Therapeutic Strategy of Papillary Microcarcinoma of the Thyroid Gland: A Nuclear Medicine Perspective

Part of the Medical Radiology book series (MEDRAD)


Patients with papillary thyroid microcarcinoma (PTMC) have an excellent prognosis with a normal life expectancy. According to the literature, the incidence of PTMC is increasing. To date, PMTCs account for up to 30 % of all differentiated thyroid cancers. Because of the differential definitions of the PTMC, the therapeutic approaches of the national Scientific Societies have not been standardised. The therapeutic algorithms have to be adjusted with regard to current thyroid surgery, radioiodine ablation and thyrotropin-suppressive therapy as well as follow-up. Recently, the Therapy Committee of the European Association of Nuclear Medicine (EANM) has recommended a risk-adapted therapy and follow-up. Risk factors which require a more aggressive therapeutic approach are multifocality, thyroid capsule infiltration, evidence of locoregional or distant metastasis and unfavourable histology. It was the aim to review the current therapeutic concepts in patients with PTMC from a nuclear medicine perspective.


Thyroid Carcinoma Papillary Thyroid Carcinoma Papillary Carcinoma Differentiate Thyroid Cancer Follicular Thyroid Carcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

1 Introduction

Differentiated thyroid carcinomas constitute about 90 % of all thyroid carcinoma (Sherman 2003). They can be further classified according to their papillary or follicular growth. Papillary thyroid carcinomas amount to about 80–90 % of thyroid cancers and follicular thyroid carcinoma to 10–15 % (Rahbar et al. 2008). In general, both papillary and follicular thyroid carcinoma have an excellent prognosis with five-year survival rates exceeding 90 %, following the hitherto therapy and follow-up (Lerch et al. 1997). In recent years, the use of ultrasound and fine-needle aspiration biopsies in the examination of the thyroid is steadily increasing, thereby allowing the detection and diagnosis of thyroid cancer much earlier than it can be clinically diagnosed. This may explain a considerable increase in the incidence of PTMC in recent years (Pelizzo et al. 2006). According to the literature, PMTCs account for up to 30–40 % of all differentiated thyroid cancers (Roti et al. 2006; Cheema et al. 2006). PTMC have been demonstrated in up to 36 % of autopsy studies depending on the intensity of the histopathological workup (Reiners et al. 2005). They occur with the same rate in each decade in adults and have an excellent prognosis (Pazaitou-Panayiotou et al. 2007). Patients with PTMC have survival rates indistinguishable from those of the normal population (Rosai et al. 2003; Hay et al. 2009; Ross et al. 2009). However, a subgroup of PTMC with a more virulent biological behaviour has to be considered if the therapeutic strategy of PTMC has to be defined (Roti et al. 2008).

2 Definition of PTCM

The conception of the “papillary thyroid microcarcinoma”

PTMC was introduced for the small papillary carcinoma ≤ 1 cm because of its excellent prognosis with survival rates indistinguishable from those of the normal population (Rosai et al. 2003). According to the literature, the PTMC is sometimes referred to as a variant of the papillary thyroid carcinoma (Fink et al. 1996; Harach et al. 1985; Yamamoto et al. 1990). In addition, a multitude of different terms have been used which can hardly be separated from each other and partly overlap (DeLellis et al. 2004):
  1. (I)


  2. (II)

    latent papillary carcinoma

  3. (III)

    minimal papillary carcinoma

  4. (IV)

    minute/tiny papillary carcinoma

  5. (V)

    occult papillary carcinoma

  6. (VI)

    small papillary carcinoma

  7. (VII)

    non-encapsulated thyroid tumour

  8. (VIII)

    occult sclerosing carcinoma

  9. (IX)

    papillary microtumour, excluding patients <19 years and metastasized tumours


Although PTMCs are frequently found at autopsy they are often not detectable in clinical examination but found incidentally during ultrasound and fine-needle aspiration and thyroidectomy for benign disease. Therefore, the new WHO classification (2004) has proposed the following characterisation of PTMC: “The term microcarcinoma should be used for a papillary carcinoma, which is found incidentally, and which measures 1 cm or less in diameter” (DeLellis et al. 2004). In individual cases, this definition may encompass tumours with multifocality, extrathyroidal extension, lymph node and distant metastasis (Roti et al. 2008).

