Correspondence

Solitary Thyroid Nodules

N Engl J Med 1993; 329:360-361July 29, 1993

Article

To the Editor:

Dr. Mazzaferri (Feb. 25 issue)1 recommends the use of radionuclide scanning when fine-needle aspiration biopsy yields indeterminate results in the evaluation of a solitary thyroid nodule. This is done to identify hot nodules that can then be observed or treated medically. A hot nodule, by definition, autonomously secretes thyroxine in sufficient quantity to suppress thyroid-stimulating hormone (TSH), with the result that the presumably normal extranodular thyroid tissue shows no uptake on scintigraphic scanning2. Thus, a hot nodule shows uptake only in the region of the nodule.

A more cost-effective method of screening would be to use a sensitive test for TSH, with thyroid scintigraphy ordered only when the test reveals below-normal TSH levels. Given 100 thyroid nodules that are read as indeterminate on fine-needle aspiration biopsy and assuming that hot nodules constitute 5 percent of all thyroid nodules,3 Mazzaferri's approach will lead to 100 thyroid scans (at a cost of roughly $200 per scan in our hospital) performed to detect five hot nodules. Using a sensitive test for TSH (at a cost of roughly $10 per test) as an initial screening method, followed by a thyroid scan only in cases of a lower-than-normal TSH level, will result in 100 TSH assays and seven scans, assuming a false positive rate of 2 percent on the sensitive TSH test (results below normal limits in euthyroid persons and excluding persons being treated with levothyroxine)4. The total cost with the first approach is $20,000; with the second, it is $2,400.

Kevin Tong, M.D.
Wilford Hall Medical Center, Lackland Air Force Base, TX 78236

4 References

1. 1

   Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med 1993;328:553-559
   Full Text | Web of Science | Medline

2. 2

   Hamburger JI. The autonomously functioning thyroid nodule: Goetsch's disease. Endocr Rev 1987;8:439-447
   CrossRef | Web of Science | Medline

3. 3

   Rojeski MT, Gharib H. Nodular thyroid disease: evaluation and management. N Engl J Med 1985;313:428-436
   Full Text | Web of Science | Medline

4. 4

   Sawin CT, Geller A, Kaplan MM, Bacharach P, Wilson PWF, Hershman JM. Low serum thyrotropin (thyroid-stimulating hormone) in older persons without hyperthyroidism. Arch Intern Med 1991;151:165-168
   CrossRef | Web of Science | Medline

To the Editor:

In reporting cytologic results of fine-needle aspiration biopsy, pathologists are likely to be conservative; when in the least doubt, they label the lesion suspicious or indicate that “cancer cannot be excluded.” Mazzaferri indicates that from 10 to 20 percent of cytologic specimens are labeled indeterminate. In my judgment the figure is higher, and an additional 3 to 6 percent are false positives. Confronted by such a report, the physician is also likely to be conservative -- i.e., to recommend surgery for the nodule.

. . . Even if every nodule were correctly identified as a carcinoma and no lesions were labeled indeterminate, physicians should be reminded that the pathologists' criteria for a diagnosis of papillary or follicular carcinoma of the thyroid bear little relation to the biologic features of these tumors. The cytologic criteria for cancer are inadequate for identifying clinically aggressive disease. Thyroid cancer is an uncommon cause of death from cancer; only 1200 patients die of this disease each year in the United States, and half of these deaths are due to anaplastic lesions, which do not present as nodules.

Robert I. Gregerman, M.D.
Audie L. Murphy Memorial Veterans Affairs Hospital, San Antonio, TX 78284

To the Editor:

Large-needle biopsy of solitary thyroid nodules may have a greater role than Dr. Mazzaferri suggests. The main advantage of the technique is that it is more accurate than fine-needle aspiration in the diagnosis of benign disease. Large-needle biopsy allows purely microfollicular lesions, which are sometimes malignant, to be distinguished from microfollicular-macrofollicular lesions, which are usually benign1. Large-needle biopsy may help differentiate benign cystic thyroid lesions from malignant lesions by allowing biopsy of the wall of the cyst2. Finally, the use of large-needle biopsy in conjunction with fine-needle aspiration biopsy increases the percentage of cancers found in thyroidectomies performed to rule out cancer in patients with dominant or solitary nodules3,4.

Large-needle biopsy should be performed by an experienced thyroid surgeon who is prepared to treat the small number of complications that occur. The chief limitation is that for technical reasons, large-needle biopsy can be performed on only two thirds of solid lesions4.

Beth Ann Zarkin, M.D.
John A. Chabot, M.D.
Paul Lo Gerfo, M.D.
Columbia-Presbyterian Medical Center, New York, NY 10032

4 References

1. 1

   Carpi A, Toni MG, Nicolini A, Sagripanti A, Di Coscio G, Shapiro B. Progress in the management of thyroid nodule patients. In: Carpi A, Sagripanti A, Mittermayer C, eds. Oncology: progress in clinical oncology. Vol. 1. Munich, Germany: Sympomed Medical Publishers, 1992:204-21.
   

