Middle thyroid vein tumor thrombus in metastatic papillary thyroid microcarcinoma: A case report and review of literature.

BACKGROUND: Although papillary thyroid microcarcinoma (PTMC) is not considered a threatening tumor, in some cases, it can be aggressive. Metastatic thrombosis of papillary thyroid carcinoma, follicular thyroid carcinoma, Hürthle cell carcinoma, poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma have been reported in the literature, but there have been no reports about PTMC. CASE
SUMMARY: A 45-year-old woman presented with a thyroid mass and thrombosis in a middle thyroid vein during a physical examination. She had no symptoms, and the physical examination showed no positive signs. Subsequent ultrasonography-guided fine-needle aspiration biopsy results indicated an atypical lesion of ambiguous significance, with some actively growing cells (TBSRTC III) and the BRAFV600E mutation not present. This patient underwent left thyroidectomy, isthmus lobectomy, prophylactic central lymph node dissection and thromboembolectomy. Postoperative pathology showed papillary microcarcinoma of the left thyroid, and the thrombus in the middle thyroid vein was a tumor thrombus.
CONCLUSION: Middle thyroid vein tumor thrombus is an extremely rare condition in PTMC, but it does exist. Lobectomy and thromboembolectomy may be an option for patients with thrombi in the middle vein of the thyroid, and we strongly suggest close follow-up of these patients. ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

Core Tip: We report the case of a 45-year-old woman presented with a thyroid mass and thrombosis in a middle thyroid vein during a physical examination. This patient underwent left thyroidectomy, isthmus lobectomy, prophylactic central lymph node dissection and thromboembolectomy. Postoperative pathology showed papillary microcarcinoma of the left thyroid, and the thrombus in the middle thyroid vein was a tumor thrombus. Middle thyroid vein tumor thrombus is an extremely rare condition in papillary thyroid microcarcinoma, but it does exist. Lobectomy and thromboembolectomy may be an option for patients with thrombi in the middle vein of the thyroid, and we strongly suggest close follow-up of these patients.

INTRODUCTION

Papillary thyroid microcarcinoma (PTMC) is a variant of papillary thyroid carcinoma (PTC) that is defined by the World Health Organization as less than or equal to 1 cm in diameter[1]. Although PTMC is not considered a threatening tumor, in some cases, it can be aggressive. Metastatic thrombosis of PTC, follicular thyroid carcinoma (FTC), Hürthle cell carcinoma (HCC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) have been reported in the literature, but there have been no reports about PTMC. We report the case of a 45-year-old woman with a middle thyroid vein thrombus. She underwent successful resection, and postoperative pathology showed papillary microcarcinoma of the left thyroid and a tumor thrombus in the middle thyroid vein. We reviewed the literature to identify reports of tumor thrombus and distant metastasis of PTMC.

CASE PRESENTATION

Chief complaints

A 45-year-old woman presented with a thyroid mass (Figure 1) and thrombosis (Figure 2) in a middle thyroid vein during a physical examination.

Figure 1

A solid nodule in the left lobe of the thyroid by ultrasound examination.

Figure 2

Ultrasound examination revealed a medially echoic mass in the middle thyroid vein.

History of present illness

The patient came to hospital because of thyroid mass found in physical examination 3 mo before. She had no symptoms. The patient requested surgery because of the stress.

History of past illness

The patient was health in the past.

Personal and family history

The patient had no family history of thyroid carcinoma and no history of radiation exposure in childhood.

Physical examination

The physical examination showed no positive signs.

Laboratory examinations

Laboratory tests showed that triiodothyronine, free triiodothyronine, thyroxine, thyroglobulin, and thyroid-stimulating hormone levels were within the normal limits.

Imaging examinations

A solid nodule in the left lobe of the thyroid by ultrasound examination. Ultrasound examination revealed a medially echoic mass in the middle thyroid vein.

Ultrasonography-guided fine-needle aspiration biopsy

Subsequent ultrasonography-guided fine-needle aspiration biopsy results indicated an atypical lesion of ambiguous significance, with some actively growing cells (TBSRTC III) and the BRAFV600E mutation not present.

FINAL DIAGNOSIS

PTMC (pT1aN0M?). Middle thyroid vein tumor thrombus.

TREATMENT

The patient and her family were fully informed of the advantages and disadvantages of total thyroidectomy and lobectomy prior to surgery. The patient declined to undergo a total thyroidectomy. Intraoperative exploration showed that the mass was located in the middle and upper left lobe of the thyroid gland, adjacent to the capsule, but the capsule was not invaded. There was a round mass in the middle thyroid vein with a diameter of 0.8 cm. The middle thyroid vein was ligated distal to the mass and cut off. Rapid freezing pathological examination showed that both the left thyroid mass and the left middle thyroid vein mass were carcinomas. These results were communicated to the patient’s family, and total thyroidectomy was again declined. Therefore, the patient underwent left thyroidectomy, isthmus lobectomy and prophylactic central lymph node dissection. Postoperative pathology showed papillary microcarcinoma of the left thyroid (single lesion, maximum diameter of 0.9 cm) (Figure 3), and the thrombus in the middle thyroid vein was a tumor (diameter of 0.6 cm) (Figure 4).

