General Information About Kaposi Sarcoma
Classic Kaposi Sarcoma
African Kaposi Sarcoma
Immunosuppressive Treatment–Related Kaposi Sarcoma
Epidemic Kaposi Sarcoma
Nonepidemic Gay–Related Kaposi Sarcoma
Kaposi sarcoma (KS) was first described in 1872 by the Hungarian
dermatologist, Moritz Kaposi. From that time until the current human
immunodeficiency virus (HIV) disease epidemic identified with the Acquired
Immunodeficiency Syndrome (AIDS), KS remained a rare tumor. While most of the
cases seen in Europe and North America have occurred in elderly men of Italian
or Eastern European Jewish ancestry, the neoplasm also occurs in several other
distinct populations: young black African adult males, prepubescent children,
renal allograft recipients, and other patients receiving immunosuppressive
therapy. The disseminated, fulminant form of KS associated with HIV disease is
referred to as epidemic KS to distinguish it from the classic, African, and
transplant-related varieties of the neoplasm. In addition, KS has been
identified in homosexual men apart from the HIV disease epidemic.[1]
Although
the histopathology of the different types of the Kaposi tumor is essentially
identical in all of these groups, the clinical manifestations and course of the
disease differ dramatically.[2] A key piece to the puzzle of KS pathogenesis
was the 1994 discovery of a gamma herpes virus, human herpes virus type 8
(HHV-8), also known as Kaposi sarcoma herpes virus.[3] HHV-8 was identified
in KS tissue biopsies from virtually all patients with classic, African,
transplant-related, and AIDS-associated KS but was absent from noninvolved
tissue.[4-7]
Classic Kaposi Sarcoma
Considered a rare disease, classic KS occurs more often in males, with a ratio
of approximately 10 to 15 males to 1 female. In North Americans and Europeans,
the usual age at onset is between 50 and 70 years. Classic KS tumors
usually present with one or more asymptomatic red, purple, or brown patches,
plaques, or nodular skin lesions. The disease is often limited to single or
multiple lesions usually localized to one or both lower extremities, especially
involving the ankles and soles.
Classic KS most commonly runs a
relatively benign, indolent course for 10 to 15 years or more, with slow
enlargement of the original tumors and the gradual development of additional
lesions. Venous stasis and lymphedema of the involved lower extremity are
frequent complications. In long-standing cases, systemic lesions can develop
along the gastrointestinal tract, in lymph nodes, and in other organs. The
visceral lesions are generally asymptomatic and are most often discovered only
at autopsy, though clinically, gastrointestinal bleeding can occur. As many as 33% of the patients with classic KS develop a second primary malignancy,
which is most often non-Hodgkin lymphoma.[8-10]
African Kaposi Sarcoma
In the 1950s, KS was recognized as a relatively common neoplasm endemic in
native populations in equatorial Africa and comprised approximately 9% of all
cancers seen in Ugandan males. African KS is seen as either an indolent
neoplasm identical to the classic disease seen in Europe and North America or
as an aggressive disease with fungating and exophytic tumors that may invade
the subcutaneous and surrounding tissue including the underlying bone. In
Africa, both the indolent and locally more aggressive forms of KS occur with a
male-to-female ratio comparable to that observed with the classic KS tumor seen
in North America and Europe. In general, however, patients in Africa are
significantly younger than their European counterparts. A lymphadenopathic
form of KS is also seen in Africa, primarily in prepubescent children
(male:female ratio 3:1). In these cases, the generalized lymphadenopathy is
frequently associated with visceral organ involvement. The prognosis is very
poor with a 100% fatality rate within 3 years.[11,12]
Immunosuppressive Treatment–Related Kaposi Sarcoma
In 1969, the first case of KS in association with immunosuppression in a renal
transplant patient was described. Since that time, a number of renal and other
organ allograft recipients who received prednisone and azathioprine developed
KS shortly after the onset of immunosuppressive therapy.[13] Estimates of the incidence of
KS in immunosuppressed renal transplant recipients are between 150 and 200 times the expected incidence of the tumor in the general
population. The average time to develop KS after transplantation is 16
months. Although the KS tumor in iatrogenically immunosuppressed patients
often remains localized to the skin, widespread dissemination with
mucocutaneous or visceral organ involvement is common. In some cases, the KS
tumors have regressed as a result of reduction or changes in immunosuppressive
therapy. Clinical management of renal transplant patients who develop KS is
difficult and requires a balance between the risk of death from generalized KS
and the risk of graft rejection and complications of renal failure that may
occur if the immunosuppressive therapy is discontinued.
