Acta Medica Okayama
Volume 60, Issue 2 2006 Article 10 APRIL 2006
Intraatrial extension of thyroid cancer: a case report.
Seiichiro Sugimoto∗ Motoi Aoe∗∗
Hiroyoshi Doihara† Shunji Sano††
Yutaka Ogasawara‡ Nobuyoshi Shimizu‡‡
∗Okayama University, †Okayama University, ‡Okayama University,
∗∗Okayama University, ††Okayama University, ‡‡Okayama University,
Copyright ⃝c 1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved.

Intraatrial extension of thyroid cancer: a case report.∗
Seiichiro Sugimoto, Hiroyoshi Doihara, Yutaka Ogasawara, Motoi Aoe, Shunji Sano, and Nobuyoshi Shimizu
Abstract
A 61-year-old man, who was diagnosed with superior vena cava syndrome by papillary thy- roid carcinoma, was referred to our hospital. A bulky thyroid tumor with tracheal invasion ex- tended from the left neck to the right atrium without distant metastases. The risk of sudden death due to airway occlusion, tumor embolism or obstruction of the tricuspid valve led us to elect surgery. Extended resection of thyroid cancer was performed with cardiopulmonary bypass. Peritoneal dissemination was found via laparotomy. A histological diagnosis of anaplastic carci- noma arising from transformation of papillary carcinoma was made. After the operation, bilateral ureteral occlusion by peritoneal dissemination and multiple lung metastases were detected. The patient died with acute renal failure on postoperative day 12. Intraatrial extension of thyroid can- cer is rare, and only 12 cases have been reported in the literature. We present a case of thyroid cancer with intraatrial extension.
KEYWORDS: superior vena cava syndrome, thyroid cancer, cardiopulmonary bypass
∗PMID: 16680191 [PubMed – indexed for MEDLINE] Copyright (C) OKAYAMA UNIVERSITY MEDICAL SCHOOL

Acta Med. Okayama, 2006 Vol. 60, No. 2, pp. 135ン140 CopyrightC2006 by Okayama University Medical School.
Sugimoto et al.: Intraatrial extension of thyroid cancer: a case report.
Case Report
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Intraatrial Extension of Thyroid Cancer: A Case Report
Seiichiro Sugimotoa*, Hiroyoshi Doiharaa, Yutaka Ogasawaraa, Motoi Aoea, Shunji Sanob, and Nobuyoshi Shimizua
Departments of aCancer and Thoracic Surgery, and bCardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
A 61-year-old man, who was diagnosed with superior vena cava syndrome by papillary thyroid carci- noma, was referred to our hospital. A bulky thyroid tumor with tracheal invasion extended from the left neck to the right atrium without distant metastases. The risk of sudden death due to airway occlusion, tumor embolism or obstruction of the tricuspid valve led us to elect surgery. Extended resection of thyroid cancer was performed with cardiopulmonary bypass. Peritoneal dissemination was found via laparotomy. A histological diagnosis of anaplastic carcinoma arising from transfor- mation of papillary carcinoma was made. After the operation, bilateral ureteral occlusion by perito- neal dissemination and multiple lung metastases were detected. The patient died with acute renal fail- ure on postoperative day 12. Intraatrial extension of thyroid cancer is rare, and only 12 cases have been reported in the literature. We present a case of thyroid cancer with intraatrial extension.
Key words: superior vena cava syndrome, thyroid cancer, cardiopulmonary bypass
S uperior vena cava syndrome (SVCS) by intra- vascular invasion is an uncommon complication of thyroid cancer. In particular, intraatrial exten- sion via superior vena cava (SVC) of the tumor has rarely been described and, to our knowledge, only 12 cases have been reported [1ン6]. Surgical treat- ment to remove the tumor thrombus was performed in 5 of these cases, and cardiopulmonary bypass (CPB) was used in only one case, in which pulmonary dissemination after the treatment with CPB was reported [5]. The use of CPB for cardiopulmonary support in operations for malignancies makes extended resection possible; however, one of the disadvantages of using CPB is the hematogenous dis- semination of tumor cells, and so the application of
Received September 6, 2005; accepted November 29, 2005.
*Corresponding author. Phone:+81ン86ン235ン7265; Fax:+81ン86ン235ン7269
E-mail:sei_nana33sugi@yahoo.co.jp (S. Sugimoto)
CPB to oncologic surgery is still controversial [5]. We herein describe a surgical case of thyroid cancer with intraatrial extension and rapid tumor spread after an operation with CPB was performed.