Until 2002, the large majority of PTMC agreed with the T1-category of the TNM-classification of the International Union Against Cancer (UICC) and the American Joint Commission on Cancer (AJCC) (5th edition, 1997). In 2002, the consistency between PMTC and the T1-category was renounced (6th edition) (Sobin and Wittekind 2002; Greene et al. 2002; Gospodarowicz et al. 2004). Therefore, the tumour size had to be documented in addition to the primary tumour stage. With respect to this difficulty, a supplement was published shortly after the introduction of the 6th edition of the TNM classification in order to divide T1-tumours into T1a for all tumours ≤1 cm and T1b for all tumours >1 cm but ≤2 cm (Wittekind et al. 2003). The proposal to classify T1-tumours into T1a and T1b was adopted in the current 7th edition of the TNM-system (Sobin et al. 2009).

3 Ultrasound and Fine-Needle Biopsy

The increased sensitivity of imaging modalities such as ultrasound, computed tomography and magnetic resonance imaging has resulted in the identification of thyroid lesions, measuring 10 mm or less. To date, ultrasound-guided fine-needle aspiration cytology is sufficiently accurate to evaluate thyroid nodules as small as 2 mm (Yang et al. 2002). However, prospective studies on the diagnostic accuracy of small lesion biopsy are still lacking. The major reason for a missed tumour diagnosis on fine-needle aspiration may be inadequate tumour sampling due to the heterogeneity of the nodule (Siddiqui et al. 2008). Interestingly, Papini et al. have found that the cancer prevalence is not significantly different in nodules between 8 and 10 mm and nodules between 11 and 15 mm (Papini et al. 2002).

Certain morphological and functional parameters are significant predictors of malignancy. Already Schober and Schwarzrock 1986 discussed the relative probabilities for malignancy in low-uptake lesions of the thyroid using sonographic criteria. In particular, irregular margins, intranodular vascular spots and microcalcifications are independent risk factors in patients with small hypoechogenic lesions (Yamamoto et al. 1990; Papini et al. 2002). Furthermore, some authors have found that an anteroposterior and transverse diameter ratio of non-palpable thyroid nodules ≥1 was associated with malignancy (Yamamoto et al. 1990; Cappelli et al. 2005). Accordingly, the American (ATA) and European Thyroid Associations (ETA) recommend that nodules up to 1 cm should be submitted to fine-needle aspiration in the event of suspicious findings at ultrasound or a history of radiation to the head and neck region (Pacini et al. 2006; Cooper et al. 2009).

Recently, Kwak et al. have defined ultrasound features of PTMC which are significantly associated with lateral lymph node metastases: upper pole location, contact of >25 % with the adjacent capsule and presence of calcifications (Kwak et al. 2009). In addition, the primary tumour size is significantly correlated with the prevalence of lymphogenic spread (Fig. 1) (Rahbar et al. 2008). As yet, the prognostic value of lymph node metastases in differentiated thyroid carcinoma is still a matter of debate (Shaha 2000; McHenry et al. 1991; Akslen et al. 1991; Mazzaferri 2000; Cady 1998). According to McHenry et al. (1991) cervical lymph node metastases were associated with a higher incidence of recurrence and occurred synchronously or preceded the development of distant metastases. However, these findings were not statistically significant for overall survival. In contrast, Akslen et al. (1991) have found a significantly reduced survival in patients with lymph node metastases.
Fig. 1

Comparison of papillary thyroid microcarcinoma (PTMC) according to tumour size: In 349 patients with PTCM the tumour size was significantly correlated with the prevalence of lymph node metastasis (p < 0.01)

