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The pathology of medullary carcinoma of the thyroid: Review of the literature and personal experience on 62 cases

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Abstract

The aim of the present review is to analyze the numerous pathological patterns of medullary carcinoma of the thyroid (MCT) and discuss the problems of differential diagnosis with other thyroid and nonthyroid tumors. In addition, morphological parameters and phenotypic features were related to the clinical outcome. The recent literature was reviewed and compared with the features of 62 MCTs observed at our institution. The most common patterns of growth are trabecular, alveolar, and spindle cells, but MCT can mimic virtually all other primary thyroid tumors and some nonthyroid neoplasms. This heterogeneity has no proven implications for prognosis, but is of relevance for diagnostic purposes, as the differential diagnosis of MCT can be difficult in nonclassical cases. In agreement also with the literature data, no relationship between histopathological parameters and outcome was found in our series, although clinically aggressive tumors had a more advanced stage at presentation. Immunocytochemical demonstration of calcitonin is apparently the only valid criterion for a correct typing of MCT. Chromogranin A is an additional sensitive marker of MCT and parallels calcitonin expression in the majority of cases.

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References

  1. Hedinger C, William ED, Sobin LH. Histological typing of thyroid tumors. World Health Organization International Histological Classification of Tumors. 2nd ed. Berlin: Springer-Verlag, 1988.

    Google Scholar 

  2. Jaquet J Ein Fall von metastasierend Amyloidtumoren (Lymphosarkoma). Virchows Arch (A) 185:251–267, 1906.

    Google Scholar 

  3. Stoffel E. Lokales Amyloid der Schilddruse. Virchows Arch Pathol Anat Physiol 201:245–252, 1910.

    Article  Google Scholar 

  4. Hazard JB, Hawk WA, Crile G Jr. Medullary (solid) carcinoma of the thyroid—a clinico-pathologic entity. J Clin Endocrinol Metab 19:152–161, 1959.

    Article  PubMed  CAS  Google Scholar 

  5. Cunliffe WJ, Black MM, Hall R, Johnston IDA, Hudgson P, Shuster S, Gudmusson TV, Joplin GF, Williams ED, Woodhouse NJY, Galante L, Mac-Intyre I. A calcitonin-secreting thyroid carcinoma. Lancet II:63–66, 1968.

    Article  Google Scholar 

  6. Melvin KEW, Tashjan AH. The syndrome of excessive thyrocalcitonin produced by medullary carcinoma of the thyroid. Proc Natl Acad Sci USA 59:1216–1222, 1968.

    Article  PubMed  CAS  Google Scholar 

  7. Bussolati G. Pearse AGE Immunofluorescent localization of calcitonin in the “C” cells of pig and dog thyroid. J Endocr 37:205–209, 1967.

    PubMed  CAS  Google Scholar 

  8. Bussolati G, Foster GV, Clark MB, Pearse AGE. Immunofluorescent localisation of calcitonin in medullary (C cell) thyroid carcinoma using antibody to the pure porcine hormone. Virchows Arch B 2:234–238, 1969.

    CAS  Google Scholar 

  9. Solcia E, Capella C, Sanpietro R, Vassallo G. The distribution of human C cell and their relationships to osteopetrosis and medullary carcinoma of the thyroid. In: Taylor S, Foster GV, eds. Calcitonin. London: Heinemann, 1970; 220.

    Google Scholar 

  10. Williams ED. A review of 17 cases of carcinoma of the thyroid and phaeochromocytoma. J Clin Pathol 18:288–292, 1965.

    Article  PubMed  CAS  Google Scholar 

  11. Williams ED, Pollock DJ. Multiple mucosal neuromata with endocrine tumours. A syndrome allied to von Recklinghausen’s disease. J Pathol Bacteriol 91:71–80, 1966.

    Article  PubMed  CAS  Google Scholar 

  12. Saad MF, Ordonez NG, Rashid RK, Guido JJ, Hill CS, Hickey RC, Sarnaan NA. Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients. Medicine (Baltimore) 63:319–342, 1984.

    CAS  Google Scholar 

  13. Wolfe HJ, Melvin KEW, Cervi-Skinner SJ, Al Saadi AA, Juliar JF, Jackson CE, Tashjian AH. C-cell hyperplasia preceding medullary thyroid carcinoma. N Engl J Med 289:437–441, 1973.

    Article  PubMed  CAS  Google Scholar 

  14. De Lellis RA, Nunnemacher G, Wolfe HJ. C-cell hyperplasia. An ultrastructural analysis. Lab Invest 36:237–247, 1977.

    Google Scholar 

  15. De Lellis RA, Dayal Y, Tischler AS, Lee AK, Wolfe HJ. Multiple endocrine neoplasia (MEN) syndromes: cellular origins and interrelationships. Int Rev Exp Pathol. 28:163–215, 1986.

