The outbreak of Kaposi's sarcoma (KS) and Pneumocystis carinii
pneumonia (PCP) among young, previously healthy, homosexual men
in early 1981 marked the initial recognition of the acquired immune
deficiency syndrome (AIDS) [1,2]. KS was among the first AIDS-defining
conditions and has remained one of the major cancers associated
with human immunodeficiency virus-type 1 (HIV-1) infection. The
sudden increase in the incidence of KS has provided considerable
new information. This article summarizes recent developments in
research on KS and proposes a coherent model for its pathogenesis.
In 1872, Moritz Kaposi first described this disease as "multiple
idiopathic pigmented hemangiosarcoma". He described the
condition as localized, nodular, brown-red to blue-red tumors
that appear first on the soles of the feet and then on the hands.
He was also aware of the multifocal nature of the disease, the
occurrence of visceral involvement, and its vascular nature.
This form of KS, known as classic KS, occurs most commonly in
Eastern Europe and North America among older men of Italian or
Jewish ancestry . In the 1950s and 1960s, a more aggressive
form of KS that occurred in younger individuals was described
in central Africa, accounting for 9% of all cancers in Uganda5].
In the mid-1970s, KS was reported among a new group of patients,
those receiving immunosuppressive therapy for renal transplantation
In early 1980, outbreaks of KS were reported among young homosexual/bisexual
men in New York and San Francisco who engaged in promiscuous sexual
activity and had signs of cellular immune defects [1,2,8-11].
Prior to the AIDS epidemic, KS was considered a rare disease .
The annual incidence of classic KS in the United States was estimated
to be 0.021 to 0.061 per 100,000 people [4,12,13]. Although this
form of KS is seen mostly in persons of Italian or Jewish descent,
it has been observed in other groups, including three persons
of Eskimoan descent  and a large group of people in Sweden
and Norway, where there is only a small Jewish population [15,16].
A twofold increase in the incidence of classic KS in Sweden during
the late 1960s was reported in the late 1980s . Other clusters
of classic KS have been reported from the Mediterranean island
of Sardinia and on the Peloponnesian peninsula.
The literature indicates a male to female ratio of 15:1 for classic
KS, but recent data suggest a ratio of 2:1 to 3:1[4,17]. Classic
KS is most common in black African people [12,13,18,19]. It accounts
for 1.3% of all cancers in Durban, South Africa, 4% in Tanzania,
and 9% to 10% in equatorial countries in Africa, such as Uganda
and the Congo [18,19].
Because of the increase in the number of organ transplants and
the more frequent use of immunosuppressive therapy for autoimmune
disorders, iatrogenically induced KS has been reported with increasing
frequency. In organ-transplant recipients, the overall prevalence
of KS is 0.52% (1.24% for liver, 0.45% for kidney, and 0.41% for
It has been established that KS occurs primarily in homosexual/bisexual
men. To a much lesser degree, it also occurs in female partners
of bisexual men and in women from certain regions of the Caribbean
and Africa who acquired HIV infection through heterosexual contact
. Other groups at risk of AIDS are reported to develop KS,
but to a lesser degree. Approximately 95% of all reported cases
of AIDS-associated KS in the United States have been in homosexual
and bisexual men, representing 26% of all homosexual men with
AIDS. In comparison, AIDS-associated KS is reported in 9% of Haitians,
3% of heterosexual intravenous drug abusers, 3% of transfusion
recipients, 3% of women with AIDS, 3% of children with AIDS, and
1% of persons with hemophilia. So far, AIDS-associated KS has
not been seen in women with AIDS who acquired HIV infection through
heterosexual contacts with men with transfusion-acquired AIDS
or with iatrogenically infected persons with hemophilia .
The incidence of AIDS-associated KS is reported to be quite high
among homosexual/bisexual men who meet their partners in places
where anonymous sex is common, such as bath houses. Specifically,
sexual practices involving rimming (oral/anal contact) and fisting
(insertion of a hand or foot into a partner's rectum) were more
commonly practiced among homosexual/bisexual men who developed
There has been a steady decline in the incidence of KS since the
Table 1). In 1992, it was reported that only 10% of
all patients with AIDS had KS. Since the beginning of the epidemic,
the overall incidence of AIDS-associated KS is 13%. Recent
changes in the definition of AIDS-defining conditions will help
reduce the ratio of AIDS-associated KS. This trend has been the
subject of several reviews and discussions [21,23]. One explanation
may be the decreased use of unlabeled amyl nitrite, an inhalant
recreational drug and a possible mitogen [22,24]. Other epidemiologic
studies suggest that changes in certain sexual practices may account
for the decreasing incidence of KS [25,26].
