Hepatocellular carcinoma presenting as spinal cord compression in Native Americans with controlled hepatitis C: two case reports

A 64-year-old Native American man presented with worsening lower back pain, and numbness and tingling radiating from his belly button down both legs. At the time of admission, he reported gradually increasing weakness in both legs for 3 days that led to an inability to walk. His past medical history is significant for hepatitis C for many years, which led to liver cirrhosis. His past surgical history is significant for a previously repaired umbilical hernia. His family history included breast cancer (sister) and lung cancer (mother). He smoked cigarettes for 1–2 years in the 1980s, but it is unknown how many cigarettes he smoked per day. In addition, he was a former heroin abuser. He never consumed alcohol. He worked as a manager in the laundry department in a hospital. Family members deny any exposure to asbestos. An ultrasound of his liver 1 year prior to the current presentation reported coarse echotexture, suggestive of underlying cirrhosis. Several years earlier, he had not responded to interferon and ribavirin treatment. However, 1 year before presentation, he did respond to ledipasvir/sofosbubir (Harvoni) treatment. Although he cut the treatment short to just 5 weeks, a recent hepatitis viral test detected no hepatitis C ribonucleic acid (RNA). He had hepatitis C virus (HCV) RNA genotype 1a. He was a prior intravenous drug user and was in a methadone program. Home medications were as follows: nadolol, spironolactone, bumetanide, and methadone. On admission, his blood pressure (BP) was 109/67 mm Hg, heart rate (HR) 57 beats per minute, and temperature 36.6 °C. A physical examination had the following results: no jugular venous distention, his lungs were clear to percussion and auscultation, his heart sounded normal, there were no murmurs, his abdomen was slightly distended, his spleen and liver were not palpable, and some spider angioma was noted on his skin. On neurological examination: he was alert and awake; he was oriented to time, his name, and his location; and his cranial nerves were grossly intact. While no gait disturbance was observed, marked weakness of his lower extremities and swelling over the T9 area of his spine were found. He had a blood urea nitrogen (BUN) of 66 mg/dL, creatinine of 2.8 mg/dL, alkaline phosphatase of 505 U/L, aspartate aminotransferase of 210 U/L, alanine aminotransferase of 66 U/L, and total bilirubin of 1.5 mg/dL. Magnetic resonance imaging (MRI) of his thoracic and lumbar spine revealed a pathologic fracture at T11 with retropulsion and severe cord compression (Fig. 1) and right chest wall and thoracic spine mass with tumor invasion into the spinal canal and thoracic cord compression at T6 (Fig. 2). In addition, numerous metastatic lesions in his thoracic and lumbar spine were noted. A MRI scan of his chest/abdomen and pelvis without contrast was performed and revealed a large right liver mass and multiple lesions in his ribs, spine, and mediastinum, suggestive of metastatic disease. He was started on intravenously administered steroids. Surgical spinal cord decompression and stabilization/fusion of his spine was performed. Pathology results of an intervertebral disc and the T9 vertebral body reported metastatic carcinoma favoring HCC (Fig. 3). Tumor cells were positive for Hep Par-1 and glypican-3 (Fig. 4), and negative for cytokeratin (CK) 7, CK20, thyroid transcription factor 1 (TTF-1), inhibin, OCT3/4, prostate-specific antigen (PSA), prostatic specific acid phosphatase (PSAP), renal carcinoma marker (RCC), and PAX8. Subsequently, he was treated with radiation to the T11 spine lesion and was scheduled to begin radioembolization with yttrium-90, but his condition deteriorated, and he died 2 months after diagnosis. An autopsy was not performed.

The second case involved a 70-year-old Native American man presenting with upper back pain and numbness of his right foot for approximately 10 days. The symptoms had worsened, and he noticed some difficulty with walking. He did not have any past medical or surgical history. He was a former tobacco smoker and stopped smoking approximately 20 years ago, but it is unknown how many packs or cigarettes per day he smoked. He drank alcohol very rarely and not significantly. He did not have family history of any significance. He was never on medications until he was diagnosed as having HCC. He worked at a warehouse in the past. His job position was unknown. He has no known environmental or drug allergies. On admission, his BP was 166/119 mm Hg, HR was 97 beats per minute, and temperature was 36.7 °C. His physical examination had the following results: he was normocephalic, he had a non-traumatic skull, he had normal hearing, he had no nasal discharge, his chest wall movement was symmetric, his breath sounds were clear, he had no rales/wheezing, his HR was within the normal limit and had regular rhythm with no murmurs or thrills, his abdomen was soft with no distension, there was no palpable mass, there was no hepatomegaly or splenomegaly, a bilateral pedal pulse was present, there was no visible joint swelling, his skin was warm to the touch, he had normal color, and he had no rash/ulcers. A neurological examination had the following results: he was alert and awake; he was oriented to time, his name, and his location; his cranial nerves were grossly intact; he had no gait disturbance or motor deficits; his superficial reflexes were intact; a slight decrease in sensation over his right lower extremity was noted. Abnormal laboratory results were as follows: aspartate aminotransferase level of 104 U/L and alanine aminotransferase level of 90 U/L. CT of his chest and abdomen revealed a 10.0 × 8.3 × 7.4 cm soft tissue mass with associated osseous destruction involving the posterior right fourth, fifth, and sixth ribs and adjacent thoracic vertebral bodies, with significant soft tissue extension into the spinal canal and evidence of spinal cord compression. An additional lesion of the left iliac wing measuring 3.6 cm was noted. There were numerous enhancing lesions throughout his liver that were suspicious for primary versus metastatic disease (Fig. 5). No signs of cirrhosis were detected on CT images. Further laboratory tests showed alpha-fetoprotein (AFP) levels of 98,884.0 ng/mL. Carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9 levels were slightly elevated. Hepatitis C RNA genotype 1a was detected. Hepatitis C RNA was 6.73 log IU/mL by reverse transcriptase polymerase chain reaction (RT-PCR).

An MRI of his thoracic spine was performed and revealed a large, posterior, left chest wall mass measuring 10.0 × 6.7 × 9.5 cm, with associated osseous destruction of the underlying right posterior fourth through seventh ribs and adjacent vertebral bodies, with complete obstruction of the right foramen and significant involvement of his spinal canal, causing spinal cord compression (Fig. 6). A biopsy of the soft tissue mass was performed and showed a metastatic, poorly differentiated carcinoma favoring hepatocellular origin (Fig. 7). Tumor cells were positive for hepatocyte, glypican-3, and pan-CK (Fig. 8), and focally positive for CK20 and CEA but were negative for CK7 and TTF-1, CA 19-9, p63, CDX2, and OCT3/4. Because of the poorly differentiated histology and atypical presentation, he was treated with oxaliplatin plus fluorouracil/leucovorin [6]. After radiation of T5–T7 and a subsequent decrease in AFP levels, he eventually refused further therapy and was placed on hospice care. He died 6 months after diagnosis. An autopsy was not performed.