Some symptoms of kidney cancer aren’t directly related to your kidneys. More than one-third of people diagnosed with renal cell carcinoma (RCC) have paraneoplastic syndromes that can cause some surprising symptoms. These effects happen when the cancer triggers problems elsewhere in the body — sometimes before the tumor itself causes any signs.

Paraneoplastic syndromes happen when a tumor releases signals or hormones that affect how organs work. These syndromes can affect many different organ systems. For example, these can include your nervous system, skin, blood, and joints. For some people, symptoms of a paraneoplastic syndrome could be the first thing they notice before a cancer diagnosis.

Paraneoplastic symptoms can also significantly impact your quality of life with RCC, so it’s important to recognize them and get proper treatment. In this article, we’ll cover a few of the paraneoplastic syndromes that develop with RCC and the unusual symptoms they may cause.

What Causes Paraneoplastic Syndromes?

Paraneoplastic syndromes develop when tumors release signaling chemicals like hormones, cytokines (proteins that control inflammation), and growth factors. Sometimes, in trying to attack the tumor, your immune system also damages healthy parts of your body. This is called an autoimmune response.

Who Develops Paraneoplastic Syndromes?

Paraneoplastic syndromes are more common with stage 4 RCC. In stage 4 RCC, the kidney cancer has spread to distant parts of the body in a process called metastasis. According to the journal Urologic Oncology: Seminars and Original Investigations, you may be more likely to develop paraneoplastic syndromes if you’re female. It may also be a risk factor if you have other medical conditions in addition to kidney cancer.

Surgery May Cure Paraneoplastic Syndromes

Although the tumor doesn’t directly cause symptoms of paraneoplastic syndromes, cancer is still the main cause. Because of this, symptoms often resolve after starting cancer treatment. In the case of RCC, these syndromes can often be cured after nephrectomy surgery.

Surgery may be a partial nephrectomy (only part of the kidney is removed) or a radical nephrectomy (the entire kidney is removed). However, if you’re living with stage 4 kidney cancer, your doctor may recommend a radical nephrectomy. In one study, paraneoplastic symptoms went away in 52 percent of people after they had a nephrectomy.

Symptoms of Paraneoplastic Syndromes in Renal Cell Carcinoma

Only about 10 percent of people with RCC experience the “classic” cancer symptoms. These include pain in the side of the body, hematuria (bloody urine), and a lump in the abdomen. Compared to the one-third of people with RCC who develop paraneoplastic syndromes before kidney cancer surgery, some of these symptoms are much more common.

1. Fatigue

Fatigue is a feeling of extreme tiredness or lack of energy that doesn’t improve with rest. It’s a common early symptom in RCC. One of the most common causes is hypercalcemia (high blood calcium levels). Studies estimate that up to 20 percent of people with renal cell cancer also have high blood calcium. Researchers aren't sure why renal cancer causes hypercalcemia.

High blood calcium causes fatigue because it affects the way nerve cells in the brain communicate, leading to slowed thinking, confusion, and low energy. Other common symptoms related to hypercalcemia include bone pain and muscle weakness. The extra calcium in your blood usually comes from your bones, which become weakened. As a result, your bones may start to hurt, and the muscles around them can feel weak.

If you’re experiencing fatigue, your oncology team may prescribe medications called bisphosphonates to slow the loss of calcium from your bones. In about half of those with hypercalcemia as a paraneoplastic syndrome, symptoms improve after nephrectomy surgery. But if hypercalcemia is caused by cancer that has spread to the bones, surgery won’t help.

2. Muscle and Weight Loss

Many people with cancer lose muscle and fat, leading to unintended weight loss. This is a syndrome known as cachexia. Among people with all types of cancer, about 40 percent have signs of cachexia when they’re first diagnosed, and up to 70 percent have it at advanced stages of cancer. In some people with cancer, cachexia is the cause of death rather than cancer itself.

Cachexia is common among people with clear cell RCC. Developing cachexia may be a sign that kidney cancer is more likely to come back after treatment. It may also mean that someone is more likely to die from kidney cancer itself, rather than another health condition.

Catching cachexia early and starting proper treatment may improve outcomes. Treatment may involve improving the appetite, getting plenty of nutrients, and reducing inflammation.

3. Brain Inflammation

One rare and surprising complication of RCC is paraneoplastic encephalitis (inflammation of the brain). One study of paraneoplastic encephalitis found three cases out of a total of 558 people with RCC.

In people with RCC, encephalitis can be caused by the body’s immune cells making proteins that target brain cells. These proteins, called antibodies, cause inflammation in the brain. The symptoms of paraneoplastic encephalitis in RCC can include cognitive and neurological issues such as:

• Confusion
• Trouble speaking
• Memory issues
• Seizures

If you have RCC and have any potential symptoms of brain inflammation, talk to your oncology team. Treatment with immunotherapy can potentially prevent cognitive symptoms from getting worse or becoming permanent in some people. Immunotherapy for kidney cancer helps the immune system specifically target tumor cells.

4. Skin Bumps and Rashes

Paraneoplastic syndromes can affect the skin in several ways. The most common kinds of skin lesions are itchy or fluid-filled blisters and bumps.

People with RCC also sometimes develop skin disorders such as:

• Acanthosis nigricans — Dark, velvety patches that appear in skin folds, like the armpits or neck
• Seborrheic keratoses — Small, molelike growths that can be black, brown, or tan, don’t itch, and often feel waxy or scaly

If you notice a new skin abnormality, talk to your care team. They can determine whether it might be related to your RCC. Your medical team can test any new growths, rashes, or patches. They can also refer you to a dermatologist who can help treat and manage these skin changes.

5. Muscle Weakness in the Face and Neck

Myasthenia gravis is an autoimmune condition in which the immune system attacks the spaces where muscle cells and nerve cells communicate. As a result, nerves can’t communicate properly with the muscles they control. This leads to muscle weakness in the eyes, face, and neck, as well as in the larger muscles of the arms and legs.

In rare cases, myasthenia gravis can develop as a paraneoplastic syndrome in kidney cancer. Researchers aren’t sure whether this condition is caused by cancer or if it just happens at the same time. One study found six cases of people with myasthenia gravis associated with RCC. The most common symptom was upper eyelid drooping. This is a frequent early symptom of myasthenia gravis, caused by weakening of the eyelid muscles.

If you’re experiencing unusual weakness of the muscles in your eyes, face, or other parts of your body, be sure to talk to your doctor. You may need a neurology referral. There are several tests that can diagnose this condition. Medications can help manage the symptoms.

Talk to Your Doctors

Your urology and oncology team is your best resource for discussing the unexpected symptoms you may be experiencing with RCC. If you have any new or worsening symptoms, even if they don’t seem related to your kidney cancer, mention them in your follow-up appointments with your urologist or oncologist. Your healthcare team can work with you to manage the symptoms. Many of these conditions can improve with cancer treatment or treatments that target the specific syndrome.

Find Your Team

On MyKidneyCancerTeam, the social network for people with kidney cancer and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with kidney cancer.

Have you or your loved one had any unusual or surprising symptoms since receiving a renal cell carcinoma diagnosis? Share your experiences in the comments below, or start a conversation by posting to your Activities page.