This steady decline in the incidence of AIDS-associated KS has
been paralleled by a decrease in the incidence of seroconversion
in homosexual men. Thus, it is believed that changes in the sexual
behavior of homosexual/bisexual men and avoidance of high-risk
behaviors for contracting HIV have been contributing factors.
AIDS-associated KS has been reported in the pediatric population,
mostly in the form of lymphadenopathic KS, which is usually detected
at autopsy [27,28]. Mucocutaneous KS has also been reported in
children who developed HIV infection via blood transfusions [29,30].
In Africa, AIDS-associated KS appears to be transmitted by heterosexual
contact and has an approximately equal incidence among men and
women . This is in contrast to the male predominance observed
in all other populations, and a male-to-female ratio of approximately
8:1 for AIDS-associated KS in the United States.
Four different types of KS are recognized: classic, endemic African,
iatrogenic, and AIDS-associated. Classic KS usually manifests
with reddish-purple macules, papules, plaques, or nodules. Lesions
may coalesce to form large plaques and tumors that may produce
fungating masses with ulceration. Lesions are frequently located
on the lower extremities but may appear anywhere on the skin or
mucous membranes. Older lesions become brown and may develop a
verrucous and hyperkeratotic surface. The lesions are initially
soft and spongy but later become hard and solid. Gastrointestinal
lesions are often asymptomatic in classic KS and are usually detected
only at autopsy. Nonpitting edema of the lower extremities may
precede or follow tumor invasion into the superficial and deep
lymphatic system. Lymph nodes and internal organs are rarely involved
. Classic KS usually runs a benign, protracted course. Rapid
progression with involvement of internal organs is rarely reported.
Clinical forms of African KS have been described as nodular, florid,
infiltrative, and lymphadenopathic (
Table 2). This classification
is based on the clinicopathologic presentation of the disease.
The lymphadenopathic form is usually seen in African children
and young adults. It manifests mainly with involvement of the
lymph nodes and has a rapidly fatal course.
Among recipients of transplants, KS is the second most common
tumor after lymphoma. It has been reported to occur more often
in patients who receive cyclosporine (Sandimmune) as part of their
immunosuppressive regimen . The mean duration of cyclosporine
therapy before the development of KS is 23 months [32,33]. In
iatrogenic KS, cutaneous involvement is most common; however,
lymphatic and visceral dissemination can occur. The disease runs
a clinical course similar to that of classic KS, but, in some
cases, the course may be more aggressive. Resolution of the disease
has been reported after withdrawal or reduction of immunosuppressive
The clinical presentation of AIDS-associated KS is markedly different
from that of other forms of the disease. AIDS-associated KS is
characterized by a multifocal, widespread distribution that may
involve any location on the skin or mucous membranes, as well
as the lymph nodes, gastrointestinal tract, and other visceral
organs [35,36]. There is considerable variability in the timing
of the initial development of KS in HIV-infected individuals.
We have seen patients with AIDS-associated KS who lacked evidence
of immune impairment [35-37]. KS may be the first sign of HIV
infection, especially in populations where HIV testing is not
routinely performed. It can also arise in the later stages of
HIV infection, even up until the last week of life, when patients
are suffering from severe immune deficiency and various opportunistic
Early lesions appear as pink to red macules or tense, purple papules.
The lesions appear mostly on the face, especially the nose, eyelids,
and ears, and on the trunk. The lower extremities may also be
involved. The lesions may progress to form plaques, nodules, and
tumors, which may eventually erode and ulcerate. The oral mucosa
may be involved, with KS lesions appearing on the palate, gingiva,
epipharynx, and larynx. Oral cavity involvement is seen in 10%
to 15% of patients with AIDS-associated KS. Considerable discomfort
and difficulty in eating and swallowing may be caused by oral
Extracutaneous KS is observed at almost every internal site, including
the gastrointestinal tract, lymph nodes, and lungs. Both the gastrointestinal
tract and lymph nodes may be the initial and/or exclusive site
of KS lesions [38-40]. KS lesions are most commonly found in the
stomach and duodenum. The lesions are frequently symptomatic,
with patients experiencing nausea, ulcerating, bleeding, and ileus.
They are localized mostly in the submucosa and are readily visible
by gastroscopy, although they are underdiagnosed by superficial
Patients with pulmonary KS often present with symptoms quite similar
to those of PCP, such as intractable cough and respiratory insufficiency
[41-43]. Accurate diagnosis is achieved by bronchoscopy, bronchoalveolar
lavage, and bronchial biopsy. The prognosis of pulmonary KS is
poor, even with aggressive systemic chemotherapy and radiation
therapy [41-43]. Involvement of bone, subcutaneous tissues and
skeletal muscle, bone marrow, peritoneal cavity and omentum, and
the heart is rarely reported [44-49].
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