary malignancy was found in 11 patients (8.6%). These results were obtained from patients with classic KS in Peru and may not be applicable to other populations. Classic KS is quite common in Peru with sporadic cases found throughout the country and some clustering in the coastal region. Classic KS in Peru has a clinical presentation that is very similar, but not identical, to the classic KS described in the Mediterranean region, exhibiting some special clinical and epidemiological characteristics with a nodular, nonsymmetric presentation that usually affects the lower extremities.

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.

Human herpesvirus type 8 infection in an area of Northern Italy with high incidence of classical Kaposi's sarcoma

Previous studies have reported a large variation in the incidence of classical Kaposi's sarcoma across different Districts of the province of Mantua (Northern Italy). To assess whether such differences might be explained by different anti-HHV8 antibody prevalence, a serological study was conducted in 343 healthy elderly individuals resident in two adjacent Districts, at the highest and the lowest classical Kaposi's sarcoma incidence rate, respectively. Qualitative and quantitative determinations of IgG antibodies against both latent and lytic HHV-8 antigens were performed by indirect immunofluorescence assay. The assay's sensitivity was studied in 26 patients with classical Kaposi's sarcoma. Overall, anti-HHV8 antibodies were detected in 25 out of 26 patients (96%), confirming the high sensitivity of this assay. The prevalence of anti-HHV-8 antibodies was higher among individuals living in the District had a high incidence of classical Kaposi's sarcoma compared to those living in the District with low incidence (19.4% vs 9.8%, and 15.9% vs 8%; P<0.05, for latent and lytic antibodies, respectively). Anti-lytic antibody GMT was higher in people living in the District at high incidence rate compared to those of the other area (328.9 vs. 180.4; P<0.01). A higher prevalence of HHV-8 infection was found among persons living in municipalities surrounded by watercourses (OR 2.2, 95% CI: 1.10-4.32). In conclusion, variation in HHV-8 prevalence appears to explain differences in the incidence rates of classical Kaposi's sarcoma observed in different areas of the province.

Sildenafil citrate‐aided radiotherapy for the treatment of Kaposi's sarcoma of the penis

We report a case of classical Kaposi's sarcoma involving multiple sites of the penis in a 62-year-old male who was treated with sildenafil citrate-aided electron beam therapy, resulting in complete resolution of the lesions.

C-Kit (CD117) Expression in AIDS-Related, Classic, and African Endemic Kaposi Sarcoma

Kaposi sarcoma (KS) is a multicentric vascular neoplasm characterized histologically by the progressive proliferation of spindle-shaped tumor cells in all epidemiologic (AIDS-related, classic, endemic, and iatrogenic) forms. Human herpesvirus 8 (HHV8) is associated with all epidemiologic forms of KS and has been shown in vitro to induce the tyrosine receptor kinase c-kit in HHV8-infected cells. To date, c-kit immunoreactivity has not been systematically studied in KS lesions. Therefore, the aim of this study was to evaluate c-kit expression by immunohistochemistry in different proliferative stages and epidemiologic forms of KS. Archival cases of formalin-fixed, paraffin-embedded KS lesions, including 9 classic, 11 AIDS-related, and 15 African (endemic) forms at various histologic stages (5 patch, 8 plaque, 22 nodular), biopsied from different sites, were stained using immunohistochemistry with antibodies to HHV8 (LNA-1) and c-kit (CD117). C-kit immunoreactivity of lesional cells was demonstrated in 15 (43%) cases overall. A total of five (56%) classic, five (45%) AIDS-related, and five (33%) endemic KS cases were positive for c-kit. There was no difference in the intensity of c-kit staining between the different epidemiologic groups and histologic stages of KS. HHV8 (LNA-1) immunoreactivity was present in all (100%) classic, 10 (91%) AIDS-related, and 9 (60%) endemic cases. LNA-1 staining was demonstrated in 13 (93%) of the c-kit-positive and 15 (75%) of the c-kit-negative KS lesions. These findings indicate that c-kit expression in lesional cells can be detected by immunohistochemistry in different epidemiologic forms and histologic stages of KS. Furthermore, the expression of c-kit does not correspond with the presence of HHV8 (LNA-1) immunoreactivity in KS lesions.

Molecular epidemiology of Kaposi's sarcoma herpesvirus (KSHV) in Cuban and German patients with Kaposi's sarcoma (KS) and asymptomatic sexual contacts

Kaposi's sarcoma (KS) shows a distinct geographical and ethnic distribution. The variable K1 gene serves to differentiate the KSHV subtypes A–E, M, N, and Q. Phylogenetic characterization of 19 classical and epidemic German KS specimens revealed the Eurasian KSHV subtypes C ( n = 13, including 6 classical KS) and A ( n = 6), while 27 Cuban specimens showed a variety of different subtypes (A: n = 16, 4 being A5; C: n = 8; B: n = 2; and the new subtype E: n = 1). Three pairs of isolates from KS patients and peripheral blood mononuclear cells (PBMC) of their sexual partners without KS were studied for the first time and found identical, strongly arguing for sexual transmission of KSHV in this unique cohort. The unique ethnic background of the Cuban population may explain the variety of different KSHV strains.