2. 2

   Lo Gerfo P, Ting W. Method for biopsy of the wall of a thyroid cyst. Am J Surg 1983;146:383-384
   CrossRef | Web of Science | Medline

3. 3

   Lo Gerfo P, Colacchio T, Caushaj F, Weber C, Feind C. Comparison of fine-needle and coarse-needle biopsies in evaluating thyroid nodules. Surgery 1982;92:835-838
   Web of Science | Medline

4. 4

   Lo Gerfo P, Starker P, Weber C, Moore D, Feind C. Incidence of cancer in surgically treated thyroid nodules based on method of selection. Surgery 1985;98:1197-1201
   Web of Science | Medline

To the Editor:

Serum calcium should probably be measured before the aspiration of a thyroid nodule. The presence of concomitant primary hyperparathyroidism may mandate neck exploration, in which case aspiration of the nodule would be redundant. If the serum calcium level is markedly elevated, the thyroid nodule will require immediate surgical attention, since it could represent a parathyroid carcinoma, in which case aspiration would be not only redundant but also potentially dangerous. Fine-needle aspiration of a thyroid cancer does not predispose a patient to local recurrence, but similar data are not available for parathyroid carcinomas.

Dr. Mazzaferri notes that cytologic examination of cystic fluid is often not diagnostic, because an insufficient number of cells are present. Our policy is to centrifuge the fluid in a rapid-spin centrifuge and to use the cell pellet for cytologic examination.

Lawrence E. Mallette, M.D., Ph.D.
Baylor College of Medicine, Houston, TX 77030

Author/Editor Response

Dr. Mazzaferri replies:

To the Editor: Dr. Zarkin and colleagues argue that large-needle biopsy is more accurate than fine-needle aspiration biopsy. This conclusion is not substantiated by their 1982 study. The false negative rate (missed diagnoses of cancer) was higher with large-needle biopsy than with fine-needle aspiration biopsy (3.7 percent vs. 0 percent) when both were performed on the same nodules; moreover, the true positive rate for the diagnosis of thyroid adenoma was lower with large-needle biopsy. Both procedures have a low accuracy rate in the diagnosis of follicular tumors1-3 because it is impossible to identify a benign lesion by needle biopsy. This can only be done by carefully examining the capsule and blood vessels of the lesion in histologic sections to exclude the possibility of tumor invasion. The paper cited does not substantiate the claim that cutting-needle biopsy is superior to fine-needle aspiration in the management of cystic thyroid lesions. The paper simply describes the technique; it gives no information about false negative results, an important problem with cystic lesions4. It states, however, that cystic lesions “often filled quite quickly with blood” after biopsy with a 14-gauge needle. In contrast, half the cystic lesions aspirated with a fine needle do not accumulate fluid again4. It is not the general experience that large-needle biopsy increases the percentage of cancers found in surgically excised nodules5. I agree that this technique cannot be used in small or inaccessible nodules deep in the neck and that it may cause serious hemorrhage.

With Dr. Tong's proposed screening strategy, more patients with hyperfunctioning nodules would undergo surgery, since over half are not initially thyrotoxic. This would add to, not reduce, the cost of management without substantially increasing the yield of cancer.

Dr. Gregerman suggests that an unnecessarily large number of patients will undergo thyroid surgery with the management strategy I proposed. There is abundant and convincing evidence, however, that about half as many patients now undergo thyroidectomy for thyroid nodules as did so before the wide use of fine-needle aspiration biopsy. The incidence of cancer has clearly increased in those undergoing surgery5.

I agree with Dr. Mallette's suggestion that serum calcium should be measured. I favor a more selective approach, measuring serum calcium in patients with symptoms of hypercalcemia, in those with cystic nodules without a clear diagnosis, and in those undergoing thyroidectomy. My colleagues and I also centrifuge the fluid from cystic aspirates and use the cell pellets for cytologic examination.

Ernest L. Mazzaferri, M.D.
Ohio State University Hospital, Columbus, OH 43210

5 References

1. 1

   Silverman JF, West RL, Finley JL, et al. Fine-needle aspiration versus large-needle biopsy or cutting biopsy in evaluation of thyroid nodules. Diagn Cytopathol 1986;2:25-30
   CrossRef | Medline

2. 2

   Miller JM, Kini SR, Hamburger JI. The diagnosis of malignant follicular neoplasms of the thyroid by needle biopsy. Cancer 1985;55:2812-2817
   CrossRef | Web of Science | Medline

3. 3

   Nishiyama RH, Bigos ST, Goldfarb WB, Flynn SD, Taxiarchis LN. The efficacy of simultaneous fine-needle aspiration and large-needle biopsy of the thyroid gland. Surgery 1986;100:1133-1137
   Web of Science | Medline

4. 4

   de los Santos ET, Keyhani Rofagha S, Cunningham JJ, Mazzaferri EL. Cystic thyroid nodules: the dilemma of malignant lesions. Arch Intern Med 1990;150:1422-1427
   CrossRef | Web of Science | Medline

5. 5

   Gharib H, Goellner JR. Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med 1993;118:282-289
   Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   Desmond Kwan-Kit Chan, Brian Hung-Hin Lang, Tsz-Ting Law. (2011) Value of fluorodeoxyglucose positron emission tomography in characterizing clinically-significant thyroid carcinomas. Surgical Practice 15:2, 34-40
   CrossRef

2. 2

   Angelo Carpi, Andrea Nicolini, Andrea Sagripanti. (1999) Protocols for the Preoperative Selection of Palpable Thyroid Nodules. American Journal of Clinical Oncology: Cancer Clinical Trials 22:5, 499
   CrossRef