Introduction
Papillary microcarcinoma of the thyroid gland is defined as a papillary carcinoma measuring 1 cm or less in diameter.Reference Hedinger, Williams and Sobin1 According to Ito and Miyauchi, these tumours are most commonly discovered in three scenarios.Reference Ito and Miyauchi2 First, incidental microcarcinoma can be found incidentally during the diagnostic evaluation or treatment of other thyroid diseases. Second, occult papillary microcarcinomas can present as metastases to lymph nodes or distant anatomic sites, without an identifiable thyroid mass. Third, latent papillary microcarcinoma can be discovered during autopsy. Autopsy series have reported papillary microcarcinoma incidence rates as high as 36 per cent.Reference Pazaitou-Panayiotou, Capezzone and Pacini3 There are two philosophies regarding the clinical significance of and approach to treating papillary microcarcinomas: many researchers believe that they are benign and should be treated conservatively,Reference Ito and Miyauchi2, Reference McDougall and Camargo4 while others report serious adverse consequences of papillary microcarcinoma and recommend appropriate treatment.Reference Pelizzo, Boschin, Toniato, Piotto, Bernante and Pagetta5–Reference Roti, Rossi, Trasforini, Bertelli, Ambrosio and Busutti7
The incidence of lymph node metastasis in papillary microcarcinoma patients varies considerably.Reference Chow, Law, Chan, Au, Yau and Lau6, Reference Baudin, Travagli, Ropers, Mancusi, Bruno-Bossio and Caillou8 Distant metastases to bone, lungs and brain have also been reported.Reference Chow, Law, Chan, Au, Yau and Lau6–Reference Lin, Chen, Chao, Hsueh and Weng12 In an autopsy series, lymph node metastases were found in 3.1–18.2 per cent of cases.Reference Chow, Law, Chan, Au, Yau and Lau6 In surgical series, rates of 13.5–64.1 per cent have been reported.Reference Ito and Miyauchi2, Reference Wada, Duh, Sugino, Iwasaki, Kameyama and Mimura13
Although it is evident from these studies that papillary carcinomas less than 10 mm in diameter can metastasise to lymph nodes,Reference Chow, Law, Chan, Au, Yau and Lau6, Reference Baudin, Travagli, Ropers, Mancusi, Bruno-Bossio and Caillou8 little is known about which specific tumour characteristics confer a greater risk of regional spread. Studies have shown lymph node metastasis of papillary microcarcinomas to be associated with tumour multifocality,Reference Chow, Law, Chan, Au, Yau and Lau6, Reference Baudin, Travagli, Ropers, Mancusi, Bruno-Bossio and Caillou8, Reference Wada, Duh, Sugino, Iwasaki, Kameyama and Mimura13–Reference Gülben, Berberoğlu, Çelen and Mersin15 tumour size,Reference Sampson, Oka, Key, Buncher and Iijima14, Reference Kasai and Sakamoto16 patient ageReference Pellegriti, Scollo, Lumera, Regalbuto, Vigneri and Belfiore17 and extrathyroidal invasion.Reference Sampson, Oka, Key, Buncher and Iijima14, Reference Gülben, Berberoğlu, Çelen and Mersin15, Reference Pellegriti, Scollo, Lumera, Regalbuto, Vigneri and Belfiore17 However, there are contradictory reports about which clinical and histopathological characteristics predict locoregional spread. This study aimed to (1) determine the incidence of lymph node metastasis in papillary microcarcinoma cases at a major university teaching hospital and (2) elucidate which papillary microcarcinoma characteristics are associated with lymph node involvement.
Methods
A retrospective review of 685 consecutive patients who underwent total thyroidectomy for both benign and malignant disease between January 2006 and December 2012 was performed by an experienced thyroid surgeon at a McGill University teaching hospital in Montreal, Canada. From 2006 onwards, all patients who underwent total thyroidectomy also underwent a modified central compartment neck dissection, regardless of pre-operative fine needle aspiration cytology (FNAC), to ensure the removal of any occult metastasis. This was done to avoid the increased morbidity associated with central neck dissection at a later date. Our investigation was approved by the hospital's Research Ethics Committee. An experienced thyroid cancer pathologist reviewed all histological specimens.