Aspects épidémiologiques de l'herpèsvirus humain 8 (HHV-8) et du sarcome de Kaposi

HHV-8 belongs to the herpesviridae family, to the gammaherpesvirinae subfamily, and to the rhadinovirus genus. Whereas several viral homologues exist in non human primates, HHV-8 is the only rhadinovirus known in human. HHV-8 is mainly the etiological agent of the four clinico-epidemiological forms of Kaposi's sarcoma (classic, endemic, post-transplant, and epidemic/HIV associated). HHV-8 is not an ubiquitous virus. It is mainly endemic in areas of high endemicity for classic or endemic Kaposi's sarcoma including the Mediterranean area and most of East and Central Africa. Its prevalence varies in the adult population, from less than 5% in the USA and Northern Europe to more than 50% in some regions of the African continent and around 10 to 20% in Italy and Greece. One can estimate that several hundred million people are HHV-8 infected worldwide with at least 150 million on the African continent. Modes of infection seem different in low and highly endemic areas. In low endemic areas, HHV-8 is mainly present in the male homosexual population, where this herpesvirus is transmitted during sexual contacts. In contrast, in highly endemic areas, as Central Africa, HHV-8 transmission occurs mainly from mother to child and between siblings. Heterosexual transmission remains low as well as transmission through blood products. Saliva seems to play a major role in the viral transmission, and may be a reservoir for HHV-8.

Reversal of some viral IL‐6 electrostatic properties compared to IL‐6 contributes to a loss of alpha receptor component recruitment

Human interleukin-6 (hIL-6) is a pleiotropic mediator of activation and proliferation across a large number of different cell types. Human herpesvirus-8 (HHV-8) has been associated with classical and AIDS-related Kaposi's sarcoma (KS). HHV-8 encodes viral IL-6 (vIL-6), a functional homolog of human interleukin-6, that promotes the growth of KS and of some lymphoma cells. Signaling induced by human IL-6 requires recruitment of the glycoprotein gp130, which acts as the signal transducing chain, and of IL-6Ralpha, which is necessary for cognate recognition and high affinity receptor complex formation. In contrast, the formation of a functional complex between vIL-6 and gp130 does not require the presence of IL-6Ralpha. The physico-chemical properties of vIL-6 have been analyzed and compared to those of hIL-6 and of the receptor chains, gp130 and IL-6Ralpha. Interaction sites on vIL-6 involve more hydrophobic residues than those of hIL-6. The electrostatic fields induced by vIL-6 and IL-6Ralpha are repulsive and prevent interaction between vIL-6 and IL-6Ralpha, whereas the electrostatic field induced by hIL-6 steers the complex formation with IL-6Ralpha. Subsequently, electrostatic binding free energy in the vIL-6/IL-6Ralpha complex is destabilizing, whereas it is stabilizing in the complex comprising hIL-6. These properties result from charge reversals between viral and human IL-6, an unusual phenomenon of amino acid substitutions within a homologous protein family. This suggests a selection pressure for vIL-6 to by-pass the IL-6Ralpha control of host defense against virus infection. This selection pressure has yielded the reversal of electrostatic properties of vIL-6 when compared to hIL-6.

Aggressive Behavior of Classical Kaposi's Sarcoma and Coexistence With Angiosarcoma

An 82-year-old Caucasian man presented with initially asymptomatic livid red plaques on the plantar surface of the feet that become confluent and evolved into invasively growing nodules accompanied by massive edema. Histology allowed a diagnosis of the classical form of Kaposi's sarcoma; the serology test result for HIV was negative, whereas the associated human herpes virus type 8 was detected by polymerase chain reaction on the skin sample. Over the subsequent 6 months, skin lesions become vegetative and partially necrotic, and extended to the hands and eyelids. Chemotherapy with vinblastine appeared to stabilize the cutaneous disease, but the patient developed a massive gastrointestinal hemorrhage secondary to dissemination to the stomach. Twelve months after the onset of the disease, vegetative and easily bleeding lesions progressively occluded the mouth of the patient: histological features were consistent with a low-grade angiosarcoma distinct from that of Kaposi's sarcoma. The patient could not chew and swallow anymore; he was put on an artificial nutrition but died shortly thereafter. This case illustrates that, even in its classical form, Kaposi's sarcoma may be a malignant, rapidly progressing tumor. a) The extent and rate of spread of initial skin lesions should be considered to be early signs of aggressive dissemination, even in the absence of other variables (i.e., histological pattern, human herpes virus type 8 positive mononuclear cells) associated with progression of the disease. b) An endoscopy may be useful given the high prevalence of gastrointestinal involvement. c) When classical Kaposi's sarcoma displays aggressive behavior a second, primary malignant tumor arising from the vascular tissue should be investigated. Even in its classical form, Kaposi's sarcoma may be a malignant, rapidly progressing tumor with visceral involvement; also, a second malignancy may occur in nearly one patient of four. Because localized skin lesions can regress completely with radiotherapy, watchful waiting is probably inappropriate in most cases.