    Google Scholar 

  16. Al Saadi AA. Ultrastructure in C cell hyperplasia in asymptomatic patients with hypercalcitoninemia and a family history of medullary thyroid carcinoma. Hum Pathol 12:617–622, 1981.

    Article  Google Scholar 

  17. Ulbright TM, Kraus FT, O’Neal LW. C-cell hyperplasia developing in residual thyroid following resection of sporadic medullary. Cancer 48:2076–2079, 1981.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  19. Capella C, Bordi C, Monga G, Buffa R, Fontana P, Bonfanti S, Bussolati G, Solcia E. Multiple endocrine cell types in thyroid medullary carcinoma. Evidence for calcitonin, somatostatin, ACTH, 5HT and small granule cells. Virchows Arch A Pathol Anat 377:111–128, 1978.

    Article  CAS  Google Scholar 

  20. Krisch K, Krisch I, Horvat G, Neuhold N, Ulrich W. The value of immunohistochemistry in medullary thyroid carcinomas: a systematic study of 30 cases. Histopathology 9:1077–1089, 1985.

    Article  PubMed  CAS  Google Scholar 

  21. Sikri KL, Varndell IN, Hamid QA, Wilson BS, Kameya T, Ponder BAJ, Lloyd RV, Bloom SR, Polak JM. Medullary carcinoma of the thyroid: an immunohistochemical and histochemical study of 25 cases using eight separate markers. Cancer 56:2481–2491, 1985.

    Article  PubMed  CAS  Google Scholar 

  22. Holm R, Sobrinho-Simões M, Nesland JM, Gould VE, Johannessen JV. Medullary carcinoma of thyroid gland: immunocytochemical study. Ultrastruct Pathol 8:25–41, 1985.

    PubMed  CAS  Google Scholar 

  23. Schröder S, Holl K, Padberg BC. Pathology of sporadic and hereditary medullary thyroid carcinoma. Rec Results Cancer Res 125:19–45, 1992.

    Google Scholar 

  24. Pagani A, Papotti M, Höfler H, Weiler R, Winkler H, Bussolati G. Chromogranin A and B gene expression in carcinomas of the breast. Am J Pathol 136:319–327, 1990.

    PubMed  CAS  Google Scholar 

  25. Hankin RC, Lloyd RV. Detection of messenger RNA in routinely processed tissue section with biotinylated oligonucleotide probes. Am J Clin Pathol 92:166–171, 1989.

    PubMed  CAS  Google Scholar 

  26. Lloyd RV, Jin L, Fields C. Detection of chromogranins A and B in endocrine tissues with radioactive and biotinylated oligonucleotide probes. Am J Surg Pathol 14:35–43, 1990.

    PubMed  CAS  Google Scholar 

  27. Ljungberg O. On medullary carcinoma of the thyroid. Acta Pathol Microbiol Scand Suppl 231:5–57, 1972.

    Google Scholar 

  28. Ljungberg O. Biopsy pathology of the thyroid and parathyroid. London: Chapman & Hall Medical, 1992.

    Google Scholar 

  29. Bergholm U, Adami HO, Bergstrom R, Johansson H, Lundell G, Telenius-Berg M, Akerstrom G, Swedish MTC study group. Clinical characteristics in sporadic and familial medullary thyroid carcinoma. A nation-wide study of 249 patients in Sweden from 1959 through 1981. Cancer 63:1196–1204, 1989.

    Article  PubMed  CAS  Google Scholar 

  30. LiVolsi VA. Surgical pathology of the thyroid. Philadelphia: Saunders, 1990.

    Google Scholar 

  31. Rosai J, Carcangiu ML, DeLellis RA. Tumors of the thyroid gland. Atlas of tumor pathology. 3rd ser. Washington, DC: Fascicle 21, Armed Forces Institute of Pathology, 1992.

  32. Putchler H, Sweat F, Levine M. On the binding of Congo red by amyloid. J Histochem Cytochem 10:355–364, 1962.

    Google Scholar 

  33. Papotti M, Botto-Micca F, Favero A, Palestini N, Bussolati G. Poorly differentiated thyroid carcinomas with primordial cell component. A group of aggressive lesions sharing insular, trabecular, and solid patterns. Am J Surg Pathol 17:291–301, 1993.

    Article  PubMed  CAS  Google Scholar 

  34. Sugyama S. The embryology of the human thyroid gland including ultimobranchial body and others related. Ergebn Anat Entwickl Gesch 44-H2:6–110, 1971.

    Google Scholar 

  35. Ljungberg O, Nilsson PO. Intermediate thyroid carcinoma in humans and ultimobranchial tumors in bulls: a comparative morphological and immunohistochemical study. Endocr Pathol 2:24–39, 1991.

