Thyroid cancer: a lethal endocrine neoplasm.

This conference focuses on the controversies about managing thyroid cancer, emphasizing the possibility that the treatment of patients with potentially fatal thyroid cancer may be improved. Although the mortality rate from thyroid cancer is low, it is the highest among cancers affecting the endocrine glands (excluding the ovary). Exposure to radiation during childhood in the 1930s and 1940s increased the incidence of but not the mortality from thyroid cancer, because these tumors are mainly papillary cancers developing in young adults. These rates may change as the exposed cohort ages. Risk factors that increase mortality include older patient age and the growth characteristics of the tumor at diagnosis, the presence of distant metastases, and cell type (for example, the tall-cell variants of papillary cancer, follicular cancer [to be distinguished from the more benign follicular variant of papillary cancer], medullary cancer, and anaplastic cancer). Local metastases in lymph nodes do not seem to increase the risk for death from papillary cancer, but they do increase the risk for death from follicular and medullary cancer. In the latter, mortality is decreased by the early detection and treatment of patients with the familial multiple endocrine neoplasia syndrome 2a. There are excellent tumor markers for differentiated cancer of the parafollicular and of the follicular cells (serum calcitonin and serum thyroglobulin levels, respectively). Measuring the calcitonin level allows early diagnosis of familial medullary cancer, whereas measuring the thyroglobulin level, although useful only after total thyroidectomy, allows early recognition of recurrence or metastases of papillary or follicular cancer. Initial surgery, protocols for follow-up, and the use of radioiodine for the ablation of any residual thyroid and the treatment of metastatic cancer are discussed. Because these tumors resist currently available chemotherapy regimens, possible ways to increase the effectiveness of radioiodine therapy are considered as are new approaches to treatment.

[1]  A. Schneider,et al.  Radiation‐Induced Tumors of the Head and Neck Following Childhood Irradiation: PROSPECTIVE STUDIES , 1985, Medicine.

[2]  W. Beierwaltes,et al.  Treatment of thyroid cancer. Death rates after surgery and after surgery followed by sodium iodide I-131. , 1970, JAMA.

[3]  M. Schemper,et al.  Surgical treatment of distant metastases in differentiated thyroid cancer: indication and results. , 1986, Surgery.

[4]  J. Fraumeni,et al.  A population-based case-control study of thyroid cancer. , 1987, Journal of the National Cancer Institute.

[5]  H. Hundeshagen,et al.  Risk Factors in Follicular Thyroid Carcinomas: A Retrospective Follow-up Study Covering a 14-Year Period with Emphasis on Morphological Findings , 1986, The American journal of surgical pathology.

[6]  S. Baylin,et al.  The molecular biology of medullary thyroid carcinoma. A model for cancer development and progression. , 1989, JAMA.

[7]  K. Kidd,et al.  Assignment of multiple endocrine neoplasia type 2A to chromosome 10 by linkage , 1987, Nature.

[8]  L. Woolner,et al.  Undifferentiated and poorly differentiated carcinoma. , 1985, Seminars in diagnostic pathology.

[9]  A. Pinchera,et al.  DIAGNOSTIC VALUE OF A SINGLE SERUM THYROGLOBULIN DETERMINATION ON AND OFF THYROID SUPPRESSIVE THERAPY IN THE FOLLOW‐UP OF PATIENTS WITH DIFFERENTIATED THYROID CANCER , 1985, Clinical endocrinology.

[10]  R. Leeper,et al.  Treatment of locally advanced thyroid carcinoma with combination doxorubicin and radiation therapy , 1987, Cancer.

[11]  C. Edmonds,et al.  Thyrotrophin receptors, tumour radioiodine concentration and thyroglobulin secretion in differentiated thyroid cancers. , 1985, British Journal of Cancer.

[12]  M. Hapke,et al.  The optically clear nucleus. A reliable sign of papillary carcinoma of the thyroid? , 1979, The American journal of surgical pathology.