4 Histology

Thyroid microcarcinomas are most often papillary (65–99 %) and only rarely follicular (0.3–23.6 %) tumours (Baudin et al. 1998; Lee et al. 2006). The wide range in prevalence of the follicular microcarcinoma may at least in part be due to its substantial similarity with the follicular variant of PTMC. However, both patients with follicular and those with papillary microcarcinoma have an excellent prognosis (Rahbar et al. 2008). At the Department of Nuclear Medicine of the University of Münster, a tertiary referral centre for differentiated thyroid cancer, thyroid microcarcinoma showed excellent event-free survival rates irrespective of their histology (Fig. 2). Accordingly, the European guidelines recommend common therapeutic algorithms for both types of differentiated microcarcinomas (Pacini et al. 2006). The PTMC is often non-encapsulated and sclerosing, although encapsulated variants exist. The tumour is commonly located near the thyroid capsule. Small PTMC <1 mm frequently present with a follicular architecture and lack stromal sclerosis (DeLellis et al. 2004). In contrast, PTMC with a mean diameter of about 2 mm often show a prominent desmoplastic stroma. Larger tumours with an average size of 5 mm are less common and often characterised by a papillary pattern. The more virulent variants of PTMC such as tall cell, columnar cell, oncocytic and diffuse sclerosing subtypes are rare. The prevalence of oncocytic and tall cell variants in PTMC is only 0.8 % (Pelizzo et al. 2004). However, the corresponding value for the sclerosing subtype amounts to 5.0 % (Pelizzo et al. 2004). Until 2009, the American and European guidelines concordantly recommended radioiodine ablation after total or near-total thyroidectomy in these more aggressive subtypes of PTMC (Cooper et al. 2006; Luster et al. 2008). In contrast, the current American guidelines have confined the use of radioiodine ablation to PTMC patients with extrathyroidal extension and lymph node or distant metastasis, respectively (Cooper et al. 2009). However, this highly restrictive approach is not shared by European stakeholders who still suggest radioiodine ablation in selected PTMC patients with T1 N0 M0 (Table 1).
Fig. 2

Event-free survival of patients with thyroid microcarcinoma of papillary (PTMC) and follicular histology (FTMC). There was no significant difference between the event rates in patients with PTMC and FTMC (p = n.s)

Table 1

Summary of the international guidelines on the indication of radioiodine ablation in patients with papillary thyroid microcarcinoma




No patients with T1 N0 M0

Selected patients with T1 N0 M0


unfavourable histology

incomplete surgery

Selected patients with T1 N0 M0


unfavourable histology

history of radiation


Patients with T3 or N1/M1-categories

Patients with T3, R1 or N1/M1-categories; relative indication for <18 years

Patients with T3 or N1/M1-categories

ATA American Thyroid Association; ETA European Thyroid Association; EANM European Association of Nuclear Medicine. Stages refer to the current AJCC classification (Edge et al. 2010) Cancer Staging Manual, 7th edition (2010), published by Springer-Verlag, New York

5 Molecular Characteristics of PTMC

From a nuclear medicine perspective, the deeper insights into the molecular characteristics of PTMC will have a growing impact on the therapeutic management of these patients. Several genetic alterations have been described in PTMC which are associated with distinct biological features. Most common mutations in papillary carcinoma are point mutations of the BRAF and RAS genes and receptor tyrosine kinase (RET) rearrangements, all of which encode proteins that act along the same intracellular signalling pathway leading to the activation of the mitogen-activated protein kinase (MAPK) cascade (Nikiforov 2008). Chromosomal rearrangements of the RET gene represent the most common structural genetic alterations in papillary carcinoma. These rearrangements have been found in up to 52 % of PTMC and represent an early event in the process of thyroid cell transformation (Adeniran et al. 2006; Viglietto et al. 1995). More aggressive PTMCs which present with cervical lymph node metastases often show loss of the p27 gene (Khoo et al. 2002). In addition, cyclin D1 showed significantly higher median expression in PTMC with metastases compared to those without, indicating a correlation to tumour aggressiveness (Londero et al. 2008). Lim et al. (2007) have shown that the absence of epidermal growth factor receptor expression is closely correlated with lymph node metastasis and extrathyroidal growth. Furthermore, they have demonstrated that the absence of cyclooxygenase-2 expression is associated with multiplicity and bilaterality.

6 Therapy

The guidelines of the ATA, ETA and the Therapy Committee of the EANM agree on a risk-adapted therapeutic management of patients with PTMC as outlined below (Pacini et al. 2006; Cooper et al. 2006a, b; Luster et al. 2008).

