Hepatocellular carcinoma with indolent T-lymphoblastic proliferation

Terminal deoxynucleotidyl transferase (TdT) labels a population of immature bone marrow T and B lymphocytes that comprise approximately 2% of the normal adult marrow population, and all early and common cortical thymocytes. TdT is a specific and sensitive marker for lymphoblastic neoplasms of both T and B lineage. Outside the bone marrow and thymus, there are practically no TdT positive cells [1]. However, Velankar et al. [2] and Strauchen [3] have previously reported an apparently new disorder named indolent T-lymphoblastic proliferation. The disease involves the oropharyngeal region, with multiple local recurrences over a long period without evidence of systemic dissemination. We report a case of hepatocellular carcinoma with TdT positive T lymphocytes infiltrating the stroma, possibly suggesting indolent T-lymphoblastic proliferation. A 45-year-old man was found to have a mass in the left lobe of the liver on a routine physical examination. Abdominal ultrasonography and magnetic resonance imaging revealed a solitary mass approximately 7 cm in diameter in the left lobe of the liver. Laboratory tests showed serum alpha-1-fetoprotein (AFP) 2212 ng/ml, but white blood cell count and bone marrow aspirate were normal. He had no fever and jaundice. There were no palpable lymph nodes. He had no history of hepatitis. Computerized tomography (CT) of the chest and abdomen revealed no mass in the mediastinum and retroperitoneum. He underwent a left hepatic lobectomy. Macroscopically, the partial hepatectomy specimen contained a well-circumscribed, non-encapsulated mass surround by normal liver parenchyma. The tumor measured 76 66 5 cm and the cut surface was tan with areas of yellowish necrosis. On microscopic examination, the tumor cells arranged in a predominantly thin trabecular pattern. These cells were polygonal with eosinophilic cytoplasm, round nuclei and prominent nucleoli. There were abundant small lymphocytes in the stroma. Some were mature small lymphocytes surrounding germinal centers. However, there were also some lymphoid cells that were slightly larger than adjacent small mature lymphocytes. The cytoplasm was scanty, and the nuclei had a fine chromatin without evident nucleoli. Mitotic figures can be seen (Figure 1a). In the adjacent normal liver tissue, there were only scattered, small, mature lymphocytes. Immunohistochemical study of paraffin-embedded tissue showed that the hepatocellular carcinoma cells were strongly positive staining for pancytokeratin and HepPar-1 and were negative for CK19. Some infiltrating small lymphocytes were positive for CD20, especially those surrounding germinal centers. There were abundant CD3 (Figure 1b), CD43 and CD45RO positive small lymphocytes. These cells also showed nuclear staining for TdT (Figure 1c) and membranous staining for CD99. They were negative for CD20, CD1a, CD15, CD30 and MPO. There were no TdT positive T-lymphocytes in the adjacent normal liver tissue. T-cell antigen receptor gene rearrangement studies were performed by the polymerase chain reaction technique on DNA extracted from the paraffin-embedded tissue. Monoclonal rearrangement of the T-cell receptor could not be detected. One week after operation, the patient’s serum AFP level dropped to 56 ng/ml. Chemotherapy with