    Google Scholar 

  36. Ljungberg O, Nilsson PO. Hyperplastic and neoplastic changes in ultimobranchial remnants and in parafollicular C cells in bulls: a histological and immunohistochemical study. Vet Pathol 22:95–103, 1985.

    PubMed  CAS  Google Scholar 

  37. Carney JA, Ryan J, Goellner JR. Hyalinizing trabecular adenoma of the thyroid gland. Am J Surg Pathol 10:672–679, 1986.

    Article  Google Scholar 

  38. Sambade C, Franssila KO, Cameselle-Teijeiro J, Nesland JM, Sobrinho-Simões M. Hyalinizing trabecular adénoma. A misnomer for a peculiar tumor of the thyroid gland. Endocr Pathol 2:83–91, 1991.

    Google Scholar 

  39. Huss LJ, Mendelsohn G. Medullary carcinoma of the thyroid gland: an encapsulated variant resembling the hyalinizing trabecular (paraganglioma-like) adenoma of thyroid. Modern Pathol 3:581–585, 1990.

    CAS  Google Scholar 

  40. Driman D, Murray D, Kovacs K, Stefaneanu L, Higgins HP. Encapsulated medullary carcinoma of the thyroid. Am J Surg Pathol 15:1089–1095, 1991.

    PubMed  CAS  Google Scholar 

  41. Mitsudo SM, Grajjower MM, Balbi H, Silver C. Malignant paraganglioma of the thyroid gland. Arch Pathol Lab Med 111: 378–380, 1987.

    PubMed  CAS  Google Scholar 

  42. Sakamoto A, Kasai N, Sugano H. Poorly differentiated carcinoma of the thyroid: a clinicopathologic entity for a high risk group of papillary and follicular carcinomas. Cancer 52:1849–1855, 1983.

    Article  PubMed  CAS  Google Scholar 

  43. Williams ED, Brown CL, Doniach I. Pathological and clinical findings in a series of 67 cases of medullary carcinoma of the thyroid. J Clin Pathol 19:103–113, 1966.

    Article  PubMed  CAS  Google Scholar 

  44. Kakudo K, Miyauchi A, Takai S, Katayama S, Kuma K, Kitamura H. C cell carcinoma of the thyroid—papillary type. Acta Pathol Jpn 29:653–659, 1979.

    PubMed  CAS  Google Scholar 

  45. Harach HR, Bergholm U. Medullary (C-cell) carcinoma of the thyroid with features of follicular oxyphilic cell tumours. Histopathology 13:645–656, 1988.

    Article  PubMed  CAS  Google Scholar 

  46. Dominguez-Malagon H, Delgado-Chavez R, Torres Najera M, Gould E, Albores-Saavedra J. Oxyphil and squamous variants of medullary thyroid carcinoma. Cancer 63:1183–1188, 1989.

    Article  PubMed  CAS  Google Scholar 

  47. Albores-Saavedra J, LiVolsi VA, Williams ED. Medullary carcinoma. Sem Diagn Pathol 2:137–146, 1985.

    CAS  Google Scholar 

  48. Mendelsohn G, Bigner SH, Egleston JC, Baylin SB, Wells SA. Anaplastic variants of medullary thyroid carcinoma. Am J Surg Pathol 4:333–341, 1980.

    PubMed  CAS  Google Scholar 

  49. Harach HR, Bergholm U. Small cell variant of medullary carcinoma of the thyroid with neuroblastoma-like features. Histopathology 21:378–380, 1992.

    Article  PubMed  CAS  Google Scholar 

  50. Eusebi V, Damiani S, Riva C, Lloyd RV, Capella C. Calcitonin free oat-cell carcinoma of the thyroid gland. Virchows Arch (A) 417:267–271, 1990.

    Article  CAS  Google Scholar 

  51. Kakudo K, Miyauchi A, Katayama S, Watanabe K. Ultrastructural study of poorly differentiated medullary carcinoma of the thyroid. Virchows Arch Pathol Anat 410:455–460, 1987.

    Article  CAS  Google Scholar 

  52. Kakudo K. Subclassification and prognostic factors of medullary (C cell) carcinoma of the thyroid. In: Lechago J, Kameya T, eds. Endocrine pathology update. New York: Field & Wood Medical, 1990; 85–97.

    Google Scholar 

  53. Martinelli G, Bazzocchi F, Govoni E, Santini D. Anaplastic type of medullary thyroid carcinoma. Virchows Arch Pathol Anat 400:61–67, 1983.

    Article  CAS  Google Scholar 

  54. Kakudo K, Miyauchi A, Ogihara T, Takai SI, Kitamura H, Kosaki G, Kumahara Y. Medullary carcinoma of the thyroid, giant cell type. Arch Pathol Lab Med 102:445–447, 1978.

