Cervical Lymph Node Fine-Needle Aspiration and Needle-Wash Thyroglobulin Reflex Test for Papillary Thyroid Carcinoma

Fine-needle aspiration (FNA) cytology coupled with needle-wash thyroglobulin (FNA-Tg) testing is recommended for cervical lymph node (LN) biopsies in patients with a history of papillary thyroid carcinoma (PTC). However, the procedure has not been standardized with the assay for FNA-Tg testing. A standard operating procedure (SOP) has been generated at our facility for cervical LN FNAs with Tg reflex testing on patients with a history of PTC. The procedure requires FNA cytology to be reviewed first, and all cases not positive for PTC are reflexed for FNA-Tg testing with the Beckman Access thyroglobulin assay. The thyroglobulin cutoff value is ≤ 1.0 ng/mL. From 2016 to 2017, 117 patients, including 71 women and 46 men, were identified as having a history of PTC. Patients' clinical characteristics were collected from medical records. A total of 143 LN biopsies were investigated for these patients. The results show that four out of 11 (36.4%) non-diagnostic LNs and five out of five (100%) atypical/suspicious LNs tested positive for FNA-Tg. Among these nine patients with positive thyroglobulin testing, LN metastases were proven histologically for all nine patients, and two patients were treated with LN ablation. Out of 68 LNs positive for PTC, three had FNA-Tg results. FNA-Tg testing was ordered for unknown reasons on two positive LNs (> 5000 ng/mL thyroglobulin) from one patient. The third LN was tested due to non-classic morphology, and the result was less than the cutoff value. Three patients with negative LN biopsies were tested to have elevated (> 1.0 ng/mL) thyroglobulin levels. One patient (FNA-Tg ng/mL) was proven to have multiple metastatic LNs through follow-up surgery. However, no positive LN was identified for the other two patients who had FNA-Tg level of 4.1 ng/mL and 37 ng/mL respectively. This is likely due to contamination, as these two patients had intact thyroids. In our practice, the FNA-Tg test is a very useful adjunct test to LN FNA specimens with a non-positive diagnosis in patients with a history of PTC. Furthermore, FNA-Tg testing increases diagnostic sensitivity among non-diagnostic and atypical/suspicious LNs. However, FNA-Tg testing should not substitute conventional cytology due to the following reasons: (1) false-negative thyroglobulin lab results; (2) PTC with loss of thyroglobulin expression; (3) LN metastasis from other origins; and (4) false-positive thyroglobulin testing due to blood contamination in patients who are not completely athyrotic.