6.1 Surgery

The optimal surgical treatment of PTMC is still debatable (Roti et al. 2006; Besic et al. 2008). In a meta-analysis, Roti et al. have found that total/near-total thyroidectomy is performed in 72 %, subtotal thyroidectomy in 11 % and lobectomy in 17 % of cases (Roti et al. 2008). According to Ito et al. therapeutic lymph node dissection is carried out in about 10 %, whereas prophylactic lymph node excision is performed in about 56 % (Ito et al. 2004).

The European guidelines recommend distinct approaches depending on the method of discovery and the risk stratification of the PTMC:
  1. (a)
    When PTMC is diagnosed after lobectomy for benign thyroid disease completion thyroidectomy should be performed in case of the following risk factors:
    1. (I)

      columnar cell variant

    2. (II)

      tall cell variant

    3. (III)

      diffuse sclerosing variant

    4. (IV)


    5. (V)

      extrathyroidal growth

    6. (VI)

      locoregional metastasis

    7. (VII)

      distant metastasis

  2. (b)

    In case of a preoperative diagnosis of the PTMC by fine-needle aspiration cytology standard (near-)total thyroidectomy should be performed. This procedure allows the elimination of multifocal disease and decreases recurrence rates.

  3. (c)

    If the PTMC presents with locoregional or distant metastases routine total or near-total thyroidectomy with lymph node dissection is recommended.


The two major complications of thyroid surgery are permanent post-operative recurrent laryngeal nerve palsy and hypocalcaemia. According to the prospective German Thyroid Multicentre Study performed 1998 through 2001, Dralle et al. have found complication rates of only 1.7 % for permanent recurrent laryngeal nerve palsy per nerves at risk and 6.8 % for permanent hypocalcaemia (Dralle et al. 2004). The complication rates depend on the indication and extent of surgery as well as the specialisation of the surgeons (Dralle and Sekulla 2005). Thus, in centres of endocrine surgery the complication rates of permanent hypocalcaemia and recurrent laryngeal nerve palsy are significantly lower than those in low-volume hospitals. In our tertiary referral centre the rates of transient and/or permanent unilateral recurrent laryngeal nerve palsy vary between 1 and 15 % and are inversely proportional to the experience of the surgeon.

6.2 Radioiodine Ablation

The relatively low prevalence and lengthy overall survival of patients with differentiated thyroid cancer and, particularly, PTMC constrain the execution of large-scale prospective studies. Therefore, the level of evidence with regard to the therapeutic management of these patients is low in many instances. Accordingly, the authors of the EANM guidelines relied significantly on their clinical experience to supplement the observations reported in the literature (Luster et al. 2008). Thereby, the current EANM guidelines provide clear and comprehensive therapeutic algorithms of high relevance to everyday practice. This is of particular importance for the adequate therapeutic management of patients with PTMC and diverse risk-profiles.

According to the results of a meta-analysis only about 17 % of patients with PTMC undergo radioiodine ablation (Roti et al. 2008). Chow et al. have found a lower rate of lymph node recurrence after radioiodine ablation in patients with initially lymph node-negative PTMC (Chow et al. 2003). However, these findings could not be confirmed (Baudin et al. 1998). Most PTMC are diagnosed incidentally after surgery for benign thyroid disease and lack the risk factors mentioned above (Pazaitou-Panayiotou et al. 2007). However, in selected patients with PTMC at higher risk (unfavourable histology, multifocality, extrathyroidal growth or metastasis) post-surgical radioiodine ablation is definitively indicated (Table 1).

In addition, the Therapy Committee of the EANM has defined further parameters which should be considered when deciding whether to perform radioiodine ablation in patients with PTMC:
  1. (I)

    positive family history

  2. (II)

    history of neck radiation exposure

  3. (III)

    larger tumour size

  4. (IV)

    closeness of the tumour to the thyroid capsule

  5. (V)

    vascular invasion

  6. (VI)

    cancer-related genetic findings (in the future).


In these cases, the decision on the post-operative radioiodine treatment should be made after individual discussions of the pros and cons with each patient. In general, radioiodine ablation has only minor side effects, such as sialadenitis, xerostomia or nausea (Dietlein et al. 2007). In addition, the patient′s needs of security or possible fears of radiation should be addressed.