    PubMed  CAS  Google Scholar 

  55. Merlino G, Barresi G, Tuccari G, Bussolati G. Histogenesis of anaplastic carcinomas of the thyroid, giant cell variety: immunocytochemical investigation. Appl Pathol 3:150–158, 1985.

    PubMed  CAS  Google Scholar 

  56. Harach HR, Bergholm U. Medullary carcinoma of the thyroid with carcinoid-like features. J Clin Pathol 46:113–117, 1993.

    Article  PubMed  CAS  Google Scholar 

  57. Carcangiu ML, Zampi G, Rosai J. Poorly differentiated (insular) thyroid carcinoma. Am J Surg Pathol 8:655–668, 1984.

    Article  PubMed  CAS  Google Scholar 

  58. Papotti M, Sapino A, Abbona G, Palestini N, Bussolari G. Pseudoangiosarcomatous features in medullary carcinoma of the thyroid. Int J Surg Pathol 3:29–36, 1995.

    Google Scholar 

  59. Marcus JH, Dise CA, LiVolsi VA. Melanin production in a medullary thyroid carcinoma. Cancer 49:2518–2526, 1982.

    Article  PubMed  CAS  Google Scholar 

  60. Kimura N, Ishioka K, Miura Y, Sasano N, Takaya K, Mouri T, Kimura T, Nakazato Y, Yamada R. Melanin-producing medullary thyroid carcinoma with glandular differentiation. Acta Cytol 33:61–66, 1989.

    PubMed  CAS  Google Scholar 

  61. Eng HL, Chen WJ. Melanin-producing medullary carcinoma of the thyroid gland. Arch Pathol Lab Med 113:377–380, 1989.

    PubMed  CAS  Google Scholar 

  62. Beerman H, Rigaud C, Bogomoletz WV, Hollander H, Veldhuizen RW. Melanin production in black medullary thyroid carcinoma. Histopathology 16:227–233, 1990.

    Article  PubMed  CAS  Google Scholar 

  63. Landon G, Ordonez NG. Clear cell variant of medullary carcinoma of the thyroid. Hum Pathol 16:844–847, 1985.

    PubMed  CAS  Google Scholar 

  64. Fernandes BJ, Bedard YC, Rosen I. Mucus-producing medullary cell carcinoma of the thyroid gland. Am J Clin Pathol 78:536–540, 1982.

    PubMed  CAS  Google Scholar 

  65. Golouh R, Us-Krasovec M, Auersperg M, Jancar J, Bondi A, Eusebi V. Amphicrinecomposite calcitonin and mucin producing carcinoma of the thyroid. Ultrastruct Pathol 8:197–206, 1985.

    PubMed  CAS  Google Scholar 

  66. Rosai J, Carcangiu ML. Pitfalls in the diagnosis of thyroid neoplasms. Pathol Res Pract 182:169–179, 1987.

    PubMed  CAS  Google Scholar 

  67. Harach HR, Williams ED. Glandular (tubular and follicular) variants of medullary carcinoma of the thyroid. Histopathology 7:83–97, 1983.

    Article  PubMed  CAS  Google Scholar 

  68. Sambade C, Baldaque-Faria A, Cardoso-Oliveira M, Sobrinho-Simões M. Follicular and papillary variants of medullary carcinoma of the thyroid. Pathol Res Pract 184:98–103, 1988.

    PubMed  CAS  Google Scholar 

  69. Lertprasertsuke N, Kakudo K, Nakamura A, Tada N, Osamura Y, Watenabe K, Kubota M. C cell carcinoma of the thyroid. Follicular variant. Acta Pathol Jpn 39:393–399, 1989.

    PubMed  CAS  Google Scholar 

  70. Sobrinho-Simões M, Johannessen JV. Surface features in human thyroid disorders. A scanning electron microscopic study of ninety-five cases. J Submicrosc Cytol 14:187–202, 1982.

    PubMed  Google Scholar 

  71. Sobrinho-Simões M, Sambade C, Nesland JM, Holm R, Damjanov I. Lectin histochemistry and ultrastructure of medullary carcinoma of the thyroid gland. Arch Pathol Lab Med 114:369–375, 1990.

    PubMed  Google Scholar 

  72. Sobrinho-Simões M. Thyroid oncology: the end of the dogmas. Endocr Pathol 2:117–119, 1991.

    Google Scholar 

  73. Sobrinho-Simões M. Mixed medullary and follicular carcinoma of the thyroid. Histopathology 23:287–289, 1993.

    Article  PubMed  Google Scholar 

  74. Albores-Saavedra J, Gozzaez de la Mora T, de la Torre-Rendon F, Gould E. Mixed medullary-papillary carcinoma of the thyroid: a previously unrecognized variant of thyroid carcinoma. Hum Pathol 21:1151–1155, 1990.

    Article  PubMed  CAS  Google Scholar 

  75. Li Volsi V. Medullary carcinoma. In: Bennington JL, ed. Surgical pathology of the thyroid. Philadelphia: Saunders, 1991; 213–252.

