Kazuhiro Kudo

HCV Virus and Lymphoid Neoplasms

Hepatitis C virus (HCV) is one of the viruses known to cause hepatic cancer. HCV is also believed to be involved in malignant lymphoma. In this paper, we investigated characteristics of malignant lymphoma cases that were anti-HCV antibody (HCV-Ab) positive. We were able to perform pathological examinations on 13 out of 14 HCV-positive cases. Of these, lymphoid tissues of 10 stained positive for HCV-Ab. There was no significant correlation between the degree of HCV staining and the rate of recurrence or resistance to treatment. However, there did appear to be a consistent decrease in the amount of HCV-RNA between pre- and posttreatment among HCV-Ab-positive cases; that is, treatment-resistant cases that exhibited resistance from the first treatment and recurrent cases more frequently had a higher HCV level at treatment termination compared to the pretreatment level. This suggests that the HCV virus either accelerates oncogenesis by direct interaction with B cells or indirectly affects lymphoma prognosis.

Systemic amyloidosis complicated with peliosis.

Dear Editor, A 75-year-old male was hospitalized in April 2006 for oral and urinary bleeding. He presented with hematoma in the left latissimus dorsi and with hepatomegaly, splenomegaly, anemia, and thrombocytopenia. His platelet count was 49× 10/μL, his prothrombin time was 15.2 s, his FDP was 196.5 μg/dL, and his fibrinogen was 121 mg/dL. His serum haptoglobin level was reduced but autoantibody and Coombs tests were negative. Serum vitamin B12 and folic acid levels were normal. These findings suggested the presence of disseminated intravascular coagulation (DIC). Computed tomography (CT) revealed hepatomegaly, splenomegaly, and several 10-mm areas of low density in the spleen (Fig. 1a). In magnetic resonance imaging (MRI) these low-density areas appeared as high-density areas in T1 and T2 images (Fig. 1b, c) but were not enhanced in the dynamic phase (Fig. 1d). We thought that the splenomegaly was complicated by hematoma, possibly related to chronic DIC. We could not identify the mechanism of this hemolysis and DIC. After prednisolone (0.5 mg/kg) was administered daily because autoimmune hemolytic anemia could not be ruled out, the anemia and thrombocytopenia decreased and the patient’s bleeding tendency decreased enough that the rate of transfusion could be reduced. Splenonectomy on 9 June 2006 revealed that the spleen weighed 175 g and contained many blood-filled spaces located perifollicularly (Fig. 2a). The spleen showed the ‘bacon spleen’ appearance characteristic of amyloidosis. The appearance of the lining of these spaces differed from that of the endothelium. Amorphous eosinophilic materials observed in the red pulp of the spleen (Fig. 2b) were positive for direct fast scarlet (DFS) stain and periodic acid Schiff (PAS) stains and were immunohistochemically positive for amyloid P component (Fig. 2c, d). The pathological diagnosis was peliosis. The anemia, thrombocytopenia, and hematoma of the left latissimus dorsi abated after the splenonectomy. Although the thrombocytopenia abated, the patient sometimes passed a bloody stool after the prednisolone was discontinued. Gastrointestinalscopy (GIS) and colonoscopy (CS) at the time of the melena revealed nothing abnormal. The patient was discharged from hospital in August 2006, but his bleeding tendency continued and in October 2006 he had a hemorrhage in the left femoris muscle. These symptoms abated after administration of carbazochrome sodium sulfonate and tranexamic acid, but the hepatomegaly gradually became more aggravated. In April 2007 he was readmitted because of uncontrollable ascites caused by portal hypertension due to the hepatomegaly. Administration of potassium canrenoate, furosemide, and albumin did not reduce the ascites, nor did a peritoneovenous shunt. The ascites was accompanied by pleural effusion, and both gradually increased until the Ann Hematol (2009) 88:917–920 DOI 10.1007/s00277-008-0690-6

HCV non-structural protein 3 and HCV RNA genome in non-Hodgkin lymphoma and transition of the serum HCV RNA level: a retrospective analysis in one institution

There have been various reports on the association of hepatitis C virus (HCV) infection with B lymphocyte proliferative disorders, such as non-Hodgkin lymphoma (NHL). We experienced a case (Case 1) of anti-HCV antibody (HCV-Ab)-positive NHL in which HCV nonstructural protein 3 (NS3) expression was observed in lymphoma tissue at the time of recurrence and in which the serum HCV RNA level exhibited a transient increase prior to recurrence. We investigated the HCV RNA genome in lymphoma tissue in Case 1, and it could be detected at recurrence. We also investigated HCV NS3 protein expression in lymphoma tissue and changes in serum HCV RNA level during the clinical course in four other cases of HCV-Ab-positive NHL treated in our hospital. We examined lymphoma tissues for HCV NS3 protein expression in four of the five cases, but it was not identified except for in Case 1 at recurrence. In three cases with no recurrence, serum HCV RNA levels showed a tendency to decrease after completion of chemotherapy and became stable thereafter. Further studies are necessary to clarify the association between serum HCV RNA and the onset and exacerbation of NHL.

Late onset toxic epidermal necrolysis induced by mogamulizumab, an anti-CC chemokine receptor 4 antibody for the treatment of adult T-cell leukaemia/lymphoma.

To the Editor Adult T-cell leukaemia/lymphoma (ATLL) is a rare type of highly aggressive peripheral T-cell malignancy induced by infection with human T-cell leukaemia virus type 1 (HTLV-1) [1]. Acute and lymphoma types of ATLL particularly display an aggressive clinical course with a poor outcome because of the resistance to conventional combination chemotherapies [2]. Mogamulizumab (MOG), a defucosylated humanized monoclonal antibody targeting CC chemokine receptor 4 (CCR4), has recently been launched for treatment of ATLL; almost all ATLL cells express CCR4 [3]. On the other hand, skin rashes have been reported as significant adverse effects of MOG [3]. It is often difficult to distinguish between a skin lesion caused by MOG and an ATLL lesion, and the detail characteristics, clinical course and treatment are still unclear, particularly in severe events including Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Here, we report a case of TEN induced by MOG for the treatment of ATLL, which developed at a very late phase after the last infusion of MOG. A 77-year-old man was introduced to our hospital for general fatigue, palpitation and abnormal lymphocytes in peripheral blood. He was diagnosed as having acute type of ATLL by flow cytometry analysis and detection of HTLV-1 antibody. He received low-dose etoposide as an initial treatment; however, lung infiltration of ATLL cells was demonstrated by bronchoalveolar lavage and transbronchial lung biopsy 7months after diagnosis. Because combination chemotherapies were considered to be a high risk for his general condition, MOG monotherapy was started for 8months. Detail clinical course of the patient following the treatment of MOG was shown in Figure 1. At the initial infusion of MOG, an infusion reaction was diagnosed for the rapid development of respiratory failure, hyperthermia and systemic skin rash. Three courses of MOG monotherapy were given in combination with a steroid, and MOG was then discontinued owing to a grade 4 adverse effect of thrombocytopenia. He achieved complete remission in both peripheral blood and lung lesions after the therapy. Serum soluble interleukin-2 receptor levels were also significantly decreased from 6290 to 1190U/ml.