A 67-year-old male presented with hoarseness and was admitted to our hospital. Cervical examination revealed a 5-cm hard mass at the lower portion of right thyroid lobe fixed with the swallowing.
Laboratory findings demonstrated that all thyroid and parathyroid functions are within the normal range: thyrotropin (TSH) 3.68 μIU/m (normal range 0.50–5.00), free triiodothyronine (T3) 3.10 pg/ml (2.30–4.00), free thyroxine (T4) 1.06 ng/dl (0.90–1.70), thyroglobulin (Tg) 31 ng/ml (≤32.7), anti-thyroglobulin antibodies (TgAb) 10.0 IU/ml (<28.0), serum calcium 9.4 mEq/l (8.8–10.1), serum phosphorus 3.2 mg/dl (2.6–4.4), and intact parathyroid hormone (PTH) 49 pg/ml (15–65).
Ultrasonography (US) and computed tomography (CT) revealed a hypoechoic area of 4.7 × 3.4 cm with an irregular margin in the right lobe of the thyroid (Fig. 1). No lymphadenopathy was detected. CT findings revealed a low-density mass of approximately 5.0 cm in the right lobe of the thyroid. The tumor had close contact with the posterior side of the trachea and the right wall of the esophagus in broad areas. The margins are indistinct, and tumor invasion was suspected (Fig. 2). Neither cervical lymph node metastasis nor distal metastasis was observed. Endoscopic findings indicated that right vocal code paralysis was observed in bronchoscopy. The tracheal lumen was deformed due to retraction by the tumor from the right posterior side. No abnormalities were found on the tracheal mucosa. The upper endoscopy did not reveal any obstructions or abnormalities on the esophagus mucosa (Fig. 3).
Fine-needle aspiration revealed cells with a large N/C ratio. No cells exhibited nuclear grooves or intranuclear cytoplasmic inclusion, suggesting that it was a poorly differentiated thyroid carcinoma (PDTC) derived from a follicular tumor.
A surgical treatment was performed, suspecting PDTC with right recurrent nerve, esophageal, and tracheal invasions. The tumor involved a right recurrent nerve and invaded the sternothyroid muscle on the ventral side and the muscular layer of esophagus and the membranous wall of trachea on the dorsal side. Some parts of the right recurrent nerve, the muscular layer of the esophagus, and the membranous wall of tracheal were resected with the tumor via thyroidectomy along with lymph nodes of the central compartment. The tumor was not macroscopically exposed. The defects of the muscular layer of the esophagus and the membranous wall of the trachea were sutured in the direction of the long axis. Then, nerve reconstruction was performed by end-to-end anastomosis between the right recurrent nerve and the right ansa cervicalis (Fig. 4).
The tumor was a solid gray white mass of 42 × 37 × 28 mm with an irregular surface invading the sternothyroid muscle, right recurrent nerve, the muscular layer of esophagus, and the membranous wall of trachea. Microscopic findings include a growing mass of atypical cells containing clear, partially oxyphillic cells, in solid and alveolar structures with broad fibrosis. Mitosis and focal coagulative necrosis were also detected. Vascular and capsular invasions were observed inside the tumor and the surrounding tissues; lymph node metastasis was positive (3/8). According to the immunostaining results, the tumor cells were slightly positive for PTH and chromogranin A and negative for TTF-1, thyroglobulin, calcitonin, CD5, and S100 proteins. The patient was diagnosed with parathyroid carcinoma, and the MIB1 index was 5% (Fig. 5).
PTH immunostaining was slightly positive and non-specific. Hence, PTH mRNA expression was analyzed by RT-PCR. Several thin-sliced sections were serially prepared on glass slides from the formalin-fixed paraffin-embedded (FFPE) tissues of the surgically removed tumor, and one of the slices was subjected to hematoxylin and eosin (H&E) staining. RNA was extracted from the area on the remaining unstained slides corresponding to the tumor identified on the H&E-stained slide using the AllPrep DNA/RAN Mini Kit (Qiagen, Germany) following the manufacturer’s protocol. The extracted tumor RNA was subjected to the RT-PCR analysis using the SuperScript® One-Step RT-PCR with Platinum® Taq kit (ThermoFisher Scientific, USA) according to the manufacturer’s protocol. Briefly, 1 μg of the extracted RNA or water as a negative control was reverse transcribed with the reverse PCR primer followed by 40 cycles of PCR amplification consisting of incubation at 94 °C for 15 s, 55 °C for 30 s and 68 °C for 30 s in one tube using the 2720 Thermal Cycler (ThermoFisher Scientific). The nucleotide sequences of the forward and reverse PCR primers were 5’-GCCAACATGACAATCATA-3’ and 5’-GTTTTCCCAGGTTATGCA-3’, respectively. These sequences were designed from exons 2 and 3 of the PTH transcript sequence deposited as NM_000315 in GenBank. RT-PCR products were detected by electrophoresis in a 2% agarose gel stained with ethidium bromide. PTH mRNA expression was observed, and finally we diagnosed this tumor as non-functioning PTC (Fig. 6).
The post-operative course was satisfactory, and no dysphagia was observed. The patient was discharged 5 days after the operation. Seven months later, a palpable lymph node of approximately 2 cm was detected on the right neck during a physical examination. The US and CT scans revealed lymphadenopathy in the right upper deep cervical lymph nodes. The patient was cytologically diagnosed with the parathyroid carcinoma. Then, right modified neck dissection was performed 9 months after the operation. Given that prophylactic irradiation therapy has a low evidence level and has not been established, we suggested the patient undergo radiation therapy, but he refused. Unfortunately, re-operation was needed for the right neck recurrent lymph nodes 25 months after the first surgery. We finally decided to apply radiation therapy to the neck after the third operation. No distal metastasis has occurred, and the patient is still alive.