Faculty Bibliography

BACKGROUND: "Follicular lesion of undetermined significance/atypia of undetermined significance" is a heterogeneous category of cases that cannot be classified into 1 of the other established categories. The use of ancillary molecular studies has not been widely explored for this diagnosis. METHODS: All thyroid cytology cases diagnosed as follicular lesion of undetermined significance/atypia of undetermined significance were retrieved from April 2007 to December 2008. During this time period, samples were collected routinely at the time of aspiration for cytologic and molecular studies. Analysis for BRAF and RAS gene mutations and RET/PTC and PAX8/PPARgamma gene rearrangements were performed and correlated with the cytologic features and surgical pathology outcome. RESULTS: From a total of 513 follicular lesion of undetermined significance/atypia of undetermined significance cases identified, 455 had adequate molecular results. Of these, 117 cases had cytologic-histologic correlation. In this group, 35 (29.9%) cases had a neoplastic outcome and 20 (17.1%) cases from 19 patients were carcinoma. Positive molecular results were found in 12 cases, all of which were papillary carcinoma. There were no false-positive molecular results. In correlating the molecular results with surgical pathology outcome, we found that the cancer probability for follicular lesion of undetermined significance/atypia of undetermined significance cases with molecular alteration was 100%, while the probability for follicular lesion of undetermined significance/atypia of undetermined significance cases without molecular alteration was 7.6% (P < .001). CONCLUSIONS: By cytomorphology alone, follicular lesion of undetermined significance/atypia of undetermined significance specimens represent cases that are intermediate in risk between the benign and "suspicious for follicular neoplasm" categories. Although not all papillary carcinoma cases are detected by molecular testing, a positive molecular test result is very helpful in refining follicular lesion of undetermined significance/atypia of undetermined significance cases into high-risk and low-risk categories.

OBJECTIVES: To determine the efficacy of combined positron emission tomography-computed tomography (PET-CT) in identifying recurrent thyroid cancer and to elucidate its role in the clinical management of thyroid carcinoma. DESIGN: Retrospective study. SETTING: Tertiary care referral academic center. PATIENTS: One hundred twenty-four patients with previously treated thyroid carcinoma who underwent PET-CT. MAIN OUTCOME MEASURES: PET-CT images were correlated with clinicopathologic information. The influence of PET-CT findings on disease status determination and the treatment plan was evaluated. RESULTS: Among 121 patients undergoing iodine I 131 ((131)I) imaging (an (131)I image was unavailable for 3 patients), 80.6% had negative findings on (131)I imaging before undergoing PET-CT. Among 75 patients who had positive findings on PET-CT, 71 were true positive results. Among 49 patients who had negative findings on PET-CT, 32 were true negative results. Therefore, PET-CT demonstrated a sensitivity of 80.7%, specificity of 88.9%, positive predictive value of 94.7%, and negative predictive value of 65.3%. A significant difference was noted in the mean serum thyroglobulin levels between patients with positive vs negative PET-CT findings (192.1 vs 15.0 ng/mL, P = .01) (to convert thyroglobulin level to micrograms per liter, multiply by 1.0). Overall, distant metastases were detected in 20.2% of patients using PET-CT. There was an alteration of the treatment plan in 28.2% of patients as a result of added PET-CT information, and 21.0% of patients underwent additional surgery. CONCLUSIONS: PET-CT is usually performed in patients with thyroid cancer having elevated thyroglobulin levels but non-(131)I-avid tumors and has high diagnostic accuracy for identifying local, regional, and distant metastases. Additional information from PET-CT in patients with (131)I-negative and thyroglobulin-positive tumors frequently guides the clinical management of recurrent thyroid carcinoma.

