Neuroendocrine Tissue Tumors in Dogs

Neuroendocrine tumors are tumors that develop from neuroendocrine cells. Unlike classic neurons, neuroendocrine cells don’t have axons and synapses. These cells are known for being able to yield and release a neuromodulator, transmitter or hormone. Solid core secretory granules are contained within neuroendocrine cells and are where the products that are released are stored. The neuroendocrine cells can release these products in a controlled way through exocytosis. 

Tumors that result from neuroendocrine cells make up a group of tumors that are known as NET’s. As a result of a wide dissemination of cells, NETs are observed in numerous locations, though they are unusual tumors in animals as well as humans. The majority of NETs are slow growing, however most will ultimately move into and destroy the structures near where they grow.

Tumors that develop from neuroendocrine cells are known as NETs or neuroendocrine tumors. While the tumors are rare, they can be found throughout the body of a dog.

The majority of neuroendocrine tumors don’t produce hormones, meaning that any problems they cause are typically a result of their size, which leads to nearby tissues being compressed. The symptoms seen in these cases will be connected to the organ that is being impacted by the tumor. A small number of the tumors cause symptoms that are not easily explained by the tumor or its spread; these are known as paraneoplastic syndromes. It is thought that this is the result of irregular hormone production resulting from cancer. Hair loss and increased levels of blood calcium are thought to be due to paraneoplastic syndromes.

The symptoms related to this type of tumor will vary greatly depending on the location. A few of the symptoms may present as follows:

• Coughing
• Shortness of breath
• Edema
• Loss of appetite
• Loss of weight
• Vomiting
• Increased thirst and unrination

Unlike classic neurons, neuroendocrine cells don’t have axons and synapses. The cause of your dog developing a neuroendocrine tumor is likely not straightforward. Cancer is non-lethal genetic damage of cells and in many cases, the result of a sequence of events. Radiation, chemicals, hormones and infections can lead to cancer, though it is not clear which of these, or if all of them, are of significance in neuroendocrine tumor development. The mutated cells in your dog’s body will disturb the typical regulation of cell death and replacement by triggering oncogenes that promote cancer growth while inactivating suppressing genes and changing the genes that govern apoptosis (cell death).

As neuroendocrine tumors do not produce hormones, symptoms that are seen in your dog will be due to the organ that is being impacted by the tumor. Upon visiting your veterinarian and explaining any symptoms you have noticed in your dog, your veterinarian will conduct a full physical examination. Based on what is seen during the exam, your veterinarian may order additional tests if he suspects that there may be a tumor. These tests include:

• X-rays
• Ultrasonography
• Computerized tomography (CT) scans
• Magnetic resonance imaging (MRI)

These tests can show that there is a tumor present; however to confirm diagnosis the tissue will need to be examined under a microscope. A biopsy will be conducted where a part of the mass (or the mass in its entirety) will be removed from your dog. In many cases, diagnosis can be confirmed through routine histopathology, though in some cases electron microscopy or immunocytochemistry may be required in order to eliminate other types of tumors. Classic neuroendocrine cell markers like chromogranin A will help the pathologist determine that it is a neuroendocrine tumor.

In order to treat your dog in the case of a neuroendocrine tumor, surgery will likely be recommended. On occasion, radiotherapy will be used should your dog have a nasal tumor.

In cases of insulinomas, should a tumor be inoperable, your dog’s condition may be able to be well managed with multiple daily feedings and administration of glucocorticoid (0.5-1 mg/kg/day). Streptozotocin, a chemotherapy drug, has been looked at for the treatment of islet cell tumors in dogs. Should your dog have an islet cell tumor, your veterinarian may consider this after your dog has undergone surgery.

In gastrin-secreting islet cell tumors, removing the tumor may not be sufficient as often these tumors will have spread to the lymph nodes and liver of your dog. Your veterinarian may recommend managing your dog’s condition with H2-receptor antagonists like famotidine or ranitidine or omeprazole (a proton-pump inhibitor) which may minimize the clinical signs your dog is demonstrating.

Either after the biopsy or tumor removal, your veterinarian will receive a histopathology report that will provide him with your dog’s diagnosis and include information on how the tumor is likely to progress going forward. This will help your veterinarian in giving a prognosis for your dog.