Endocrine
Aradhya Nigam, MD (he/him/his)
Resident Physician
Medstar Georgetown University Hospital
Washington, District of Columbia, United States
Aradhya Nigam, MD (he/him/his)
Resident Physician
Medstar Georgetown University Hospital
Washington, District of Columbia, United States
Aradhya Nigam, MD (he/him/his)
Resident Physician
Medstar Georgetown University Hospital
Washington, District of Columbia, United States
Bin Xu, MD, PhD
Assistant Attending
Memorial Sloan Kettering, United States
Philip Spanheimer, MD (he/him/his)
Attending
University of North Carolina, North Carolina, United States
R Michael Tuttle, MD
Attending
Memorial Sloan Kettering, United States
Richard Wong, MD, PhD
Attending
Memorial Sloan Kettering, United States
Ashok R. Shaha, MD (he/him/his)
Attending
Memorial Sloan Kettering, New York, United States
Ian Ganly, MD, PhD
Attending
Memorial Sloan Kettering, United States
Rony Ghossein, MD
Attending
Memorial Sloan Kettering, United States
Brian R. Untch, MD
Attending
Memorial Sloan Kettering
New York, New York, United States
The International Medullary Thyroid Carcinoma Grading System (IMTCGS) is a newly established grading system for MTC. When compared to low-grade tumors, patients with high-grade tumors have worse recurrence and survival. We aimed to investigate the impact of grade on somatic/germline mutation status, lymph node burden, and post-resection outcomes in MTC.
Methods:
A retrospective cohort analysis was performed at a tertiary care cancer center (Memorial Sloan Kettering Cancer Center, New York, NY) between 1/1/1986-1/1/2018. Thyroid specimens were categorized as high-grade if found to have a mitotic index ≥ 5 /2mm2, Ki67 ≥ 5%, and/or necrosis present. Molecular profiling of somatic and germline mutations were assessed with a 400 gene sequencing assay (MSK-IMPACT). Competing risk modeling was used to analyze post-resection local recurrence (LR), distant recurrence (DR), and survival. Significance was set at p< 0.05.
Results:
Amongst 122 patients, 98 (80.3%) were low-grade and 24 (19.7%) were high-grade. In high grade tumors, somatic/germline RET mutations (25%) were present in a significantly greater proportion compared to RAS (4%) and non-RAS/RET (4%) mutations (p< 0.05 for both) but not in low grade. Regardless of grade, RET-mutant tumors had a greater lymph node burden (5.0, IQR 2-16) compared to RAS (0, IQR 0-4;p< 0.05) and non-RAS/RET (1.0, IQR 0-3.5,p< 0.05) tumors. Patients with high grade tumors were found to have a greater number of involved lymph nodes. Despite a similar proportion of patients with low-grade (73%) and high-grade (75%) tumors undergoing central neck dissection (p=0.2), the median number of involved lymph nodes was greater in high-grade tumors (4.5, IQR 0.3-11.2 vs 1.0, 0-2.0;p< 0.05). Ipsilateral lateral neck dissection (ILND) was performed in a significantly greater proportion of patients with high-grade (71%) compared to low-grade tumors (45%;p< 0.05). Among ILND cohorts, median number of involved lymph nodes was significantly greater in high-grade (6.0, 4.0-19.0) than low-grade (4.0, 1.0-6.0;p< 0.05) tumors. In patients undergoing ILND, competing risk modeling demonstrated worse LR (5yr incidence: 56% vs 19%), DR (5yr incidence: 38% vs 0%), and survival (60% vs 97%) in patients with high-grade tumors.
Conclusions:
Patients with high-grade MTC are associated with worse initial lymph node burden in the central and ipsilateral lateral neck compartments. RET-mutant tumors of any grade had more positive lymph nodes. Tumor grading and RET mutation status can guide surgical planning and postoperative surveillance strategies.