Grading of medullary thyroid carcinoma on the basis of tumor necrosis and high mitotic rate is an independent predictor of poor outcome Journal Article

   

Authors:	Alzumaili, B.; Xu, B.; Spanheimer, P. M.; Tuttle, R. M.; Sherman, E.; Katabi, N.; Dogan, S.; Ganly, I.; Untch, B. R.; Ghossein, R. A.
Article Title:	Grading of medullary thyroid carcinoma on the basis of tumor necrosis and high mitotic rate is an independent predictor of poor outcome
Abstract:	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. © 2020, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
Keywords:	adolescent; adult; child; aged; major clinical study; histopathology; follow up; lymph node metastasis; cancer grading; tumor volume; cohort analysis; calcitonin; distant metastasis; mitosis rate; codon; lobectomy; disease specific survival; pathologist; thyroid medullary carcinoma; tumor necrosis; mitosis index; calcitonin blood level; local recurrence free survival; lymph vessel metastasis; distant metastasis free survival; human; male; female; priority journal; article
Journal Title:	Modern Pathology
Volume:	33
Issue:	9
ISSN:	0893-3952
Publisher:	Nature Research
Date Published:	2020-09-01
Start Page:	1690
End Page:	1701
Language:	English
DOI:	10.1038/s41379-020-0532-1
PUBMED:	32313184
PROVIDER:	scopus
PMCID:	PMC7483270
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85084057579&doi=10.1038%2fs41379-020-0532-1&partnerID=40&md5=09d985f1aa672228721db6d29343cafb
Notes:	Article -- Export Date: 1 October 2020 -- Source: Scopus

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