Abstract
We report our experience in the identification of metastatic medullary thyroid cancer (MTC) using syringe washing calcitonin estimation in specimens obtained by ultrasound (US)-guided fine-needle aspiration (FNA) biopsy of cervical lymph nodes. The standard surgery performed for MTC is total thyroidectomy with central compartment neck dissection (1). Even after apparent complete resection of the cancer, a biochemical cure is achieved in less than 50% of patients (2). Localization studies commonly used are computed tomography (CT), US, magnetic resonance imaging (MRI), and positron emission tomography scans. These modalities have limitations (3 –5). The majority of patients undergo FNA biopsy confirmation prior to neck dissections. The frequency of false negative or inaccurate reading of FNA cytology of lymph nodes with metastatic MTC is unknown. Calcitonin elevation in the syringe washout fluid in patients with cytology-confirmed MTC has been reported (6,7). We applied this technique in five consecutive MTC patients who underwent FNA biopsy prior to surgery. In two of the subjects, despite confusing cytological reports or indeterminate cytology, the calcitonin elevation in the syringe washout specimen aided localization of metastatic lymph nodes.
A 52-year-old man underwent total thyroidectomy with central compartment neck dissection for the treatment of MTC due to RET proto-oncogene mutation C609Y. Pre-operative calcitonin was 399.2 pg/mL (male normal, 0.0‱11.5 pg/mL). The left lobe contained 1 × 1 cm MTC and 4 out of 19 lymph nodes were positive for metastatic MTC. Unstimulated serum calcitonin was 49.3 pg/mL 6 months after the surgery. Whole body CT, MRI, and radionucleotide bone scan revealed no masses suspicious for metastasis. Neck ultrasonography revealed a lymph node in the left level 3 region of the neck measuring 1.3 × 0.5 × 0.4 cm with irregular margins and distorted hilum. After performing FNA biopsy and cytology evaluation, the leftover aspirate was rinsed with 2 mL of normal saline and subjected to calcitonin estimation. The calcitonin concentration in the syringe washout fluid was 3242.4 pg/mL. Cytology revealed an intense histiocytic giant cell response compatible with postoperative reactive changes. Following the results of the calcitonin estimation, re-evaluation of the cytology specimen revealed cells suspicious for metastatic medullary thyroid carcinoma. One of the 66 lymph nodes removed during left modified neck dissection contained MTC. The serum calcitonin remains at <2.0 pg/mL several months after the neck dissection.
A 56-year-old woman with sporadic MTC underwent total thyroidectomy for a solitary right lobe MTC measuring 1.1 cm. Multifocal microscopic, 3-mm papillary thyroid cancers (PTC) were also discovered. Of the two central compartment lymph nodes removed, one contained metastatic PTC. The postoperative serum calcitonin level was 121 ng/mL. Cervical ultrasonography revealed a right lower neck lymph node corresponding to right level III region. This lymph node measured 10 × 7 × 6 mm without fatty hilum. Due to the posterior location and partial obscuration by great vessels, biopsy was attempted twice in a guarded manner using a 27-gauge needle. Cytological assessment of the FNA smears revealed blood and was deemed unsatisfactory for interpretation. The needle was rinsed with 1.5 mL of saline and submitted for calcitonin estimation. The FNA syringe calcitonin was 257 pg/mL with a simultaneous serum calcitonin level of 121 pg/mL. She underwent right neck dissection that revealed one lymph node containing metastatic MTC and one other lymph node containing PTC out of 72 lymph nodes that were excised. Three months following surgery her serum calcitonin level is 5.1 pg/mL.
In the three other patients, the calcitonin levels from the FNA aspirate were elevated (Table 1). This test did not add further to the cytological diagnosis of metastatic MTC in them. It is notable to mention that in all patients, the lymph nodes exhibited findings suggestive of metastasis, namely, the lack of fatty hilum or rounded appearance independent of their small size (Table 1).
Post thyroidectomy. Three uninvolved lymph nodes (not shown) had FNA calcitonin level of <1 to 6.6 pg/mL.
FNA, fine-needle aspiration.
These cases illustrate the difficulties involved in the diagnosis and management of metastatic MTC. US-guided FNA was performed on a total of seven lymph nodes. Despite the normal size of these lymph nodes, abnormal US features such as rounded shape or no visible hilum were observed. In four of the seven sampled lymph nodes, the syringe washout fluid calcitonin levels were significantly elevated (Table 1). In the remaining three uninvolved lymph nodes, the calcitonin level was low (<1‱6.6 pg/mL). In patient 1, the presence of reactive histiocytes led to the misinterpretation of cytology as findings consistent with reactive lymph node. In the case of patient 2, despite the smears being inadequate with mostly red blood cells, the syringe washout calcitonin was greater than the simultaneously drawn serum calcitonin level (257 pg/mL and 121 pg/mL, respectively). In this patient, surgery was performed based upon FNA syringe washing findings. Following surgical neck dissection, serum calcitonin is undetectable in one subject and has dropped by >80% in three other subjects, predicting a favorable outcome (8).
In our observation, this technique is especially useful in situations that yield scant specimen and when the number of biopsy passes is limited by the deep location of lymph nodes that are partially obscured by great vessels. In the latter situation, multiple attempts may be fraught with higher risk of complications. We conclude that calcitonin estimation in syringe washout fluid after FNA biopsy is a simple technique that can be easily performed. This technique is complementary to the cytological evaluation of metastatic cervical lymph node. It is especially useful in cases where the cytological specimen is deemed indeterminate or in cases with confusing cytological findings due to lymph nodes manifesting postoperative reactive changes. We have been able to use commercially available calcitonin assays and have not encountered limitations with reimbursements.