Presidential address: Beyond risk groups[mdash ]A new look at differentiated thyroid cancer
1998; Elsevier BV; Volume: 124; Issue: 6 Linguagem: Inglês
10.1067/msy.1998.93106
ISSN1532-7361
Autores Tópico(s)Advances in Oncology and Radiotherapy
ResumoI am sure that you are all tired of hearing me, a perpetual nag, talk yet again about risk group assessment and therapeutic alternatives in differentiated thyroid cancer. Let me point out, however, that this is the entire purpose of being a surgical oncologist: to know how to balance the aggressiveness of your surgical and adjuvant therapy to the risk of the particular cancer.1Cady B. Basic principles in surgical oncology.Arch Surg. 1997; 132: 338-346Crossref PubMed Scopus (114) Google Scholar One need only look at the development of treatment modifications in contemporary cancer surgery to see these alternatives developed: in melanoma, appearing at ever earlier stages because of public and professional education, surgical margins have dramatically been reduced and routine node dissections abandoned by the use of sentinel node biopsy2Reintgen D Balch CM Kirkwood J Merrick R. Recent advances in the care of the patient with malignant melanoma.Ann Surg. 1997; 225: 1-14Crossref PubMed Scopus (137) Google Scholar; in breast cancer, where mammography has increasingly discovered ever smaller and lower-grade cancers, the door has been opened to more conservative treatment by developing excision only as appropriate surgery for duct carcinoma in situ3Silverstein MJ. Predicting residual disease and local recurrence in patients with ductal carcinoma in situ.J Natl Cancer Inst. 1997; 89 ([editorial]): 1330-1331Crossref PubMed Scopus (18) Google Scholar and T1a and T1b4Cady B Stone MD Wayne J. New therapeutic possibilities in primary invasive breast cancer.Ann Surg. 1993; 218: 338-349Crossref PubMed Scopus (91) Google Scholar mammographically discovered breast cancers with the abandonment of both axillary dissection and routine radiotherapy.3Silverstein MJ. Predicting residual disease and local recurrence in patients with ductal carcinoma in situ.J Natl Cancer Inst. 1997; 89 ([editorial]): 1330-1331Crossref PubMed Scopus (18) Google Scholar, 4Cady B Stone MD Wayne J. New therapeutic possibilities in primary invasive breast cancer.Ann Surg. 1993; 218: 338-349Crossref PubMed Scopus (91) Google Scholar In rectal carcinoma, the pioneer disease for application of radical surgical therapy by abdominoperineal resection, screening and early detection have enabled a significant proportion of smaller and lower-grade cancers to be only locally resected with or even without radiation therapy.5Graham RA Garnsey L Jessup JM. Local excision of rectal carcinoma.Am J Surg. 1990; 160: 306-312Abstract Full Text PDF PubMed Scopus (177) Google Scholar Sarcomas of the extremity are now routinely managed by limb-sparing surgery.6Valle AA Kraybill WG. Management of soft tissue sarcomas of the extremity in adults.J Surg Oncol. 1996; 63: 271-279Crossref PubMed Scopus (17) Google Scholar This story of increasing conservation of tissue because of small size or good prognosis is being told in other cancers such as those of the larynx7Shah JP Karnell LH Hoffman HT Ariyan S Brown GS Fee WE et al.Patterns of care for cancer of the larynx in the United States.Arch Otolaryngol Head Neck Surg. 1997; 123: 475-483Crossref PubMed Scopus (125) Google Scholar and anus8Myerson RJ Karnell LH Menck HR. The national cancer data base report on carcinoma of the anus.Cancer. 1997; 80: 805-815Crossref PubMed Scopus (91) Google Scholar also. The adoption of a more conservative surgical approach and elimination of adjuvant therapy in excellent-prognosis cancers has been substantiated by clinical outcome reports, frequently without the benefit or burden of randomized controlled trials. The exploratory stages of reduced surgical therapy are usually promoted by individuals before large multi-institutional randomized prospective trials prove their effectiveness.3Silverstein MJ. Predicting residual disease and local recurrence in patients with ductal carcinoma in situ.J Natl Cancer Inst. 1997; 89 ([editorial]): 1330-1331Crossref PubMed Scopus (18) Google Scholar, 5Graham RA Garnsey L Jessup JM. Local excision of rectal carcinoma.Am J Surg. 1990; 160: 306-312Abstract Full Text PDF PubMed Scopus (177) Google Scholar, 6Valle AA Kraybill WG. Management of soft tissue sarcomas of the extremity in adults.J Surg Oncol. 