The Ratio of Thyroglobulin in Wash-Out Fluid From Fine-Needle Aspiration to Serum Thyroglobulin Level in the Evaluation of Metastatic Cervical Lymph Nodes in Patients With Papillary Thyroid Cancer
Authors: Ibraheem Hamad Mohammad Khair Ahmad , Shdid Reham Abo , Saleh Ahmed Osman , El Mabrok Abufaied Mohamad Mahmoud , Jaber Tania , Farghaly Hanan , Rohani Zaina Seros , Zirie Mahmoud A , Naem Emad 
Published: May 2021

Abstract
Fine needle aspiration with cytology analysis and thyroglobulin level of the aspirated biopsy (FNAB-Tg), is an important tool to assess metastasis to cervical lymph nodes (CLN) in patients with papillary thyroid cancer (PTC) who have suspicious lymph node features on ultrasound. Despite the great diagnostic accuracy of the FNAB-Tg, studies failed to define the best cutoff value for FNAB-Tg. In our study, we describe a novel way in performing the Tg washout and process it locally at our laboratory (tertiary care center). We used the FNAB-Tg to serum thyroglobulin level (FNAB-Tg/ Tg serum) ratio to help overcome the heterogeneity in both cutoff values and the assays used to detect thyroglobulin level. We conducted a retrospective analysis of 22 PTC or suspected PTC patients, who have suspicious cervical lymph nodes on ultrasound. All patients underwent fine-needle aspiration, with cytology analysis and FNAB-Tg from the suspicious CLNs. FNAB-Tg was obtained in all subjects using the following method: Blood samples are drawn from the patient’s peripheral vein and placed in two yellow top tubes (3 ml of blood in each tube). 1 ml of normal saline (NS) is added to Tube # 1 (Tg Serum tube). The suspected lymph node aspirate is obtained via US-guided FNA. It is washed in 1 ml of NS and added to tube #2 (FNAB-Tg washout tube). Both tubes are sent to our local laboratory for Tg assay. The FNAB-Tg/ Tg serum ratio is calculated. If FNAB-Tg/Serum-Tg ratio&gt;3, this is suggestive of CNL metastasis. We compared our results to the histopathology reports after neck dissection.59% (13/22) patients had cytology results consistent with metastatic PTC. 12 out of these 13 patients had an FNAB-Tg/serum Tg ratio &gt;3 and one had FNAB-Tg/serum TG ratio &lt; 3, though the FNAB-Tg was 4474 ng/ml and serum Tg was 2444 ng/ml. Metastatic PTC to these CLNs was confirmed on pathology report from total thyroidectomy or neck dissection. Six patients of the 22 studied (27%) had negative cytology with FNAB-Tg/serum Tg ratio &gt; 3. 5 of these patients underwent neck dissection in our institute and confirmed to have metastatic PTC to these CLNs. One patient elected to have surgery in his home country and the pathology report is not available at this time. Three patients of the 22 studied (14%) had negative cytology and FNAB-Tg/serum Tg ratio &lt;3. 2 of them underwent thyroid surgery or neck dissection and the final pathology report was concordant with the FNAB-Tg results. The FNAB-Tg/serum Tg ratio is a novel method to overcome the differences in cutoff values and assays used to measure the Tg level both in serum and FNAB. An FNAB–Tg/serum Tg ratio &gt;3 is more accurate than cytology in detecting cervical lymph node metastasis in patients with papillary thyroid cancer (PTC). In our study, 27% of CLN metastasis would have been missed if FNAB cytology was used alone. This will help to optimize the surgical approach in patients with PTC before initial surgery or for suspected recurrence.