    Google Scholar 

  76. Tanaka T, Yoshimi N, Kanai N, Mori H, Nagai K, Fujii A, Sakata S, Tokimitsu N. Simultaneous occurrence of medullary and follicular carcinoma in the same thyroid lobe. Hum Pathol 20:83–86, 1989.

    Article  PubMed  CAS  Google Scholar 

  77. Ishida T, Kawai T, Iino Y. Concurrent medullary carcinoma adjacent to papillary carcinoma. Gan No Rinsho 3:1814–1820, 1985.

    Google Scholar 

  78. Lamberg B-A, Reissel P, Stenman S, Koivunienmi A, Ekblom M, Makinen J, Franssila K. Concurrent medullary and papillary thyroid carcinoma in the same thyroid lobe and in siblings. Acta Med Scand 209:421–424, 1981.

    Article  PubMed  CAS  Google Scholar 

  79. Gonzalez-Campora R, Lopez-Garrido J, Martin-Lacave I, Miralles-Sanchez EJ, Villar JL. Concurrence of a symptomatic encapsulated follicular carcinoma, an occult papillary carcinoma and a medullary carcinoma in the same patient. Histopathology 21:380–382, 1992.

    Article  PubMed  CAS  Google Scholar 

  80. Hales M, Rosenau W, Okerlund MD, Galante M. Carcinoma of the thyroid with a mixed medullary and follicular pattern. Cancer 50:1352–1359, 1982.

    Article  PubMed  CAS  Google Scholar 

  81. Ljungberg O, Ericsson U-B, Bondeson L, Thorell J. A compound follicular parafollicular cell carcinoma of the thyroid: a new tumor entity. Cancer 52:1053–1061, 1983.

    Article  PubMed  CAS  Google Scholar 

  82. Pfaltz M, Hedinger CE, Mühlethaler JP. Mixed medullary and follicular carcinoma of the thyroid. Virchows Arch A 400:53–59, 1983.

    Article  CAS  Google Scholar 

  83. Parker LN, Hollin J, Wu SY, Rypins EB, Juler GL. Carcinoma of the thyroid with a mixed medullary, papillary follicular and undifferentiated pattern. Arch Intern Med 145:1507–1509, 1985.

    Article  PubMed  CAS  Google Scholar 

  84. Tanda F, Massarelli G, Mingioni V, Bonsicu L, Moroni R, Cossu A. Mixed follicular-parafollicular carcinoma of the thyroid. A light, electron microscopic and histoimmunologic study. Surg Pathol 1990; 3:65–74.

    Google Scholar 

  85. Noel M, Delehaye MC, Segond N, Lasmoles F, Caillou IB, Gardet P, Fragu P, Moukhtar MS. Study of cacitonin and thyroglobulin gene expression in human mixed follicular and medullary thyroid carcinoma. Thyroid 1:249–256, 1991.

    PubMed  CAS  Google Scholar 

  86. Carlei F, Famulari A, Muzi P, Sciaratta F, Mariani P, Lomanto D, D’Alessandro M. Carcinoma della tiroide con decorso bifasico e con evoluzione in carcinorna midollare variante follicolare. Min Chir 47: 773–775, 1992.

    CAS  Google Scholar 

  87. Kashima K, Yokoyama S, Inoue S, Daa T, Kodama M, Nakayama I, Noguchi S. Mixed medullary and follicular carcinoma of the thyroid: report of two cases with an immunohistochemical study. Acta Pathol Jpn 43: 428–433, 1993.

    PubMed  CAS  Google Scholar 

  88. Mizukami Y, Michigishi T, Nonomura A, Nakamura S, Noguchi M, Hashimoto T, Itoh N. Mixed medullary-follicular carcinoma of the thyroid occurring in familial form. Histopathology 22:284–287, 1993.

    Article  PubMed  CAS  Google Scholar 

  89. Apel RL, Alpert LC, Rizzo A, LiVolsi VA, Asa SL. A metastasizing composite carcinoma of the thyroid with distinct medullary and papillary components. Arch Pathol Lab Med 118:1143–1147, 1994.

    PubMed  CAS  Google Scholar 

  90. Lax SF, Beham A, Kronberg-Schonecker D, Lansteger W, Denk H. Coexistence of papillary and medullary carcinoma of the thyroid gland. Mixed or collision tumour? Clinicopathological analysis of three cases. Virchows Arch 424:441–447, 1994.

    Article  PubMed  CAS  Google Scholar 

  91. Matias-Guiu X, Caixas A, Costa I, Cabezas R, Prat J. Compound medullary-papillary carcinoma of the thyroid: true mixed tumour. Histopathology 25:183–185, 1994.