6.3 Thyrotropin-Suppressive Therapy

The American and European guidelines recommend a differential L-thyroxine therapy according to the risk profile of the patients with PTMC mentioned above (Pacini et al. 2006; Cooper et al. 2009). In low-risk patients, L-thyroxine replacement therapy is adequate. In these cases Schlumberger et al. recommend to aim for a serum TSH level within the lower part of the normal range (0.5–1.0 mU/l) (Schlumberger et al. 2004). In high-risk PTMC patients with apparent remission after treatment TSH-suppressive therapy (serum TSH ≤ 0.1 mU/l) may be persued for 3–5 years in order to inhibit the TSH-dependent growth of residual cancer cells (Cooper et al. 1998; McGriff et al. 2002). In high-risk patients considered in complete remission therapy can be shifted from suppressive to replacement (Pazaitou-Panayiotou et al. 2007).

7 Conclusion

In summary, the PTMC comprises a spectrum of thyroid carcinomas with different risk stratifications. Therefore, the term PTMC is not suited for planning of the therapeutic management of individual patients. However, the European guidelines have defined distinct risk factors which should be considered in clinical routine. In particular, the Therapy Committee of the EANM has published an excellent guideline for risk-adapted therapy and follow-up of this multi-faceted thyroid cancer from a nuclear medicine perspective. This guideline has successfully integrated all relevant procedures with regard to clinical routine. In general, patients with PTMC have a normal life expectancy. Therefore, it should be the joint aim of the interdisciplinary medical team to guarantee an excellent quality of life. In addition, there is no difference in the clinical outcome of patients with papillary and follicular microcarcinoma (Rahbar et al. 2008; Riemann and Schober 2007). Accordingly, the therapeutic algorithms of patients with PTMC can be transferred to those with follicular microcarcinoma.


