Endocrine Abstracts

Introduction: medullary thyroid carcinoma (MTC) is a neuroendocrine thyroidal cancer. World Health Organization recognizes a grading system for almost all neuroendocrine tumors; however, a shared grading system for MTC is still lacking. We performed a clinical and pathological review of 257 MTCs to evaluate which histologic features have an impact on the disease specific survival and to propose a new grading system.

Method: We retrospectively reviewed clinical data of 257 consecutive patients with sporadic MTC, surgically treated at the Endocrine Surgery Unit and followed at the Endocrine Unit of the University Hospital of Pisa, from 2000 to 2018. In this cohort, MTC histopathologic variants (classical, follicular, papillary, oncocytic, clear cell, small cell and spindle cell), desmoplastic reaction (fibrosis ≥ 10%), number of mitosis for 10 high-power field (x10HPF), Ki67 percentage and necrosis were evaluated.

Results: Patients were followed for a median time of 9.3 years. The MTC variants were distributed as follows: 164/257 (63.3%) classical variant, 50/257 (19.3%) spindle cell variant and 43/257 (17.4%) other variants with a frequency <5% each. Desmoplastic reaction was present in 159/257 (61.9%). Number of mitosis and Ki-67 percentage higher than 2 were present in 57/257 (22.2%) and 97/257 (37.7%), respectively. Necrosis was present in 19/257 samples (7.4%). According to Kaplan-Meier analysis, MTC with desmoplastic reaction, mitosis number > 2, Ki-67 > 2% or necrosis had lower disease specific survival (P< 0.001). After preliminary analysis, we proposed the following grading system composed by desmoplastic reaction and Ki-67 percentage: high grade (presence of desmoplastic reaction and Ki-67 > 2%) and low grade (all other combinations). At Kaplan-Meier analysis, high grade MTC had lower disease specific survival compared to low grade (74.7% vs 98.6%, P< 0.001). Intriguingly, this grading system was able to predict DSM, both in intrathyroidal (stage I-II) (P=0.034) and extrathyroidal (stage III-IV) MTCs (P< 0.001).

Conclusions: In our large MTC series, presence of desmoplastic reaction and necrosis, mitosis number ×10HPF > 2, and Ki-67 > 2% were negative prognostic factors for DSM. Grading system composed by Ki-67 > 2% and desmoplastic reaction was able to identify the MTCs with the worst prognosis, both in lower (I-II) than in more advanced (III-IV) stages.