1996; 63: 271-279Crossref PubMed Scopus (17) Google Scholar, 8Myerson RJ Karnell LH Menck HR. The national cancer data base report on carcinoma of the anus.Cancer. 1997; 80: 805-815Crossref PubMed Scopus (91) Google Scholar Early reports frequently show the way, with later confirmation by larger, more formal studies. In every human cancer prospective randomized trials have indicated that more extensive removal of the primary organ is never accompanied by an increased cure rate!1Cady B. Basic principles in surgical oncology.Arch Surg. 1997; 132: 338-346Crossref PubMed Scopus (114) Google Scholar The situation should be similar in the majority of differentiated thyroid carcinomas because the disease-specific survival rate achieved in a large number of retrospective reports has clearly been established at better than 97% or 98% at follow-up times ranging from 5 to 20 years.9Hay ID Bergstralh EJ Goellner JR Ebersold JR Grant CS. Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989.Surgery. 1993; 114: 1050-1057PubMed Google Scholar, 10Cady B. Our AMES is true: how an old concept still hits the mark: or, risk group assignment points the arrow to rational therapy selection in differentiated thyroid cancer.Am J Surg. 1997; 174 ([Hayes Martin Lecture]): 462-468Abstract Full Text PDF PubMed Scopus (109) Google Scholar, 11Noguchi M Katev N Miwa K. Therapeutic strategies and long-term results in differentiated thyroid cancer.J Surg Oncol. 1998; 67: 52-59Crossref PubMed Scopus (20) Google Scholar Uniquely in thyroid cancer, however, current published therapeutic guidelines, such as those of the American Association of Clinical Endocrinology12AACE clinical practice guidelines for the management of thyroid carcinoma.Endocrine Pract. 1997; 3: 60-71Google Scholar and the American Thyroid Association13Solomon BL Wartofsky L Burman KD. Current trends in the management of well differentiated papillary thyroid carcinoma.J Clin Endocrinol Metab. 1996; 81: 333-339PubMed Google Scholar and as displayed in a recent review in the New England Journal of Medicine, 14Schlumberger MJ. Papillary and follicular thyroid carcinoma.N Engl J Med. 1998; 338: 297-306Crossref PubMed Scopus (1331) Google Scholar consistently suggest therapeutic efforts that are greatly in excess of what would be required for cure in such patients. In sarcomas and melanomas and breast, colon, rectum, lung, gastric, esophagus, and urologic and gynecologic cancers, disease presentations that carry less than a 5% or 10% mortality would seldom be considered for routine adjuvant systemic therapy of any kind. Yet in thyroid cancer treatment guidelines routinely today still recommend total thyroidectomy for the purpose of uniform use of adjuvant radioactive iodine (RAI) and thyroid-stimulating hormone (TSH) suppression by hormone usage.12AACE clinical practice guidelines for the management of thyroid carcinoma.Endocrine Pract. 1997; 3: 60-71Google Scholar, 13Solomon BL Wartofsky L Burman KD. Current trends in the management of well differentiated papillary thyroid carcinoma.J Clin Endocrinol Metab. 1996; 81: 333-339PubMed Google Scholar, 14Schlumberger MJ. Papillary and follicular thyroid carcinoma.N Engl J Med. 1998; 338: 297-306Crossref PubMed Scopus (1331) Google Scholar RAI is completely unnecessary in young patients at low risk; its use displays a doctrinaire commitment to a treatment program designed for disease that carries a far worse prognosis. The problem remains that the message of apportioning radicalness of surgery and adjuvant treatment to the danger of cancer has not been adopted by the majority of endocrine surgeons, particularly endocrinologists, throughout the world regarding low-risk differentiated thyroid cancer. The admonition to “make the punishment (of the treatment) fit the crime (of the cancer)”1Cady B. Basic principles in surgical oncology.Arch Surg. 1997; 132: 338-346Crossref PubMed Scopus (114) Google Scholar is nowhere more routinely ignored than in