The occurrence of microcarcinomas in the patients after thyroidectomy – retrospective analysis

Summary

Background.
Microcarcinomas, minimum carcinomas, are tumors, which are in clinical practice defined as tumors ≤1cm in size. WHO defines thyroid microcarcinomas as tumors ≤ 2cm in size, which have different biological behavior. The aim of the study was to analyze the occurrence of MC in post-operative patients.

Methodology.
Using retrospective analysis we evaluated the occurrence of thyroid microcarcinoma in post-operative patients. Except for basic demographic data, carcinoma size and histological variance, we evaluated the occurrence of bilateral impairment, presence of multi-focuses and occurrence of regional throat metastases.

Results.
From 2004 to 2008 we performed thyroid surgeries in 400 patients. Microcarcinoma was diagnosed in 34 patients (8.5%); 5 men and 29 women. The average age of patients with microcarcinoma was 52 years, and unlike other patients undergoing surgery. Histologically, 32 cases (94%) were papillary carcinoma, from which 4 cases were papillary follicular and 2 were follicular carcinomas. There were multifocal findings of microcarcinomas in 5 patients (15%), and 4 patients (12%) had bilateral involvement. The average size of the tumors was 5mm, sd 2.6. Two patients (6%) had metastases in the lymph nodes of the neck. We carried out total thyroidectomies in 32 patients (94%) and hemithyroidectomies in 2 patients (6%). Five patients (15%), i. e. both patients with metastases in the lymph nodes of the neck and three patients with bilateral multifocal carcinomas underwent postoperative adjuvant radioiodine 131I ablation therapy.

Conclusion.
We do not consider microcarcinomas to be harmless, almost insignificant findings, due to the possibility of their future growth, metastasizing and reoccurrence. The increased risk of the MC occurrence was found in chronic lymphoplasmocellular thyroiditis (17%).

Key words:
Microcarcinoma - thyroidectomy- radiotherapy 131I

INTRODUCTION

In the last decades we have experienced a growing occurrence of little advanced forms of thyroid carcinomas, microcarcinomas (MC) (1,2,3). According to the WHO definition from 1974, these are tumors with a maximum diameter of < 2cm, which are surrounded by normal thyroid tissue with no capsular invasion or extrathyroidal spreading having occurred. Clinical manifestations and the biological behavior of thyroid microcarcinomas can vary from occult to aggressive, with locoregional metastases and local relapses. MCs are often accidental histopathological findings in glands operated on due to some benign disease. The first clinical manifestations of MC can also be an occurrence of metastases in the lymph nodes of the neck in so far occult gland tumor. Furthermore, there are microcarcinomas that could be revealed by an accidental sectional finding in glands of patients in which thyroid disease was not diagnosed during their life. According to some published data, MC found in sectional findings occurs in approximately 1-35% of total cases (2). The prognosis of patients with MC is generally good; the ten-year survival rate is around 93 % (2,3,4). We demonstrate the occurrence of microcarcinomas in post-operative patients and the most frequent histopathological changes in thyroid using the retrospective analysis for the period of 4 years.

METHOGOLOGY.

Retrospective analysis of thyroid microcarcinomas in patients having surgery at the Otolaryngology-Head and Neck Surgery Department of the “Nemocnice Na Homolce” Hospital. The endocrinologists there indicated surgeries and their scope, i.e. hemi- or total thyroidectomy, in patients with thyroid impairment. Patients approved their consent to the surgery and its scope by signing the “Informed Consent” form.

Except for the basic demographic data of patients (age and sex), we evaluated histopathological findings, multifocal and bilateral occurrence and presence of metastases in the neck lymph nodes.

Statistical Analysis

Category data are presented as absolute and relative. Hypothesis regarding the compliance in percentage presentation were tested using the Fisher’s exact test. The data were analyzed using the Stata package software, release 9.2 (Stata Corp.LP, College Station, USA). All procedures and protocols were in conformance with the Declaration of Helsinki. The Ethical Committee of the “Nemocnice na Homolce” Hospital agrees with the presentation of the data herein.