Figure 3

Hematoxylin and eosin staining of left lobe thyroid mass, it shows papillary thyroid microcarcinoma. A: 4×; B: 10×; C: 20×; D: 40×.

Figure 4

Hematoxylin and eosin staining of the thrombus, it shows carcinoma tissues. A: 4×; B: 10×; C: 20×; D: 40×.

OUTCOME AND FOLLOW-UP

No metastases were observed in the central lymph nodes. Initial TSH suppression was treated with 75 μg levothyroxine. Three months later, 18F-FDG positron emission tomography-computed tomography scanning did not detect local recurrence or distant metastasis (Figure 5). No complications occurred. Fearing recurrence and metastasis, the patient underwent genetic testing at a third-party testing facility. No genetic variation was detected in BRAFV600, BRAFK601, TERT, KRAS, NRAS, EIFIAX or RET. No gene fusion mutations were detected in PAX8/PPARγ, RET/PTC1, or RET/PTC3. Six months after surgery, the patient had no obvious discomfort, and no tumor recurrence or distant metastasis was observed. The patient took 50 μg levothyroxine once daily, and the serum TSH was 0.49 mIU/L.

Figure 5

Systemic positron emission tomography metabolism imaging showed no obvious signs of malignancy.

DISCUSSION

Thyroid carcinoma that causes tumor thrombus is rare. Forty-seven cases have been reported in the English literature since May 1, 2021. The details of these cases are shown in Table 1. The patients included 12 males and 35 females; their ages ranged from 26 years to 84 years, and the median age was 62 years. The location of the thrombus included the brachiocephalic vein, internal jugular vein, superior vena cava, subclavian vein, innominate vein, middle cerebral artery, pulmonary vein, external jugular veins, axillary vein, right atrium, ascending aorta, pulmonary artery, valvular endocardium and right ventricle. In almost all cases, the thrombus was located in the large vessels. Our patient had a thrombus in the middle thyroid vein, which may represent early-stage disease. Early-stage diagnosis and treatment are of great significance to patient prognosis.

Table 1

Reported cases of vein tumor thrombus in thyroid carcinoma

Ref.	Sex	Age	Lesion size (cm)	Pathology	Blood vessel of thrombus
Banerjee and Chopra[2], 1972	F	60	-	FTC	Middle cerebral artery
Thompson et al[3], 1978	F	67	-	FTC	JV, BV, SVC, RA
Perez and Brown[4], 1984	F	48	-	FTC	SVC
Sirota[5] , 1989	F	61	-	PTC	Axillary vein
Thomas et al[6], 1991	M	60	-	PDTC	Bilateral IJV
Onaran et al[7], 1998	M	48	-	HCC	IJV
Onaran et al[7], 1998	F	48	-	-	IJV
Onaran et al[7], 1998	F	69	-	HCC	IJV
Bussani and Silvestri[8], 1999	F	67	-	FTC	Pulmonary artery, valvularendocardium
Wiseman et al[9], 2000	M	84	-	-	IJV, BV
Koike et al[10], 2002	F	26	7.8	PTC	BV
Yoshimura et al[11], 2003	F	65	-	ATC	IJV, SV
Panzironi et al[12], 2003	F	68	-	ATC	Bilateral IJV
Gross et al[13], 2004	M	49	3.2 × 2.5 × 3	ATC, HCC	IJV
Sugimoto et al[14], 2006	M	61	-	ATC	BV, SVC, RA
Taib and Hisham[15], 2007	F	45	-	FTC	IJV
Taib and Hisham[15], 2007	F	62	-	FTC	RA
Taib and Hisham[15], 2007	F	66	-	FTC	IJV, SVC, RA
Tripathi et al[16], 2008	F	48	-	FTC	BV, SVC, IJV
Yamagami et al[17], 2008	M	74	2	PTC	JV, IV, SVC, atrium
Hyer et al[18], 2008	F	81	-	FTC	IJV, SVC
Agrawal et al[19], 2009	M	48	-	FVPTC	IJV, SVC, SV
Wada et al[20], 2009	M	64	-	FTC	IJV, BV, SVC
Sanioglu et al[21], 2009	M	64	2 × 1.5	PTC	Ascending aorta
Wada et al[20], 2009	F	74	-	PTC	BV, SVC
Mugunthan et al[20], 2010	F	51	-	PTC	IJV,SVC,RA
Bukhari et al[23], 2011	M	67	-	FTC	SVC
Nakashima et al[24], 2012	F	54	-	FTC	IJV, SV, BV
Babu et al[25], 2012	F	68	-	PTC	IJV
Onoda et al[26], 2012	F	70	7	FTC	IJV, SVC
Stickel et al[27], 2013	F	77	-	ATC	RV
do Nascimento et al[28], 2014	F	54	-	FTC	IJV
Al-Jarrah et al[29], 2014	F	62	3 × 5	PTC	IJV
Dikici et al[30], 2015	F	52	5.5 × 5.5	PTC	IJV, IV
Luo et al[31], 2015	F	57	-	HCC	RA
Franco et al[32], 2015	F	59	-	FTC	IV
Manik et al[33], 2016	F	65	-	FTC	SVC, RA
Kawano et al[34], 2016	F	75	4.5 × 3	ATC	IJV, IV, SUV, sigmoid sinus
Chiofalo et al[35], 2018	M	58	5	FTC	IJV
Chiofalo et al[35], 2018	F	64	3 × 17	FTC	IJV
Chiofalo et al[35], 2018	F	75	3.5 × 2.3	FTC	IJV, IV
Jain et al[36], 2019	F	44	-	-	IJV
Khoo and Chen[37], 2019	F	57	17	FTC	SVC, RA
Lad et al[38], 2020	F	52	-	FTC	IJV, SVC, RA
Cassar and Stirrup[39], 2020	F	75	-	FTC	Inferior pulmonary vein, left atrium
Čolović et al[40], 2020	M	67	-	FTC	IJV,BV
Kavanal et al[41], 2021	F	64	-	FTC	BV