[13]  M. Girelli,et al.  Nonparallel patterns of calcitonin and carcinoembryonic antigen levels in the follow‐up of medullary thyroid carcinoma , 1984, Cancer.

[14]  J. Hamming,et al.  Multivariate analysis of survival in differentiated thyroid cancer: the prognostic significance of the age factor. , 1988, European journal of cancer & clinical oncology.

[15]  J. Hazard,et al.  Medullary (solid) carcinoma of the thyroid; a clinicopathologic entity. , 1959, The Journal of clinical endocrinology and metabolism.

[16]  K. Franssila Value of histologic classification of thyroid cancer. , 1971, Acta pathologica et microbiologica Scandinavica. Supplement.

[17]  G. Beebe,et al.  Thyroid nodularity and chromosome aberrations among women in areas of high background radiation in China. , 1990, Journal of the National Cancer Institute.

[18]  L. Hempelmann Risk of Thyroid Neoplasms after Irradiation in Childhood , 1968, Science.

[19]  C. Mathew,et al.  A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10 , 1987, Nature.

[20]  C. Edmonds,et al.  The long-term hazards of the treatment of thyroid cancer with radioiodine. , 1986, The British journal of radiology.

[21]  B. Modan,et al.  Thyroid neoplasia following low-dose radiation in childhood. , 1989, Radiation research.

[22]  C. Weber,et al.  Immunotherapy of thyroid cancer by induction of autoimmune thyroiditis. , 1983, Surgery.

[23]  J. Robbins,et al.  Ablation of nonmalignant thyroid remnants with low doses of radioactive iodine: concise communication. , 1982, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[24]  S. McKinney,et al.  Papillary and follicular thyroid cancer. Prognostic factors in 1,578 patients. , 1987, The American journal of medicine.

[25]  K. Gautvik,et al.  Early liver metastases in patients with medullary carcinoma of the thyroid gland , 1989, Cancer.

[26]  K. Franssila,et al.  Thyroglobulin immunostaining in follicular thyroid carcinoma: relationship to the degree of differentiation and cell type , 1988, Histopathology.

[27]  L. Woolner,et al.  Papillary thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome. , 1986, Mayo Clinic proceedings.

[28]  N. Samaan,et al.  131I therapy in differentiated thyroid carcinoma: M. D. Anderson hospital experience , 1981 .

[29]  L. Pickle,et al.  Thyroid cancer in Connecticut, 1935-1975: an analysis by cell type. , 1980, American journal of epidemiology.

[30]  H. Morris,et al.  The myotropic and plasma-calcium modulating effects of calcitonin gene-related peptide (CGRP) , 1984, Neuropeptides.

[31]  A R Zinsmeister,et al.  Fine-Needle Aspiration Biopsy of the Thyroid: The Problem of Suspicious Cytologic Findings , 1984 .

[32]  B. Cady,et al.  Nonfamilial medullary thyroid carcinoma. , 1980, American journal of surgery.

[33]  N. Takeichi,et al.  Cancer of the thyroid and salivary glands , 1986 .

[34]  K. Kusakabe,et al.  Production of monoclonal antibody to thyroglobulin from malignant thyroid carcinoma. , 1989, The Japanese journal of experimental medicine.

[35]  B. Cady,et al.  Surgically incurable well-differentiated thyroid carcinoma. Prognostic factors and results of therapy. , 1988, Archives of surgery.

[36]  J. Rosai,et al.  Follicular variant of thyroid papillary carcinoma: A clinicopathologic study of six cases , 1977, The American journal of surgical pathology.

[37]  C. Fürst,et al.  Cancer incidence after radiotherapy for skin hemangioma: a retrospective cohort study in Sweden. , 1988, Journal of the National Cancer Institute.

[38]  J. Norton,et al.  Localization and resection of clinically inapparent medullary carcinoma of the thyroid. , 1980, Surgery.

[39]  W. Cance,et al.  Multiple endocrine neoplasia. Type IIa. , 1985, Current problems in surgery.

