Neuroendocrine Tumors

By Debbie Stoewen DVM, MSW, RSW, PhD

Tumors, Pet Services

What are neuroendocrine tumors?

Neuroendocrine tumors are a group of tumors that develop from the disorganized uncontrolled proliferation of the cells of the neuroendocrine system. The neuroendocrine system is made up of special cells called neuroendocrine cells.

Neuroendocrine cells are like nerve cells (neurons), but they also make hormones like cells of the endocrine system (endocrine cells). They receive messages from the nervous system and respond by making and releasing hormones. These hormones enter the blood and travel all over the body to control many body functions, including:

  • the release of digestive enzymes to break down food
  • how fast food moves through the gastrointestinal tract
  • air and blood flow through the lungs
  • blood pressure and heart rate
  • the amount of sugar (glucose) in the blood
  • bone and muscle growth and development

Neuroendocrine cells are found throughout the body. Neuroendocrine tumors, therefore, can grow in many places, including the pancreas, digestive tract (esophagus, stomach and intestines), adrenal glands, thyroid gland, liver, bronchi (airways), lungs, heart, skin, and several chemoreceptor (sense) organs – such as the aortic body (found in the chest) or the carotid bodies (found in the neck).

"There are many types of neuroendocrine tumors."

There are many types of neuroendocrine tumors. Insulinomas, gastrinomas, and glucagonomas arise in the pancreas. Medullary thyroid carcinomas occur in the thyroid. Carcinoids are a widespread group of tumors that can grow in various regions of the body, including the digestive tract, liver, heart, and lungs. Small-cell lung carcinomas are another type of neuroendocrine tumor that also develop in the lungs. Chemodectomas occur in the chemoreceptor organs (organs that sense chemical changes in the body), including the aortic body (in the chest) and the carotid bodies (in the neck). For more information on chemodectomas, see the handout “Chemodectomas (Aortic and Carotid Artery Neuroendocrine Tumors”. Pheochromocytomas occur in the adrenal gland, and Merkel cell carcinomas develop in the skin.

These tumors can be benign (non-cancerous and only grow locally) or malignant (cancerous and spread to other areas of the body). Some tumors are functional in that they oversecrete their normal hormone product, and the excessive levels result in the signs of disease. Other tumors are nonfunctional, and the signs of disease instead result from the presence of the physical mass and/or metastasis (spread to other areas of the body). Even if benign, a growing tumor can damage the nearby healthy tissues and, in some cases, secrete excess hormone. Generally, neuroendocrine tumors are rare in dogs and cats. Very rarely, more than one type of neuroendocrine tumor may occur at the same time.

What causes these tumors?

The reason why a particular pet may develop this, or any tumor or cancer, is not straightforward. Very few tumors and cancers have a single known cause. Most seem to be caused by a complex mix of risk factors, some environmental and some genetic or hereditary. Chemodectomas are seen most often in brachycephalic (flat-faced) dogs such as Boxers and Boston Terriers. Overall, no specific risk factors or cause have been identified with neuroendocrine tumors.

What are the signs of these tumors?

The signs of these tumors depend on the type of, location, and size of the tumor, as well as the degree of infiltration into the surrounding tissues, and whether the tumor has spread to other areas of the body. It also depends on whether the tumors are functional (i.e., whether they produce excessive hormone).

"The signs of these tumors depend on the type of, location, and size of the tumor, as well as the degree of infiltration into the surrounding tissues, and whether the tumor has spread to other areas of the body."

The signs of insulinomas relate to the excessive secretion of the hormone insulin. Excessive insulin lowers the blood sugar, and low blood sugar can lead to intermittent weakness, lethargy, incoordination, mental confusion, muscle twitching, and episodes of seizures or collapse.

Gastrinomas also produce excessive hormone, but in this case, gastrin. As gastrin stimulates the secretion of gastric acid (HCl), the signs of gastrinomas relate to excessive gastric (stomach) acid and consequent ulcers (openings in the lining of the stomach). If your pet has gastric ulcers, you may see a loss of appetite, vomiting (sometimes with blood), diarrhea, weight loss, and signs of dehydration.

Carcinoids in the intestine can cause symptoms similar to gastrinomas, and as they grow in size can even lead to an intestinal obstruction.

Diarrhea is the most common sign of medullary thyroid carcinomas, although you may also notice weakness, fatigue, weight loss, and sometimes excessive drinking and urination in your pet, all related to excessive thyroid hormone.

The signs of pheochromocytomas (caused by excessive stress hormone production) are quite similar to thyroid carcinomas, but may also include loss of appetite, panting or trouble breathing, swelling of the abdomen, and collapse. Sometimes there may be no signs of cancer with pheochromocytomas and your pet may appear perfectly healthy.

