An 85-year-old Asian man presented with complaints of anorexia for the few days prior to being examined. The doctor, who had previously treated the patient, confirmed hepatic and renal disorders and administered intravenous fluids, and gave a possible diagnosis of dehydration. The rest of the physical examination was otherwise unremarkable. Past medical history and family history were insignificant. He had not previously been treated with antiviral therapies, he was not jaundiced or febrile, and he had stable vital signs. His superficial lymph nodes were not palpable.
Blood tests revealed anemia with a hemoglobin level of 10.7 g/dL and a slight thrombocytopenia of 10.5 × 104/µL, with a normal total and differential white blood cell count. The serum albumin level was low, at 3.4 g/dL, and the lactate dehydrogenase (LDH) level was high, at 822 IU/L. Liver function test results were abnormal, with elevated levels of alanine aminotransferase (ALT) (120 IU/L), aspartate aminotransferase (AST) (139 IU/L), alkaline phosphatase (ALP) (354 IU/L), gamma-glutamyl transpeptidase (γ-GTP) (79 IU/L), and total bilirubin (0.87 mg/dL). Renal function test results were abnormal, with elevated levels of creatinine (2.23 mg/dL) and blood urea nitrogen (32.0 mg/dL). A serological test for the hepatitis C virus (HCV) was positive, but serological tests for the hepatitis B virus (HBV) and human immunodeficiency virus (HIV) were negative.
An abdominal ultrasound (US) revealed multiple well-defined hypoechoic lesions in both lobes of the liver as well as splenomegaly (Fig. 1). Non-contrast-enhanced computed tomography (CT) scans of the abdomen and pelvis showed that the liver lesions were hypodense (Fig. 2). Because of renal dysfunction, the patient was unable to undergo a contrast-enhanced CT. Abdominal magnetic resonance imaging (MRI) of the hepatic lesions showed hyperintense signals on T2-weighted imaging (T2WI) and marked signal restriction on diffusion-weighted imaging (DWI) (Fig. 3). Although the patient had splenomegaly, there were no lesions within the splenic parenchyma visible upon US, CT, or MRI. The mesenteric, para-aortic, and retroperitoneal lymph nodes were not enlarged. The image was suggestive of metastatic liver tumors with liver cirrhosis without any identifiable primary tumor or extrahepatic lymphadenopathy.
Further workups were carried out to exclude a possible primary origin. Levels of tumor markers alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), squamous cell carcinoma (SCC) antigen, pro-gastrin-releasing peptide (Pro-GRP), and prostate-specific antigen (PSA) were within the normal range. The upper gastrointestinal endoscopy and total colonoscopy reveal no abnormality. CT scans of the chest and neck were negative for primary pulmonary lesions, and the hilar, mediastinal, and cervical lymph nodes were not enlarged. Based on these findings, we provisionally diagnosed the patient as having a cancer of unknown primary origin with liver metastases.
Endoscopic ultrasound (EUS) revealed a 17.4 × 16.9-mm almost hypoechoic nodule in the left lobe (Fig. 4a). A 19-gauge fine needle biopsy (FNB) was performed one time on the tumor in the left lobe of the liver using a transgastric approach (Fig. 4b). The needle, with suction applied using a 20-mL syringe, was moved through the entire diameter of the tumor lesion for ten strokes, and the needle was then withdrawn from the lesion. The apparatus used was a convex-type EUS gastrovideoscope (model GF-UCT260; OLYMPUS Co., Ltd., Tokyo., Japan) and a EUS processor (EU-ME2; (OLYMPUS Co., Ltd.) at a frequency of 7.5 MHz. The needle used for the EUS-LB was a disposable 19-gauge needle (Acquire; Boston Scientific Co., Natick, MA, USA). Histological analysis showed diffuse proliferation of large atypical lymphoid cells (Fig. 5). Immunohistochemistry revealed that the atypical lymphoid cells were largely positive for CD20 and Bcl-2 and negative for CD3 (Fig. 6a, b). The results of additional staining of these cells for CD56, synaptophysin, and chromogranin A were negative (Fig. 6c–e). We could therefore exclude the possibility of a small cell carcinoma.
Histopathology of the liver tissue was consistent with a diffuse large B-cell lymphoma (DLBCL). The serum soluble interleukin-2 receptor (sIL-2R) level was extremely high at 25,700 U/mL after the biopsy. Finally, we diagnosed a PHL. Although we recommended that the patient consult with a hematologist, he chose best supportive care but refused hospice care. He received regular visits from palliative care doctors and daily nursing care. He died of the disease at his home 26 days after being discharged from our hospital.