Kaposi’s sarcoma: Etiology and pathogenesis, inducing factors, causal associations, and treatments: Facts and controversies

Abstract

Kaposi's sarcoma (KS), an angioproliferative disorder, has a viral etiology and a multifactorial pathogenesis hinged on an immune dysfunction. The disease is multifocal, with a course ranging from indolent, with only skin manifestations to fulminant, with extensive visceral involvement. In the current view, all forms of KS have a common etiology in human herpesvirus (HHV)-8 infection, and the differences among them are due to the involvement of various cofactors. In fact, HHV-8 infection can be considered a necessary but not sufficient condition for the development of KS, because further factors (genetic, immunologic, and environmental) are required. The role of cofactors can be attributed to their ability to interact with HHV-8, to affect the immune system, or to act as vasoactive agents. In this contribution, a survey of the current state of knowledge on many and various factors involved in KS pathogenesis is carried out, in particular by highlighting the facts and controversies about the role of some drugs (quinine analogues and angiotensin-converting enzyme inhibitors) in the onset of the disease. Based on these assessments, it is possible to hypothesize that the role of cofactors in KS pathogenesis can move toward an effect either favoring or inhibiting the onset of the disease, depending on the presence of other agents modulating the pathogenesis itself, such as genetic predisposition, environmental factors, drug intake, or lymph flow disorders. It is possible that the same agents may act as either stimulating or inhibiting cofactors according to the patient's genetic background and variable interactions. Treatment guidelines for each form of KS are outlined, because a unique standard therapy for all of them cannot be considered due to KS heterogeneity. In most cases, therapeutic options, both local and systemic, should be tailored to the patient's peculiar clinical conditions.

Isolated classic Kaposi Sarcoma in an old female patient

“…The best therapeutic results are obtained in the classic KS with only local treatment [12,13] . Treatment of HIV-associated KS requires anti-retroviral therapy, which leads to both immune reconstitution and control of HIV viremia [14] .…”

“…Treatment of HIV-associated KS requires anti-retroviral therapy, which leads to both immune reconstitution and control of HIV viremia [14] . Radiotherapy is effective and often represents the best local treatment for palliation of pain, bleeding or edema, with response and complete remission rates of more than 90% and 70%, respectively [12] . Based on the patient's clinical and laboratory findings, radiotherapy suggested to the patient but the patient did not accept the radiotherapy.…”

Kaposi Sarcoma with Abscessing Clinicopathologic Morphology

“…In the pre-HIV/AIDS era, the incidence of KS in Europe and North America ranged from 0.01 to 0.06 per 100,000, although an increased incidence was noted in patients post-renal transplantation and on immunosuppression [1,2]. In a transplant setting, a patient is 400-500 times more likely to develop KS within 3 to 124 months, than in the general population [14].…”

“…The average patient age was 27.8 (range: 12-50) years. The patients presented with painful, expanding masses in the toe (10), thigh (4), trunk (1), arm (1), palate (1), neck (1) and anus (1). The mass lesions were recognized as abscesses clinically and the walls thereof were biopsied during the incision and drainage procedure.…”

Infections After Orthotopic Liver Transplantation

“…For patients with visceral KS, chemotherapy agents such as bleomycin sulfate, doxorubicin hydrochloride liposome, and vincristine sulfate have been used with some success. 134 HHV-8 is sensitive in vitro to ganciclovir, foscarnet, and cidofovir.…”