differentiated thyroid cancer in young and low-risk patients. The application of adjuvant therapy is, in every cancer, accompanied by a proportional reduction in recurrence, thus indicating that extremely good prognostic cases will achieve little absolute gain; even a proportional reduction of recurrence risk of 50% may amount to only 2% or 1% (or less) absolute reduction in recurrence in low-risk differentiated thyroid cancer and even less reduction in deaths. Our background in medical school and surgical training drives us to strive for perfection; this laudable goal, however, should be accompanied by an understanding that “perfection is the enemy of good” and that, in particular, attempted perfection for a few individuals may well be the enemy of good for the entire group. The routine application of excessive measures for possibly saving 1 life of 100 may well jeopardize the health, comfort, lifestyle, and sanity of the other 99. Such an approach is tolerated in our society only because of the metaphoric “baggage” of the cancer terminology, particularly when it occurs in young people.15Sontag S. Illness as metaphor. Farrar, Straus, and Giroux, New York1977Google Scholar Part of the issue of the treatment of cancer has to do with American public attitudes about cancer as a disease. There is no question that the cancer terminology has assumed metaphoric implications in the public's mind (held by tuberculosis at the end of the last century) that frequently is out of all proportion to its real threat. Susan Sontag described this metaphoric conundrum in her book Illness as Metaphor. 15Sontag S. Illness as metaphor. Farrar, Straus, and Giroux, New York1977Google Scholar Cancer is the untamed, inexorable, unknown, silent, mysterious destroyer of young lives that cannot be predicted or prevented.15Sontag S. Illness as metaphor. Farrar, Straus, and Giroux, New York1977Google Scholar We may see a neighbor or friend after a coronary occlusion or an episode of congestive heart failure (both of which may carry a 50% or greater mortality within 5 years) discussing it, half bragging, at a cocktail party, apparently oblivious to the real threat, whereas the patient with early breast cancer or low-risk thyroid cancer is in turmoil because of the personal and societal panic about the cancer diagnosis. Rationality and reason frequently disappear from the therapeutic decision process for patients and physicians. It is not unusual to see a young patient with differentiated thyroid cancer smoking a pack of cigarettes a day, yet more frightened about the thyroid cancer and willing to undergo any kind of treatment, no matter how excessive, while still not dealing with the tobacco addiction, which carries at least a 30% to 50% mortality rate over time! These same confused and illogical public attitudes toward aspects of their health and environment are no where better displayed by the fact that, in a society with the safest drinking water in the world, millions of dollars are being made by selling bottled water! All this, while the daily appeal of extreme sports, fast driving, unguarded sex, gun ownership, and risky avocations are admired and promoted. Why do these attitudes prevail in cancer, and particularly, in differentiated thyroid cancer in low risk patients? I would speculate that it reflects not only the metaphoric weight of the diagnosis of “cancer” in the American public but also the bias of physicians and surgeons to do more rather than less in treating cancer despite imposing morbidity and extra cost, the reluctance to appear “unconventional,” the adverse impact of standardization and treatment guidelines on the ability to individualize cases, the economics of medical practice, the illogical pursuit of a perfect outcome, and the ever-present threat of lawyers. Polls among endocrinologists show that “in a 1996 survey of U.S. thyroidologists, most favored a bilobar resection as the primary surgical treatment for papillary thyroid cancer.”13Solomon BL Wartofsky L Burman KD. Current trends in the management of well differentiated papillary thyroid carcinoma.J Clin Endocrinol Metab. 