Papillary-Type Carcinoma of the Thyroglossal Duct Cyst: The Case for Conservative Management.

OBJECTIVES: Thyroglossal duct cyst (TGDC) is the most common congenital neck mass, presenting in up to 7% of the population. TGDC carcinoma is much less common, occurring in roughly 1% of patients diagnosed with TGDC. The vast majority of these tumors are papillary-type thyroid cancer. Given its rarity, there is wide variation in management recommendations for this disease. Extent of surgical management and need for adjuvant therapy including radioactive iodine ablation (RAI) are particularly debated, with some authors arguing aggressive therapy including RAI for any patients who undergo concurrent thyroidectomy with the Sistrunk procedure for TGDC carcinoma. We present a series of patients treated for TGDC carcinoma at our institutions and discuss our management algorithm. METHODS: This is a retrospective chart review of patients with TGDC treated at 2 separate institutions. Factors reviewed included patient age, sex, preoperative diagnosis, preoperative work-up, extent of therapy, and use of adjuvant therapy. RESULTS: Six patients who were treated for TGDC carcinoma at our institutions were identified. One patient was excluded because the patient had been treated at an outside facility prior to referral. All patients had papillary-type thyroid cancer. One patient underwent the Sistrunk procedure alone, and the remaining 4 underwent the Sistrunk procedure plus total thyroidectomy. Two of 4 patients were noted to have malignancy in the thyroid. Two of 4 patients who underwent thyroidectomy additionally received adjuvant RAI. CONCLUSION: Thyroglossal duct cyst carcinoma is uncommon and management is controversial. In low-risk patients (single tumor focus, negative margins, normal preoperative neck/thyroid imaging, no extension of TGDC carcinoma beyond the cyst wall), the Sistrunk procedure alone with observation of the thyroid may be sufficient. In this patient population, RAI is unlikely to be of any substantial benefit.

Phospholipid scramblase 1 binds to the promoter region of the inositol 1,4,5-triphosphate receptor type 1 gene to enhance its expression.

Phospholipid scramblase 1 (PLSCR1) is a multiply palmitoylated, endofacial membrane protein originally identified based on its capacity to promote accelerated transbilayer phospholipid movement in response to Ca(2+). Recent evidence suggests that this protein also participates in cell response to various growth factors and cytokines, influencing myeloid differentiation, tumor growth, and the antiviral activity of interferon. Whereas plasma membrane PLSCR1 was shown to be required for normal recruitment and activation of Src kinase by stimulated cell surface growth factor receptors, PLSCR1 was also found to traffic into the nucleus and to tightly bind to genomic DNA, suggesting a possible additional nuclear function. We now report evidence that PLSCR1 directly binds to the 5'-promoter region of the inositol 1,4,5-triphosphate receptor type 1 gene (IP3R1) to enhance expression of the receptor. Probing a CpG island genomic library with PLSCR1 as bait identified four clones with avidity for PLSCR1, including a 191-bp fragment of the IP3R1 promoter. Using electrophoretic mobility shift and transcription reporter assays, the PLSCR1-binding site in IP3R1 was mapped to residues (-101)GTAACCATGTGGA(-89), and the segment spanning Met(86)-Glu(118) in PLSCR1 was identified to mediate its transcriptional activity. The significance of this interaction between PLSCR1 and IP3R1 in situ was confirmed by comparing levels of IP3R1 mRNA and protein in matched cells that either expressed or were deficient in PLSCR1. These data suggest that in addition to its role at the plasma membrane, effects of PLSCR1 on cell proliferative and maturational responses may also relate to alterations in expression of cellular IP3 receptors.