F: Female; M: Male; PTC: Papillary thyroid carcinoma; FTC: Follicular thyroid carcinoma; HCC: Hürthle cell carcinoma; PDTC: Poorly differentiated thyroid carcinoma; ATC: Anaplastic thyroid carcinoma; FVPTC: Follicular variant of papillary thyroid carcinoma; IJV: Internal jugular vein; SVC: Superior vena cava; SV: Subclavian vein; RA: Right atrium; RV: Right ventricle; IV: Innominate vein; BV: Brachiocephalic vein; JV: Jugular vein.

Pathological types included PTC, FTC, HCC, ATC and PDTC. Ten of these cases were PTC (one of the follicular variants of PTC, FVPTC), 24 were FTC, 3 were HCC, 1 was PDTC, 5 were ATC, 1 was ATC with HCC and 3 were not described in the literature. Most of these case reports did not describe the size of the thyroid lesion. From the 12 cases with size data available, the maximum diameter of the lesions ranged from 2 cm to 17 cm (the average was 6.6 ± 5.2 cm). Our patient had PTMC (the maximum diameter was 0.8 cm), which had not been previously reported. Middle thyroid vein tumor thrombus in metastatic PTMC is extremely rare. It is necessary to consider how to perform TNM staging for such cases. Kawano et al[34] suggested setting management criteria. Unfortunately, there are still no related standards or guidelines for such criteria. Here, we emphasize the importance of aggressive treatment and close follow-up for these patients. Tumor cells are exposed to the circulatory system in this clinical presentation, and embolus shedding may also cause serious complications, such as pulmonary embolism. While there is a lack of objective clinical data to support this hypothesis, we will continue to monitor future occurrences.

In terms of treatment for tumor thrombi in metastatic PTMC, there is also no standard. Treatments include surgery, RAI therapy, external beam radiation therapy and chemotherapy. Most patients choose surgery combined with radioiodine therapy. Kavanal et al[41] reported that 131I therapy as a single modality may be considered for a subset of patients who have been rigorously screened. If the pathologic type is PDTC with no surgical opportunity and refractory to radioactive iodine, targeted therapy such as tyrosine kinase inhibitors may be another choice for this subset of patients[42].

Overall, we have demonstrated a middle thyroid vein tumor thrombus in PTMC. Our patient will continue to attend follow-up appointments. In the absence of other risk factors, lobectomy and thromboembolectomy may be an option for patients with thrombi in the middle vein of the thyroid. We strongly suggest a close follow-up of these patients.

CONCLUSION

Middle thyroid vein tumor thrombus is an extremely rare condition in PTMC, but it does exist. Lobectomy and thromboembolectomy may be an option for patients with thrombi in the middle vein of the thyroid, and we strongly suggest close follow-up of these patients.

ACKNOWLEDGEMENTS

We thank the thyroid and neck tumor specialist, ultrasound specialist and pathologist of the Tianjin Medical University Cancer Institute and Hospital for their valuable help.