Journal List > J Korean Med Assoc > v.61(4) > 1043281

Moon and Park: Diagnosis and treatment of low-risk papillary thyroid microcarcinoma

Abstract

Recent guidelines for the treatment of thyroid nodules and differentiated thyroid cancer include active surveillance as an alternative option for the treatment of low-risk papillary thyroid microcarcinoma (PTMC). PTMC is defined as having a tumor diameter of ≤1 cm, and low-risk PTMC is defined as PTMC without currently known risk factors (e.g., metastases, local invasion, or cytologic evidence of aggressive disease). Some researchers have suggested that active surveillance can be the first-line treatment of low risk PTMC based on reports showing that the oncological outcomes of active surveillance and immediate surgery were similarly excellent and that immediate surgery can occasionally be accompanied by surgical complications. Nonetheless, many concerns still exist about the full implementation of active surveillance in current clinical practice because the biology of PTMC still has not been fully elucidated and there is little evidence regarding the longterm prognosis of active surveillance. In this review, we discuss the current concept of low-risk PTMC and its treatment modalities, comparing immediate surgery and active surveillance in terms of clinical applications, prognosis, adverse effects, quality of life, and medical costs. This review aims to enable healthcare providers to provide patients with well-balanced information about immediate surgery and active surveillance for the treatment of low-risk PTMC.

