Endocrine Abstracts

Background: The 2022 WHO Classification of Endocrine and Neuroendocrine Tumors has introduced, as other neuroendocrine neoplasms, new pathological features to classify medullary thyroid carcinoma (MTC) in low/high grade. However, whether it can be reliable in clinical practice should be confirm by further studies.

Aim: To verify the predictive value of the 2022 WHO grading system in patients with MTC.

Materials and Methods: Tumor tissue from 45 patients with MTC were reviewed to assess mitotic count, Ki67 proliferative index and necrosis and classified in high grade in presence of at least one of the following features: mitotic count ≥5 per 2 mm², Ki67 ≥5% or tumor necrosis. Uni- and multivariate analyses were performed to identify clinicopathological factor associated with persistent/recurrent disease.

Results: Data of 45 patients with MTC (14 M, 31 F). Necrosis was present in 24 (53.3%) of tissue specimens: 21 had focal and 3 had diffuse necrosis. No patient had mitotic count ≥5 per 2 mm², indeed median mitotic count was 1 (range 0-3). Median Ki67 was 2% (range 1-15) and 6 patients had Ki67 ≥5%. Therefore, 27 (60%) patients were classified as high grade, whereas 18 (40%) were low grade MTC. During a median follow-up of 89.8 months (IQR 51-106 months), 13 (28.9%) patients had persistent/recurrent disease with a median time to progression (TTP) of 8.6 months (IQR 3.2-48.7). Factors associated with event of disease during the follow-up were: tumor size (HR=1.09, 95%CI=1.05-1.15; P < 0.001), lymph node metastases (HR=4.37, 95%CI=1.37-13.97; P = 0.01) and ki67 (HR=1.24, 95%CI=1.07-1.45; P = 0.005). No different risk of progressive disease was observed between low and high grade because both features necrosis and mitosis count didn’t lead to worse outcome. At multivariate analysis, tumor size and ki67 were independently associated with persistent/recurrent disease. Progressive disease was more likely in patients with Ki67≥2 (HR=3.15, 95%CI=1.05-9.45; P = 0.04) and survival analysis demonstrated a trend across patients with ki67≤2, 2<ki67<5 and ki67≥5: median TTP was 6.4 months for the latter (log-rank p value for trend=0.01).

Discussion: We didn’t observe a prognostic role for mitotic count and necrosis, contrary to ki67 in patients with MTC. Although we analyzed only 45 patients, we speculate that a two-tiered grading (low/high) may be not totally accurate. Indeed, we observed a slight increased risk of progressive disease also in patients with 2<ki67<5. Therefore, a third category of intermediate grade may be suitable if other studies confirm our findings.

Conclusions: Ki67 index is a reliable prognostic factor and further studies are needed to better investigate its role in patients with MTC.