Definitive diagnosis of thyroid malignancy

Thyroid tumors are relatively uncommon in dogs, accounting for only 1 percent to 4 percent of all tumors. The majority of diagnosed thyroid tumors in dogs are malignant, because adenomas are clinically silent and found incidentally on necropsy.

There is no documented cause of thyroid tumors in dogs, although certain breeds, such as Beagles, Boxers and Golden Retrievers, have a higher incidence of them. It has been suggested that hypothyroidism in Beagles, and possibly in other breeds, may contribute to the development of these tumors because of the chronic stimulation of the thyroid gland from excessive TSH production, although this is unproven.

The most common presenting complaint is a mass in the neck, although clinical signs such as a change in voice, dyspnea and facial edema are common, too. Only 10 percent of thyroid tumors are functional, and these dogs typically present with weight loss, polyphagia, polyuria and polydipsia.

The differential diagnosis for a neck mass should include carotid body tumors, granuloma or abscess, metastasis from other neoplasia such as tonsillar squamous-cell carcinoma or salivary-gland diseases. Thyroid tumors can be located anywhere in the neck, although adjacent to the larynx is most common. Ectopic tumors have been reported in sites such as the mediastinum and base of the tongue.

Obtaining a definitive diagnosis of a thyroid malignancy may be challenging. Malignant thyroid tumors have a well-developed vascular supply so that blood contamination limits the diagnostic accuracy of cytology to 50 percent. On cytology, the majority of thyroid tumors appear relatively well differentiated, so that often it is not possible to make a diagnosis of malignancy. Cytology can be helpful in establishing an alternative diagnosis, such as metastatic squamous-cell carcinoma, allowing a thyroid tumor to be ruled out.

An incisional biopsy of a thyroid tumor needs to be approached with caution, given the vascularity of these tumors. Tru-cut biopsies, although less invasive, are not well suited for tumors with a high risk of post-biopsy hemorrhage. There is still the risk of excessive hemorrhage with an open biopsy, although it may be easier to control than a Tru-cut biopsy.

Prognostic factors

In addition to being locally invasive, thyroid tumors have a relatively high rate of metastasis, mainly to the lungs and regional lymph nodes. At the time of diagnosis, as many as 40 percent of the dogs have detectable metastasis. Ultimately, up to 80 percent of thyroid tumors metastasize.

Reported prognostic factors include size, movability and grade.

Multiple studies have shown that smaller tumors (<3 cm) are associated with a better prognosis because they have a lower metastatic rate and are more amenable to surgical excision. Tumors that are freely movable have a better prognosis, presumably because they can be removed successfully with surgery.

The histologic subtypes are medul-lary, solid/compact, follicular, papillary and anaplastic.

As would be expected, high-grade tumors are associated with a poor prognosis; however, there is no accepted grading scheme for thyroid tumors. Histologic features, such as vascular or capsular invasion, a high mitotic index or a pleomorphic population of cells, are consistent with a high-grade tumor.

Imaging of thyroid tumors

Prior to surgical excision, it may be appropriate to consider more advanced imaging, including a CT scan, cervical ultrasound and/or nuclear scintigraphy. A CT scan or MRI can identify the extent of the tumor as well as the degree of invasiveness into surrounding structures such as the larynx and other cervical structures.

This information is critical for surgical planning. The most common uses of nuclear scintigraphy are to identify ectopic thyroid tumors, residual disease following surgery and occult metastasis. Both I-131 and 99mTc-pertechnetate can be used to image both functional and non-functional tumors. The only requirement is that the tumor be capable of trapping pertechnetate or trapping and organifying I-131, but it does not need to produce a functional thyroid hormone.

On pertechnetate scans, it is possible to identify capsular invasion, which appears as a heterogenous and poorly circumscribed uptake of the pertechnetate. There is no advantage to using a pertechnetate scan for the identification of pulmonary metastasis compared to thoracic radiographs.

I-131 scans appear to be more sensitive than pertechnetate scans in identifying the primary tumor and metastatic disease; however, pertechnetate scans are more readily available, less expensive and require shorter holding times.

Treatment options

Treatment options for thyroid tumors include surgery, radiation therapy, chemotherapy and I-131 therapy.

Surgery is the preferred option, if possible. Freely movable tumors that are excised have reported survival times greater than three years (Klein 1995).

