Clinical review: Incidentally discovered medullary thyroid cancer: diagnostic strategies and treatment

Abstract

Context: Medullary thyroid carcinoma (MTC) is diagnosed only after thyroidectomy in approximately 10-15% of cases. This delay in diagnosis can have adverse consequences such as missing underlying pheochromocytoma or hyperparathyroidism in unrecognized multiple endocrine neoplasia type 2 and choosing a suboptimal extent of surgery. Barriers to accurate preoperative diagnosis and management strategies after the discovery of occult MTC are reviewed.

Evidence acquisition: We reviewed PubMed (1975-September 2010) using the search terms medullary carcinoma, calcitonin, multinodular goiter, Graves' disease, calcium/diagnostic use, and pentagastrin/diagnostic use.

Evidence synthesis: The combined prevalence of occult MTC in thyroidectomy series is approximately 0.3%. Routine calcitonin measurement in goiter patients identifies C-cell hyperplasia as well as MTC. Challenges include interpreting intermediate values and unavailability of pentagastrin stimulation testing in the United States. Early studies have begun to identify appropriate cutoff values for calcium-stimulated calcitonin. For management of incidentally discovered MTC, we highlight the role of early measurement of calcitonin and carcinoembryonic antigen, RET testing, and comprehensive neck ultrasound exam to direct further imaging, completion thyroidectomy, and lymph node dissection.

Conclusions: Occult MTC is an uncommon, but clinically significant entity. If calcium stimulation testing cutoff data become well-validated, calcitonin screening would likely become more widely accepted in the diagnostic work-up for thyroid nodules in the United States. Among patients with incidental MTC, those with persistently elevated serum calcitonin levels, positive RET test, or nodal disease are good candidates for completion thyroidectomy and lymph node dissection in selected cases, whereas patients with undetectable calcitonin, negative RET testing, and no sonographic abnormalities often may be watched conservatively.

Fig. 1.

A, Transverse view of left thyroid lobe obtained at time of ultrasound-guided FNA of a 4.9 × 2.3 × 3.4-cm complex cystic nodule of a 36-yr-old female. The central cystic portion of the complex nodule is seen, along with a posterior solid portion (arrow). FNA cytopathology demonstrated scant cellularity with few groups of follicular cells and blood, but overall, the specimen was inadequate. The patient underwent left hemithyroidectomy for compressive dysphagia; surgical pathology revealed a 2.9-cm, partially cystic MTC on a background of nodular hyperplasia. B, Surgical section low-power view, showing cystic medullary thyroid cancer with a fragment of hyperplastic normal thyroid (top) (hematoxylin and eosin). C, Higher power view. D, Calcitonin immunohistochemistry revealing dense homogeneous reactivity. The postoperative calcitonin was undetectable, and CEA was 2.6. RET-protooncogene testing was negative for exons 10, 11, and 13–16. Completion thyroidectomy was deferred, and serum calcitonin, CEA, and neck ultrasound have remained normal through 3-yr follow-up.