Case Report
A 61-year-old man, who was diagnosed with SVCS and thyroid papillary carcinoma by fine-needle aspiration biopsy cytology, was referred to our hospital for treatment. The patient had a growing anterior neck mass for a year, hoarseness and dysphagia for 10 months, and head and neck edema for 3 months. He had stridor, a fist-sized neck tumor involving the left supraclavicular fossa, dilated veins in the anterior chest wall and edema of the face, neck, and bilateral arms suggesting SVCS. Laboratory tests showed a mild elevation of C-reactive protein and fibrinogen, but the patient’s
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136 Sugimoto et al.
white blood cell (WBC) count, thyroglobulin, triiodothyronine, thyroxine and thyroid-stimulating hormone were within normal limits (Table 1). A large bulky thyroid tumor with tracheal invasion and extensive nodal involvement in the neck and upper mediastinum, which extended into the left internal jugular vein, the bilateral brachiocephalic veins, the SVC, and the right atrium with thrombosis, was revealed by chest computed tomography (CT) (Fig. 1), magnetic resonance imaging (MRI) (Fig. 2), 131I-scintigraphy, and venography. Fiberoptic bronchoscopy demonstrated the left vocal cord palsy and tracheal mucosa invasion. The patient’s electrocardiogram was normal and transthoracic echocardiography showed the tumor invasion attached
Table 1 Laboratory data on admission
White blood cell 6600/μl Red blood cell 350×104/μl Hemoglobin 10.4g/dl Hematocrit 31.50オ Platelet 20.4×104/μl
Total protein 7.04g/dl Albumin 3.07g/dl
Acta Med. Okayama Vol. 60, No. 2
to the tricuspid valve. There was no evidence of brain, bone, lung or liver metastases as determined by brain MRI, bone scintigraphy, and chest and abdominal CT. The patient was preoperatively diagnosed with SVCS by intraatrial extension of thyroid papillary carcinoma. Consideration of these factors, as well as the risk of sudden death from airway occlusion, tumor embolism or obstruction of the tricuspid valve, led us to elect surgical treatment.
The patient was anesthetized and intubated safely despite tracheal invasion of the tumor, though prepa- rations had been made to place him on CPB. Total thyroidectomy and bilateral modified neck dissection were performed through an extended collar incision,
Total bilirubin
Aspartate aminotransferase Alanine aminotransferase Alkaline phosphatase γ-glutamyl transpeptidase Lactate dehydrogenase
0.50mg/dl 16IU/l 11IU/l 159IU/l 22IU/l 255IU/l
C-reactive protein Free triiodothyronine
Free thyroxine
Thyroid-stimulating hormone
Thyroglobulin 14.3ng/ml
Acta Medica Okayama, Vol. 60 [2006], Iss. 2, Art. 10
Na 142mEq/l K 3.8mEq/l Cl 103mEq/l Ca 8.9mg/dl
3.8mg/dl 1.75pg/dl
Blood urea nitrogen
Creatinine
Fasting blood glucose
Fibrinogen 527mg/dl
12.5mg/dl 0.66mg/dl 73mg/dl
1.36ng/dl 4.21μU/ml
AB
Fig. 1 Chest computed tomography. A large bulky thyroid tumor with tracheal invasion extended into the left internal jugular vein (A)
and the right atrium (B).
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Sugimoto et al.: Intraatrial extension of thyroid cancer: a case report.
April 2006
Fig. 2 Magnetic resonance imaging. The tumor extended into the left internal jugular vein, the bilateral brachiocephalic veins, the superior vena cava and the right atrium.
Intraatrial Extension of Thyroid Cancer 137
and then median sternotomy was performed. The bilateral brachiocephalic veins and SVC were filled with the tumor thrombus and were dilated widely, and thus they had to be resected because of their total occlusion and adherence of the tumor thrombus to the venous wall. A right atriotomy was performed and the great veins with the tumor, hanging like a pear into the right atrium and nearly obstructing the tricuspid valve (Fig. 3A), were removed by using CPB via femoral-femoral cannulation. The right phrenic nerve was resected with SVC. A vascular graft (expanded polytetrafluoroethylene ; Gore-Tex) was interposed between the right internal jugular vein and the right atrium to reconstruct the venous vascular system (Fig. 3B). Sleeve resection of the trachea and tracheostomy were performed after the patient was weaned from CPB. Peritoneal dissemi- nation was then found during laparotomy for tube jejunostomy.
Macroscopically, a large tumor replaced the whole thyroid lobes and invaded into the tracheal
AB
Fig. 3 Operative findings. A, The tumor, hanging like a pear into the right atrium, was exposed ; B, A vascular graft was interposed
between the right internal jugular vein and the right atrium to reconstruct the venous vascular system.