1996; 81: 333-339PubMed Google Scholar It can be predicted at any period of time that “the most favored” or “most popular” reflects an attitude based on previous experience that may not reflect current reality. Physicians, like generals, are frequently fighting the last war, or the usual cancer, and are reluctant to break the restraints of the “standard” and “popular,” even to acknowledge the most rational. In an attempt to aid this re-examination process in the field of differentiated thyroid cancer, it might be useful to reinterpret the data regarding the majority of patients who are of young age with an excellent prognosis in differentiated thyroid cancer. It should be appreciated that there are a number of biologic aspects of the disease in young patients that are distinctively different than in older patients with differentiated thyroid cancer, which could be interpreted as indicating different diseases, not merely different stages of a common disease. These biologically unique aspects that are apparent in young people with differentiated thyroid cancer are displayed by no other human cancer. This then is the purpose of my talk today, to suggest to this sophisticated audience a new way of looking at this cancer. To that end, I have examined a large group of patients, most previously reported, from the Lahey Clinic and the Deaconess Hospital in Boston, with the gracious help of L.E. Saunders, MD, at the Lahey Clinic, but contrasted in a unique way, comparing only those patients from 20 to 40 years old with those 60 to 80 years old over the 40-year period from 1951 to 1990 (Table I). This unusual analysis is done deliberately and with malice aforethought to emphasize features of what I believe are 2 different diseases by eliminating entirely patients between 40 and 60 years old, who may represent an admixture of the contrasting cancers. The different biologic aspects of these 2 groups of patients are highlighted to re-emphasize my thesis (Table II). Table IDifferentiated thyroid cancer 1951 to 1990, young (20 to 40 years old) versus old (60 to 80 years old) (N = 493)Young patientsOld patientsNo. of patientsDeath with or of diseaseNo.%No.339 (69%)154 (31%)Median follow-up (y)14 y (1-46y)8y (0-27y)25% Follow-up (y)19 y12yDeaths4 (1.2%)48 (31%)Median survival, deaths (y)9 (1-36)5 (0-15)Median age at diagnosis, deaths (y)3669 Age (y) 20-4033941.2 60-801544831 60-64561221 65-69511529 70-7425936 75-80221255Total15448 Open table in a new tab Table IIDifferentiated thyroid carcinoma: differences between old and young patientsYoungOldEtiology and epidemiology Sex ratioWomen predominateWomen and men equal Radiation associationYesNo Dietary iodineAdequateLowClinical presentation Size of primarySmallerLarger Impalpable primaryCommonRare Palpable lymph node metastasesFrequentInfrequent No. of lymph node metastasesHighLow Pathologic typePapillary predominatesMore follicularPrognosis Size related to cureNoYes Extraglandular extensionCurability highCurability low Gross residual diseaseCurableIncurable Lymph or blood vessel involvementNot related to cureRelated to cureRecurrence Wound implantationNeverDoes occur Lymph nodes as percent of recurrenceHighLow Distant metastasesAlmost all lungMultiple organs Curability of distant metastasesHighLow or absent Open table in a new tab The first biologic aspect is the fact that the morbidity and mortality of differentiated thyroid cancer in young patients changed dramatically and significantly about 1950 in the New England area16Cady B Sedgwick CE Meissner WA Bookwalter JR Romagosa V Werber J. Changing clinical, pathologic, therapeutic, and survival patterns in differentiated thyroid carcinoma.Ann Surg. 1976; 183: 541-553Crossref Scopus (277) Google Scholar and about 1960 in the Midwest,17Crile Jr., G Conservative management of cancer of the thyroid.in: Proceedings of the International Workshops on Cancer of the Head and Neck. Butterworths, London1967: 430-434Google Scholar the center of the original American “goiter belt.” These changes, in terms of relative mortality and recurrence rates, reported by us in New England16Cady B Sedgwick CE Meissner WA Bookwalter JR Romagosa V Werber J. Changing clinical, pathologic, therapeutic, and survival patterns in differentiated thyroid carcinoma.Ann Surg. 1976; 183: 541-553Crossref