Management of solitary thyroid nodules: the dilemma of multinodular goiter as false-positive cases.

Mohammad Talepoor, MD; Assistant professor of Surgery, Tehran University of Medical Sciences, Tehran, Iran.

Mojgan Karbakhsh, MD, MPH; Assistant professor of Community medicine, Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Fath-Ali Mirzaii, MD; investigator, Tehran University of Medical Sciences, Tehran, Iran.

Moosa Zargar, MD; Associate professor of Surgery; Head, Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Introduction:

Thyroid nodules are common, with a reported prevalence of about 4-7 percent. (1,2). This prevalence has been derived from a non-goitrous areas and may be much higher in areas of iodine deficiency (1), like our country, Iran. Malignancy may exist in 5 (2 ) to as many as 30%(3) of all palpable solitary nodules; thus great emphasis is placed upon finding diagnostic modalities that may improve the ability to differentiate between benign and malignant conditions, to avoid unnecessary extensive procedures and repeated operations(3). Pre-operative assessment of thyroid nodules in generally performed by radio- nuclide scanning and fine needle aspiration (FNA). FNA biopsy is described as the most preferred test that has improved selection of patients for thyroid surgery (4).This study aims to review the existing protocol for the management of solitary thyroid nodules in our country and to assess the accuracy of the available diagnostic modalities in appropriate selection of patients.

Materials and Methods:

The records of all consecutive patients presenting with solitary thyroid nodules who underwent surgery from 1992 to 1997 in Imam Khomeini hospital were reviewed. We excluded the cases that lacked the final histologic result of the thyroid nodule. Thus, 400 patients entered the study. According to the final histologic report, patients were categorized into four diagnostic groups:1) benign solitary nodule,2) benign multinodular goiter, 3) malignant solitary nodule and 4) malignant multinodular goiter. Fine-needle aspiration (FNA) diagnoses were also placed into three categories: benign, malignant and suspicious. The existing protocol involves history, clinical examination, fine needle aspiration of the lesion, redionucleide scan, and excision whenever indicated. SPSS version 10 was used for statistical analysis. α = 0.05 was considered as the level of significance.

Results:

Mean age of our patients was 38.6 years (± 13.5). Women comprised 78% of our cases (n=312). Malignancy was detected in 18.8% of cases (n=75) among which 15.8% (n=63) were reported as malignant solitary nodule and 3% (n=12) as malignant multinodular goiter. Other pathologic reports of cases were benign solitary nodule in 29.3% (n=113), benign multinodular goiter in 49.5% (n=198) and others (like GraveÕs thyroiditis) in 2.5% (n=10).

74.7% of malignant cases were female (n=56). The most common malignancy was papillary carcinoma in 73.3% (n=55), followed by follicular carcinoma in 16% (n=12), medullary carcinoma in 4% (n=3) and other malignancies in 6.7% (n=5).

144 cases had an FNA report of the nodule. The FNA repord was ÒfollicularÓ in 72.9% (n=105), ÒmalignantÓ in 8.3% (n=12) and ÒsuspiciousÓ in 18.8% (n=27).Table 1 demonstrates the results of FNA compared with the final histological findings.

According to this table, the sensitivity of FNA in detecting malignancy would be 25 %. If we consider suspicious results in malignant group the sensitivity would rise to 70%.

A significant relationship was observed between the pathologic report of specimens and the time after the nodule had been present (according to the patientÕs report) (P=0.02)(Table 2).

375 of our cases had a report of thyroid radionuclide scan in their records. Table 3 demonstrates thyroid scan reports compared with the final hystologic findings. According to this table, the sensitivity and positive predictive value of thyroid scan were 91.4 and 20%, respectively.

The most common type of surgery among our series was right lobectomy isthmectomy in 53.3%, followed by left lobectomy-isthmectomy in 26%, subtotal thyroidectomy in 16.3%, isthmectomy or nodulectomy in 2.8%, total thyroidectomy in 1.3% and near total thyroidectomy in 0.8%. Table 4 demonstrates the frequency distribution of cases according to the type of surgery and the final histologic report.

