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Independent Validation of the International Grading System for Medullary Thyroid Carcinoma: A Single Institution Experience.

ABSTRACT: Medullary thyroid carcinoma (MTC), an uncommon C cell thyroid malignancy, accounts for a disproportionate number of thyroid cancer deaths. To predict MTC clinical behavior, the recent international MTC grading system (IMTCGS) was published combining features from the Memorial Sloan Kettering Cancer Center and Royal North Shore Hospital grading systems that incorporates mitotic count, necrosis, and Ki67 proliferative index (Ki67PI). The IMTCGS appears promising, but independent validation data are limited. Here, we applied the IMTCGS to our institutional MTC cohort and assessed its ability to predict clinical outcomes. Our cohort comprised 87 MTCs (30 germline and 57 sporadic). Slides for each case were reviewed by 2 pathologists and histologic features recorded. Ki67 immunostaining was performed on all cases. Each MTC was graded with the IMTCGS based on tumor necrosis, Ki67PI, and mitotic count. Cox regression analysis was performed to assess the impact of various clinical and pathological data on disease outcomes, including overall survival (OS), disease-free survival, disease-specific survival (DSS), and distant metastasis-free survival. In our MTC cohort, 18.4% (n = 16/87) were IMTCGS high grade. IMTCGS grade was strongly prognostic for OS, disease-free survival, DSS, and distant metastasis-free survival on univariate analysis and multivariable analysis in both the entire MTC cohort and in the sporadic subset. Among the individual IMTCGS parameters, while all 3 were associated with poorer survival outcomes on univariate analysis, necrosis had the strongest association with all survival parameters on multivariable analysis, whereas Ki67PI or mitotic count was associated only with OS and DSS. This retrospective study independently demonstrates that the IMTCGS is valid for grading MTCs. Our findings support incorporating IMTCGS into routine pathology practice. IMTCGS grading may help clinicians to better predict the prognosis of MTC. Future studies may shed light on how MTC grading should impact treatment protocols.

SUBMITTER: Lubin DJ

PROVIDER: S-EPMC10528047 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Independent Validation of the International Grading System for Medullary Thyroid Carcinoma: A Single Institution Experience.

Lubin Daniel J DJ Behrman David Blake DB Goyal Subir S Magliocca Kelly K Shi Qiuying Q Chen Amy Y AY Viswanathan Kartik K

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 20230601 9

Medullary thyroid carcinoma (MTC), an uncommon C cell thyroid malignancy, accounts for a disproportionate number of thyroid cancer deaths. To predict MTC clinical behavior, the recent international MTC grading system (IMTCGS) was published combining features from the Memorial Sloan Kettering Cancer Center and Royal North Shore Hospital grading systems that incorporates mitotic count, necrosis, and Ki67 proliferative index (Ki67PI). The IMTCGS appears promising, but independent validation data ar ...[more]

PMID: 37270155

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Project description:Medullary thyroid carcinoma (MTC) is a rare nonfollicular cell-derived tumor. A robust grading system may help better stratify patients at risk for recurrence and death from disease. In total, 144 MTC between 1988 and 2018 were subjected to a detailed histopathologic evaluation. Clinical and pathologic data were correlated with disease specific survival (DSS), local recurrence free survival (LRFS) and distant metastasis free survival (DMFS). Median age was 53 years (range: 3-88). Median tumor size was 1.8 cm (range: 0.2-11). Lymph node metastases were present in 84 (58%) cases while distant metastases at presentation were found in 9 (6%) patients. Seven (5%) had ≥5 mitoses/10 HPFs. Tumor necrosis was present in 30 cases (20%) while lymphovascular invasion occurred in 41 (28%) of tumors. Extra-thyroidal extension was found in 44 (31%) and positive margins were seen in 19 (14%). There was a strong correlation between increasing tumor size and tumor necrosis (p < 0.001). Median follow up was 39 months. In univariate analysis, male gender, higher American Joint Committee on Cancer (AJCC) stage group, larger tumor size, tumor necrosis, high mitotic index (≥5/10 HPF), nodal status, size of largest nodal metastasis, and elevated postoperative serum calcitonin predicted worse DSS, LRFS, and DMFS (p < 0.05). Extra-thyroidal extension correlated with DSS and DMFS while positive margins and distant metastasis at presentation imparted worse DSS (p < 0.05). In multivariate analysis, tumor necrosis and mitotic activity (5 mitosis/10 HPFs as the cutoff) were the only independent predictors for DSS (p = 0.008 and 0.026, respectively). Tumor necrosis was the sole independent prognostic factor for LRFS and DMFS (p = 0.001 and 0.003, respectively). The presence of tumor necrosis and high mitotic rate are powerful independent prognostic factors in MTC and outperform serum calcitonin and stage. We propose a grading system based on tumor necrosis and mitotic activity to better stratify MTC patients for counseling, post-resection surveillance, and therapy.

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Independent Validation of the International Grading System for Medullary Thyroid Carcinoma: A Single Institution Experience.

Publications

Independent Validation of the International Grading System for Medullary Thyroid Carcinoma: A Single Institution Experience.

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