Scopus (277) Google Scholar and by Crile17Crile Jr., G Conservative management of cancer of the thyroid.in: Proceedings of the International Workshops on Cancer of the Head and Neck. Butterworths, London1967: 430-434Google Scholar in Ohio undoubtedly reflected the impact of the iodization of dietary salt, which began in the mid 1930's as a public health measure to control goiter; this dietary additive changed large areas of our country from inadequate to adequate dietary iodine and altered the face of thyroid disease, including thyroid cancer. In our reports the mortality rate in young patients with differentiated thyroid cancer dropped from 7% to 1%, and the recurrence rate dropped from 18% to 5% before and after 1950. Such a dramatic change did not occur in older patients at that time, although subsequently there has been a generally downward drift in both recurrence and mortality in older patients, but for patients over age 75 years, the risk of death from differentiated thyroid cancer exceeds 50% even today (Table I). Since 1950 in our reports from New England10Cady B. Our AMES is true: how an old concept still hits the mark: or, risk group assignment points the arrow to rational therapy selection in differentiated thyroid cancer.Am J Surg. 1997; 174 ([Hayes Martin Lecture]): 462-468Abstract Full Text PDF PubMed Scopus (109) Google Scholar and in other reports from across the United States,9Hay ID Bergstralh EJ Goellner JR Ebersold JR Grant CS. Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989.Surgery. 1993; 114: 1050-1057PubMed Google Scholar, 18Shaha AR Shah JP Loree TR. Low-risk differentiated thyroid cancer: the need for selective treatment.Ann Surg Oncol. 1997; 4: 328-333Crossref PubMed Scopus (157) Google Scholar the long-term mortality rate of young and low-risk patients, who make up 75% to 85% of all differentiated thyroid cancer patients, has been less than 2%. How much better can we get? Another significant biologic difference of this disease is the sex ratio, 4 or 5 women to 1 man in the young, but now with a slight male predominance in older patients.10Cady B. Our AMES is true: how an old concept still hits the mark: or, risk group assignment points the arrow to rational therapy selection in differentiated thyroid cancer.Am J Surg. 1997; 174 ([Hayes Martin Lecture]): 462-468Abstract Full Text PDF PubMed Scopus (109) Google Scholar This marked female predominance in young patients has persisted unchanged throughout the 65 years of reports from our institutions, whereas in older patients the sex ratio changed from roughly 3 women to 1 man before 1940 to a slight majority of men since the 1970's. These simplistic data suggest a difference between these 2 age groups and perhaps emphasize that these are entirely different diseases. Radiation-associated thyroid cancer involves young patients, not older patients. Adequate dietary iodine is associated with an increasing proportion of papillary cancer in young patients but not older patients (Table II). The average age of differentiated thyroid cancer patients in iodine-adequate areas is younger than that in iodine-deficient areas. The proportion of follicular carcinomas, particularly in older patients, is lower in the iodine-adequate than in the iodine-deficient areas. Most strikingly, the proportion of cases that are anaplastic has declined dramatically since dietary iodine became adequate but remains high in iodine deficient areas even today.19Deandrea M Gallone G Veglio M Balsamo A Grassi A Sapelli S et al.Thyroid cancer histotype changes as observed in a major general hospital in a 21-year period.J Endocrinol Invest. 