  1. Adeniran AJ, Zhu Z, Gandhi M, Steward DL, Fidler JP, Giordano TJ, Biddinger PW, Nikiforov YE (2006) Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am J Surg Pathol 30:216–222PubMedCrossRefGoogle Scholar
  2. Akslen LA, Haldorsen T, Thoresen SO, Glattre E (1991) Survival and causes of death in thyroid cancer: a population-based study of 2479 cases from Norway. Cancer Res 51:1234–1241PubMedGoogle Scholar
  3. Baudin E, Travagli JP, Ropers J, Mancusi F, Bruno-Bossio G, Caillou B, Cailleux AF, Lumbroso JD, Parmentier C, Schlumberger M (1998) Microcarcinoma of the thyroid gland: the Gustave-Roussy Institute experience. Cancer 83:553–559PubMedCrossRefGoogle Scholar
  4. Besic N, Pilko G, Petric R, Hocevar M, Zgajnar J (2008) Papillary thyroid microcarcinoma: prognostic factors and treatment. J Surg Oncol 97:221–225PubMedCrossRefGoogle Scholar
  5. Cady B (1998) Presidential address: beyond risk groups—a new look at differentiated thyroid cancer. Surgery 124:947–957PubMedCrossRefGoogle Scholar
  6. Cappelli C, Pirola I, Cumetti D, Micheletti L, Tironi A, Gandossi E, Martino E, Cherubini L, Agosti B, Castellano M, Mattanza C, Rosei EA (2005) Is the anteroposterior and transverse diameter ratio of nonpalpable thyroid nodules a sonographic criteria for recommending fine-needle aspiration cytology? Clin Endocrinol 63:689–693CrossRefGoogle Scholar
  7. Cheema Y, Olson S, Elson D, Chen H (2006) What is the biology and optimal treatment for papillary microcarcinoma of the thyroid? J Surg Res 134:160–162PubMedCrossRefGoogle Scholar
  8. Chow SM, Law SC, Chan JK, Au SK, Yau S, Lau WH (2003) Papillary microcarcinoma of the thyroid-prognostic significance of lymph node metastasis and multifocality. Cancer 98:31–40PubMedCrossRefGoogle Scholar
  9. Cooper DS, Specker B, Ho M, Sperling M, Ladenson PW, Ross DS, Ain KB, Bigos ST, Brierley JD, Haugen BR, Klein I, Robbins J, Sherman SI, Taylor T, Maxon HR 3rd (1998) Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: results from the National Thyroid Cancer Treatment Cooperative Registry. Thyroid 8:737–744PubMedCrossRefGoogle Scholar
  10. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Sherman SI, Tuttle RM, American Thyroid Association Guidelines Taskforce (2006) Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 16:109–142Google Scholar
  11. 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, American Thyroid Association Guidelines Taskforce (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19:1167–1214Google Scholar
  12. DeLellis RA, Lloyd RV, Heitz PU, Eng C (2004) World Health Organisation Classification of tumours. In: Pathology and genetics of tumours of endocrine organs. IARC Press, LyonGoogle Scholar
  13. Dietlein M, Dressler J, Eschner W, Grünwald F, Lassmann M, Leisner B, Luster M, Moser E, Reiners C, Schicha H, Schober O, Deutsche Gesellschaft für Nuklearmedizin; Deutsche Gesellschaft für Medizinische Physik (2007) Procedure guidelines for radioiodine therapy of differentiated thyroid cancer (version 3). Nuklearmedizin 46:213–219Google Scholar
  14. Dralle H, Sekulla C, Haerting J, Timmermann W, Neumann HJ, Kruse E, Grond S, Mühlig HP, Richter C, Voss J, Thomusch O, Lippert H, Gastinger I, Brauckhoff M, Gimm O (2004) Risk factors of paralysis and functional outcome after recurrent laryngeal nerve monitoring in thyroid surgery. Surgery 136:1310–1322PubMedCrossRefGoogle Scholar
  15. Dralle H, Sekulla C (2005) Thyroid surgery: generalist or specialist (in German)? Zentralbl Chir 130:428–432PubMedCrossRefGoogle Scholar
  16. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (2010) AJCC cancer staging manual, 7th edn. Springer, New YorkGoogle Scholar
  17. Fink A, Tomlinson G, Freeman JL, Rosen IB, Asa SL (1996) Occult micropapillary carcinoma associated with benign follicular thyroid disease and unrelated thyroid neoplasms. Mod Pathol 9:816–820PubMedGoogle Scholar
  18. Gospodarowicz MK, Miller D, Groome PA, Greene FL, Logan PA, Sobin LH (2004) The process for continuous improvement of the TNM classification. Cancer 100:1–5PubMedCrossRefGoogle Scholar