Epidemic Kaposi Sarcoma
In 1981, a fulminant and disseminated form of KS in young homosexual or
bisexual men was first reported as part of an epidemic now known as AIDS.[14]
The etiology of AIDS is a T-cell lymphotropic retrovirus known as HIV. The
underlying immunologic deficiency that characterizes HIV disease is an acquired
profound disorder of cell-mediated immune functions. This immunologic
deficiency and immune dysregulation predisposes the host to a variety of
opportunistic infections and unusual neoplasms, especially KS. HIV may
play an indirect role in the development of KS.[15]
Approximately 95% of all the cases of epidemic KS in the United States have
been diagnosed in homosexual or bisexual men. In the past, approximately 26%
of all homosexual males with HIV disease presented with, or eventually
developed, KS during the course of their illness. By comparison, fewer than 3%
of all heterosexual intravenous drug users with HIV disease developed KS. The
proportion of HIV disease patients with KS has steadily decreased since the
epidemic was first identified in 1981.[16] About 48% of AIDS patients in 1981
had KS as their presenting AIDS diagnosis. By August 1987, the cumulative
proportion of AIDS patients with KS had diminished to fewer than 20%. The
introduction of highly active antiretroviral therapy (HAART) has delayed or
prevented the emergence of drug-resistant HIV strains, profoundly decreased viral
load, led to increased survival, and lessened the risk of opportunistic
infections.[17,18] The use of HAART has been associated with a sustained and substantial decline in KS incidence in multiple large cohorts.[19-24]
The lesions that develop may involve the skin; oral mucosa; lymph
nodes; and visceral organs, such as the gastrointestinal tract, lung, liver and
spleen. Most patients with HIV disease who present with the mucocutaneous
lesions of KS feel healthy and are usually free of systemic symptoms, as
compared to patients with HIV disease who first develop an opportunistic
infection. The sites of disease at presentation of epidemic KS are much more
varied than the sites seen in other types of this neoplasm. In an early report
on the clinical manifestations of the disease, 49 patients were described.[25]
Of these patients, 8% had no skin involvement, 27% had localized or fewer than five skin
lesions, and 63% had innumerable skin lesions widely distributed over the skin
surface area. Of these patients, 61% had generalized
lymphadenopathy at the time of the first examination. Four of these patients,
who had generalized lymphadenopathy in the absence of skin lesions or
detectable visceral organ involvement at the time of presentation, were found to
have biopsy-proven KS localized to the lymph nodes. In 45% of the patients
studied, KS lesions were found in one or more sites along the gastrointestinal
tract. Of these patients, 29% had either unexplained fever or
unexplained weight loss when first seen. While most patients present with skin
disease, KS involvement of lymph nodes or the gastrointestinal tract may
occasionally precede the appearance of the cutaneous lesions.
Eventually, most patients with epidemic KS develop disseminated disease. The disease often progresses in an orderly fashion from a few localized or
widespread mucocutaneous lesions to more numerous lesions and generalized skin disease
with lymph node, gastrointestinal tract disease, and other organ involvement.
Pleuropulmonary KS is an ominous sign usually occurring late in the course of
the disease, especially in those patients whose death is directly attributed to
KS.[26] Most patients with epidemic KS die of one or more complicating
opportunistic infections.
Nonepidemic Gay–Related Kaposi Sarcoma
Several reports documented KS in homosexual men who
persistently had no evidence of HIV infection. These patients had an
indolent and cutaneous form of the disease, which caused new lesions to appear every
few years. Lesions occur most commonly on the extremities and genitalia but
can occur anywhere on the skin.[1] These cases may indicate the presence of
causal factors other than HIV that homosexual men may be exposed to because of
their lifestyle.
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