Endocrine Pathology

, Volume 9, Issue 4, pp 287–292 | Cite as

Clonality in thyroid nodules: The hyperplasia-neoplasia sequence

  • Zubair W. Baloch
  • Virginia A. LiVolsi
Clinical Research


The evaluation of clonality in nodular proliferations of the thyroid gland has identified a large proportion of monoclonal nodules even in the setting of nonendemic nodular goiter. The literature on this topic is reviewed and an attempt is made to explain the available data. In the absence of a clear understanding of the biological impact and potential of these molecular events, a recommendation is made for continued use of current histomorphologic nomenclature when diagnosing such thyroid lesions in the day-to-day practice of surgical pathology.

Key Words

Thyroid nodule clonality RFLP 


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  1. 1.
    LiVolsi VA. Surgical pathology of the thyroid. Philadelphia: WB Saunders; 1990.Google Scholar
  2. 2.
    Beckers C. Thyroid nodules. J Clin Endocrinol Metab 8:181–192, 1979.CrossRefGoogle Scholar
  3. 3.
    Rosai J, Carcangiu ML, DeLellis RA. Tumors of the thyroid gland. In: Atlas of tumor pathology, 3rd ser., fasc. 5. Armed Forces Institute of Pathology; 1992.Google Scholar
  4. 4.
    Studer H, Peter HJ, Gerber H. Natural heterogeneity of thyroid cells: The basis of understanding thyroid function and nodular goiter growth. Endocr Rev 10:125–135, 1989.PubMedCrossRefGoogle Scholar
  5. 5.
    Thomas GA, Williams D, Williams ED. The clonal origin of thyroid nodules end adenomas. Am J Pathol 134:141–147, 1989.PubMedGoogle Scholar
  6. 6.
    Hicks DG, LiVolsi VA, Neidich JA, Puck JM, Kant JA. Clonal analysis of solitary follicular nodules in thyroid. Am J Pathol 137:553–562, 1990.PubMedGoogle Scholar
  7. 7.
    Namba H, Matsuo K, Fagin JA. Clonal composition of benign and malignant human thyroid tumors. J Clin Invest 86:120–125, 1990.PubMedGoogle Scholar
  8. 8.
    Aeschimann S, Kopp PA, Kimura ET, Zbaeren J, Tobler A, Fey MF, et al. Morphological and functional polymorphism within clonal thyroid nodules. J Clin Endocrinol Metab 77:846–851, 1993.PubMedCrossRefGoogle Scholar
  9. 9.
    Kopp P, Kimura ET, Aeschimann S, Oestrecher M, Tobler A, Fey MF, Studer H. Polyclonal and monoclonal thyroid nodules coexist within human multinodular goiters. J Clin Endocrinol Metab 79:134–139, 1994.PubMedCrossRefGoogle Scholar
  10. 10.
    Studer H, Gerber H, Zbaeren J, Peter HJ. Histomorphological and immunohistochemical evidence that human nodular goiters growth by episodic replication of multiple clusters of thyroid follicular cells. J Clin Endocrinol Metab 75:1151–1158, 1992.PubMedCrossRefGoogle Scholar
  11. 11.
    Apel RL, Ezzat S, Bapat BV, Pan N, LiVolsi VA, Asa SL. Clonality of thyroid nodules in sporadic goiter. Diagn Mol Pathol 4:113–121, 1995.PubMedCrossRefGoogle Scholar
  12. 12.
    Ramelli F, Studer H, Bruggisser D. Pathogenesis of thyroid nodules in multinodular goiter. Am J Pathol 109:215–223, 1982.PubMedGoogle Scholar
  13. 13.
    Gerber H, Peter HJ, Studer H, Laempi J. Apparently clonal thyroid adenomas may contain heterogenously growing and functional cell subpopulations. In: Medeiros-neto G, Gaitan E, eds. Frontiers in thyroidology, vol 2, Plenum, New York; pp 901–905, 1987.Google Scholar
  14. 14.
