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Amphicrine Medullary Thyroid Carcinoma — a Case-Based Review Expanding on Its MUC Expression Profile

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Abstract

Amphicrine phenotype in medullary thyroid carcinoma (MTC) is a rare phenomenon characterized by tumor cells that show both endocrine differentiation (calcitonin secretion) and exocrine differentiation (mucin production and secretion). Not much is known about the pathobiology of amphicrine MTCs. This report undertook a case-based review approach by discussing the cytological, histopathological, and ultrastructural features of this rare enigmatic entity, expanding on the radiological and novel MUC immunohistochemistry findings from a 28-year-old MEN2B syndrome patient with C cell hyperplasia and multifocal MTC with amphicrine features. The patient had widespread hematogenous metastases at presentation. MUC immunoexpression analysis revealed evidence of micro-lumina formation, and unique to-date unreported expression patterns of MUC1, MUC5AC, and MUC6 in an amphicrine subtype of MTC. Review of the literature identified five other MTC cases with well-documented amphicrine features. Of these six cases, two were associated with MEN2B syndrome, and four had metastatic disease. Follow-up was available in three patients, and two died of disease. Recognition of this rare subtype of MTC may be of clinical interest given their frequent link to MEN2B syndrome and biological aggressiveness.

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References

  1. Wells SA, Asa SL, Dralle H et al. (2015) Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma. Thyroid 25:567–610. https://doi.org/10.1089/thy.2014.0335

    Article  PubMed  PubMed Central  Google Scholar 

  2. Randle RW, Balentine CJ, Leverson GE et al. (2017) Trends in the presentation, treatment, and survival of patients with medullary thyroid cancer over the past 30 years. Surgery 161:137–146. https://doi.org/10.1016/j.surg.2016.04.053

    Article  PubMed  Google Scholar 

  3. Zaatari GS, Saigo PE, Huvos AG (1983) Mucin production in medullary carcinoma of the thyroid. Arch Pathol Lab Med 107:70–74

    CAS  PubMed  Google Scholar 

  4. Farhat NA, Onenerk AM, Krane JF et al. (2017) Primary Benign and Malignant Thyroid Neoplasms With Signet Ring Cells: Cytologic, Histologic, and Molecular Features. American Journal of Clinical Pathology 148:251–258. https://doi.org/10.1093/ajcp/aqx074

    Article  CAS  PubMed  Google Scholar 

  5. Mlynek M-L, Richter HJ, Leder L-D (1985) Mucin in carcinomas of the thyroid. Cancer 56:2647–2650. https://doi.org/10.1002/1097-0142(19851201)56:11<2647::AID-CNCR2820561119>3.0.CO;2-8

    Article  CAS  PubMed  Google Scholar 

  6. Golouh R, Us-krasovec, Auersperg et al. (1985) Amphicrine — Composite Calcitonin and Mucin-Producing — Carcinoma of the Thyroid. Ultrastructural Pathology 8:197–206. https://doi.org/10.3109/01913128509142153

    Article  CAS  PubMed  Google Scholar 

  7. Baloch ZW, Asa SL, Barletta JA, Ghossein RA, Juhlin CC, Jung CK, LiVolsi VA, Papotti MG, Sobrinho-Simões M, Tallini G, Mete O. Overview of the 2022 WHO Classification of Thyroid Neoplasms. Endocr Pathol. 2022 Mar;33(1):27-63.

    Article  Google Scholar 

  8. Haleem A, Akhtar M, Ali MA, Iqbal Z (1990) Fine-needle aspiration biopsy of mucus-producing medullary carcinoma of thyroid: Report of a case with cytologic, histologic, and ultrastructural correlations. Diagnostic Cytopathology 6:112–117. https://doi.org/10.1002/dc.2840060208

    Article  CAS  PubMed  Google Scholar 

  9. Dominguez-Malagon H, Macias-Martinez V, Molina-Cardenas H, Suster S (1997) Amphicrine Medullary Carcinoma of the Thyroid with Luminal Differentiation: Report of an Immunohistochemical and Ultrastructural Study. Ultrastructural Pathology 21:569–574. https://doi.org/10.3109/01913129709016373

    Article  CAS  PubMed  Google Scholar 

  10. Osaka M, Soga J, Tamiya Y, Suzuki T (1999) Dedifferentiation of neoplastic cells in medullary thyroid carcinoma: report of a case. Surg Today 29:1189–1194. https://doi.org/10.1007/BF02482271

    Article  CAS  PubMed  Google Scholar 

  11. Kinjo M, Yohena C, Kunishima N (2003) Intracytoplasmic Lumina in Medullary Carcinoma of the Thyroid Gland. Acta Cytologica 47:663–667. https://doi.org/10.1159/000326585

    Article  PubMed  Google Scholar 

  12. Mardi K (2021) Cytodiagnosis of mucin-producing medullary carcinoma of the thyroid gland. South Asian J Cancer 02:210–210

    Google Scholar 

  13. Dhanisha SS, Guruvayoorappan C, Drishya S, Abeesh P (2018) Mucins: Structural diversity, biosynthesis, its role in pathogenesis and as possible therapeutic targets. Critical Reviews in Oncology/Hematology 122:98–122. https://doi.org/10.1016/j.critrevonc.2017.12.006

    Article  PubMed  Google Scholar 

  14. Lau SK, Weiss LM, Chu PG (2004) Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study. Am J Clin Pathol 122:61–69. https://doi.org/10.1309/9R66-73QE-C06D-86Y4