[40]  Dunn El,et al.  Hürthle cell lesions of the thyroid gland. , 1974, Surgery, gynecology & obstetrics.

[41]  B. Cady,et al.  Further evidence of the validity of risk group definition in differentiated thyroid carcinoma. , 1985, Surgery.

[42]  G. van Belle,et al.  Thyroid neoplasia in Marshall Islanders exposed to nuclear fallout. , 1987, JAMA.

[43]  I. Brown Astatine-211: its possible applications in cancer therapy. , 1986, International journal of radiation applications and instrumentation. Part A, Applied radiation and isotopes.

[44]  I. Carrió,et al.  Lithium as an adjuvant of iodine-131 uptake when treating patients with well-differentiated thyroid carcinoma. , 1987, Clinical nuclear medicine.

[45]  L. M. Cobb,et al.  Toxicity of Astatine-211 in the Mouse , 1988, Human toxicology.

[46]  T. K. Hunt,et al.  Medullary Thyroid Carcinoma: The Need for Early Diagnosis and Total Thyroidectomy , 1989 .

[47]  B. M. Dobyns,et al.  Malignant and benign neoplasms of the thyroid in patients treated for hyperthyroidism: a report of the cooperative thyrotoxicosis therapy follow-up study. , 1974, The Journal of clinical endocrinology and metabolism.

[48]  R. Lloyd,et al.  An analysis of "ablation of thyroid remnants" with I-131 in 511 patients from 1947-1984: experience at University of Michigan. , 1984, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[49]  G. Steel,et al.  Inhibition of recovery from damage induced by ionizing radiation in mammalian cells. , 1988, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[50]  D. Berman,et al.  The significance of 1-131 scan dose in patients with thyroid cancer: determination of ablation: concise communication. , 1981, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[51]  V S Hertzberg,et al.  Relation between effective radiation dose and outcome of radioiodine therapy for thyroid cancer. , 1983, The New England journal of medicine.

[52]  Kahn Nf,et al.  Follicular carcinoma of the thyroid: an evaluation of the histologic criteria used for diagnosis. , 1983 .

[53]  L. Anspaugh,et al.  The global impact of the Chernobyl reactor accident. , 1988, Science.

[54]  J. Høie,et al.  Distant metastases in papillary thyroid cancer. A review of 91 patients , 1988, Cancer.

[55]  S. Petursson,et al.  Metastatic medullary thyroid carcinoma: Complete response to combination chemotherapy with dacarbazine and 5‐fluorouracil , 1988, Cancer.

[56]  S. Jansson,et al.  Reoperation in the treatment of asymptomatic metastasizing medullary thyroid carcinoma. , 1986, Surgery.

[57]  E. Mazzaferri Papillary thyroid carcinoma: factors influencing prognosis and current therapy. , 1987, Seminars in oncology.

[58]  A. L. Vickery,et al.  Thyroid papillary carcinoma. Pathological and philosophical controversies. , 1983, The American journal of surgical pathology.

[59]  J. Nesland,et al.  Columnar-cell carcinoma. Another variant of poorly differentiated carcinoma of the thyroid. , 1988, American journal of clinical pathology.

[60]  S. Refetoff,et al.  Retrospective and prospective study of radiation-induced thyroid disease. , 1983, The American journal of medicine.

[61]  H. Gharib,et al.  Anaplastic carcinoma of the thyroid: a clinicopathologic study of 82 cases. , 1985, Mayo Clinic proceedings.

[62]  R. Lloyd,et al.  Prognostic Implications of the Tall Cell Variant of Papillary Thyroid Carcinoma , 1988, The American journal of surgical pathology.

[63]  B. Caillou,et al.  Long‐term results and prognostic factors in patients with differentiated thyroid carcinoma , 1985, Cancer.

[64]  E. Pochin Radioiodine therapy of thyroid cancer. , 1971, Seminars in nuclear medicine.

[65]  F. H. Tyler,et al.  Thyroid nodularity in children. , 1975, JAMA.