    Peter HJ, Studer H, Forster R, Gerber H. The pathogenesis of “hot” and “cold” follicles in multinodular goiter. J Clin Endocrinol Metab 55:941–946, 1982.PubMedGoogle Scholar
  15. 15.
    Teuscher J, Peter HJ, Gerber H, Berchtold R, Studer H. Pathogenesis of nodular goiter and its implications for surgical management. Surgery 103:87–93, 1988.PubMedGoogle Scholar
  16. 16.
    Vogelstein D, Featon ER, Hamilton SR, Preisinger AC, Willard HF, Michelson AM, et al. Clonal analysis using recombinant DNA probes from the X-chromosome. Cancer Res 47:4806–4813, 1987.PubMedGoogle Scholar
  17. 17.
    Lyon MF. X-chromosome inactivation and developmental patterns in mammals. Biol Rev 47:1–35, 1972.PubMedCrossRefGoogle Scholar
  18. 18.
    Beutler E, Yeh M, Fairbanks VF. The normal human female as a mosaic of X-chromosome activity: studies using the gene for G-6-PD deficiency as a marker. Proc Natl Acad Sci USA 48:9–16, 1962.PubMedCrossRefGoogle Scholar
  19. 19.
    Vogelstein B, Fearon ER, Hamilton SR, Feinberg AP. Use of restriction fragment length polymorphisms to determine the clonal origin of human tumors. Science 227:642–645, 1985.PubMedCrossRefGoogle Scholar
  20. 20.
    Bird AP, Sothern EM. Use of restriction enzymes to study enkaryotic DNA methylation: I. the methylation pattern in ribosomal DNA fromXenopus laevis. J Mol Biol 118:27–47, 1978.PubMedCrossRefGoogle Scholar
  21. 21.
    Fey MF, Peter H-J, Hinds HL, Zimmermann A, Liechti-Gallati S, Gerber H, et al. Clonal analysis of human tumors with M27b, a highly informative polymorphic X chromosomal probe. J Clin Invest 89:1438–1444, 1992.PubMedCrossRefGoogle Scholar
  22. 22.
    Gale RE, Wheadon H, Linch DC. Assessment of X-chromosome inactivation patterns using the hypervariable probe M27β in normal hematopoietic cells and acute myeloid leukemic blasts. Leukemia 6:649–655, 1992.PubMedGoogle Scholar
  23. 23.
    Kim HS, Lee YJ, Nam JH, Jung JJ, Montone KT, Park CS. The clinical application of clonal analysis in nodular lesions of the thyroid. Mod Pathol 11:57A, 1998.Google Scholar
  24. 24.
    Fialkow PJ. Clonal origin of human tumors. Biochim Biophys Acta 458:283–321, 1976.PubMedGoogle Scholar
  25. 25.
    Salmon I, Gasperin P, Pasteels JL, Helmann R, Kiss R. Relationship between histopathologic typing and morphonuclear assessments of 238 thyroid lesions. Am J Clin Pathol 97:776–786, 1992.PubMedGoogle Scholar
  26. 26.
    Arnold A, Kim HG. Clonal loss of one chromosome 11 in a parathyroid adenoma. J Clin Endocrinol Metab 69:496–499, 1989.PubMedCrossRefGoogle Scholar
  27. 27.
    Falchetti A, Bale AK, Amorosi A, Bordi C, Cicchi P, Bandini S, et al. Progression of uremic hyperparathyroidism involves allelic loss on chromosome 11. J Clin Endocrinol Metab 76:139–144, 1993.PubMedCrossRefGoogle Scholar
  28. 28.
    Arnold A, Staunton CE, Kim HG, Gaz RD, Kronenberg HM. Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas. N Engl J Med 318:658–662, 1988.PubMedCrossRefGoogle Scholar
  29. 29.
    Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 61:759–767, 1990.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 1998

Authors and Affiliations

  1. 1.Anatomic Pathology, Department of Pathology and Laboratory MedicineUniversity of Pennsylvania Medical CenterPhiladelphia

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