Patients were included if a papillary microcarcinoma was identified in a thyroid specimen. Diagnoses were made according to the World Health Organization Classification of Thyroid Tumors,Reference Hedinger, Williams and Sobin1 which defines papillary microcarcinoma as a lesion less than or equal to 10 mm in diameter, with no previous suspicion that the lesion is malignant. Patients with concurrent papillary carcinomas larger than 10 mm were excluded to ensure that all cases of lymph node metastasis resulted from extension of a papillary microcarcinoma. Patient demographics, tumour characteristics and central compartment lymph node status were noted.
Statistical analysis
We evaluated the influence of gender, patient age, tumour multifocality, presence of thyroid capsular invasion and tumour bilaterality on lymph node metastasis. To identify the clinical and histopathological variables affecting lymph node metastasis, the one-tailed Fisher's exact test was used for univariate analysis. A p value of less than 0.05 was considered significant. Results are expressed as mean ± standard deviation.
Results
The mean age of the 685 patients reviewed in this study was 53.62 ± 12.47 years (range 20–91 years). A total of 162 had benign disease, 353 had a non-papillary microcarcinoma malignancy and 170 had papillary microcarcinoma without a simultaneous papillary thyroid carcinoma less than 10 mm in size. The study population mainly consisted of females (84.7 per cent) and 65.3 per cent were older than 45 years. Of the suitable 170 patients, 72 (42.4 per cent) harboured multifocal disease and 28 (16.5 per cent) had bilateral tumours. Extrathyroidal extension of papillary microcarcinoma was present in 16 patients (9.4 per cent; Table I).
Table I Characteristics of Papillary Microcarcinoma Patients
PMC = papillary microcarcinoma
Furthermore, 23 patients (13.5 per cent; 4 males and 19 females) had central compartment lymph node metastases. Of these, 11 patients were aged 45 years or younger and 12 were older. Eleven patients had tumours that extended beyond the thyroid capsule, 12 had multifocal tumours and 7 had bilateral tumours (Table II).
Table II Characteristics of Patients with Lymph Node Metastases
*Number of patients with lymph node metastases out of the total number of papillary microcarcinoma patients with that particular characteristic. p < 0.05 is considered statistically significant
Associations between lymph node metastasis and gender, age, papillary microcarcinoma bilaterality and papillary microcarcinoma multifocality were not statistically significant (p > 0.05). In contrast, thyroid capsule invasion correlated significantly with lymph node metastasis (p = 0.0001).
Discussion
The incidence of papillary microcarcinoma is increasing in North America. Many authors attribute this finding to an increased detection of subclinical disease resulting from improved imaging techniques, rather than an actual increase in thyroid cancer incidence.Reference Roti, Rossi, Trasforini, Bertelli, Ambrosio and Busutti7, Reference Gülben, Berberoğlu, Çelen and Mersin15, Reference Davies and Welch18 Our group previously reported a papillary microcarcinoma rate of 49.9 per cent in a cohort of more than 800 thyroidectomy patients.Reference Pakdaman, Rochon, Gologan, Tamilia, Garfield and Hier19
There is considerable controversy regarding the most appropriate management of these tumours. Burman claims that the lack of long-term controlled data means that any suggested approach is, to a certain extent, simply an opinion.Reference Burman20 Prospective clinical trials to determine the optimal approach for papillary microcarcinoma management are difficult because, by definition, papillary microcarcinomas are incidental findings.Reference Gülben, Berberoğlu, Çelen and Mersin15, Reference Orsenigo, Beretta and Fiacco21 Previously, Ito et al. followed papillary microcarcinoma patients who chose observation with serial ultrasound over surgical management, and showed reduction or no change in tumour growth in 70 per cent over an average of 46 months.Reference Ito, Uruno, Nakano, Takamura, Miya and Kobayashi22 However, they also reported an incidence of lymph node metastasis greater than 50 per cent in patients who chose surgical management. It is firmly established that papillary microcarcinoma can metastasise to both lymph nodes and distant regions of the body.Reference Chow, Law, Chan, Au, Yau and Lau6–Reference Baudin, Travagli, Ropers, Mancusi, Bruno-Bossio and Caillou8, Reference Wada, Duh, Sugino, Iwasaki, Kameyama and Mimura13, Reference Gülben, Berberoğlu, Çelen and Mersin15–Reference Pellegriti, Scollo, Lumera, Regalbuto, Vigneri and Belfiore17 Thus, more definite management guidelines for papillary microcarcinoma patients, comprising routine follow up with ultrasound or surgical management, must be established.
