A 54-year-old man was admitted for weight loss, upper abdominal distension with a palpable mass, and epigastric pain for one month. Dull pain had worsened and the abdominal mass had become increasingly evident for the preceding week. His history was remarkable for Hepatitis B infection for more than 20 years. Physical examination was negative for spider angioma, shifting dullness, jaundice or scleral icterus, hand flapping tremor, or thyroid mass. Laboratory data were normal: serum aspartate aminotransferase, 18 IU/L; alanine aminotransferase, 18 IU/L; creatinine, 0.8 mg/dL. Abdominal ultrasonography revealed a mixed echoic mass at level S3–4 (maximum diameter, 9.8 cm), and the entire liver parenchyma had heterogeneous echogenicity. Computed tomography (CT) of the liver revealed multiple foci of heterogeneously enhanced mass lesions. The largest was roughly 8.9 cm × 6.7 cm. Serum alpha-fetoprotein was elevated with a level of 162.4 ng/mL (normal, < 12 ng/ml).
Left hepatic lobectomy was performed two weeks after initial diagnosis, and histopathologic analysis revealed a moderately to poorly differentiated HCC. The cut surface revealed a well-defined, tan-white, firm tumor measuring 8.4 cm × 6.5 cm × 5.5 cm with obvious necrosis. The tumor directly invaded the liver capsule and was adherent to fat on the anterior superior surface. The surgical margin was 1 cm from the tumor and microscopically negative for tumor cells. Intraoperatively, two well-defined, black spongy tumors measuring up to 2 cm in diameter were noted near the main tumor mass. No liver cirrhosis, cholestasis, or portal vein thrombosis was seen.
Microscopically, the tumor featured cells growing in solid nests and a pseudoglandular, as well as a focal trabecular pattern. Individual cells showed marked nuclear pleomorphism and prominent nucleoli with abundant eosinophilic granular cytoplasm and frequent mitotic figures. There was extensive fibrosis and necrosis. Perineural invasion was found near the hilum, but no invasion of blood or lymphatic vessels was evident. Mucicarmine stain was negative for mucin in the carcinoma. In scattered areas, cells were immunochemically positive for cytokeratin (CK) 7 and negative for CK 20. The two small black and spongy tumors were typical of cavernous hemangioma. No liver cirrhosis was noted. After complete pathologic examination, the patient's pTNM stage according to the AJCC Cancer Staging Manual (6th
] was pT1N0M0 (solitary tumor without vascular invasion).
At follow-up two months after surgery, no local recurrence or metachronous HCC was observed. The patient had a normal CT and alpha-fetoprotein level had markedly decreased to 66.5 ng/mL. Four months after surgery, abdominal CT revealed multiple poorly defined hypodense lesions (largest about 1 cm) in segments VII and VIII. Alpha-fetoprotein level was 119.7 ng/mL. Transarterial embolization therapy was performed for recurrent disease. Seven months after surgery alpha-fetoprotein level was 102.9 ng/mL and recurrent HCC was found. Transarterial embolization therapy was performed again. At this time the patient reported new-onset dyspnea and several neck nodules. Physical examination revealed a firm, hard left thyroid mass with bilateral lymphadenopathy. Ultrasonography revealed multiple nodules in the left thyroid with heterogeneous echogenicity (Figure ). Fine needle aspiration of the largest thyroid nodule was performed, and cytology revealed poorly differentiated carcinoma.
Computed tomography of the neck revealed the left thyroid tumor (arrow).
Immunohistochemical staining showed that the thyroid carcinoma was negative for thyroid transcription factor-1 (TTF-1), CK 7, CK 20, and thyroglobulin. Because the carcinoma was similar microscopically to the HCC found in the liver (Figure ) and positive for alpha-fetoprotein (Figure ), a tentative diagnosis of metastatic HCC with bilateral lymph node involvement was made. Eight months after the original hepatic lobectomy, the patient underwent total thyroidectomy with bilateral regional lymph node dissection. Both dysphagia and dyspnea resolved postoperatively. The patient expired eight months after the thyroidectomy due to recurrent HCC complicated by sepsis.
A. Metastatic hepatocellular carcinoma (HCC) in the thyroid gland (hematoxylin-eosin, 400×). B. Primary HCC (hematoxylin-eosin, 400×).
A. Immunohistochemical staining of the metastatic carcinoma was positive for alpha-fetoprotein (arrow). B. Negative control staining picture.