[66]  L. Degroot,et al.  Comparison of 30- and 50-mCi doses of iodine-131 for thyroid ablation. , 1982, Annals of internal medicine.

[67]  M. Sonenberg,et al.  The relation of radioiodine dosimetry to results and complications in the treatment of metastatic thyroid cancer. , 1962, The American journal of roentgenology, radium therapy, and nuclear medicine.

[68]  P Fraser,et al.  Radiation dose and second cancer risk in patients treated for cancer of the cervix. , 1988, Radiation research.

[69]  V. Livolsi Surgical pathology of the thyroid , 1990 .

[70]  H. Gharib,et al.  Suppressive therapy with levothyroxine for solitary thyroid nodules. A double-blind controlled clinical study. , 1987, The New England journal of medicine.

[71]  S. Lippman,et al.  The prognostic and biological significance of cellular heterogeneity in medullary thyroid carcinoma: a study of calcitonin, L-dopa decarboxylase, and histaminase. , 1982, The Journal of clinical endocrinology and metabolism.

[72]  L. M. Cobb,et al.  Relative concentration of astatine-211 and iodine-125 by human fetal thyroid and carcinoma of the thyroid in nude mice. , 1988, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[73]  J. Sisson,et al.  Determination of iodine-131 diagnostic dose for imaging metastatic thyroid cancer. , 1986, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[74]  Hawk Wa,et al.  The many appearances of papillary carcinoma of the thyroid. , 1976 .

[75]  D. Schoenfeld,et al.  A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma , 1985, Cancer.

[76]  H. Ernst,et al.  Chemotherapy of thyroid carcinoma , 1987, Journal of endocrinological investigation.

[77]  S. Adelstein,et al.  Radiobiologic implications of the microscopic distribution of energy from radionuclides. , 1987, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology.

[78]  O. Clark,et al.  Thyroid cancer: the case for total thyroidectomy. , 1988, European journal of cancer & clinical oncology.

[79]  N. Samaan,et al.  Medullary thyroid carcinoma: prognosis of familial versus sporadic disease and the role of radiotherapy. , 1988, The Journal of clinical endocrinology and metabolism.

[80]  M. Atkins,et al.  Hypothyroidism after treatment with interleukin-2 and lymphokine-activated killer cells. , 1988, The New England journal of medicine.

[81]  J. Lubin,et al.  Thyroid nodularity after childhood irradiation for lymphoid hyperplasia: a comparison of questionnaire and clinical findings. , 1990, Journal of clinical epidemiology.

[82]  K. Wiklund,et al.  Thyroid cancer after diagnostic doses of iodine-131: a retrospective cohort study. , 1988, Journal of the National Cancer Institute.

[83]  B. Pasternack,et al.  Thyroid tumors following thymus irradiation. , 1985, Journal of the National Cancer Institute.

[84]  J. Rosai,et al.  Papillary carcinoma of the thyroid. A discussion of its several morphologic expressions, with particular emphasis on the follicular variant. , 1983, The American journal of surgical pathology.

[85]  J L Humm,et al.  Dosimetric aspects of radiolabeled antibodies for tumor therapy. , 1986, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[86]  L. Sobin,et al.  The WHO histological classification of thyroid tumors: A commentary on the second edition , 1989, Cancer.

[87]  M. Merino,et al.  Histopathologic differential diagnosis of the thyroid. , 1981, Pathology annual.

[88]  R. Prentice,et al.  Radiation exposure and thyroid cancer incidence among Hiroshima and Nagasaki residents. , 1982, National Cancer Institute monograph.

[89]  H. Evans Columnar-cell carcinoma of the thyroid. A report of two cases of an aggressive variant of thyroid carcinoma. , 1986, American journal of clinical pathology.

[90]  S. Wells,et al.  Early diagnosis and treatment of medullary thyroid carcinoma. , 1985, Archives of internal medicine.

[91]  L. Woolner,et al.  Incidence of carcinoma in thyroid glands removed at 1000 consecutive routine necropsies. , 1955, Surgical forum.