REFERENCES

1. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016; 26:1–133.
crossref
2. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009; 19:1167–1214.
crossref
3. Ito Y, Miyauchi A. A therapeutic strategy for incidentally detected papillary microcarcinoma of the thyroid. Nat Clin Pract Endocrinol Metab. 2007; 3:240–248.
crossref
4. Harach HR, Franssila KO, Wasenius VM. Occult papillary carcinoma of the thyroid: a “normal” finding in Finland: a systematic autopsy study. Cancer. 1985; 56:531–538.
crossref
5. Thorvaldsson SE, Tulinius H, Bjornsson J, Bjarnason O. Latent thyroid carcinoma in Iceland at autopsy. Pathol Res Pract. 1992; 188:747–750.
crossref
6. Ito Y, Uruno T, Nakano K, Takamura Y, Miya A, Kobayashi K, Yokozawa T, Matsuzuka F, Kuma S, Kuma K, Miyauchi A. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid. 2003; 13:381–387.
crossref
7. Ito Y, Miyauchi A, Inoue H, Fukushima M, Kihara M, Higashiyama T, Tomoda C, Takamura Y, Kobayashi K, Miya A. An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg. 2010; 34:28–35.
crossref
8. Miyauchi A. Clinical trials of active surveillance of papillary microcarcinoma of the thyroid. World J Surg. 2016; 40:516–522.
crossref
9. Yi KH. The revised 2016 Korean Thyroid Association guidelines for thyroid nodules and cancers: differences from the 2015 American Thyroid Association guidelines. Endocrinol Metab (Seoul). 2016; 31:373–378.
crossref
10. Piana S, Ragazzi M, Tallini G, de Biase D, Ciarrocchi A, Frasoldati A, Rosai J. Papillary thyroid microcarcinoma with fatal outcome: evidence of tumor progression in lymph node metastases: report of 3 cases, with morphological and molecular analysis. Hum Pathol. 2013; 44:556–565.
11. Jeon MJ, Kim WG, Choi YM, Kwon H, Lee YM, Sung TY, Yoon JH, Chung KW, Hong SJ, Kim TY, Shong YK, Song DE, Kim WB. Features predictive of distant metastasis in papillary thyroid microcarcinomas. Thyroid. 2016; 26:161–168.
crossref
12. Miyauchi A, Ito Y, Oda H. Insights into the management of papillary microcarcinoma of the thyroid. Thyroid. 2018; 28:23–31.
crossref
13. Fukuoka O, Sugitani I, Ebina A, Toda K, Kawabata K, Yamada K. Natural history of asymptomatic papillary thyroid microcarcinoma: time-dependent changes in calcification and vascularity during active surveillance. World J Surg. 2016; 40:529–537.
crossref
14. Ito Y, Kobayashi K, Tomoda C, Uruno T, Takamura Y, Miya A, Matsuzuka F, Kuma K, Miyauchi A. Ill-defined edge on ultrasonographic examination can be a marker of aggressive characteristic of papillary thyroid microcarcinoma. World J Surg. 2005; 29:1007–1011.
crossref
15. Hirokawa M, Kudo T, Ota H, Suzuki A, Miyauchi A. Pathological characteristics of low-risk papillary thyroid microcarcinoma with progression during active surveillance. Endocr J. 2016; 63:805–810.
crossref
16. Xing M, Liu R, Liu X, Murugan AK, Zhu G, Zeiger MA, Pai S, Bishop J. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol. 2014; 32:2718–2726.
crossref
17. Sugitani I, Toda K, Yamada K, Yamamoto N, Ikenaga M, Fujimoto Y. Three distinctly different kinds of papillary thyroid microcarcinoma should be recognized: our treatment strategies and outcomes. World J Surg. 2010; 34:1222–1231.
crossref
18. Uruno T, Miyauchi A, Shimizu K, Tomoda C, Takamura Y, Ito Y, Miya A, Kobayashi K, Matsuzuka F, Amino N, Kuma K. Usefulness of thyroglobulin measurement in fine-needle aspiration biopsy specimens for diagnosing cervical lymph node metastasis in patients with papillary thyroid cancer. World J Surg. 2005; 29:483–485.
crossref
19. Ito Y, Oda H, Miyauchi A. Insights and clinical questions about the active surveillance of low-risk papillary thyroid microcarcinomas. Endocr J. 2016; 63:323–328.
20. Brito JP, Ito Y, Miyauchi A, Tuttle RM. A clinical framework to facilitate risk stratification when considering an active surveillance alternative to immediate biopsy and surgery in papillary microcarcinoma. Thyroid. 2016; 26:144–149.
crossref
21. Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A. Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation. Thyroid. 2014; 24:27–34.
crossref
22. Kwon H, Jeon MJ, Kim WG, Park S, Kim M, Song DE, Sung TY, Yoon JH, Hong SJ, Kim TY, Shong YK, Kim WB. A comparison of lobectomy and total thyroidectomy in patients with papillary thyroid microcarcinoma: a retrospective individual risk factor-matched cohort study. Eur J Endocrinol. 2017; 176:371–378.
crossref
23. Kwon H, Jeon MJ, Kim WG, Park S, Kim M, Kim TY, Han M, Song DE, Sung TY, Yoon JH, Hong SJ, Ryu JS, Shong YK, Kim WB. Lack of efficacy of radioiodine remnant ablation for papillary thyroid microcarcinoma: verification using inverse probability of treatment weighting. Ann Surg Oncol. 2017; 24:2596–2602.
crossref
24. Park S, Kim WG, Han M, Jeon MJ, Kwon H, Kim M, Sung TY, Kim TY, Kim WB, Hong SJ, Shong YK. Thyrotropin suppressive therapy for low-risk small thyroid cancer: a propensity score-matched cohort study. Thyroid. 2017; 27:1164–1170.
crossref
25. Sugitani I, Fujimoto Y, Yamada K. Association between serum thyrotropin concentration and growth of asymptomatic papillary thyroid microcarcinoma. World J Surg. 2014; 38:673–678.
crossref
26. Kim HI, Jang HW, Ahn HS, Ahn S, Park SY, Oh YL, Hahn SY, Shin JH, Kim JH, Kim JS, Chung JH, Kim TH, Kim SW. High serum TSH level is associated with progression of papillary thyroid microcarcinoma during active surveillance. J Clin Endocrinol Metab. 2018; 103:446–451.
crossref
27. Hay ID. Management of patients with low-risk papillary thyroid carcinoma. Endocr Pract. 2007; 13:521–533.
crossref
28. Mazzaferri EL. Management of low-risk differentiated thyroid cancer. Endocr Pract. 2007; 13:498–512.
crossref
29. Oda H, Miyauchi A, Ito Y, Yoshioka K, Nakayama A, Sasai H, Masuoka H, Yabuta T, Fukushima M, Higashiyama T, Kihara M, Kobayashi K, Miya A. Incidences of unfavorable events in the management of low-risk papillary microcarcinoma of the thyroid by active surveillance versus immediate surgery. Thyroid. 2016; 26:150–155.
crossref
30. Ito Y, Miyauchi A, Kudo T, Ota H, Yoshioka K, Oda H, Sasai H, Nakayama A, Yabuta T, Masuoka H, Fukushima M, Higashiyama T, Kihara M, Kobayashi K, Miya A. Effects of pregnancy on papillary microcarcinomas of the thyroid re-evaluated in the entire patient series at Kuma Hospital. Thyroid. 2016; 26:156–160.
crossref
31. Kwon H, Oh HS, Kim M, Park S, Jeon MJ, Kim WG, Kim WB, Shong YK, Song DE, Baek JH, Chung KW, Kim TY. Active surveillance for patients with papillary thyroid microcarcinoma: a single center's experience in Korea. J Clin Endocrinol Metab. 2017; 102:1917–1925.
crossref
32. Kim TY, Shong YK. Active surveillance of papillary thyroid microcarcinoma: a mini-review from Korea. Endocrinol Metab (Seoul). 2017; 32:399–406.
crossref
33. Oda H, Miyauchi A, Ito Y, Sasai H, Masuoka H, Yabuta T, Fukushima M, Higashiyama T, Kihara M, Kobayashi K, Miya A. Comparison of the costs of active surveillance and immediate surgery in the management of low-risk papillary microcarcinoma of the thyroid. Endocr J. 2017; 64:59–64.
crossref
34. Lang BH, Wong CK. A cost-effectiveness comparison between early surgery and non-surgical approach for incidental papillary thyroid microcarcinoma. Eur J Endocrinol. 2015; 173:367–375.
crossref
35. Venkatesh S, Pasternak JD, Beninato T, Drake FT, Kluijfhout WP, Liu C, Gosnell JE, Shen WT, Clark OH, Duh QY, Suh I. Cost-effectiveness of active surveillance versus hemithyroidectomy for micropapillary thyroid cancer. Surgery. 2017; 161:116–126.
crossref
36. Dupuy DE, Monchik JM, Decrea C, Pisharodi L. Radiofrequency ablation of regional recurrence from well-differentiated thyroid malignancy. Surgery. 2001; 130:971–977.
crossref
37. Lim CY, Yun JS, Lee J, Nam KH, Chung WY, Park CS. Percutaneous ethanol injection therapy for locally recurrent papillary thyroid carcinoma. Thyroid. 2007; 17:347–350.
crossref

