Sandbox: Kaposi

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Pathophysiology

  • Kaposi's sarcoma arises from endothelial cells, which are epithelial cells that are normally lines the interior surface of blood vessels and lymphatic vessels.

Kaposi's sarcoma (KS) is a tumor caused by Human herpesvirus 8 (HHV8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV).

Despite its name, it is generally not considered a true sarcoma, which is a tumor arising from mesenchymal tissue.

KS actually arises as a cancer of lymphatic endothelium and forms vascular channels that fill with blood cells, giving the tumor its characteristic bruise-like appearance.

Micrograph of a Kaposi's sarcoma showing the characteristic spindle cells, high vascularity and intracellular hyaline globs. H&E stain.

KS lesions contain tumor cells with a characteristic abnormal elongated shape, called spindle cells.

The tumor is highly vascular, containing abnormally dense and irregular blood vessels, which leak red blood cells into the surrounding tissue and give the tumor its dark color.

Inflammation around the tumor may produce swelling and pain.

Although KS may be suspected from the appearance of lesions and the patient's risk factors, definite diagnosis can be made only by biopsy and microscopic examination, which will show the presence of spindle cells.

Detection of the KSHV protein LANA in tumor cells confirms the diagnosis.


Transmission

In Europe and North America, KSHV is transmitted through saliva. Thus, kissing is a theoretical risk factor for transmission. Higher rates of transmission among gay and bisexual men have been attributed to "deep kissing" sexual partners with KSHV.[1] Another alternative theory suggests that use of saliva as a sexual lubricant might be a major mode for transmission. Prudent advice is to use commercial lubricants when needed and avoid deep kissing with partners with KSHV infection or whose status is unknown.

KSHV is transmissible during organ transplantation [2] and to a lesser extent through blood transfusion.[3] Testing for the virus before these procedures is likely to effectively limit iatrogenic transmission.

They used representational difference analysis (a method to subtract out all of the human DNA from a sample) to isolate the viral genes.
They then used these small DNA fragments as starting points to sequence the rest of the viral genome in 1996. 
This, the eighth human herpes virus (HHV-8)—now known as Kaposi's sarcoma-associated herpesvirus (KSHV)—has since been found in all KS lesions tested, and is considered the cause of the disease. 

KSHV is a unique human tumor virus that has incorporated cellular genes that cause tumors into its genome ("molecular piracy");

the stolen cellular genes may help the virus escape from the immune system, but in doing so it also causes cells to proliferate. 
It is related to Epstein-Barr virus, a very common herpes virus that can also cause human cancers.