Diagnosing Kaposi’s sarcoma involves careful examination of the skin and other body areas where lesions may appear, followed by specific tests that confirm the presence of cancerous cells and help doctors understand how far the disease has spread.

Introduction: Who Should Seek Diagnostic Testing

Not everyone needs to worry about Kaposi’s sarcoma, but certain groups of people should pay extra attention to unusual changes in their skin or general health. If you notice purple, red, or brown spots on your skin that don’t go away like normal bruises, it’s important to have them checked out. These spots might be flat at first, or they could be raised above the surrounding skin. Unlike regular bruises, they won’t change color or fade when you press on them.^[1]

People living with HIV or AIDS should be particularly vigilant about any skin changes. This is the group most commonly affected by Kaposi’s sarcoma in the United States, especially men who have sex with men. If you’re HIV-positive and develop any unusual skin lesions, mouth sores, or experience unexplained symptoms like coughing up blood or digestive problems, seeking medical attention promptly is crucial.^[2]

Those who have received an organ transplant and are taking medicines that weaken the immune system, called immunosuppressants, also need to watch for signs of this disease. The same applies to older men of Mediterranean, Eastern European, or Ashkenazi Jewish descent, who may develop what’s called classic Kaposi’s sarcoma. In these cases, lesions typically appear on the lower legs or feet first.^[3]

Because Kaposi’s sarcoma can affect not just the skin but also internal organs like the lungs, digestive system, and lymph nodes, it’s advisable to seek diagnostic testing if you experience symptoms that seem unrelated but might indicate internal lesions. These could include difficulty breathing, persistent coughing, blood in your stool, unexplained belly pain, or painful swelling in your arms or legs.^[2]

Classic Diagnostic Methods

Diagnosing Kaposi’s sarcoma begins with a thorough physical examination conducted by your healthcare provider. During this exam, the doctor will carefully inspect your skin, looking for any lesions that have the characteristic appearance of Kaposi’s sarcoma—typically purple, red, or brown patches or bumps. They will also examine the inside of your mouth, as lesions can develop there as well. The provider will ask detailed questions about your medical history, including whether you have HIV, have had an organ transplant, or belong to one of the groups at higher risk for this disease.^[2]

The most reliable way to confirm Kaposi’s sarcoma is through a biopsy, which means removing a small piece of tissue from a suspected lesion so it can be examined under a microscope. There are several types of biopsies that doctors can perform. In an excisional biopsy, the entire skin growth is removed using a scalpel. An incisional biopsy removes only part of the growth. A core biopsy uses a wider needle to take out a portion of tissue, while a fine-needle aspiration uses a thin needle to extract cells from the lesion.^[8]

Once the tissue sample reaches the laboratory, a specialist called a pathologist examines it to look for signs of cancer. A key finding that confirms Kaposi’s sarcoma is the presence of a viral protein called LANA, which comes from human herpesvirus-8 (HHV-8), the virus that causes this disease. The pathologist will also look for the characteristic features of Kaposi’s sarcoma cells, including new blood vessels, cancer cells, and collections of red and white blood cells.^[11]

If the skin biopsy confirms Kaposi’s sarcoma, additional tests may be needed to determine whether the disease has spread beyond the skin to internal organs. A chest X-ray is often performed to check whether lesions have developed in the lungs. This simple imaging test uses radiation to create pictures of the organs inside your chest. If the X-ray shows something unusual, more detailed imaging may be ordered.^[8]

A CT scan, also called computed tomography, is a more sophisticated imaging test that uses X-rays to create detailed, three-dimensional pictures of the inside of your body. For Kaposi’s sarcoma, CT scans of the chest, abdomen, or pelvis can reveal whether lesions are present in the lungs, digestive tract, or other internal organs. During a CT scan, you lie still on a table that slides through a large, doughnut-shaped machine that takes pictures from multiple angles.^[9]

To check for Kaposi’s sarcoma in the digestive system, doctors may perform an endoscopy. This procedure involves inserting a thin, flexible tube with a light and camera on the end through your mouth or rectum. An upper endoscopy examines the esophagus, stomach, and first part of the small intestine, while a colonoscopy looks at the colon and rectum. If the doctor sees any suspicious lesions during these procedures, they can take small tissue samples for biopsy right then and there.^[9]