Your pet may also appear perfectly healthy with small-cell lung carcinomas and chemodectomas. It is only when the disease becomes very advanced that you may notice any signs. In these cases you may see coughing or trouble breathing, weakness, fatigue, and weight loss.

If your pet has a glucagonoma or Merkel cell carcinoma you will see skin lesions. Glucagonomas cause crusting sores of the nose, elbows, genital area, and footpads, which can be very sore. Merkel cell carcinomas can appear as a single firm, flesh-colored or red nodule or plaque on the lips, ears, or toes or in the mouth.

How are these tumors diagnosed?

These tumors are diagnosed in a variety of ways, in relation to where they are located and how they affect the body. Some tumors are diagnosed in part with blood work. For example, with insulinomas blood work will show a low blood sugar along with a normal or high blood insulin. With gastrinomas, there will be higher than normal levels of gastrin in the blood. And with glucagonomas a specialized blood analysis (testing for amino acid, glucagon, and zinc levels) can be helpful for diagnosis.

"These tumors are diagnosed in a variety of ways, in relation to where they are located and how they affect the body."

Imaging can be also be helpful to diagnose these tumors. This includes radiographs (X-rays), ultrasounds, computed tomography (CT scans), and magnetic resonance imaging (MRI). Imaging may demonstrate one or more tumor masses or signs that the tumor has spread to other areas of the body (such as the lungs). Some neuroendocrine tumors are found incidentally in the course of taking images for a completely different reason. This is very common with small-cell lung carcinomas and chemodectomas.

To arrive at a definitive (exact) diagnosis, a tissue biopsy is needed. A tissue biopsy may be obtained by surgically removing the entire tumor or a portion of the tumor. To identify the type of cancer, the tumor or pieces of the tumor are examined by a veterinary pathologist under the microscope. This is called histopathology. For neuroendocrine tumors, special procedures are often necessary to make a diagnosis. Histopathology is not only helpful to make a diagnosis but can indicate how the tumor is likely to behave.

How do these tumors typically progress?

Most of these tumors have the tendency to spread to other areas of the body. The rate and extent of metastasis depends on the type of tumor. Common sites of metastasis include the lymph nodes, lungs, liver, kidneys, heart, bone, and brain. Staging (searching for potential spread to other locations in the body) is highly recommended for these tumors. This may include bloodwork, urinalysis, X-rays of the lungs, and an abdominal ultrasound or other imaging procedures. If any lymph nodes are enlarged or feel abnormal, further sampling may be pursued to determine if spread is present.

What are the treatments for these tumors?

The choice of treatments for these tumors depends on the type, size, and malignancy of the tumor, as well as the presence of metastasis. Treatment typically involves several options, including surgery, chemotherapy, radiation therapy, and medical and dietary approaches. Your veterinarian may refer your pet to a veterinary oncologist to develop a plan of care.

"Treatment typically involves several options, including surgery, chemotherapy, radiation therapy, and medical and dietary approaches."

Surgery is considered the best option for insulinomas, followed by chemotherapy to suppress the spread of the tumor. When surgery is not an option, the symptoms of low blood sugar may be managed for a while with diet, the frequency of feeding, sugar supplements, steroids (hormones related to cortisol that raise blood sugar), and an oral medication that suppresses insulin secretion.

Gastrinomas may also be treated medically if surgery is not an option, using medications to suppress gastric acid production and protect the lining of the stomach.

As with insulinomas and gastrinomas, glucagonomas may be surgically removed from the pancreas. If surgery is not possible, dietary supplements and medications for the skin lesions (e.g., antibiotics) may be helpful.

The treatment for medullary thyroid carcinomas may include surgery, radiation, chemotherapy, and radioactive iodine therapy. For carcinoids, surgery may be possible depending on the location of the tumor, followed by chemotherapy. For small-cell lung carcinomas, a lobectomy (removal of a lobe of lung) may be recommended, followed by chemotherapy.

Adrenalectomy (surgical removal of the adrenal gland) is the treatment of choice with pheochromocytomas, along with medication to manage blood pressure. For Merkel cell carcinomas, the treatment may be surgery to remove the skin tumor followed by chemotherapy or radiation. As surgery is not usually possible with chemodectomas, they are often treated with chemotherapy and radiation.

Is there anything else I should know?

As neuroendocrine tumors are rare, should these tumors be suspected or diagnosed, your veterinarian may refer you to a veterinary oncologist. Because many of the signs of these tumors are symptomatic of many common illnesses, and may wax and wane, these tumors can be difficult to diagnose. With treatment, the prognosis for your pet may range from good to poor, depending on the type of tumor, its effects on the body, whether it has metastasized, and the health status of your pet to start with.

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