    Article  PubMed  CAS  Google Scholar 

  92. Bussolati G, Monga G. Medullary carcinoma of the thyroid with atypical patterns. Cancer 44:1769–1777, 1979.

    Article  PubMed  CAS  Google Scholar 

  93. Holm R, Sobrinho-Simões M, Nesland JM, Sambade C, Johannessen JV. Medullary thyroid carcinoma with thyroglobulin immunoreactivity. A special entity? Lab Invest 57:258–268, 1987.

    PubMed  CAS  Google Scholar 

  94. Pacini F, Basolo F, Elisei R, Fugazzola L, Cola A, Pinchera A.. Medullary thyroid cancer. An immunohistochemical and humoral study using six separate antigens. Am J Clin Pathol 95:300–308, 1991.

    PubMed  CAS  Google Scholar 

  95. De Micco C, Chapel F, Dor AM, Garcia S, Ruf J, Carayon P, Henry JF, Lebreuil G. Thyroglobulin in medullary thyroid carcinoma: immunohistochemical study with polyclonal and monoclonal antibodies. Hum Pathol 24:256–262, 1993.

    Article  PubMed  Google Scholar 

  96. Kovacs C, Masé RM, Kovacs K, Nguyen GK, Chik C. thyroid medullary carcinoma with thyroglobulin immunoreactivity in sporadic multiple endocrine neoplasia type 2-B. Cancer 74:928–932, 1994.

    Article  PubMed  CAS  Google Scholar 

  97. Sobrinho-Simões M. Tumors of the thyroid: a brief overview with emphasis on the most controversial issues. Curr Diagn Pathol 2:15–22, 1995.

    Article  Google Scholar 

  98. Sobrinho-Simões M, Sambade C. Poorly differentiated carcinomas of the thyroid gland. Prog Surg Pathol 13:1995. In press.

  99. Ljungberg O, Bondeson L, Bondeson AG. Differential thyroid carcinoma intermediate type: a new tumor entiry with features of follicular and parafollicular carcinoma. Hum Pathol 15: 218–228, 1984.

    Article  PubMed  CAS  Google Scholar 

  100. Milhaud G, Calmettes C, Dreyfus G, Moukhtar MS. An unusual trabecular thyroid carcinoma producing calcitonin. Experientia 26:1381–1383, 1970.

    Article  PubMed  CAS  Google Scholar 

  101. Calmettes C, Caillou B, Moukhtar MS, Milhaud G, Gerard-Marchant R. Calcitonin and carcinoembryonic antigen in poorly differentiated follicular carcinoma. Cancer 49:2342–2348, 1982.

    Article  PubMed  CAS  Google Scholar 

  102. Sobrinho-Simões M, Fonseca E. Recently described tumors of the thyroid. In: Anthony PP, McSween RNM, eds. Recent advances in histopathology. vol. 16. Edinburgh: Churchill Livingstone, 1994: 213–229.

    Google Scholar 

  103. Bussolati G, Van Noorden S, Bordi C. Calcitonin and ACTH-producing cells in a case of medullary ACTH-producing cells in a case of medullary carcinoma of the thyroid. Virchows Arch Pathol Anat 360:123–127, 1973.

    Article  CAS  Google Scholar 

  104. Harach HR, Wilander E, Grimelius L, Bergholm U, Westermark P, Falkmer S. Chromogranin A immunoreactivity compared with argyrophilia, calcitonin immunoreactivity, and amyloid as tumor markers in the histopathological diagnosis of medullary (C-cell) thyroid carcinoma. Pathol Res Pract 188:123–130, 1992.

    PubMed  CAS  Google Scholar 

  105. Lloyd RV, Sisson JC, Marangos PJ. Calcitonin, carcinoembryonic antigen and neuron-specific enolase in medullary thyroid carcinoma. An immunohistochemical study. Cancer 51: 2234–2239, 1983.

    Article  PubMed  CAS  Google Scholar 

  106. Mendelsohn G, Wells SA Jr, Baylin SB. Relationship of tissue carcinoembryonic antigen and calcitonin to tumor virulence in medullary thyroid carcinoma. Cancer 54:657–662, 1984.

    Article  PubMed  CAS  Google Scholar 

  107. Schröder, S, Kloppel G. Carcinoembryonic antigen and non specific cross-reacting antigen in thyroid cancer. An immunocytochemical study using polyclonal and monoclonal antibodies. Am J Surg Pathol 11:100–108, 1987.

    Article  PubMed  Google Scholar 

  108. Gould VE, Wiedenmann B, Lee I, Schwechheimer K, Dockhorn B, Radosevich JA, Moll R, Franke WW. Synaptophysin expression in neuroendocrine neoplasms as determined by immunocytochemistry. Am J Pathol 126: 243–257, 1987.

