Multifocal Papillary Thyroid Carcinoma
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Shattuck et al. (June 9 issue)1 demonstrate that multiple foci of papillary thyroid carcinoma are often tumors of independent clonal origins and conclude that such tumors should receive aggressive treatment. Microcarcinomas have a high prevalence in the general population2 and may remain clinically silent even when they are multicentric or occur concomitantly with a clinical papillary thyroid carcinoma. Since subclinical papillary thyroid carcinoma with a low growth potential is diagnosed with increasing frequency, the problem arises for the surgeon as to whether selective treatment may be appropriate.
Multicentricity is not considered a prognostic determinant for the categorization of tumors as low risk or high risk.3,4 Cause-specific survival may reach 100 percent in low-risk patients, independently of multicentricity and remnant ablation.4,5 Hence, multicentricity per se does not appear to be an indication for routine administration of radioiodine but rather for total thyroidectomy instead of hemithyroidectomy to improve disease-free survival. Whether the arbitrary threshold for hemithyroidectomy6 of 1 cm may be extended to the new pT1 stage3 (2 cm) is uncertain.
Ernst W. Gemsenj?ger, M.D.
Gellertstr. 18
CH 4052 Basel, Switzerland
gemsen@bluewin.ch
Philipp U. Heitz, M.D.
Nagelfluh
CH 8804 Au, Switzerland
Ingrid Schweizer, M.D.
Kreisspital
CH 8708 M?nnedorf, Switzerland
References
Shattuck TM, Westra WH, Ladenson PW, Arnold A. Independent clonal origins of distinct tumor foci in multifocal papillary thyroid carcinoma. N Engl J Med 2005;352:2406-2412.
Bramley MD, Harrison BJ. Papillary microcarcinoma of the thyroid gland. Br J Surg 1996;83:1674-1683.
Sobin LH, Wittekind C, eds. TNM classification of malignant tumors. 6th ed. New York: Wiley-Liss, 2002.
Hay ID, Thompson GB, Grant CS, et al. Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients. World J Surg 2002;26:879-885.
Gemsenj?ger E, Perren A, Seifert B, Schuler G, Schweizer I, Heitz PU. Lymph node surgery in papillary thyroid carcinoma. J Am Coll Surg 2003;197:182-190.
Thyroid Carcinoma Task Force. AACE/AAES medical/surgical guidelines for clinical practice: management of thyroid carcinoma. Endocr Pract 2001;7:202-221.
To the Editor: Shattuck et al. conclude that their finding that papillary-cancer foci may have independent origins "provides theoretical support for the appropriateness of bilateral thyroidectomy and radioablation of remaining tissue." Should their findings have been to the contrary — that multiple foci arise from one focus, which would support the concept of intrathyroidal metastases — their conclusion would have been the same. Therefore, without disparaging the importance of their report, I doubt whether their findings will influence the widely debated issue of the need for total thyroidectomy as opposed to hemithyroidectomy when a low-risk papillary carcinoma is diagnosed.1
J. Hans DeVries, M.D., Ph.D.
Academic Medical Center
1105 AZ Amsterdam, the Netherlands
j.h.devries@amc.uva.nl
References
Mazzaferri EL, Kloos RT. Current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab 2001;86:1447-1463.
The authors reply: Dr. Gemsenj?ger and colleagues question the therapeutic implications of our demonstration of distinct clonal origins for multicentric papillary thyroid cancers in one half or more of affected patients — a finding that implies that there are independent sites of cancer formation in the glands of these patients. We agree that clinical observations have shown that mortality is not greater in patients with multifocal papillary cancer than in those with unifocal disease, and we are uncertain whether multifocal disease entails a greater risk of disease recurrence. It is in the context of this clinical uncertainty that our observations lend biologic plausibility to therapies that eradicate remnant thyroid tissue, particularly in patients such as those whom we have studied whose tumors were clinically evident, rather than incidentally detected.
On the other hand, Dr. DeVries doubts the therapeutic import of our findings because, he argues, the alternative explanation for multicentricity — intraglandular metastases — also would have justified aggressive treatment. During decades of debate, many have not found this argument to be persuasive. Practically speaking, our study now renders this debate irrelevant since it is clear that affected patients often do have separate de novo sites of cancer development in glands that could well be predisposed to more of the same.
The contrasting views of these correspondents — one favoring less treatment and the other more treatment — illustrate the long-standing controversy surrounding the management of multifocal papillary thyroid cancer. Although our study cannot settle this issue with the same certainty that a randomized clinical trial might, our findings shed light on the underlying biology of this common presentation of a type of tumor whose incidence is increasing more rapidly than any other cancer among U.S. women.1
Paul W. Ladenson, M.D.
Johns Hopkins University School of Medicine
Baltimore, MD 21287
Andrew Arnold, M.D.
University of Connecticut School of Medicine
Farmington, CT 06030
molecularmedicine@uchc.edu
William H. Westra, M.D.