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138 Sugimoto et al.
mucosa. The bilateral brachiocephalic veins and
Fig. 4 Macroscopic findings of the resected specimen. A large thyroid tumor invaded the tracheal mucosa, and the bilateral brachiocephalic veins and superior vena cava were filled with the tumor, which was fixed firmly to the venous wall.
Acta Med. Okayama Vol. 60, No. 2
SVC were filled with the tumor, which was fixed firmly to the venous wall (Fig. 4). Microscopically, the majority of the tumor was composed of spindle- shaped cells with high mitotic figures and areas of necrosis, suggesting undifferentiated carcinoma (Fig. 5A). The tumor cells consisted of papillary carci- noma and undifferentiated carcinoma around the tra- chea (Fig. 5B). Therefore, the pathological diagno- sis was spindle-cell anaplastic thyroid carcinoma arising from the transformation of papillary carci- noma. Immunohistochemical examination revealed that the tumor cells were stained with a polyclonal antibody against granulocyte colony stimulating fac- tor (G-CSF).
After surgery, weaning from a ventilator was performed on postoperative day (POD) 4 as a result of left phrenic nerve palsy. Leukocytosis without signs of infection was observed in the postoperative course. Suddenly, renal dysfunction appeared on POD 10, and marked leukocytosis over 30,000/mm3 was revealed at that time. Computed tomography showed multiple lung metastases, bilateral ureteral occlusion and hydronephrosis by peritoneal dissemination. Metastasis, ischemia or thrombosis of the renal vessels causing intrinsic acute renal failure were not seen in either kidney. In spite of the ureteral stent insertion, the patient died due to
Acta Medica Okayama, Vol. 60 [2006], Iss. 2, Art. 10
AB
Fig. 5 Histological findings of the resected specimen. A, The majority of the tumor was composed of spindle-shaped cells with high mitotic figures and areas of necrosis, suggesting undifferentiated carcinoma (hematoxylin and eosin, ×200) ; B, Tumor cells consisted of papillary carcinoma and undifferentiated carcinoma around the trachea (hematoxylin and eosin, ×200).
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Author
Kaufmann1 Billroth1 Springer1 Wylegschnanin1 Holt1 Mencarelli3 Kim2 Thompson3 Niederle4
Hasegawa5 Sugimoto
Year Sex Age Symptom Diagnosis 1879 F 58 G, SVCS At autopsy
1898 F 51 G At autopsy 1901 F 44 G, SVCS At autopsy 1930 F 52 G, SVCS At autopsy
Extension
SVC, RA
SVC, RA
SVC, RA, RV SVC, RA
SVC, RA, RV, IVC SVC, RA, RV SVC, RA, RV, PO SVC, RA
SVC, RA SVC, RA SVC, RA SVC, RA SVC, RA
Pathology Treatment MC None
GC Subtotal thyroidectomy SC Tracheostomy FC None
AC None
NTC None FC None FC Tumor thrombectomy FC Tumor thrombectomy FC Tumor thrombectomy FC Tumor thrombectomy PC Extended resection UC Extended resection
Outcome
Died 2 months Died after surgery Died 2 months Died 2 months Died 5 days Sudden death Died 14 days Alive 36 months Died 13 months Alive 50 months Died 8 months Died 36 days Died 12 days
Sugimoto et al.: Intraatrial extension of thyroid cancer: a case report.
April 2006
Table 2 Review of 13 cases: intraatrial extension of thyroid cancer
Intraatrial Extension of Thyroid Cancer 139
1934 M
1934 M
1966 M
1978 F 67 G, SVCS Venography 1990 M 57 G, SVCS Venography, CT
72 G, SVCS At autopsy 56 SVCS At autopsy 64 G, SVCS At autopsy
F 79 G, SVCS At surgery
F 53 G, SVCS Venography, CT 2002 F 78 G At surgery
present M 61 G, SVCS CT, Venography
G, goiter; SVCS, superior vena cava syndrome; CT, computed tomography; SVC, superior vena cava; RA, right atrium;
RV, right ventricle; IVC, inferior vena cava; PO, pulmonary outflow; MC, medullary cancer; GC, giant cell; SC, sarcoma;
FC, follicular cancer; AC, adenocarcinoma; NTC, nontypical thyroid cancer; PC, papillary cancer; UC, undifferntiated cancer.
postrenal acute renal failure caused by bilateral ureteral obstruction on POD 12. An autopsy was not performed.
