In the latest Case Record of the Massachusetts General Hospital, a 52-year-old woman was seen in the thyroid clinic of a hospital because of a mass in her neck. Imaging revealed abnormal cervical lymph nodes and two thyroid nodules with calcifications. A diagnostic procedure was performed.
Serum thyrotropin is measured to assess the functionality of a thyroid mass. When the thyrotropin level is subnormal, radionuclide scanning with 123I is performed to determine whether the nodule is autonomously secreting thyroid hormone. Hyperfunctioning nodules are almost never malignant, and fine-needle aspiration is not required. In addition, the serum level of thyrotropin correlates directly with the risk of cancer.
• What is in the differential diagnosis of a thyroid nodule and cervical lymphadenopathy?
The most likely diagnosis would be papillary thyroid cancer with nodal metastases. Follicular thyroid cancer spreads hematogenously, and cervical-node metastases are uncommon, except in the oxyphil cell (Hurthle-cell) variant. Medullary thyroid cancer is also commonly associated with nodal metastases, but fewer than 4% of thyroid cancers are medullary. Poorly differentiated thyroid cancer is also possible. Anaplastic thyroid cancer and primary thyroid lymphoma usually manifest as rapidly growing neck masses; lymphoma is markedly hypoechoic on imaging. Two uncommon possibilities are tumors that are metastatic to the thyroid and a reactive or lymphoproliferative disorder associated, frequently incidentally, with adenomatous goiter or Hashimoto’s thyroiditis.
• What is the surgical management of papillary thyroid carcinoma?
The surgical goal for a patient with papillary thyroid cancer is to resect all gross disease in the thyroid and in macroscopically involved cervical nodal beds. Lymph-node involvement is common and increases locoregional recurrence but has minimal effect on survival. A distinction should be made between small-volume microscopic nodal disease, which occurs in up to 80% of cases of papillary thyroid cancer and is not associated with an increased risk of recurrence, and clinically apparent macroscopic nodes which occur in 35% of cases of papillary thyroid cancer and are associated with an increased risk of nodal recurrence. Compartment-oriented dissection targeting macroscopic nodal disease has replaced more isolated nodal resection, termed “berry picking.”
Morning Report Questions
Q: What conditions are associated with medullary carcinoma of the thyroid and what initial evaluation should be done in suspected cases?
A: Twenty percent of cases of medullary thyroid cancer are familial or associated with multiple endocrine neoplasia type 2 (MEN-2). If the diagnosis is known preoperatively, either measurements of plasma metanephrine levels or 24-hour urine studies of metanephrines and catecholamines are used to screen for pheochromocytoma. The convenience and high negative predictive value of normal plasma metanephrine levels make this a useful first test. A positive test for hyperparathyroidism can be addressed at the time of thyroidectomy. Levels of calcitonin and CEA are proportional to tumor burden and differentiation. Levels of calcitonin greater than 100 pg per milliliter (reference range, <8) are highly predictive of medullary thyroid cancer.
Q: What is the prognosis of medullary carcinoma of the thyroid?
A: When calcitonin and CEA levels normalize after surgery, the prognosis is excellent. The prognosis is less favorable in patients with involved cervical nodes, persistently elevated calcitonin and CEA levels, and distant metastases at diagnosis. Nonetheless, the 10-year survival of patients with distant metastasis was 48% in one large retrospective series. Some patients survive only a few years, but other patients, even those with distant metastases, can survive for decades. Thus, the challenge is to differentiate between patients who will live with medullary thyroid cancer for many years and those who will die soon from their disease and who are most in need of systemic therapy.