    PubMed  CAS  Google Scholar 

  109. Schmid KW, Fischer-Colbrie R, Hagn C, Jasani B, Williams ED, Winkler H. Chromogranin A and B and secretogranin 11 in medullary carcinomas of the thyroid. Am J Surg Pathol 11:551–556, 1987.

    Article  PubMed  CAS  Google Scholar 

  110. Buffa R, Rindi G, Sessa F, Gini A, Capella C, Jahn R, Navone F, DeCamilli P, Solcia E. Synaptophysin immunoreactivity and small clear vesicles in neuroendocrine cells and related tumors. Mol Cell Probes 2:367–381, 1988.

    Google Scholar 

  111. Weiler R, Fischer-Colbrie R, Schmid KW, Feichtinger H, Bussolati G, Grimelius L, Krisch K, Kerl H, O’Connor D, Winkler H. Immunological studies on the occurrence and properties of chromogranin A and B and secretogranin 11 in endocrine tumors. Am J Surg Pathol 12:877–884, 1988.

    PubMed  CAS  Google Scholar 

  112. Hayashida CY, Alves VAF, Kanamura C, Ezabella MCL, Abelin NM, Nicolau W, Bisi H, Toledo SPA. Immunohistochemistry of medullary thyroid carcinoma and C-cell hyperplasia by an affinity purified anti-human calcitonin antiserum. Cancer 72: 1356–1363, 1993.

    Article  PubMed  CAS  Google Scholar 

  113. Schmid KW, Kirchmair R, Ladurner D, Fischer-Colbrie R, Bocker W. Immunohistochemical comparison of chromogranins A and B secretogranin 11 with calcitonin gene-related peptide expression in normal hyperplastic and neoplastic C-cell of the human thyroid. Histopathology 21:225–232, 1992.

    Article  PubMed  CAS  Google Scholar 

  114. Neuhold N, Ulrich R. Secretogranin IV immunoreactivity in medullary thyroid carcinoma: an immunohistochemical study of 62 cases. Virchows Arch A 423:85–89, 1993.

    Article  CAS  Google Scholar 

  115. Reubi JC, Chayvialle JA, Franc B, Cohen R, Calmettes C, Modigliani E. Somatostatin receptors and somatostatin content in medullary thyroid carcinomas. Lab Invest 64:567–573, 1991.

    PubMed  CAS  Google Scholar 

  116. Mendelshon G. Markers as prognostic indicators in medullary thyroid carcinoma. Am J Clin Pathol 95:297,298, 1991.

    Google Scholar 

  117. Hijazi YM, Nieman LK, Medeiros LJ. Medullary carcinoma of the thyroid as a cause of Cushing’s syndrome: a case with ectopic adrenocorticotropin secretion characterized by double enzyme immunostaining. Hum Pathol 23:592–596, 1992.

    Article  PubMed  CAS  Google Scholar 

  118. Mougin C, Guitteny AF, Fouque, B. Viennet G, Teoule R, Bloch B. Histochemical detection of the messenger RNAs coding for calcitonin and calcitonin gene-related peptide in medullary thyroid carcinomas with radioactive and biotinylated oligonucleotide probes. J Pathol 160:187–194, 1990.

    Article  PubMed  CAS  Google Scholar 

  119. Demjin M, De Weger RA, Van Unnik JAM, Den Otter W, Lips CJM. Detection of calcitonin gene-related peptide mRNA in human medullary thyroid carcinoma. A retrospective study. J Pathol 169:53–60, 1993.

    Article  Google Scholar 

  120. Komminoth P, Roth J, Saremaslani P, Matias-Guiu X, Wolfe H, Heitz PhU. Polysialic acid of the neural adhesion molecule in the human thyroid: a marker for medullary thyroid carcinoma and primary C-cell hyperplasia. Am J Surg Pathol 18:399–411, 1994.

    Article  PubMed  CAS  Google Scholar 

  121. Klimpfinger M, Ruhri C, Putz B, Pfranger R, Wirnsberger G, Hofler H. Oncogene expression in a medullary thyroid carcinoma. Virchows Arch B 54:256–259, 1988.

    Article  PubMed  CAS  Google Scholar 

  122. Roncalli M, Viale G, Grimelius L, Johansson H, Wilander E, Alfano RM, Springall D, Battezzati PM, Polak JM, Coggi G. Prognostic value of N-myc immunoreactivity in medullary thyroid carcinoma. Cancer 74: 134–141, 1994.

    Article  PubMed  CAS  Google Scholar 

  123. Santoro M, Rosati R, Grieco M, Berlingieri RT, D’Amato GL, deFranciscis V, Fusco A. The RET proto-oncogene is consistently expressed in human pheochromocytomas and thyroid medullary carcinomas. Oncogene 5:1595–1598, 1990.