Discussion
SVCS by intraluminal extension is an uncommon complication of thyroid cancer. SVCS is more com- monly produced by external compression caused by a malignant retrosternal goiter or lymph node metasta- ses [4]. Intraatrial extension of the tumor has sel- dom been described. To our knowledge, only 12 cases have been reported in the literature. A review of these cases and ours (Table 2) shows that 11 of 13 patients had SVCS, the most common clinical pre- sentation of patients with thyroid cancer extending into the great veins [3]. Only one patient had distant metastases preoperatively [4]. Intraatrial extension of thyroid cancer shows high mortality rates; how- ever, 4 patients underwent tumor thrombectomy involving a great vein tumor thrombus [6] and sur- vived from 8 to 50 months. The last 2 patients, including our case, underwent extended resection with CPB and had early postoperative tumor dissemi- nation. Pathologically, 6 of 13 were diagnosed as follicular carcinoma, which has a well-documented microscopic characteristic of angioinvasion. Thompson et al. [3] reported that there were 2 types of involvement of the heart in thyroid cancer. In the first type, the right cardiac chambers may be
filled with a tumor extending directly through the thyroid veins by way of SVC. Intraluminal infiltration of cancer cells into a great vein initiates the deposition of fibrin on the cells, which allows their continued growth into the lumen of the vessel [4]. It is rare for remote metastases to occur in this type of involvement [3]. The second type has the character of a truly remote metastasis and usually involves widespread metastases, especially of the lungs and bone. Cardiac metastases occur in no more than 1オ of patients who die from thyroid carcinoma [3]. In our case, the intraatrial extension was the same as in the first type, and peritoneal dissemination was seen during the operation, though distant metastases rarely occur in this type. The pathologic diagnosis might account for the cause of the rare metastases, for anaplastic thyroid carcinoma is a locally and systemically aggressive disease in contrast to well-differentiated thyroid carcinoma. Anaplastic thyroid carcinoma has occasionally produced G-CSF [7]. Although the WBC count in this case was within normal limits preoperatively, leukocytosis without signs of infection was observed after surgery, suggesting that the tumor may have produced G-CSF. We could not measure the serum level of G-CSF, but immunostaining disclosed that the tumor was positive for G-CSF. In addition, CPB may favor the onset of leukocytosis. Misoph M et al. [8] reported that a significant increase in leukocyte counts was detected during CPB, resulting in a
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140 Sugimoto et al.
marked leukocytosis postoperatively. CPB might increase the risk of leukocytosis without signs of infection in this case.
The clinical course of differentiated thyroid can- cer is usually good, and the presence of massive intravascular invasion is no contraindication for aggressive surgical treatment [4]. In this case, pre- operative evidence showed that the patient had a pap- illary carcinoma without any distant metastases, though the tumor extended from the neck to the right atrium. The risk of sudden death from airway occlu- sion, tumor embolism or obstruction of the tricuspid valve led us to elect surgery. In general, when an endocrine tumor extends into the venous lumen, the actual tumor mass will be within a fibrous capsule; as a result, the tumor may not invade into the endothe- lium [4]. However, it was impossible to remove the tumor thrombus by thrombectomy because of the total occlusion and adherence to the venous wall, and the extended resection with CPB had to be per- formed. We believe that the intraatrial extension of differentiated thyroid cancer is no contraindication for surgical treatment because of the good prognosis with adjuvant radioiodine, but we do not elect sur- gery with the preoperative diagnosis of anaplastic thyroid carcinoma because of the poor survival rate. The most important factor is the preoperative histo- logical type of thyroid cancer. We should have per- formed a preoperative needle biopsy of the intralumi- nal tumor in the left internal jugular vein or intraoperative incisional biopsy of the tumor before the extended resection.
The use of CPB in oncologic surgery is still controversial because of the likelihood of hematoge- nous tumor dissemination. Hasegawa et al. [5] reported 2 possible mechanisms of this dissemination. First, tumor cells contaminating the reservoir blood might spread through the arterial cannula, particu- larly in situations involving a long CPB period, the re-use of suctioned blood, or the intravascular exten- sion of the tumor, though CPB might be used with- out increasing the risk of hematogenous tumor dis- semination [9]. Second, modification of homeostasis by CPB may liberate tumor cells that have already been spread preoperatively, but whose growth or migration has been suppressed by the host defense
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system. In our case, intravascular invasion with thrombosis and intraatrial extension was seen. Although suctioned blood from the surgical field was re-used through the Cell-Saver System, it is strongly suspected that CPB played a significant role in the postoperative spread of the tumor. CPB should only be applied to patients without distant metastasis or dissemination, and exploratory thoracotomy or lapa- rotomy should be performed to confirm pleural or peritoneal dissemination intraoperatively before using CPB.
In conclusion, it is possible to use CPB to resect intraatrial extension of thyroid carcinoma that cannot be removed by tumor thrombectomy. This extensive operation can prevent sudden death due to tumor embolism or obstruction of the tricuspid valve, and yet the prognosis for this disease may still be extremely poor.
References

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