1997; 20: 52-58PubMed Google Scholar Anaplastic thyroid cancer sometimes represents conversion of long-standing or recurrent papillary cancer by clonal overgrowth of aggressive cells; anaplastic cancer makes up less than 3% of patients with thyroid cancer in our country today, however, and continues to decline. The last patient that I encountered with a clear clinical history of conversion from long-standing, recurrent papillary cancer to anaplastic cancer was 18 years ago. Although such cases may occasionally be seen today, they are far less frequent compared with the 1940's when almost 20% of our thyroid cancers were undifferentiated and anaplastic.16Cady B Sedgwick CE Meissner WA Bookwalter JR Romagosa V Werber J. Changing clinical, pathologic, therapeutic, and survival patterns in differentiated thyroid carcinoma.Ann Surg. 1976; 183: 541-553Crossref Scopus (277) Google Scholar The scenario of an impalpable, tiny microscopic primary cancer with bulky palpable lymph node metastases has been a regular feature of differentiated thyroid cancer in young patients.10Cady B. Our AMES is true: how an old concept still hits the mark: or, risk group assignment points the arrow to rational therapy selection in differentiated thyroid cancer.Am J Surg. 1997; 174 ([Hayes Martin Lecture]): 462-468Abstract Full Text PDF PubMed Scopus (109) Google Scholar, 16Cady B Sedgwick CE Meissner WA Bookwalter JR Romagosa V Werber J. Changing clinical, pathologic, therapeutic, and survival patterns in differentiated thyroid carcinoma.Ann Surg. 1976; 183: 541-553Crossref Scopus (277) Google Scholar In the 1930's this was misinterpreted as “lateral aberrant thyroid” and considered an embryologic rest because patients never died, but now it is recognized as lymph node metastases from differentiated papillary carcinoma of the thyroid in the young, but not the old. When routine neck dissections are performed, lymph node metastases are detected in 35% to 80% of young patients11Noguchi M Katev N Miwa K. Therapeutic strategies and long-term results in differentiated thyroid cancer.J Surg Oncol. 1998; 67: 52-59Crossref PubMed Scopus (20) Google Scholar but few older patients. More than 10% of young patients with papillary carcinoma have more than 10 lymph node metastases,10Cady B. Our AMES is true: how an old concept still hits the mark: or, risk group assignment points the arrow to rational therapy selection in differentiated thyroid cancer.Am J Surg. 1997; 174 ([Hayes Martin Lecture]): 462-468Abstract Full Text PDF PubMed Scopus (109) Google Scholar, 16Cady B Sedgwick CE Meissner WA Bookwalter JR Romagosa V Werber J. Changing clinical, pathologic, therapeutic, and survival patterns in differentiated thyroid carcinoma.Ann Surg. 1976; 183: 541-553Crossref Scopus (277) Google Scholar yet not one of them has died of disease after prolonged follow-up (Table III). Table IIIDifferentiated thyroid carcinoma 1951-1990, relationship of number of lymph node metastases to outcomeFollow-up (y)Proportion surviving (%)1-3 positive nodes4-10 positive nodes>10 positive nodesYoung, 20-40 y (No. of cases)5650145100%100%100%10100%100%100%20100%100%100%Old, 60-80 y (No. of cases)1992578%75%50%1071%60%0%2059%45%0% Open table in a new tab By contrast, in every other human cancer, including papillary cancer in older patients, it is uncommon to survive if more than 5 lymph nodes display metastases. I know of no exceptions to this linear relationship between increasing numbers of lymph node metastases and increasing mortality from cancer1Cady B. Basic principles in surgical oncology.Arch Surg. 1997; 132: 338-346Crossref PubMed Scopus (114) Google Scholar except in differentiated papillary carcinoma of the thyroid in young patients. Clearly, this unique disease of papillary cancer in young patients must have a unique genetic pattern that permits adherence and retention of cells in regional lymph nodes that are unrelated to the capacity to grow in other organs. This represents another example of the organ specificity of metastatic cells that has been demonstrated in animal models and clinical cases.20Fidler IJ Balch CM. The biology of cancer metastasis and implications for therapy.Curr Probl Surg. 1987; 24: 134-209Abstract Full Text PDF Scopus (177) Google Scholar Work by Nip et al21Nip J Rabbani SA Shibata HR Brodt P. Coordinated expression of the vitronectin receptor and the urokinase-type plasminogen activator receptor in metastatic melanoma cells.J Clin Invest. 