    PubMed  CAS  Google Scholar 

  124. Pierotti MA, Santoro M, Jenkis RB, Sozzi G, Bongarzone I, Grieco M, Monzini M, Miotti M, Herrmann MA, Fusco A, Hay ID, Della Porta G, Vecchio G. Characterization of an inversion on the long arm of chromosome 10 juxtaposing D10S170 and RET/PTC. Proc Natl Acad Sci USA 89:1616–1620, 1992.

    Article  PubMed  CAS  Google Scholar 

  125. Nakamura T, Ishizaka Y, Nagao M, Hara M, Ishikawa T. Expression of the RET proto-oncogene product in human normal and neoplastic tissues of neural crest origin. J Pathol 172:255–260, 1994.

    Article  PubMed  CAS  Google Scholar 

  126. Van Heyningen V. One gene-four syndromes. Nature 367:319,320, 1994.

    Article  PubMed  Google Scholar 

  127. Hofstra R, Landsvater R, Ceccherini I, Stulp R, Stelwagen T, Luo Y, Pasini B, Hoppener J. Ploos van Amstel H, Romeo Q., Lips, C., Buys C. Amutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature 367:375,376, 1994.

    Article  PubMed  CAS  Google Scholar 

  128. Komminoth P, Kunz E, Hiort O. Schröder S. Matias-Guiu X, Christiansen G, Roth J, Heitz PhU. Molecular diagnosis of MEN in paraffin-embedded tumor tissues. 84th Annual Meeting of the United States and Canadian Academy of Pathology, Toronto, 1995.

  129. DiRenzo MF, Olivero M, Ferro S, Prat M, Bongarzone I, Pilotti S, Belfiore A, Costantino A, Vigneri R, Pierotti MA, Comoglio PM. Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas. Oncogene 7:2549–2553, 1992.

    CAS  Google Scholar 

  130. Carr K, Heffess C, Jin L, Lloyd RV. Immuno-histochemical analysis of thyroid carcinomas utilizing antibodies to p53 and Ki67. Appl Immunohistochem 1:201–207, 1993.

    Google Scholar 

  131. Tangen KO, Lindmo T, Sobrinho-Simões M, Johannessen JV. A flow cytometric DNA analysis of medullary thyroid carcinoma. Am J Clin Pathol 79:172–177, 1983.

    PubMed  CAS  Google Scholar 

  132. Auer GU, Backdahl, Forsslund GH, Askenstenu G. Ploidy levels in non neoplastic and neoplastic thyroid cells. Anal Quant Cytol Histol 7:97–105, 1985.

    PubMed  CAS  Google Scholar 

  133. Schröder S, Bocker W, Baish H, Burk CG, Arps H, Meiners I, Kastendieck H, Heitz PhU, Kloppel G. Prognostic factors in medullary thyroid carcinomas. Cancer 62:806–816, 1988.

    Article  Google Scholar 

  134. Galera-Davidson H, Gonzàles-Càmpora R, Mora-Marin JA, Matilla-Vincente A, Dytch HE, Bartels PH, Lerma-Puertas E, Andrada-Bacerra E, Bibbo M. Cytophotometric DNA measurements in medullary thyroid carcinoma. Cancer 65:2255–2260, 1990.

    Article  PubMed  CAS  Google Scholar 

  135. Hall PA, Coates PJ. Assessment of cell proliferation in pathology. What next? Histopathology 26:105–112, 1995.

    Article  PubMed  CAS  Google Scholar 

  136. Katoh R, Bray CE, Suzuki K, Komiyama A, Hemmi A, Kawaoi A, Oyama T, Sugai T, Sasou S. Growth activity in hyperplastic and neoplastic human thyroid determined by an immunohistochemical staining procedure using monoclonal antibody MIB-1. Hum Pathol 26:139–146, 1995.

    Article  PubMed  CAS  Google Scholar 

  137. Matias-Guiu X, Peiro G, Esquius J, Oliva R, Cabezas R, Colomer A, Prat J. Proliferative activity C-cell hyperplasia and medullary thyroid carcinoma. Pathol Res Pract 191: 42–47, 1995.

    PubMed  CAS  Google Scholar 

  138. Simpson WJ, Carruthers JS, Malkin D. Results of a screening program for C-cell disease (medullary thyroid cancer and C-cell hyperplasia). Cancer 65:1570–1576, 1990.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Biomedical Sciences and Oncology, University of Turin, Via Santena 7, I-10126, Torino, Italy

    Mauro Papotti MD, Daniela Sambataro MD, Carla Pecchioni BSc & Gianni Bussolati MD, FRCPath

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  1. Mauro Papotti MD
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  2. Daniela Sambataro MD
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Papotti, M., Sambataro, D., Pecchioni, C. et al. The pathology of medullary carcinoma of the thyroid: Review of the literature and personal experience on 62 cases. Endocr Pathol 7, 1–20 (1996). https://doi.org/10.1007/BF02739911

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