We report a 13.5 per cent overall incidence of central compartment lymph node metastasis in patients with papillary microcarcinoma without concomitant papillary carcinoma who underwent central neck dissection. Lymph node metastasis rates of 3.1–18.2 per cent in autopsy studies and of 13.5–64.1 per cent in surgical series have been reported.Reference Ito and Miyauchi2, Reference Chow, Law, Chan, Au, Yau and Lau6 A strength of our study is the high degree of certainty regarding the incidence of lymph node metastasis because all patients undergoing total thyroidectomy also underwent central neck dissection.
There is growing interest in determining which clinical and histological characteristics of papillary microcarcinoma are associated with lymph node metastasis. We did not find a statistically significant effect of gender or age on lymph node involvement. However, some authors have reported a significantly increased risk in men compared with women,Reference Sampson, Oka, Key, Buncher and Iijima14 and in patients aged over 45 years.Reference Pellegriti, Scollo, Lumera, Regalbuto, Vigneri and Belfiore17
• Papillary microcarcinoma of the thyroid gland is an incidental finding of papillary carcinoma measuring 1 cm or less in diameter
• It is unclear which characteristics of papillary microcarcinoma predict lymph node metastasis
• We report a 13.5 per cent overall incidence of central compartment lymph node metastases in patients with papillary microcarcinoma
• For isolated papillary microcarcinoma without concomitant papillary carcinoma, thyroid capsule invasion is the only characteristic to correlate with lymph node metastasis
Previous studies identified multifocality as a prognostic factor for lymph node metastasis.Reference Chow, Law, Chan, Au, Yau and Lau6, Reference Baudin, Travagli, Ropers, Mancusi, Bruno-Bossio and Caillou8, Reference Wada, Duh, Sugino, Iwasaki, Kameyama and Mimura13–Reference Gülben, Berberoğlu, Çelen and Mersin15 Furthermore, increased aggressiveness has been reported for bilateral papillary microcarcinoma. Pellegriti et al. demonstrated that bilateral papillary microcarcinoma can be a strong prognostic indicator of persistent or recurrent disease.Reference Pellegriti, Scollo, Lumera, Regalbuto, Vigneri and Belfiore17 However, although bilateral disease was associated with a trend towards a higher percentage of lymph node metastasis, this was not statistically significant in our study.
Thyroid capsule invasion of papillary microcarcinoma is reported to be associated with lymph node metastasis.Reference Sampson, Oka, Key, Buncher and Iijima14, Reference Gülben, Berberoğlu, Çelen and Mersin15, Reference Pellegriti, Scollo, Lumera, Regalbuto, Vigneri and Belfiore17 Our study clearly demonstrates that in a large cohort of isolated papillary microcarcinoma patients without concomitant papillary carcinoma, thyroid capsule invasion is the only characteristic to correlate with lymph node metastasis. In our series of 170 patients, nearly 70 per cent of those with capsule invasion had lymph node metastases, whereas less than 10 per cent of those without capsule invasion had lymph node metastases.
Conclusion
Studies such as ours should provide clinicians with the tools to more objectively predict which patients may develop lymph node metastases. In cases with thyroid capsule invasion, additional cautionary measures should be added to the current recommendations for managing these tumours when central compartment dissection has not been undertaken during surgery. For instance, post-surgical ultrasonographic assessment and follow up of neck lymph nodes by a dedicated neck ultrasound specialist should be strongly encouraged. Standard management of suspicious lymph nodes, comprising FNAC and thyroglobulin measurement on needle washout, followed by surgical removal if positive, should follow. Furthermore, in selected cases, addressing the central compartment lymph nodes would essentially require a second operation regardless of imaging findings. In other cases, thyroid-stimulating hormone suppression and regular follow up with thyroglobulin may be all that is necessary.