1995; 95: 2096-2103Crossref PubMed Scopus (83) Google Scholar at McGill University has revealed animal models of lymph node–specific metastatic cells that do not have the capacity to grow in other organs and that provide the biologic rationale for the lymph node metastatic predominance without associated mortality from distant metastases found uniquely in papillary carcinoma of the thyroid in young patients. One hundred percent survival of our young patients with extensive lymph node metastases emphasizes this unique phenomena. Older patients or patients with medullary carcinoma of the thyroid arising from parafollicular “c” cells that happen to reside in the thyroid gland of humans (but as separate organs in other species) do not have this benign implication from lymph node metastases. Another phenomenon displaying the unique disease in young patients with thyroid cancer is the lack of relationship of prognosis to size or disease extent (Tables IV and V). For instance, there is no survival impairment with larger size, extraglandular extension, or the presence of gross residual disease by surgeon estimate (Table V) or by blood vessel, muscular, or soft tissue invasion, demonstrated pathologically (Table VI) in young patients with differentiated thyroid cancer in contrast to old patients with similar clinical or histologic findings. Table VIDifferentiated thyroid carcinoma 1951 to 1990, relationship of pathologic definition to outcomePath involvementFollow-up (y)Proportion surviving (%)Blood vessel involvementSoft tissue involvementMuscle involvement–+–+–+Young (20-40 y)510010010010010010010999999100991002099999910099100Old (60-80 y)58773865383631079547028715020604564196217All differences between plus and minus in old are significant. Open table in a new tab Table IVDifferentiated thyroid carcinoma 1951-1990, relationship of measured size to outcomeFollow-up (y)Proportion surviving (No. [%]) 4 cmYoung, 20-40 y (No. [%] of cases)*147 [55%]9030 [11%]5100%100%97%10100%98%93%20100%98%93%Old, 60-80 y (No. [%] of cases)†46 [37%]4534 [27%]595%79%75%1086%67%63%2071%67%40%*P = .2299. †P = .0185. Open table in a new tab Table VDifferentiated thyroid carcinoma 1951-1990, relationship of surgeon's description of extent of disease to outcomeFollow-up (y)Proportion surviving (No. [%] )Extrathyroidal extensionGross disease remainsYoung, 20-40 y (No. [%] of cases)28 [8%]14 [4%]5100%100%1096%92%2096%92%Old, 60-80 y (No. [%] of cases)38 [25%]*25 [16%]*554%43%1035%28%2026%17%*P = .0001. Open table in a new tab All differences between plus and minus in old are significant. Thus, considering the usual anatomic staging requirements of the American Joint Committee on Cancer (AJCC),22American Joint Committee on Cancer Thyroid gland.in: AJCC cancer staging manual. 5th ed. Lippincott-Raven, Philadelphia1997: 39-44Google Scholar assuming that the same disease occurs in the young as in the old, and assigning increasing size to higher “T” categories and increasing nodal involvement to higher “N” categories and stage IV to the presence of distant metastases, the result is confusion with description of survival curves and inability to stage coherently. Only by recognition that young patients with differentiated thyroid cancer may have a totally different disease does coherence and logic return. This has been recognized in part by the TNM staging at the cost of abandoning the traditional size relationship of the “T” category, ignoring the survival impact of variations in “N” category, and placement of distant metastatic disease (“M”) in other than stage IV by accepting age as a modifier, implicit recognition of my thesis. This biologic uniqueness can be displayed in the pattern of recurrences in the young versus the old with differentiated thyroid cancer (Table II). Wound implantation is unknown after neck dissection or thyroidectomy in young patients but is a recognized phenomenon in older patients with traditional disease relationships. Thus the concept of “berry picking” or isolated lymphatic resection or lymph node resections of regional lymph node metastases while preserving the sternocleidomastoid muscle, jugular vein, and spinal accessory nerve for functional integrity is practiced safely in the young because it is never accompanied by recurrence in the dissected neck; such a violation of the “en-bloc” concept of regional node dissection would be a disaster in melanoma or head and neck squamous cell cancer. This merely re-emphasizes tha
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