Progression of classic Kaposi's sarcoma with rituximab

Rituximab is a monoclonal antibody directed against the CD20 antigen of B cells and is being used increasingly for treatment of antibody-mediated autoimmune diseases. We observed the rapid progression of Kaposi's sarcoma after our patient received rituximab for autoimmune hemolytic anemia. We postulate that by very specifically depleting B cells, rituximab affects T-cell function (eliminating B- and T-cell interactions), resulting in impaired T-cell-mediated immunity. Dermatologists should use caution when offering rituximab for off-label use.

A Common Genetic Variant inFCGR3A-V158F and Risk of Kaposi Sarcoma Herpesvirus Infection and Classic Kaposi Sarcoma

Associations of FCGR3A among men with HIV/acquired immunodeficiency syndrome suggest that host responses affect the pathogenesis of Kaposi sarcoma herpesvirus (KSHV) infection and risk of acquired immunodeficiency syndrome-associated Kaposi sarcoma. Using DNA from two HIV seronegative case-control populations in Italy, we examined whether the functional FCGR3A-V158F variant was associated with risk of KSHV infection or classic Kaposi sarcoma (CKS). In population I, we examined FCGR3A variants and risk of KSHV infection in 34 KSHV latent nuclear antigen (LANA)-seropositive and 120 LANA-seronegative adults from Sardinia (52% male; median age, 45 years; range, 31-60), whereas in population II, we examined risk of CKS from 133 CKS cases and 172 KSHV LANA-seropositive controls from Sicily, Rome, and Naples (70% males; median age, 74 years; range, 29-91). FCGR3A variants were determined by direct sequence analysis of a nested PCR of genomic DNA assay using allele-specific primers. KSHV LANA was determined by immunofluorescence assay. Overall, compared with the 158F allele, 158V was overrepresented among controls from both Mediterranean populations (frequency = 0.52 and 0.51, respectively). After controlling for age, 158V homozygous women were at increased risk of KSHV infection and CKS compared with 158F homozygous women [odds ratio (OR), 8.7; 95% confidence interval (95% CI), 0.8-98 and OR, 3.8; 95% CI, 1.0-14, respectively], whereas homozygous men were at decreased risk (OR, 0.4; 95% CI, 0.1-2.3 and OR, 0.4; 95% CI, 0.2-0.8, respectively). Significant gene-dose effects were observed among men and women at risk for CKS (P(trend) < or = 0.05). Our findings suggest that gender differences could possibly modify the effect of FCGR3A on risk of KSHV infection and CKS. Additional studies are required to confirm these relationships and determine their etiologic significance.

Angiosarcoma arising in a lymphedematous abdominal pannus with histologic features reminiscent of Kaposi's sarcoma: report of a case and review of the literature

Despite common endothelial origins, angiosarcoma and Kaposi's sarcoma are clinically and histologically distinct vascular proliferations. The development of angiosarcoma in a chronically edematous abdominal pannus is extremely uncommon. Similarly, tumors with the combined histologic features of angiosarcoma and Kaposi's sarcoma have rarely been described. We reviewed the literature on angiosarcoma arising in a lymphedematous abdominal pannus and evaluated an 81-year-old morbidly obese woman who had profound, long-standing edema of the lower abdominal wall in which an aggressive vascular tumor developed. Three clinically similar cases were identified in the literature. All patients were women who generally experienced rapid disease progression. In addition, in our patient, sequential cutaneous sampling from different lesional sites demonstrated disparate histologic changes, ranging from those of classic Kaposi's sarcoma to high-grade angiosarcoma, to areas with combined features of the two tumors. A polymerase chain reaction performed on lesional tissue was negative for human herpesvirus-8 DNA. It is important to note that angiosarcoma may develop in the abdomen in association with chronic lymphedema, as demonstrated by the cases noted in this report. In addition, our case highlights the difficulty in differentiating histologically angiosarcoma from Kaposi's sarcoma in some situations, and demonstrates the value of close clinicopathologic correlation and sequential tissue sampling in evaluating problematic cases.

Classic Kaposi's sarcoma in the Inuit of northern Quebec

Classic Kaposi's sarcoma (KS) is predominantly a disease of eastern Mediterranean and Ashkenazi Jewish elderly men. Nevertheless, the disease has been reported to occur in people from various other ethnic and regional backgrounds. We report, for the first time, the occurrence of classic KS in five Inuit people living in northern Quebec, Canada. We describe the case of a 69-year-old Inuit man with classic KS, and report four other cases of KS in the Inuit population, identified by a review of our hospital's dermatopathology records. The discovery of classic KS in the Inuit population of northern Quebec brings with it new questions as to the origins of the KS-associated herpes virus in this population. It is our belief that the answers to these questions are in the genotype of the virus that is present in this community.