Constitutive Cytomorphologic Features of Medullary Thyroid Carcinoma Using Different Staining Methods

Chih-Yi Liu 1, 2, Chien-Chin Chen 3, 4, Andrey Bychkov 5, 6, Shipra Agarwal 7, Yun Zhu 8, Jen-Fan Hang 9, Chiung-Ru Lai 9, 10, Hee Young Na 11, So Yeon Park 11, Weiwei Li 12, Zhiyan Liu 13, Deepali Jain 7, Ayana Suzuki 14, Mitsuyoshi Hirokawa 14, Noel Chia 15, Min En Nga 15, Tikamporn Jitpasutham 16, Somboon Keelawat 16, Shinya Satoh 17, Dilini Gunawardena 18, Priyanthi Kumarasinghe 18, Chan Kwon Jung 19, Kennichi Kakudo 20

Affiliations
  1. Division of Pathology, Sijhih Cathay General Hospital, New Taipei City 221, Taiwan.
  2. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 221, Taiwan.
  3. Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 600, Taiwan.
  4. Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan.
  5. Department of Pathology, Kameda Medical Center, Kamogawa, Chiba 296-8602, Japan.
  6. Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
  7. Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India.
  8. Department of Pathology, Jiangsu Institution of Nuclear Medicine, Wuxi 214063, China.
  9. Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan.
  10. School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
  11. Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
  12. Department of Pathology, Shandong University School of Basic Medical Sciences, Jinan 250012, China.
  13. Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China.
  14. Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe 650-0011, Japan.
  15. Department of Pathology, National University Hospital, Singapore 119074, Singapore.
  16. Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
  17. Department of Endocrine Surgery, Yamashita Thyroid and Parathyroid Clinic, Fukuoka 812-0034, Japan.
  18. School of Pathology & Laboratory Medicine, University of Western Australia, Perth, WA 6009, Australia.
  19. Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
  20. Department of Pathology and Thyroid Disease Center, Izumi City General Hospital, Izumi, Osaka 594-0073, Japan.

ABSTRACT

(1) Background: Accurate preoperative identification of medullary thyroid carcinoma (MTC) is challenging due to a spectrum of cytomorphologic features. However, there is a scarcity of studies describing the cytomorphologic features as seen on fine-needle aspiration (FNA) smears prepared using different staining methods. (2) Methods: We performed a retrospective study on MTC cases with available FNA slides from 13 hospitals distributed across 8 Asia-Pacific countries. The differences in the constitutive cytomorphologic features of MTC with each cytopreparatory method were recorded. A comparative analysis of cytologic characteristics was carried out with appropriate statistical tests. (3) Results: Of a total of 167 MTC samples retrospectively recruited, 148 (88.6%) were interpreted as MTC/suspicious for MTC (S-MTC). The staining methods used were Papanicolaou, hematoxylin-eosin, and Romanowsky stains. Seven out of the eleven cytologic criteria can be readily recognized by all three cytopreparatory methods: high cellularity, cellular pleomorphism, plasmacytoid cells, round cells, dyshesive cells, salt-and-pepper chromatin, and binucleation or multinucleation. An accurate diagnosis was achieved in 125 (84.5%) of the 148 samples whose FNAs exhibited five or more atypical features. Conclusions: The present work is the first study on MTC to compare the morphological differences among the cytologic staining techniques. We investigated the constitutive features and the reliability of diagnostic parameters. A feasible scoring system based upon cytomorphologic data alone is proposed to achieve a high degree of diagnostic accuracy.

Keywords: cytology; fine-needle aspiration; medullary thyroid carcinoma; sensitivity; specificity; thyroid.

>Diagnostics (Basel). 2021 Aug 2;11(8):1396. doi: 10.3390/diagnostics11081396.

Co-Occurrence of Differentiated Thyroid Cancer and Second Primary Malignancy: Correlation with Expression Profiles of Mismatch Repair Protein and Cell Cycle Regulators

Chih-Yi Liu 1, 2, Ching-Shui Huang 3, 4, Chi-Cheng Huang 5, 6, Wei-Chi Ku 2, Hsing-Yu Shih 3, Chi-Jung Huang 7, 8

Affiliations
  1. Division of Pathology, Sijhih Cathay General Hospital, New Taipei City 221, Taiwan.
  2. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan.
  3. Division of General Surgery, Department of Surgery, Cathay General Hospital, Taipei 106, Taiwan.
  4. School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
  5. Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, Taipei 1121, Taiwan.
  6. School of Public Health, College of Public Health, National Taiwan University, Taipei 100, Taiwan.
  7. Department of Medical Research, Cathay General Hospital, Taipei 106, Taiwan.
  8. Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan.

ABSTRACT

Some patients with thyroid cancer develop a second primary cancer. Defining the characteristics of patients with double primary cancers (DPCs) is crucial and needs to be followed. In this study, we examine molecular profiles in DPC. We enrolled 71 patients who received thyroid cancer surgery, 26 with single thyroid cancer (STC), and 45 with DPC. A retrograde cohort was used to develop immunohistochemical expressions of mismatch repair (MMR) proteins and cell-cycle-related markers from tissue microarrays to produce an equation for predicting the occurrence of DPC. The multivariate logistic model of 67 randomly selected patients (24 with STC and 43 with DPC) identified that the expression of deficient MMR (dMMR) (odds ratio (OR), 10.34; 95% confidence interval (CI), 2.17-49.21) and pRb (OR, 62.71; 95% CI, 4.83-814.22) were significantly associated with a higher risk of DPC. In contrast, the expression of CDK4 (OR, 0.19; 95% CI, 0.04-0.99) and CDK6 (OR, 0.03; 95% CI, 0.002-0.44) was significantly associated with a lower risk of DPC. Collectively, dMMR, pRb, CDK4, and CDK6 have a sensitivity of 88.9% (95% CI, 75.1-95.8) and a specificity of 69.2% (95% CI, 48.1-84.9) for occurrence of DPC in all 71 patients. This is the first report to demonstrate the molecular differentiation of STC and DPC. Overall, the integral molecular profile performed excellent discrimination and denoted an exponential function to predict the probability of DPC.

Keywords: DNA mismatch repair; cell cycle; immunohistochemistry; multiple primary; neoplasms; second primary; thyroid neoplasms.

>Cancers (Basel). 2021 Oct 31;13(21):5486. doi: 10.3390/cancers13215486.