  19. Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, Morrow M (2002) AJCC cancer staging manual, 6th edn. Springer, New YorkCrossRefGoogle Scholar
  20. Harach HR, Franssila KO, Wasenius VM (1985) Occult papillary carcinoma of the thyroid. A “normal” finding in Finland. A systematic autopsy study. Cancer 56:531–538PubMedCrossRefGoogle Scholar
  21. Hay ID, Hutchinson ME, Gonzalez-Losada T, McIver B, Reinalda ME, Grant CS, Thompson GB, Sebo TJ, Goellner JR (2009) Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery 144:980–987CrossRefGoogle Scholar
  22. Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Kuma K, Miyauchi A (2004) Preoperative ultrasonographic examination for lymph node metastasis: usefulness when designing lymph node dissection for papillary microcarcinoma of the thyroid. World J Surg 28:498–501PubMedCrossRefGoogle Scholar
  23. Khoo ML, Freeman JL, Witterick IJ, Irish JC, Rotstein LE, Gullane PJ, Asa SL (2002) Underexpression of p27/Kip in thyroid papillary microcarcinomas with gross metastatic disease. Arch Otolaryngol Head Neck Surg 128:253–257PubMedCrossRefGoogle Scholar
  24. Kwak JY, Kim EK, Kim MJ, Son EJ, Chung WY, Park CS, Nam KH (2009) Papillary microcarcinoma of the thyroid: predicting factors of lateral neck node metastasis. Ann Surg Oncol 16:1348–1355PubMedCrossRefGoogle Scholar
  25. Lee J, Rhee Y, Lee S, Ahn CW, Cha BS, Kim KR, Lee HC, Kim SI, Park CS, Lim SK (2006) Frequent, aggressive behaviors of thyroid microcarcinomas in Korean patients. Endocr J 53:627–632PubMedCrossRefGoogle Scholar
  26. Lerch H, Schober O, Kuwert T, Saur HB (1997) Survival of differentiated thyroid carcinoma studied in 500 patients. J Clin Oncol 15:2067–2075PubMedGoogle Scholar
  27. Lim DJ, Baek KH, Lee YS, Park WC, Kim MK, Kang MI, Jeon HM, Lee JM, Yun-Cha B, Lee KW, Son HY, Kang SK (2007) Clinical, histopathological, and molecular characteristics of papillary thyroid microcarcinoma. Thyroid 17:883–888PubMedCrossRefGoogle Scholar
  28. Londero SC, Godballe C, Krogdahl A, Bastholt L, Specht L, Sørensen CH, Pedersen HB, Pedersen U, Christiansen P (2008) Papillary microcarcinoma of the thyroid gland: is the immunohistochemical expression of cyclin D1 or galectin-3 in primary tumour an indicator of metastatic disease? Acta Oncol 47:451–457PubMedCrossRefGoogle Scholar
  29. Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJ, Tennvall J, Bombardieri E (2008) Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 35:1941–1959PubMedCrossRefGoogle Scholar
  30. Mazzaferri EL (2000) Long-term outcome of patients with differentiated thyroid carcinoma: effect of therapy. Endocr Pract 6:469–476PubMedCrossRefGoogle Scholar
  31. McGriff NJ, Csako G, Gourgiotis L, Lori CG, Pucino F, Sarlis NJ (2002) Effects of thyroid hormone suppression therapy on adverse clinical outcomes in thyroid cancer. Ann Med 34:554–564PubMedCrossRefGoogle Scholar
  32. McHenry CR, Rosen IB, Walfish PG (1991) Prospective management of nodal metastases in differentiated thyroid cancer. Am J Surg 162:353–356PubMedCrossRefGoogle Scholar
  33. Nikiforov YE (2008) Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Pathol 21:S37–S43PubMedCentralPubMedCrossRefGoogle Scholar
  34. Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JW, Wiersinga W, European Thyroid Cancer Taskforce (2006) European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 154:787–803Google Scholar
  35. Papini E, Guglielmi R, Bianchini A, Crescenzi A, Taccogna S, Nardi F, Panunzi C, Rinaldi R, Toscano V, Pacella CM (2002) Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features. J Clin Endocrinol Metab 87:1941–1946PubMedCrossRefGoogle Scholar
  36. Pazaitou-Panayiotou K, Capezzone M, Pacini F (2007) Clinical features and therapeutic implication of papillary thyroid microcarcinoma. Thyroid 17:1085–1092PubMedCrossRefGoogle Scholar
  37. Pelizzo MR, Boschin IM, Toniato A, Pagetta C, Piotto A, Bernante P, Casara D, Pennelli G, Rubello D (2004) Natural history, diagnosis, treatment and outcome of papillary thyroid microcarcinoma (PTMC): a mono-institutional 12-year experience. Nucl Med Commun 25:547–552PubMedCrossRefGoogle Scholar