    Article  PubMed  Google Scholar 

  15. Ho SB, Shekels LL, Toribara NW et al. (1995) Mucin Gene Expression in Normal, Preneoplastic, and Neoplastic Human Gastric Epithelium. Cancer Res 55:2681

    CAS  PubMed  Google Scholar 

  16. Wang X-T, Kong F-B, Mai W et al. (2016) MUC1 Immunohistochemical Expression as a Prognostic Factor in Gastric Cancer: Meta-Analysis. Dis Markers 2016:9421571. https://doi.org/10.1155/2016/9421571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jing X, Liang H, Hao C et al. (2019) Overexpression of MUC1 predicts poor prognosis in patients with breast cancer. Oncology Reports 41:801–810. https://doi.org/10.3892/or.2018.6887

    Article  CAS  PubMed  Google Scholar 

  18. Do S-I, Kim K, Kim D-H et al. (2013) Associations between the Expression of Mucins (MUC1, MUC2, MUC5AC, and MUC6) and Clinicopathologic Parameters of Human Breast Ductal Carcinomas. J Breast Cancer 16:152–158. https://doi.org/10.4048/jbc.2013.16.2.152

    Article  PubMed  PubMed Central  Google Scholar 

  19. Betge J, Schneider NI, Harbaum L et al. (2016) MUC1, MUC2, MUC5AC, and MUC6 in colorectal cancer: expression profiles and clinical significance. Virchows Arch 469:255–265. https://doi.org/10.1007/s00428-016-1970-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang J, Guli Q-R, Ming X-C et al. (2018) Primary mucinous carcinoma of thyroid gland with prominent signet-ring-cell differentiation: a case report and review of the literature. Onco Targets Ther 11:1521–1528. https://doi.org/10.2147/OTT.S158975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Alves P, Soares P, Fonseca E, Sobrinho-Simões M (1999) Papillary thyroid carcinoma overexpresses fully and underglycosylated mucins together with native and sialylated simple mucin antigens and histo-blood group antigens. Endocr Pathol 10:315–324. https://doi.org/10.1007/BF02739774

    Article  CAS  PubMed  Google Scholar 

  22. Bèche I, Ruffet E, Zweibaum A et al. (1997) MUC1 Mucin Gene, Transcripts, and Protein in Adenomas and Papillary Carcinomas of the Thyroid. Thyroid 7:725–731. https://doi.org/10.1089/thy.1997.7.725

    Article  Google Scholar 

  23. Li Q, Jin W-X, Jin Y-X et al. (2018) Clinical effect of MUC1 and its relevance to BRAF V600E mutation in papillary thyroid carcinoma: a case–control study. Cancer Manag Res 10:1351–1358. https://doi.org/10.2147/CMAR.S161501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Renaud F, Gnemmi V, Devos P et al. (2014) MUC1 Expression in Papillary Thyroid Carcinoma Is Associated with BRAF Mutation and Lymph Node Metastasis; the Latter is the Most Important Risk Factor of Relapse. Thyroid 24:1375–1384. https://doi.org/10.1089/thy.2013.0594

    Article  CAS  PubMed  Google Scholar 

  25. Li Y, Gao W, Cai X et al. (2021) Exploring Somatic Alteration Associating With Aggressive Behaviors of Papillary Thyroid Carcinomas by Targeted Sequencing. Frontiers in Oncology 11:4029. https://doi.org/10.3389/fonc.2021.722814

    Article  Google Scholar 

  26. Farahmand L, Merikhian P, Jalili N et al. (2018) Significant Role of MUC1 in Development of Resistance to Currently Existing Anti-cancer Therapeutic Agents. Curr Cancer Drug Targets 18:737–748. https://doi.org/10.2174/1568009617666170623113520

    Article  CAS  PubMed  Google Scholar 

  27. Pillai K, Pourgholami MH, Chua TC, Morris DL (2015) MUC1 as a Potential Target in Anticancer Therapies. American Journal of Clinical Oncology 38:108–118. https://doi.org/10.1097/COC.0b013e31828f5a07

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, First Floor, Teaching Block, All India Institute of Medical Sciences, New Delhi, 110029, India

    Hena Khandakar, Shipra Agarwal & Mehar Chand Sharma

  2. Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India

    Devasenathipathy Kandasamy

  3. Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India

    Chandrasekhar Bal

  4. Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India

    Yashvant Rathode & Rijuta Aphale

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  1. Hena Khandakar
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  2. Shipra Agarwal
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  4. Devasenathipathy Kandasamy
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  5. Chandrasekhar Bal
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Contributions

HK and SA wrote the main manuscript text, and prepared Figs. 2, 3, and 4; DK, CB, YR, and RA prepared the images in Fig. 1, while MCS prepared the images in Fig. 3C–E. All the authors reviewed the manuscript.

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Correspondence to Shipra Agarwal.

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Ethical approval was waived by the institutional review board in view of the retrospective nature of the study and all the procedures being performed were part of the routine care.

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Khandakar, H., Agarwal, S., Sharma, M.C. et al. Amphicrine Medullary Thyroid Carcinoma — a Case-Based Review Expanding on Its MUC Expression Profile. Endocr Pathol 33, 378–387 (2022). https://doi.org/10.1007/s12022-022-09725-1

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  • DOI: https://doi.org/10.1007/s12022-022-09725-1

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