Johns Hopkins Medical Institutions
Baltimore, MD 21231
References
National Cancer Institute. SEER cancer statistics review, 1975-2002. (Accessed August 22, 2005, at http://seer.cancer.gov/csr/1975_2002/.)
Multicentricity is not considered a prognostic determinant for the categorization of tumors as low risk or high risk.3,4 Cause-specific survival may reach 100 percent in low-risk patients, independently of multicentricity and remnant ablation.4,5 Hence, multicentricity per se does not appear to be an indication for routine administration of radioiodine but rather for total thyroidectomy instead of hemithyroidectomy to improve disease-free survival. Whether the arbitrary threshold for hemithyroidectomy6 of 1 cm may be extended to the new pT1 stage3 (2 cm) is uncertain.
Ernst W. Gemsenj?ger, M.D.
Gellertstr. 18
CH 4052 Basel, Switzerland
gemsen@bluewin.ch
Philipp U. Heitz, M.D.
Nagelfluh
CH 8804 Au, Switzerland
Ingrid Schweizer, M.D.
Kreisspital
CH 8708 M?nnedorf, Switzerland
References
Shattuck TM, Westra WH, Ladenson PW, Arnold A. Independent clonal origins of distinct tumor foci in multifocal papillary thyroid carcinoma. N Engl J Med 2005;352:2406-2412.
Bramley MD, Harrison BJ. Papillary microcarcinoma of the thyroid gland. Br J Surg 1996;83:1674-1683.
Sobin LH, Wittekind C, eds. TNM classification of malignant tumors. 6th ed. New York: Wiley-Liss, 2002.
Hay ID, Thompson GB, Grant CS, et al. Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients. World J Surg 2002;26:879-885.
Gemsenj?ger E, Perren A, Seifert B, Schuler G, Schweizer I, Heitz PU. Lymph node surgery in papillary thyroid carcinoma. J Am Coll Surg 2003;197:182-190.
Thyroid Carcinoma Task Force. AACE/AAES medical/surgical guidelines for clinical practice: management of thyroid carcinoma. Endocr Pract 2001;7:202-221.
To the Editor: Shattuck et al. conclude that their finding that papillary-cancer foci may have independent origins "provides theoretical support for the appropriateness of bilateral thyroidectomy and radioablation of remaining tissue." Should their findings have been to the contrary — that multiple foci arise from one focus, which would support the concept of intrathyroidal metastases — their conclusion would have been the same. Therefore, without disparaging the importance of their report, I doubt whether their findings will influence the widely debated issue of the need for total thyroidectomy as opposed to hemithyroidectomy when a low-risk papillary carcinoma is diagnosed.1
J. Hans DeVries, M.D., Ph.D.
Academic Medical Center
1105 AZ Amsterdam, the Netherlands
j.h.devries@amc.uva.nl
References
Mazzaferri EL, Kloos RT. Current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab 2001;86:1447-1463.
The authors reply: Dr. Gemsenj?ger and colleagues question the therapeutic implications of our demonstration of distinct clonal origins for multicentric papillary thyroid cancers in one half or more of affected patients — a finding that implies that there are independent sites of cancer formation in the glands of these patients. We agree that clinical observations have shown that mortality is not greater in patients with multifocal papillary cancer than in those with unifocal disease, and we are uncertain whether multifocal disease entails a greater risk of disease recurrence. It is in the context of this clinical uncertainty that our observations lend biologic plausibility to therapies that eradicate remnant thyroid tissue, particularly in patients such as those whom we have studied whose tumors were clinically evident, rather than incidentally detected.
On the other hand, Dr. DeVries doubts the therapeutic import of our findings because, he argues, the alternative explanation for multicentricity — intraglandular metastases — also would have justified aggressive treatment. During decades of debate, many have not found this argument to be persuasive. Practically speaking, our study now renders this debate irrelevant since it is clear that affected patients often do have separate de novo sites of cancer development in glands that could well be predisposed to more of the same.
The contrasting views of these correspondents — one favoring less treatment and the other more treatment — illustrate the long-standing controversy surrounding the management of multifocal papillary thyroid cancer. Although our study cannot settle this issue with the same certainty that a randomized clinical trial might, our findings shed light on the underlying biology of this common presentation of a type of tumor whose incidence is increasing more rapidly than any other cancer among U.S. women.1
Paul W. Ladenson, M.D.
Johns Hopkins University School of Medicine
Baltimore, MD 21287
Andrew Arnold, M.D.
University of Connecticut School of Medicine
Farmington, CT 06030
molecularmedicine@uchc.edu
William H. Westra, M.D.
Johns Hopkins Medical Institutions
Baltimore, MD 21231
References
National Cancer Institute. SEER cancer statistics review, 1975-2002. (Accessed August 22, 2005, at http://seer.cancer.gov/csr/1975_2002/.)