BACKGROUND: To date, a mutation of the BRAF oncogene is the most common genetic alteration found in papillary thyroid carcinoma (PTC) and is associated with extrathyroidal extension, lymph node metastasis, and tumor recurrence. It is not known whether pre-operative identification of BRAF mutations in cytologic specimens should alter surgical management. METHODS: From 2006 to 2008, the clinical, cytologic, and pathologic parameters of 106 consecutive surgically treated patients with BRAF-positive PTC were compared with a concurrent cohort of 100 patients with BRAF-negative PTC. RESULTS: In all, 99 BRAF-positive PTC patients underwent initial treatment, and 7 BRAF-positive patients had surgical resection of recurrent/persistent PTC. BRAF mutations were identified on preoperative cytologic samples (31 patients) or after thyroidectomy (75 patients). All 31 patients with BRAF-positive fine-needle aspiration (FNA) had PTC at thyroidectomy (specificity 100%). At short-term follow-up, 11/106 BRAF-positive patients have required reoperation for recurrent/persistent disease compared with 3 BRAF-negative patients (P = .04). Preoperative knowledge of BRAF mutation positivity could have productively altered initial PTC surgical management in 24% of patients. CONCLUSION: In PTC, BRAF mutations are associated with cervical recurrence and with reoperation. Pre-operative cytologic identification of BRAF mutation has high specificity and may guide the initial extent of thyroidectomy and node dissection.

Tumor-to-tumor metastasis in thyroid neoplasms is exceedingly uncommon. Two unusual cases of breast carcinoma and renal cell carcinoma metastatic to follicular variant papillary carcinoma are reported. On histologic sections, the donor tumor cells infiltrated the substance of the recipient tumor and the angiolymphatic channels, but the bulk of metastatic tumor was confined within the thyroid carcinoma. Immunohistochemical stains as well as molecular studies confirmed the origin of both donor tumors, as well as the diagnosis of follicular variant of papillary carcinoma in the recipient tumors. Distinguishing between two such tumor populations may be difficult when the donor tumor cells morphologically resemble primary neoplasms of the recipient organ. A history of previous malignancy and ancillary studies can be helpful in making this distinction and rendering the correct diagnosis. A brief review of literature and discussion of tumor-to-tumor metastasis in thyroid neoplasms is also presented.

Thyrotoxicosis is a condition resulting from elevated levels of thyroid hormone. In this article, the authors review the presentation, diagnosis, and management of various causes of thyrotoxicosis.

BACKGROUND: Management of a hyperthyroid patient unable to take oral or rectal medication is a difficult clinical problem. The need for an alternative parenteral route of antithyroid medication administration in thyrotoxic patients occurs in certain rare cases, such as emergent gastrointestinal surgery, bowel ileus or obstruction, or severe vomiting and diarrhea. We report a simple and successful protocol for the preparation and use of intravenous methimazole (MMI) for treatment of hyperthyroidism in patients intolerant of orally and rectally administered thionamides. METHODS: Five hundred milligrams of methimazole USP powder was reconstituted with pH-neutral 0.9% sodium chloride solution to a final volume of 50 mL using aseptic technique, then filtered through a 0.22-microm filter. MMI injection was administered as a slow intravenous push over 2 minutes and followed by a saline flush. CASES: A 76-year-old man, intolerant of oral and rectal medications because of an ileus and intractable diarrhea, who developed worsening thyrotoxicosis after an emergent spinal cord decompression, and a 42-year-old man with chronic liver disease and hyperthyroidism, requiring emergent exploratory laparotomy and maintenance of complete bowel rest because of persistent gastrointestinal bleeding were rendered euthyroid using intravenous MMI. CONCLUSION: Two cases of hyperthyroidism successfully treated with a preparation of intravenous MMI are described.

BACKGROUND: The use of immunosuppressant agents is mandatory in the long-term management of transplant recipients. Herein, we report a case of near fatal cardiac arrhythmia related to the use of intravenous tacrolimus in a 35-year-old woman undergoing renal transplantation. METHODS: The patient had no previous history of cardiac disease, but an initial electrocardiogram demonstrated slightly prolonged QT and QTc intervals and normal sinus rhythm. Postsurgical immunosuppression included intravenous tacrolimus and methylprednisolone. During intravenous tacrolimus infusion, marked QT prolongation occurred. The patient suffered recurrent runs of torsade de pointes, refractory to aggressive medical management and requiring numerous defibrillations. Rapid atrial pacing eventually controlled the arrhythmia. RESULTS: We note not only a temporal association, but also a direct linear relationship, between this arrhythmia and blood tacrolimus levels. CONCLUSION: We believe this case presents a little recognized hazard associated with the use of intravenous tacrolimus and points to the need for careful predrug screening for QT prolongation. Tacrolimus has been shown to effect intracellular calcium and to prolong the action potential duration experimentally. This suggests that an increase in the intracellular calcium may underlie torsades de pointes associated with intravenous tacrolimus.