Discussion:

Thyroid nodules are said to be the most common condition presenting to the endocrine surgeon and may be a feature of many thyroid disease processes (1). The high prevalence of multinodular goiter in the countries where goiter is endemic complicates the selection of patients presenting with solitary nodules for surgery(4).

Nevertheless, itÕs said that a careful, selective approach to diagnosis and treatment of thyroid nodules can increase a cancer yield of 15% to 20 and even 50 %(1). In our study malignancy was detected in 18.8% of cases selected for operation for a solitary thyroid nodule. This percentage is higher than results of two unpublished results in the same hospital (Imam Khomeini hospital) (10.2% and 12%) (5-6).

Fine-needle aspiration biopsy is considered as the most cost-effective, safe and reliable examination for the evaluation of a thyroid nodule (7-9). It is reported to have a sensitivity of 65 to 98 percent (over all 83%) and a specificity of 72 to 100 percent (over all 92%), which is influenced by the categorization of ÒsuspiciousÓ results (10). If ÒsuspicionsÓ findings are considered positive (= malignant), the sensitivity will increase (e.g. in our study it increased from 25% to 70%). False negative results are of special concern because of fear of missed malignancy. The reported false-negative rate of FNA (1-sensitivity) is between 1 to 9% (4), which was as high as 30% in our setting (even if we consider suspicious results as positive).In a similar study in Turkey, rather low performance of FNA was attributed to lack of expertise of pathologists who routinely read FNA specimens in developing countries (4).

Considering the performance of isothope scans, finding a hot nodule makes malignancy unlikely (due to its higher sensitivity than FNA in our setting). Nevertheles, it is still probable that in some cases a cold focus of cancer be adjacent to a benign hot lesion, so the scan report would be wrongly interpreted(1).

As supported elsewhere (11), in our study, a history of rapid increase in size was related with the malignant nature of a thyroid nodule.

Considering final histologic finding, for detecting 63 malignancy among (really) solitary nodules, 113 benign solitary nodules had also been operated upon (odds=1.8). In comparison, 198 benign multinodular goiter had an unnecessary operation in order to find 12 cases with malignancy in multinodular goiter (odds=16.5).To put it another way, if we could put aside multinodular goiters in the approach to Òclinically detectedÓ solitary thyroid nodules and operate for ÒrealÓ solitary thyroid nodules, the yield of cancer detection would significantly rise (to about 35%).

On the other hand, only 35 out of 198 cases with benign multinodular goiter(17.7%) in this protocol had sustained an appropriate surgical procedure (subtotal, total or near total thyroidectomy); the rest of these cases(n=163) needed a re-operation for their multinodular goiter.

In conclusion, the current protocol could not effectively isolate benign from malignant disease. This is similar to SardaÕs report from an endemic goitrous area (16). The problem of multinodular goiters sustaining operation as solitary thyroid noules also mandates special attention or revision of current protocols. We see that there is still a need for an approach that improves the yield of patient selection for surgical approach to solitary thyroid nodule, especially in areas where iodine-deficiency is endemic. For example, ultrasonography allows a clear delineation of multonodularity(13) and could help in ruling our multinodular goiter before trying fine needle aspiration for thyroid nodules(14,15).

References

1) Wong CK, Wheeler MH. Thyroid nodules: rational management. World J Surg. 2000 Aug;24(8):934-41.

2) Welker MJ, Orlov D. Thyroid nodules. Am Fam Physician. 2003 Feb 1;67(3):559-66.

3) Duek SD, Goldenberg D, Linn S, Krausz MM, Hershko DD. The role of fine-needle aspiration and intraoperative frozen section in the surgical management of solitary thyroid nodules. Surg Today. 2002;32(10):857-61.

