Kaposi's sarcoma

Kaposi's sarcoma is a type of cancer that forms from the lining of blood and lymphatic vessels. It is characterized by the development of purplish, reddish-blue, or dark brown/black skin nodules or plaques. The disease is caused by an infection with Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, and its clinical presentation is heavily influenced by the host's immune status.

Signs and symptoms

The most common initial manifestation is the appearance of cutaneous lesions, which often present on the lower limbs, face, oral mucosa, and genitalia. These lesions can range from flat patches to raised plaques and nodular tumors, and may be associated with lymphedema due to lymphatic obstruction. Involvement of internal organs is frequent, particularly in immunosuppressed individuals, affecting the gastrointestinal tract, lungs, and lymph nodes, which can lead to gastrointestinal bleeding, shortness of breath, and pleural effusions.

Causes and risk factors

The essential causative agent is Human herpesvirus 8, a gammaherpesvirus. Infection with this virus is necessary but not sufficient for development; cofactors related to immune suppression are critical. Major risk factors include infection with HIV-1, particularly in individuals not receiving effective antiretroviral treatment, and iatrogenic immunosuppression following solid organ transplantation. Other risk groups include elderly men of Mediterranean or Eastern European descent (classic form) and children and adults in certain regions of Sub-Saharan Africa (endemic form).

Pathophysiology

Following infection, Human herpesvirus 8 establishes latency primarily in B lymphocytes and endothelial cell precursors. Viral oncogenes, such as latency-associated nuclear antigen (LANA), v-cyclin, and v-FLIP, drive cellular proliferation and inhibit programmed cell death. The resulting lesions are composed of proliferating spindle cells of endothelial origin, aberrant angiogenesis, and chronic inflammatory infiltrates. The cytokine milieu, especially in the context of HIV-1 co-infection and high levels of HIV Tat protein and inflammatory cytokines, further promotes tumor growth.

Diagnosis

Definitive diagnosis requires a skin or tissue biopsy for histopathological examination. Characteristic findings include proliferations of spindle-shaped cells forming slit-like vascular spaces, extravasated red blood cells, and hemosiderin deposition. Immunohistochemical staining for markers like CD34 and CD31 (endothelial markers) and latency-associated nuclear antigen (HHV-8) is confirmatory. For suspected internal involvement, imaging studies such as chest CT or gastrointestinal endoscopy may be employed.

Treatment

Management is highly dependent on the extent of disease and the patient's underlying immune status. For patients with HIV/AIDS, initiation or optimization of combination antiretroviral therapy is the cornerstone of treatment and often leads to regression. Localized disease can be treated with local radiation or procedures like cryosurgery. For widespread or symptomatic disease, systemic therapies are used, including liposomal anthracyclines, paclitaxel, and interferon-alpha. In iatrogenic cases, reduction of immunosuppressive medication is attempted when possible.

Epidemiology

The epidemiology is distinctly heterogeneous, correlating with the prevalence of Human herpesvirus 8 and associated risk factors. Before the HIV/AIDS pandemic, it was a rare neoplasm, primarily seen in older men from the Mediterranean basin and in parts of Equatorial Africa. The advent of the AIDS epidemic led to a dramatic increase in incidence, making it a common AIDS-defining illness. With the widespread use of highly active antiretroviral therapy in countries like the United States, its incidence has declined sharply, though it remains a significant public health problem in Sub-Saharan Africa.