A fecal occult blood test is a simple test that checks your stool for hidden blood, which might indicate bleeding from Kaposi’s sarcoma lesions in your digestive tract. If this test comes back positive, it usually prompts further investigation with an endoscopy or colonoscopy to find the source of the bleeding.^[9]

For suspected Kaposi’s sarcoma in the lungs, a bronchoscopy may be performed. This is similar to an endoscopy, but the flexible tube goes through your nose or mouth into your airways and lungs. The doctor can see any lesions in your breathing passages and take tissue samples if needed. This test is particularly important if you’re experiencing symptoms like difficulty breathing, persistent coughing, or coughing up blood.^[8]

Distinguishing Kaposi’s Sarcoma from Other Conditions

Because Kaposi’s sarcoma lesions can look similar to other skin conditions, doctors must carefully distinguish it from several other diseases during the diagnostic process. The purple or brown skin spots might resemble conditions such as blue rubber bleb nevus syndrome, pyogenic granuloma, melanocytic nevi (moles), or even melanoma, a serious type of skin cancer. This is why biopsy and laboratory examination are so critical—visual inspection alone isn’t enough to make a definitive diagnosis.^[5]

The appearance of the lesions provides important clues but can also be misleading. Kaposi’s sarcoma lesions typically don’t cause pain or itching, and they maintain their color when pressed, unlike regular bruises that blanch or fade under pressure. They may start out flat and small, almost looking harmless, but can grow larger over time and even merge together. Some develop into nodules that may ulcerate and bleed.^[6]

Diagnostics for Clinical Trial Qualification

When patients are being considered for enrollment in clinical trials studying new treatments for Kaposi’s sarcoma, additional diagnostic procedures and standardized assessments are typically required. Clinical trials have specific entry criteria to ensure that participants are appropriate for the experimental treatment being tested and that results can be accurately measured and compared.

A confirmed tissue diagnosis through biopsy is almost always mandatory for clinical trial participation. The biopsy must clearly show the presence of Kaposi’s sarcoma cells and, in most cases, evidence of HHV-8 infection. This ensures that all participants truly have the disease being studied, which is essential for evaluating whether the treatment works.^[11]

Comprehensive imaging studies, including CT scans of the chest, abdomen, and pelvis, are usually required before entering a clinical trial. These baseline scans document exactly where lesions are located and how extensive the disease is at the start of the study. This information allows researchers to accurately measure whether the treatment causes tumors to shrink, stay the same, or grow during the trial.^[8]

Blood tests are another standard requirement for clinical trial qualification. These typically include complete blood counts to measure red blood cells, white blood cells, and platelets, as well as tests of liver and kidney function. For patients with HIV-related Kaposi’s sarcoma, additional blood work measures the level of HIV in the blood (called viral load) and counts CD4 cells, which are a type of immune cell that HIV attacks. These measurements help determine the severity of immune suppression and whether patients meet the trial’s eligibility criteria.^[14]

Many clinical trials classify patients into different risk groups based on specific criteria. For epidemic Kaposi’s sarcoma associated with HIV/AIDS, factors such as the extent of tumor involvement, immune system status (CD4 count), and whether there’s disease in internal organs help determine whether a patient is considered “good risk” or “poor risk.” This classification influences which treatment approaches might be most appropriate and helps ensure that patients enrolled in a trial are comparable to one another.^[15]

Functional status assessments are also common in clinical trials. These measure how well you can perform daily activities and whether the disease is affecting your ability to care for yourself. Healthcare providers use standardized scales to evaluate your performance status, which helps determine whether you’re healthy enough to tolerate the experimental treatment being studied.

Documentation of any previous treatments for Kaposi’s sarcoma is essential for clinical trial participation. Researchers need to know what treatments you’ve already tried, how you responded to them, and when you received them. Some trials specifically enroll patients who haven’t received any prior treatment, while others focus on people whose disease didn’t respond to standard treatments.