4) Taneri F, Poyraz A, Tekin E, Ersoy E, Dursun A. Accuracy and Significance of Fine-Needle Aspiration Cytology and Frozen Section in Thyroid Surgery. Endocr Regul. 1998 Dec;32(4):187-191.

5) Kasaian R. The study of 765 solitary cold thyroid nodules operated upon in Imam Khomeini hospital from 1979-1989. Thesis for an MD degree. Tehran University of Medical Sciences, Tehran, Iran, 1990.

6) Faraji, S. The frequency of malignancy among cold thyroid nodules operated upon in Imam Khomeini hospital from 1990-1994. Thesis for an MD degree. Tehran University of Medical Sciences, Tehran, Iran, 1994.

7) Moisson-Meer A, Franc B, Duprey J, Goeau-Brissonniere O, Sultan M, Lifchitz E, Ducornet B. Reliability of needle biopsy of solitary thyroid nodules in view of surgical indications. Rev Med Interne. 1996;17(9):732-7.

8) Kaur K; Sonkhya N; Bapna AS; Mital P A comparative study of fine needle aspiration cytology, Ultrasonography and radionuclide scan in the management of solitary thyroid nodule : a prospective analysis of fifty cases.Indian Journal of Otolaryngology and Head and Neck Surgery. 2002 Apr-Jun; 54(2): 96-101

9) Kim N, Lavertu P. Evaluation of a thyroid nodule. Otolaryngol Clin North Am. 2003 Feb;36(1):17-33.

10)Gharib H. Fine needle aspiration biopsy of thyroid: an appraisal. Ann Int Med 1993;118:282–289

11)Fraker DL, Skarulis M, Livolsi V. Thyroid tumors In: Devia VT, Hellman S, Rosenberg S. Cancer: Principles and Practice of Oncology, Philadelphia, Lippincott Williams and Wilkins, Section 38.2, 6^th edition, 2001.

12)Sarda AK, Gupta A, Jain PK, Prasad S. Management options for solitary thyroid nodules in an endemic goitrous area. Postgrad Med J. 1997 Sep;73(863):560-4

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14)Tomimori EK, Camargo RY, Bisi H, Medeiros-Neto G. Combined ultrasonographic and cytological studies in the diagnosis of thyroid nodules. Biochimie. 1999 May;81(5):447-52.

15)Peccin S, de Castsro JA, Furlanetto TW, Furtado AP, Brasil BA, Czepielewski MA. Ultrasonography: is it useful in the diagnosis of cancer in thyroid nodules? J Endocrinol Invest. 2002 Jan;25(1):39-43.

Table 1. Results of Fine-Needle Aspiration and Corresponding final histology.

	Benign		Malignant	Total
Final histology	Solitary nodule	Multinodular goiter	Malignant	Total
FNA Follicular lesion	14	85	6	105
Malignant lesion	3	4	5	12
Suspicious	5	12	9	26
Total	22	101	20	143

Table 2. Frequency distribution of cases according to the pathologic report and the time lapse after the nodule has developed.

	Pathologic report		Total
Time	benign	malignant	Total
< 1 year	69	28	97
1-5 years	117	16	133
> 5 years	49	5	54
Total	235	49	284

Table 3. Results of radionuclide thyroid scan and the corresponding final histology.

	Benign
Final histology	Solitary nodule	Multinodular goiter	Malignant	Total
Thyroid Scan Report
Cold nodule	105	151	64	320
Hot nodule	7	19	0	26
Multinodular goiter	2	21	6	29
Total	114	191	70	375

Table 4. Frequency distribution of cases according to the type of surgery and the final histologic report

	Benign
Final histology	Solitary nodule	Multinodular goiter	Malignant	Total
Type of Surgery
Lobectomy- Isthmectomy	105	158	46	309
Thyroidectomy (subtotal total, near total)	9	35	27	71
Isthmectomy or/ nodulectomy	3	5	2	10
Total	117	198	75	390

First Published in Medicine On-Line January 2005

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