  38. Pelizzo MR, Boschin IM, Toniato A, Piotto A, Bernante P, Pagetta C, Rampin L, Rubello D (2006) Papillary thyroid microcarcinoma (PTMC): prognostic factors, management and outcome in 403 patients. Eur J Surg Oncol 32:1144–1148PubMedCrossRefGoogle Scholar
  39. Pisello F, Geraci G, Sciumè C, Li Volsi F, Modica G (2007) Total thyroidectomy of choice in papillary micro carcinoma (in Italian). G Chir 28:13–19PubMedGoogle Scholar
  40. Rahbar K, Hutzenlaub V, Fischer RJ, Schober O, Riemann B (2008) Risk-profile and outcome of small papillary and follicular thyroid carcinomas. Nuklearmedizin 47:188–194PubMedGoogle Scholar
  41. Reiners C, Geling M, Luster M, Farahati J, Mäder U (2005) Epidemiologie des Schilddrüsenkarzinoms. Onkologe 11:11–19CrossRefGoogle Scholar
  42. Riemann B, Schober O (2007) Das “kleine“ Schilddrüsenkarzinom (in German). Nuklearmedizin 46:113–114Google Scholar
  43. Rosai J, LiVolsi VA, Sobrinho-Simoes M, Williams ED (2003) Renaming papillary microcarcinoma of the thyroid gland: the Porto proposal. Int J Surg Pathol 11:249–251PubMedCrossRefGoogle Scholar
  44. Ross DS, Litofsky D, Ain KB, Brierley JD, Cooper DS, Haugen BR, Jonklaas J, Ladenson PW, Magner J, Robbins J, Skarulis MC, Steward DL, Maxon HR, Sherman SI (2009) Recurrence after treatment of micropapillary thyroid cancer. Thyroid 19:1043–1048PubMedCrossRefGoogle Scholar
  45. Roti E, Rossi R, Trasforini G, Bertelli F, Ambrosio MR, Busutti L, Pearce EN, Braverman LE, Degli Uberti EC (2006) Clinical and histological characteristics of papillary thyroid microcarcinoma: results of a retrospective study in 243 patients. J Clin Endocrinol Metab 91:2171–2178PubMedCrossRefGoogle Scholar
  46. Roti E, degli Uberti EC, Bondanelli M, Braverman LE (2008) Thyroid papillary microcarcinoma: a descriptive and meta-analysis study. Eur J Endocrinol 159:659–673Google Scholar
  47. Schlumberger M, Berg G, Cohen O, Duntas L, Jamar F, Jarzab B, Limbert E, Lind P, Pacini F, Reiners C, Sánchez Franco F, Toft A, Wiersinga WM (2004) Follow-up of low-risk patients with differentiated thyroid carcinoma: a European perspective. Eur J Endocrinol 150:105–112PubMedCrossRefGoogle Scholar
  48. Schober O, Schwarzrock R (1986) The thyroid gland with low uptake lesions: evaluation by ultrasound. Radiology 158:277–278PubMedCrossRefGoogle Scholar
  49. Shaha AR (2000) Thyroid cancer: extent of thyroidectomy. Cancer Control 7:240–245PubMedGoogle Scholar
  50. Sherman SI (2003) Thyroid carcinoma. Lancet 361:501–511PubMedCrossRefGoogle Scholar
  51. Siddiqui MA, Griffith KA, Michael CW, Pu RT (2008) Nodule heterogeneity as shown by size differences between the targeted nodule and the tumor in thyroidectomy specimen: a cause for a false-negative diagnosis of papillary thyroid carcinoma on fine-needle aspiration. Cancer 114:27–33PubMedCrossRefGoogle Scholar
  52. Sobin LH, Wittekind C (2002) UICC TNM classification of malignant tumors, 6th edn. Wiley-Liss, New YorkGoogle Scholar
  53. Sobin LH, Gospodarowicz MK, Wittekind C (2009) UICC TNM classification of malignant tumors, 7th edn. Wiley-Liss, New YorkGoogle Scholar
  54. Viglietto G, Chiappetta G, Martinez-Tello FJ, Fukunaga FH, Tallini G, Rigopoulou D, Visconti R, Mastro A, Santoro M, Fusco A (1995) RET/PTC oncogene activation is an early event in thyroid carcinogenesis. Oncogene 11:1207–1210PubMedGoogle Scholar
  55. Wittekind C, Greene FL, Henson DE, Hutter RVP, Sobin LH (2003) TNM supplement. A commentary on uniform use, 3rd edn. Wiley-Liss, New YorkGoogle Scholar
  56. Yamamoto Y, Maeda T, Izumi K, Otsuka H (1990) Occult papillary carcinoma of the thyroid. A study of 408 autopsy cases. Cancer 65:1173–1179PubMedCrossRefGoogle Scholar
  57. Yang GC, LiVolsi VA, Baloch ZW (2002) Thyroid microcarcinoma: fine-needle aspiration diagnosis and histologic follow-up. Int J Surg Pathol 10:133–139PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg  2012

Authors and Affiliations

  1. 1.Department of Nuclear MedicineUniversity Hospital of MünsterMünsterGermany

Personalised recommendations