For tumors that are grossly excised but have invasion beyond the capsule, follow-up radiation therapy should be considered. Ideally, radiation therapy should be started two to four weeks after surgery. Protocols for radiation therapy may vary between facilities, but typically involve the use of 15 to 19 treatments over three to four weeks. Control rates for radiation therapy in the adjuvant setting have not been well documented, but clinical experience suggests that long-term control (i.e., more than two years) can be achieved with the combination of radiation therapy and surgery.

Definitive or full-course radiation therapy typically is reserved for patients with microscopic disease. However, definitive radiation therapy still may provide long-term control, even in dogs in which surgery is not an option. In one study, eight dogs treated with definitive radiation therapy had a median survival time of two years, and all eventually had complete resolution of the tumor. In a second study, 25 dogs with measurable disease were treated with a definitive course of radiation therapy. The one-year and three-year progression-free survival times were 80 percent and 72 percent, respectively.

Interestingly, in both studies the tumor did not achieve a maximum response for six to 22 months following treatment. The slow regression of these tumors following radiation therapy is most likely why radiation therapy previously was not considered effective as part of the treatment of these tumors.

Palliative radiotherapy may be effective in controlling these tumors for prolonged periods. This involves the use of several larger doses of radiation over one to four weeks. For thyroid tumors, a better term would be hypo-fractionated or coarsely fractionated radiation therapy, because the goal of this treatment is palliation and tumor control.

In an early study, 13 dogs were treated with four weekly treatments of radiation therapy. Ten out of the 13 achieved a complete or partial response, and the overall survival time was 96 weeks. Benefits of this type of radiation therapy would be lower cost, fewer treatments and minimal side effects. However, it is expected that the response rate and duration will be inferior to definitive radiation therapy protocols.

Thyroid tumors have a moderate rate of metastasis, so that chemo-therapy is indicated in the treatment of these tumors with possibly the exception of smaller movable tumors. Chemo-therapy can be used either alone or in combination with surgery and/or radiation therapy.

The most commonly used drugs include doxorubicin, cisplatin and carboplatin. Both cisplatin and doxorubicin have been shown to have measurable responses when used to treat gross disease; as a primary treatment, their response rates have been reported to be as high as 40 percent to 50 percent.

Chemotherapy is recommended currently as an adjuvant to surgical excision radiation therapy, as well as in combination with radiation therapy for non-resectable tumors. The typical treatment schedule for any of these drugs is once every three weeks for a total of four to six treatments. Potential side effects include gastrointestinal toxicity, myelosuppression, nephrotoxicity (secondary to cisplatin) and cardiomyopathy (with cumulative doses of doxorubicin); however, the risk of a significant side effect is only 5 percent to 10 percent.

Radioactive iodine therapy can be considered to treat dogs with both functional and non-functional thyroid tumors. In a recent study, 39 dogs with measurable disease were treated with radioactive iodine. Those with non-functional tumors were fed a low iodine diet for the three weeks preceding treatment to enhance the uptake of I-131. The median survival time for all was 27.6 months.

Twelve dogs had surgery three to six weeks after I-131 therapy, but this did not improve survival times. I-131 may provide an advantage over external-beam radiation therapy for dogs that have ectopic thyroid tumors or metastatic disease. Drawbacks of I-131 therapy include travel, given the limited facilities that can provide this service, prolonged isolation times, cost and potential for significant bone-marrow suppression.

The dose of radioactive iodine that is required to treat dogs is significantly higher compared to hyperthyroid cats. This means there are few facilities capable of treating dogs and the holding time is significantly longer — in some cases up to two weeks.

In the above study, three dogs died of complications from bone-marrow suppression. There is the potential for radiation pneumonitis for those dogs that have pulmonary metastasis or ectopic tumors in the thorax.

Dr. Cronin earned her DVM degree from Cornell University in 1990. She completed an internship at the Animal Medical Center in New York and a medical oncology residency at North Carolina State University. She is a diplomate of the American College of Veterinary Internal Medicine in the specialty of oncology. After completing her residency, she was lecturer at the University of Pennsylvania Veterinary Teaching Hospital and medical oncologist at Angell Memorial Animal Hospital in Boston. In 2001, she co-founded the New England Veterinary Oncology Group in Waltham, Mass.