Table 1.
Contraindications for the active surveillance of papillary thyroid microcarcinomas
Type Contraindication
Clinical high-risk features N1 (may present on imaging studies) or M1 (very rare) Signs or symptoms of invasion to the recurrent laryngeal nerve or trachea
  High-grade malignancy on cytology (very rare) Cases showing progression signs such as size enlargement or a novel appearance of lymph node metastasis during active surveillance
Features unsuitable for observation, although it is unclear whether they are associated with biological aggressiveness Imaging studies indicate that the tumor may invade the trachea or recurrent laryngeal nerve

Reproduced from Miyauchi et al. Thyroid 2018;28:23-31, with permission from Mary Ann Liebert [12].

Table 2.
A risk stratified approach to decision making in probable or proven papillary thyroid microcarcinoma
Candidates for observation r Tumor/neck US characteristics Patient characteristics Medical team characteristics
Ideal Solitary thyroid nodule Well-defined margins Surrounded by ≥ 2 mm normal thyroid parenchyma Older patients (>60 years) Willing to accept an active surveillance approach Understands that a surgical intervention Experienced multidisciplinary management team High quality neck ultrasonography
  No evidence of extrathyroidal extension Previous US documenting stability cN0 cM0 may be necessary in the future Expected to be compliant with followup plans Supportive significant others (including other members of their health care team) Life-threatening co-morbidities Prospective data collection Tracking/reminder program to ensure proper followup
Appropriate Multifocal papillary microcarcinomas Subcapsular locations not adjacent to RLN without evidence of extrathyroidal extension Ill defined margins Middle aged patients (18-59 years) Strong family history of papillary thyroid cancer Child bearing potential Experienced endocrinologist or thyroid surgeon Neck ultrasonography routinely available
Background ultrasonographic findings that will make follow up difficult (thyroiditis, non-specific lymphadenopathy, multiple other benign appearing thyroid nodules) FDG avid papillary microcarcinomas
Inappropriate Evidence of aggressive cytology on FNA (rare) Subcapsular locations adjacent to RLN Evidence of extrathyroidal extension Clinical evidence of invasion of RLN or trachea (rare) N1 disease at initial evaluation or identified during followup M1 disease (rare) Documented increase in size of ≥3 mm in a confirmed papillary thyroid cancer tumor Young patients (<18 years) Unlikely to be compliant with followup plans Not willing to accept an observation approach Reliable neck ultrasonography not available Little experience with thyroid cancer management

Reproduced from Brito et al. Thyroid 2016;26:144-149, with permission from Mary Ann Liebert [20]. US, ultrasonography; RLN, recurrent laryngeal nerve; FDG, fluorodeoxyglucose; FNA, fine-needle aspiration.

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