Revisiting the Significance of Prominent C Cells in the Thyroid


C cell hyperplasia is considered a precursor lesion for hereditary forms of medullary thyroid carcinoma. It has therefore been suggested as a morphological marker to distinguish hereditary from sporadic medullary thyroid carcinoma and to triage genetic testing in resource poor settings. However, numerous definitions for C cell hyperplasia have been suggested, and there is surprisingly little data regarding the number of C cells present in thyroid glands removed for conditions other than medullary carcinoma. We therefore sought to investigate the specificity of different criteria for C cell hyperplasia. We examined the number of C cells and solid cell nests (ultimobranchial body remnants) present in 118 completion thyroidectomy specimens from patients without medullary carcinoma and with no risk factors for MEN2. Morphological review was performed on all H&E-stained slides, and immunohistochemistry for calcitonin was performed on one block from each case. Solid cell nests were found in 4 (3.3%) of thyroids. Increased numbers of C cells sufficient to fulfil criteria for C cell hyperplasia were found in 5 (4.2%) to 36 (30.5%) cases depending on the criteria used. We conclude that large numbers of C cells are commonly found in thyroids not associated with medullary carcinoma. Therefore, regardless of which criteria are used, the presence of C cell hyperplasia is not a specific marker for hereditary medullary thyroid carcinoma.

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  1. 1.

    Chan JKC (2007) Tumours of the thyroid and parathyroid glands. In: Fletcher CDM (ed) Diagnostic histopathology of tumors, 3rd edn. Churchill Livingstone Elsevier, New York, pp.1223–1232.

  2. 2.

    Tashjian AH, Wolfe HJ, Voelkl EF (1974) Human calcitonin: immunologic assay, cytologic localization and studies on medullary thyroid carcinoma. Am J Med 56:840–849.

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    Harach HR (1988) Solid cell nests of the thyroid. Journal of Pathology 155:191–200.

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Harach HR (1985) Histological markers of solid cell nests of the thyroid. With emphasis on their expression in thyroid ultimobranchial-related tumors. Acta Anatomica 124:111–116.

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Gimm O, Morrison CD, Suster S et al (2004) Multiple endocrine neoplasia type 2. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C (eds) Pathology and genetics of tumours of endocrine organs. IARC Press, Lyon, pp.211–217.

  6. 6.

    Reagh J, Bullock M, Andrici J, Turchini J, Sioson L, Clarkson A, Watson N, Sheen A, Lim G, Delbridge L, Sidhu S, Sywak M, Aniss A, Shepherd P, Ng D, Oei P, Field M, Learoyd D, Robinson BG, Clifton-Bligh RJ, Gill AJ (2017) NRASQ61R mutation-specific immunohistochemistry also identifies the HRASQ61R mutation in medullary thyroid cancer and may have a role in triaging genetic testing for MEN2. Am J Surg Pathol, 41:75–81.

    Article  PubMed  Google Scholar 

  7. 7.

    Saggiorato E, Rapa I, Garino F, Bussolati G, Orlandi F, Papotti M, Volante M (2007) Absence of RET gene point mutations in sporadic thyroid C-cell hyperplasia. J Mol Diag 9(2):214–219.

    Article  CAS  Google Scholar 

  8. 8.

    Wells SA Jr, Asa SL, Dralle H et al (2015) Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 25:567–610.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Wolfe HJ, Melvin KEW, Cervi-Skinner SJ, al Saadi AA, Juliar JF, Jackson CE, Tashjian Jr AH (1973) C-cell hyperplasia preceding medullary thyroid carcinoma. NEJM 289:437–441.

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Williams ED, Ponder BJ, Craig RK (1987) Immunohistochemical study of calcitonin gene-related peptide in human medullary carcinoma and C-cell hyperplasia. Clin Endocrinol 27:107–114.

    Article  CAS  Google Scholar 

  11. 11.

    Ekblom M et al (1987) Familial and sporadic medullary thyroid carcinoma: clinical and immunohistochemical findings. Quarterly Journal of Medicine 247:899–910.

    Google Scholar 

  12. 12.

    Albores-Saavedra J, Monforte H, Nadji M, Morales AR (1988) C-cell hyperplasia in thyroid tissue adjacent to follicular cell tumors. Hum Pathol 19(7):795–799.

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    LiVolsi V, DeLellis R, Komminoth P et al (2017) Multiple endocrine neoplasia type 2. In: Lloyd RV, Osamura RY, Kloppel G, Rosai J (eds) WHO classification of tumours of endocrine organs, 4th edn. IARC Press, Lyon, pp.248–250.

  14. 14.

    Guyetant S, Rousselet M-C, Durigon M et al (1997) Sex-related C-cell hyperplasia in the normal human thyroid: a quantitative autopsy study. J Clin Endocrinol Metab 82:42–47.

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Albores-Saavedra JA, Krueger JE (2001) C-cell hyperplasia and medullary thyroid microcarcinoma. Endocrine Pathology 12:365–377.

    Article  CAS  PubMed  Google Scholar 

  16. 16.

    Guyetent S, Blechet C, Saint-Andre JP (2006) C-cell hyperplasia. Annals of Endocrinology (Paris) 67:190–197.

    Article  Google Scholar 

  17. 17.

    Scognamiglio T (2017) C-cell and follicular epithelial cell precursor lesions of the thyroid. Arch Pathol Lab Med 141:1646–1652.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Anthony J. Gill.

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This study was approved by the local institutional ethics committee.

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Fuchs, T.L., Bell, S.E., Chou, A. et al. Revisiting the Significance of Prominent C Cells in the Thyroid. Endocr Pathol 30, 113–117 (2019).

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  • Medullary thyroid carcinoma
  • C cell hyperplasia
  • MEN2