Molecular Alterations in Partially-Encapsulated/Well-Circumscribed Follicular Variant of Papillary Thyroid Carcinoma
Brooke E Howitt, Lynette M Sholl, Justine A Barletta. Brigham and Women's Hospital, Boston, MA
Background: Recent studies have described encapsulated and infiltrative forms of follicular variant of papillary thyroid carcinoma (FVPTC). Encapsulated tumors have been reported to have virtually no metastatic potential or recurrence risk and to harbor RAS mutations but not BRAF mutations. In contrast, infiltrative tumors have significant metastatic potential, a risk of recurrence, and a BRAF mutation frequency of approximately 25%. In our experience, a substantial number of FVPTCs are neither fully encapsulated nor infiltrative, but instead are partially-encapsulated (PE) or well-circumscribed (WC). We have previously reported that PE/WC FVPTCs behave in an indolent fashion similar to encapsulated tumors. The purpose of the current study was to evaluate the molecular alterations in PE/WC FVPTC.
Design: We identified 28 PE/WC FVPTCs resected consecutively at our institution between 2005 and 2006. The following pathologic and clinical parameters were recorded: patient age, gender, resection type, tumor size, extrathyroidal extension, margin status, lymphovascular invasion (LVI), lymph node (LN) status, radioactive iodine (RAI) treatment, and development of recurrences. All tumor slides were reviewed. DNA was extracted from formalin-fixed paraffin embedded blocks. Targeted mutation analysis of 41 genes including members of the RAS and RAF families was performed using single-base extension chemistry and mass spectrometry (Sequenom).
Results: The PE/WC tumors were from 23 women and 5 men, with a mean age at resection of 49 years (range 24-75 years). Tumor size ranged from 1 to 7.6 cm (mean 2.4 cm). Extrathyroidal extension and LVI were absent and surgical resection margins were negative in all cases. LN metastases were absent in all cases of PE/WC tumors with sampled lymph nodes. RAI was given to 14 (50%) patients. No patients developed tumor recurrences (mean follow-up time 63 months). Overall, 13 (46%) cases harbored RAS mutations, including 7 (25%) with NRAS mutations (p.Gln61Arg), and 6 (21%) with HRAS mutations (5 had p.Gln61Arg and 1 had a p.Gln61Lys). No tumors had BRAF mutations.
Conclusions: Our results confirm our previous finding that PE/WC FVPTCs pursue an indolent clinical course similar to encapsulated FVPTCs. Additionally, we found that PE/WC tumors have a similar molecular profile to encapsulated FVPTCs, with frequent RAS mutations (46%) and no BRAF mutations. These molecular results provide further evidence that PE/WC and encapsulated FVPTCs are biologically similar and should be distinguished from more aggressive infiltrative FVPTCs.
Monday, March 4, 2013 2:45 PM
Proffered Papers: Section H, Monday Afternoon