A 61-year-old man had been referred to the Department of Hepatobiliary and Pancreatic Surgery of our hospital for multiple hepatic giant hemangiomas with no significant progression, 5 years before his first visit to our department. The hepatic hemangioma was diagnosed at age 52 during a routine physical examination. Computed tomography (CT), performed in June 20XX, showed newly emerging lesions, such as multiple nodules in both lungs, a right axillary tumor, and the already-known hepatic lesion (multiple enlarged hepatic hemangiomas). He was referred to our department for further examination of the axillary tumor.
Soluble interleukin-2 receptor (391 U/mL) and carcinoembryonic antigen (2.6 ng/dL) were within their normal ranges, while thyroglobulin was high at 226 ng/mL. Fluorodeoxyglucose–positron emission tomography (FDG–PET)/CT images were obtained in July of the same year. Whereas the thyroid gland showed faint FDG accumulation and multiple lung nodules showed no accumulation, FDG accumulation with a standardized uptake value maximum of 5.1 was observed in the right axillary tumor (Fig. 1a–d). A decrease in FDG accumulation in the liver, consistent with hepatic lesions was observed (Fig. 1e).
Cervical ultrasonography showed masses in both lobes of the thyroid gland. Both tumors were irregularly shaped and hypoechoic with indistinct borders, and the mass in the right lobe was suspected of having capsular invasion (Fig. 2a, b). The right cervical lymph nodes were swollen, suggesting metastasis of the thyroid tumor. A hypoechoic mass was found in the right axilla (Fig. 2c). It was lobulated with well-defined and rough borders and showed internal heterogeneity. The majority of the mass was hypoechoic with some hyperechoic areas. The mass was 30 mm in diameter, and there was no apparent enlargement of the other axillary lymph nodes. In bilateral breast ultrasonography, there were no abnormal findings in his right breast.
Contrast-enhanced CT showed multiple nodules with calcification in both thyroid gland lobes. In the right axilla, there was an oval mass with a high-density area and well-defined borders. The contrast enhancement was poor, and there was no evidence of either muscle or chest wall invasion (Fig. 3a, b). In the frontal view, the subclavian artery was intact, but the dorsal thoracic artery could not be identified (Fig. 3c). Multiple nodules up to 7 mm were found in both lobes of the lung. The liver nodules demonstrated early staining in the arterial phase and the contrast effect spread to the center of the tumor in the portal phase, corresponding to a known hemangioma (Fig. 4a–e). Since these CT findings were typical of hepatic hemangiomas, we diagnosed liver nodules with hepatic cavernous hemangioma. FDG–PET/CT findings also supported that this space-occupying lesion (SOL) in the liver was not highly suspicious of being a malignant tumor (Fig. 1e). In addition, left renal angiomyolipoma, left adrenal adenoma, and a subcutaneous lipoma was detected.
Fine-needle aspiration cytology was performed on the thyroid tumors, cervical lymph nodes, and right axillary tumor: the right thyroid tumor was class IV, raising suspicion of PTC; the left thyroid tumor was class V, also raising suspicion of PTC; the right cervical lymph node was class II, benign; the left cervical lymph node was class V, raising suspicion of metastasis of PTC; and the right axillary tumor was class III. Cytological examination of the axillary tumor revealed epithelial-like cells with rhombic to pleomorphic sporophytes that were solitary and scattered, accompanied by a mass of mesenchymal tissue. Immunohistochemically, thyroid transcription factor-1 was negative.
The patient was thus diagnosed with PTC and an unspecified right axillary tumor. The presumptive histology of the axillary tumor was consistent with a mesenchymal tumor. The differential diagnosis of the axillary tumor included a lymph node metastasis from PTC and occult breast cancer.
The multiple lung nodules were clinically diagnosed as metastatic tumors derived from thyroid cancer. We diagnosed these diseases as PTC of T1b(m)N1bM1(lung) Stage IVB and a right axillary tumor.
The patient underwent total thyroidectomy, cervical lymph node dissection and axillary tumor resection. The axillary tumor showed no obvious direct invasion of the axillary arteriovenous system. However, direct invasion of the dorsal thoracic artery was observed, and the artery was ligated at the branch from the axillary artery and resected.
In postoperative pathology, multiple nodules were macroscopically observed in both lobes of the thyroid more than expected preoperatively. The pathological diagnosis was PTC. The axillary tumor was 45 mm in its longest diameter, and gross examination showed hemorrhage, calcification and necrosis within the tumor (Fig. 5a). Histologically, the tumor was angiocentric in origin and invaded surrounding soft tissue, adipose tissue, and nerve tissue in a lobulated manner with fibrous septa (Fig. 5b). The borders were relatively clear. The background was a myxohyaline substrate, and epithelioid to spindle-shaped cells proliferated in cord-like and vesicular patterns, some of which formed blood vessels. The individual tumor cells had mildly pleomorphic nuclei and eosinophilic cytoplasm and were observed to form primitive vascular spaces in which red blood cells were present (Fig. 5c). There was marked nuclear atypia in the cells, and mitotic nuclei were detected in three cells/2 mm2 (Fig. 5d). Immunostaining showed the axillary tumor to be positive for cluster of differentiation (CD) antigen 34, CD31 (Fig. 5e, f) and erythroblast transformation specific-related gene, while negative for cytokeratin AE1/3, epithelial membrane antigen, and thyroid transcription factor-1 (data not shown). In addition, distinct nucleoli, extensive necrosis, and sinusoidal vascular lumen formation, which were typical features of hemangiosarcoma, were not observed. Consequently, the tumor was diagnosed as EHE without containing lymphatic tissue. The large tumor size, nuclear atypia, and high mitotic activity indicated that our case should be classified as high-risk EHE.
Finally, the patient was diagnosed with PTC (pT3bN1bM1[lung] stage IVB) and primary axillary EHE. After surgery, we administered radioiodine therapy (131I 100 mCi, 3.7 GBq) twice for lung metastases of thyroid cancer, and the patient is currently receiving follow-up care. The hepatic hemangioma is also under follow-up in the Hepatobiliary and Pancreatic Surgery department. As for the EHE, the patient remains free of recurrence to date.