Thyroglobulin, Tumor Marker, Fine-Needle Aspiration (FNA)-Needle Wash, Lymph Node
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Thyroglobulin (Tg) is a 660,000 molecular weight glycoprotein produced exclusively by the follicular cells of the thyroid. It is secreted into the follicular lumen, where it serves as the precursor of, and storage reservoir for, thyroxine (T4) and triiodothyronine (T3). T4 and T3 are released after Tg is endocytosed and proteolytically degraded in the thyrocyte. Since Tg is produced only by follicular thyrocyte-derived cells, measurement of serum Tg levels in athyrotic patients enables detection of persistence, recurrence, or metastasis of differentiated thyroid carcinoma. In addition, because of the thyroid specificity of Tg, its measurement in biopsy specimens of nonthyroidal tissues may assist in confirming and localizing metastatic disease.
In the most common type of thyroid cancer, papillary thyroid carcinoma (PTC), >80% of all thyroid cancer cases, most metastatic disease occurs in loco-regional lymph nodes in the neck, which are easily examined by ultrasound. Most suspicious nodes undergo ultrasonography-guided fine-needle aspiration (FNA) cytology to determine a diagnosis. Unfortunately, in up to 20% of the specimens, inadequate cellularity or nonrepresentative sampling precludes the diagnosis.
Several studies have reported that the detection of Tg in fine needle aspiration (FNA)-needle washes improves the evaluation of suspicious lymph nodes in patients with differentiated thyroid carcinoma.(1-3) A recent study reported that a Tg cutoff of 1 ng/mL for FNA-needle wash specimens provided 100% sensitivity and 96.2% specificity for the detection of metastatic thyroid carcinoma in lymph nodes.(3) The diagnostic performance of needle wash Tg at the 1-ng/mL cutoff compared favorably with cytology (95.1% overall agreement) and allowed accurate diagnosis in 18 of the 19 cases in which cytology was nondiagnostic or not performed.(3) Additionally, when measuring Tg in FNA-needle wash specimens, the clinical performance of FNA Tg is unaffected by the presence of Tg antibodies, a frequent problem when measuring Tg levels in serum.
Cytologic examination and measurement of Tg can be performed on the same specimen. To measure Tg, the FNA needle is rinsed with a small volume of normal saline solution immediately after a specimen for cytological examination has been expelled from the needle for a smear or CytoTrap preparation. Tg levels are measured in the needle wash.
An adjunct to cytologic examination of fine-needle aspiration specimens in athyrotic individuals treated for differentiated thyroid cancer, to confirm or exclude metastases in enlarged or ultrasonographically suspicious lymph nodes
In athyrotic patients with a history of differentiated thyroid carcinoma, a fine-needle aspiration (FNA)-Tg value >1.0 ng/mL suggests the presence of metastatic differentiated follicular cell-derived thyroid carcinoma in the biopsied area.
FNA-Tg measurements yield reliable results in most cases with nondiagnostic cytology, and are approximately equal in diagnostic accuracy to cytological examinations that are deemed sufficient for diagnosis.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Fine-needle aspiration (FNA)-Tg should not be used to screen asymptomatic individuals for neoplastic disease.
This test has been validated only in single lymph nodes from athyrotic patients. While the needle washes from several distinct needle passes or aspirations from a single node should be pooled, biopsies from different nodes should be submitted as separate specimens.
For specimens from other sources, contact Mayo Medical Laboratories.
Do not interpret FNA-Tg levels as absolute evidence of the presence or absence of malignant disease. Results should be used in conjunction with information from the clinical evaluation of the patient, cytology, and imaging procedures.
Immunometric assays can, in rare occasions, be subject to interferences such as "hooking" at very high analyte concentrations (false-low results) and heterophilic antibody interference (false-high results). If the clinical picture does not fit the laboratory result, these possibilities should be considered. While autoantibody interference (typically false-low results in immunometric assays) is reported to not be an issue in FNA-needle wash specimens, the report was based on a small number of cases; therefore, the possibility of autoantibody interference should also be considered.
Results are dependent on accurate sampling and a maximum needle wash volume of < or =1.5 mL.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
< or =1.0 ng/mL
This cutoff has been validated for total needle wash volumes of < or =1.5 mL of normal saline. If wash volumes are substantially larger, a lower cutoff might apply.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Pacini F, Fugazzola L, Lippi F, et al: Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses: a clue to the diagnosis of metastatic differentiated thyroid cancer. J Clin Endocrinol Metab 1992;74(6):1401-1404
2. Frasoldati A, Toschi E, Zini M, et al: Role of thyroglobulin measurement in fine-needle aspiration biopsies of cervical lymph nodes in patients with differentiated thyroid cancer. Thyroid 1999;9(2):105-111
3. Snozek CL, Chambers EP, Reading CC, et al: Serum thyroglobulin, high-resolution ultrasound, and lymph node thyroglobulin in diagnosis of differentiated thyroid carcinoma nodal metastases. J Clin Endocrinol Metab 2007;92(11):4278-4281