RESULTS

In the period from 2004 to 2008, 400 patients (66 men and 334 women) underwent thyroid surgeries. Benign lesions were diagnosed in 336 patients (84%) who had undergone surgery, malignant tumors in 30 patients (7.5%) and microcarcinoma was verified in 34 patients (8.5%), out of which 29 were women and 5 men. The risk of the MC occurrence was almost identical (p=0.497) in both sexes in case of the thyroid impairment. The average age of patients was 52 years ± 11.6 (range 30-78 years) and unlike in other patients that had undergone surgery. During preoperative fine needle aspiration biopsy examinations under US control, MC was verified in 10 patients (29.4%). There were accidental MC findings during postoperative histopathological thyroid examinations in 23 patients (67.6%). In one case (2.9%), the MC was diagnosed based on the examination of metastasis resected from a lymph node of the neck, see Table 1. Pathological anatomical changes in thyroid, due to which patients were indicated for surgery; in 76 cases there were single nodule and in 172 cases multinodular goiters, in 76 cases thyreotoxicosis and in 12 cases chronic lymphoplasmocytic thyroiditis, see table 2. Papillary carcinoma was found in 32 patients (94%), out of which 4 cases were papillary follicular carcinoma subtypes; follicular carcinoma was found in 2 patients (5.8%). The average MC size was 5 mm, sd 2.6 mm; in two-thirds of patients, the carcinoma size was 2 to 7 mm and a third ranged between 8 and 10 mm. Multifocal occurrence of MC (2 - 4 focuses) was detected in 5 patients (15%), out of which one was unilateral and four bilateral. Two patients (6%) had metastases in the neck lymph nodes, and two patients (6%) had both MC and lung carcinoma. A total thyroidectomy was carried out in 32 patients (94%), out of which 6 underwent two-stage surgeries and 2 had (6%) hemithyroidectomies. Five patients (15%), i.e. both patients with locoregional metastases and 3 patients with bilateral multifocal microcarcinomas received postoperative adjuvant radioiodine 131I therapy. The average monitoring period was 28.1 months (range 2 - 69 months), sd 22.8 and median 20.7, and included a controlled ultrasonography of the neck and a laboratory examination of thyreoglobulin (TGL). During the monitored period, no local relapse or distant metastases occurred.

DISCUSSION

An ultrasound-guided fine needle biopsy of the nodal goiter is essential for the determination of its biological character. When a sufficient cell tissue sample is obtained and assessed by an experienced cytopathologist, the sensitivity and specificity of the method exceeds 85% (5). Despite this, most MCs are only diagnosed during histopathological examinations. MCs exhibit a varied biological behavior. Most authors regard microcarcinomas as significant lesions leading to both morbidity and lethality (3). We had only one case of papillary microcarcinoma with an aggressive behavior in our set, when a 2 mm tumor metastasized into a jugulo-carotid lymph node, which was the first clinical manifestation. Roli et al. and other authors consider the tumor size to be a significant risk factor of metastases in lymph nodes of the neck (6). No metastases were found in tumors under 8 mm in size, whereas in larger ones metastases did occur. Our second patient with locoregional metastases had multifocal, bilateral MCs with focuses of 5-7mm on one side and 8-10 mm on the other side. Except for tumor size, other risk factors of locoregional metastases are follicular variants of papillary carcinoma (7). Roli et al. report incidental MC findings during histopathological examinations when treating, until then, benign thyreopathy in 21.4% of the cases; in our set they constituted almost 68% of the cases (6). Roli and Sakorafas report the occurrence of minimum carcinomas in the form of occult tumors during thyroid autopsies in 36% of cases (6,8). In 1985 Harach et al. revealed high incidences (77%) of MC during thyroid autopsies with findings spread evenly through the individual life stages (9). There are geographical differences in MC incidences, which are determined genetically and environmentally. Furthermore, they are influenced by the use of histopathological examination methods (10). Lupoli states that prevalence of familiar non-medullary thyroid carcinomas ranges between 3.5 and 6.2%, and their biological behavior is more aggressive with a much worse prognosis than in cases of sporadically occurring carcinomas (11). Most surgeons accept total thyroidectomy as a consensus treatment. The reasons are the high incidence of multifocal and bilateral MC findings, decreasing the risk of local recurrence by removing the central compartment lymph nodes; easier postoperative and post-radiation monitoring of plasma thyreoglobulin (TGL); and easier ultrasonographic detection of neck metastases (12). Dvořák et al. recommended total thyroidectomy in patients older than 65 years and with a tumour □≤ 1 cm; TTE together with postoperative adjuvant 131I therapy in patients younger than 65 years with bilateral or multifocal occurrence of MC; and TTE together with selective modified neck dissection and postoperative adjuvant 131I therapy in patients with metastases in regional lymph nodes of the neck. Patients with multifocal occurrence of carcinomas and tumors ≥ 1 cm must be subjected to the postoperative L-thyroxine suppression therapy and close follow-ups monitoring TSH, fT4 and TGL, as well as ultrasonographic examination once in every six months. A sufficient follow-up of other patients with MC is once a year (3). The most frequent histological type of thyroid carcinoma is its papillary form, which occurs in 65% - 99% of cases, and we obtained corresponding results (94%). Bramley et al. state that 30% of papillary carcinomas are papillary microcarcinomas (1). Follicular variant of papillary carcinoma occurred in 6% of cases.

CONCLUSION

Women and age over 45 are the thyroid impairment risk group. We regard microcarcinomas as clinically serous lesions that must be radically solved and patients must be subjected to close follow-ups. As for the pathological anatomical changes in thyroid, the most frequent MC occurrence was found in patients with chronic lymphoplasmocellular thyroiditis (17%).

Abbreviations used:

• FNAB -Fine-needle aspiration biopsy
• MC - microcarcinoma
• WHO - World Health Organization
• sd - standard deviation
• TTE - total thyroidectomy
• nTTE -near- total thyroidectomy
• TSH - thyroid stimulating hormone
• fT4 -thyroxine free
• TGL - thyroglobulin

The authors would like to thank prof. MUDr. J. Dvořák , Ph.D., from Oddělení chirurgie Karlovarské krajské nemocnice for obtain comments.