Acute lymphoblastic leukemia with eosinophilia lacking peripheral blood leukemic cell: a rare entity.

We describe a 57-year-old woman who was diagnosed as precursor B-cell acute lymphoblastic leukemia with marked eosinophilia (ALL-eo). She presented with low grade fever and eosinophilia (absolute count 16.5 × 10(9)/l). Most of eosinophils had hypogranular cytoplasm. Immature cells were absent in her peripheral blood. Since her platelet count was low, bone marrow examination was carried out. 57.2 % of nucleated cells were blastic cells positive for CD10, 19, and 20. Chromosomal analysis revealed a karyotype of 46,XX,t(5;14)(q31;q32). Despite induction chemotherapy, her disease progressed and she died of sepsis a month later. ALL-eo is extremely rare and the diagnosis might be delayed unless leukemic cells are seen in peripheral blood. Therefore, bone marrow should be examined as soon as possible in cases with eosinophilia not only for the differential diagnosis of eosinophilic disorders but also not to overlook ALL-eo.

Inversion of chromosome 7q22 and q36 as a sole abnormality presenting in myelodysplastic syndrome: a case report.

INTRODUCTION: Deletions of chromosome 7 are often detected in myelodysplastic syndrome. The most commonly deleted segments are clustered at band 7q22. A critical gene is therefore suggested to be located in this region. We report a patient with myelodysplastic syndrome whose marrow cells carried an inversion of 7q22 and q36 as a sole karyotypic abnormality. How this extremely rare chromosomal aberration contributes to the pathogenesis of myelodysplastic syndrome should be clarified by accumulating clinical data of such cases. CASE PRESENTATION: A 74-year-old Japanese man presented with pancytopenia incidentally detected by routine medical check-up. His complete blood cell counts revealed that his white blood cells had decreased to 2100/mm3, neutrophils 940/mm3, red blood cells 320×104/mm3, hemoglobin 11.1g/dL, hematocrit 33.1%, and platelets 12.6×104/mm3. Bone marrow examination showed normal cellularity with nucleated cells of 9.4×104/mm3. The proportion of blasts was 4%. A morphological examination showed only basophilic stippling of erythroblasts which was seen as dysplasia. According to World Health Organization classification, the diagnosis was myelodysplastic syndrome-u. Karyotypic analysis showed 46,XY,inv(7)(q22q36) in all of 20 metaphases examined. Additional analysis revealed the karyotype of his lymphocytes was 46,XY. He is asymptomatic and cytopenia has slowly progressed. CONCLUSIONS: To the best of our knowledge, this karyotype from a clinical sample of de novo malignancies has never been documented although the identical karyotype from secondary myelodysplastic syndrome was reported. Despite the extremely low frequency, inversion of 7q22 appears to play a crucial role for myelodysplastic syndrome in this patient.

Case of autoimmune hepatitis with markedly enlarged hepatoduodenal ligament lymph nodes.

Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology. The disease is characterized histologically by interface hepatitis, biochemically by increased aspartate aminotransferase and alanine aminotransferase levels, and serologically by increased autoantibodies and immunoglobulin G levels. Here we discuss AIH in a previously healthy 37-year-old male with highly elevated serum levels of soluble interleukin-2 receptor and markedly enlarged hepatoduodenal ligament lymph nodes (HLLNs, diameter, 50 mm). Based on these observations, the differential diagnoses were AIH, lymphoma, or Castleman's disease. Liver biopsy revealed the features of interface hepatitis without bridging fibrosis along with plasma cell infiltration which is the typical characteristics of acute AIH. Lymph node biopsy revealed lymphoid follicles with inflammatory lymphocytic infiltration; immunohistochemical examination excluded the presence of lymphoma cells. Thereafter, he was administered corticosteroid therapy: after 2 mo, the enlarged liver reached an almost normal size and the enlarged HLLNs reduced in size. We could not find AIH cases with such enlarged lymph nodes (diameter, 50 mm) in our literature review. Hence, we speculate that markedly enlarged lymph nodes observed in our patient may be caused by a highly activated, humoral immune response in AIH.

Factors associated with the overall survival of elderly patients with hepatocellular carcinoma.

AIM: To identify the factors associated with overall survival of elderly patients with hepatocellular carcinoma (HCC). METHODS: A total of 286 patients with HCC (male/female: 178/108, age: 46-100 years), who were diagnosed and treated by appropriate therapeutic procedures between January 2000 and December 2010, were enrolled in this study. Patients were stratified into two groups on the basis of age: Elderly (≥ 75 years old) and non-elderly (< 75 years old). Baseline clinical characteristics as well as cumulative survival rates were then compared between the two groups. Univariate and multivariate analyses were used to identify the factors associated with prolonged overall survival of patients in each group. Cumulative survival rates in the two groups were calculated separately for each modified Japan Integrated Stage score (mJIS score) category by the Kaplan-Meier method. In addition, we compared the cumulative survival rates of elderly and non-elderly patients with good hepatic reserve capacity (≤ 2 points as per mJIS). RESULTS: In the elderly group, the proportion of female patients, patients with absence of hepatitis B or hepatitis C viral infection, and patients with coexisting extrahepatic comorbid illness was higher (56.8% vs 31.1%, P < 0.001; 27.0% vs 16.0%, P = 0.038; 33.8% vs 22.2%, P = 0.047; respectively) than that in the non-elderly group. In the non-elderly group, the proportion of hepatitis B virus (HBV)-infected patients was higher than that in the elderly group (9.4% vs 0%, P = 0.006). The cumulative survival rates in the elderly group were 53.7% at 3 years and 32.9% at 5 years, which were equivalent to those in the non-elderly group (55.9% and 39.4%, respectively), as shown by a log-rank test (P = 0.601). In multivariate analysis, prolonged survival was significantly associated with the extent of liver damage and stage (P < 0.001 and P < 0.001, respectively), but was not associated with patient age. However, on individual evaluation of factors in both groups, stage was significantly (P < 0.001) associated with prolonged survival. Regarding mJIS scores of ≤ 2, the rate of female patients with this score was higher in the elderly group when compared to that in the non-elderly group (P = 0.012) and patients ≥ 80 years of age tended to demonstrate shortened survival. CONCLUSION: Survival of elderly HCC patients was associated with liver damage and stage, but not age, except for patients ≥ 80 years with mJIS score ≤ 2.

Adenoendocrine cell carcinoma of the gallbladder producing a high level of alpha-fetoprotein.

We present the case of a 78-year-old Japanese woman with adenoendocrine cell carcinoma of the gallbladder accompanied by a high serum alpha-fetoprotein level. The patient visited our hospital with a complaint of a large mass in the right hypochondrium. Ultrasonography and computed tomography revealed multiple large hepatic tumors, swelling of lymph nodes in the hepatic hilum and para-aortic regions, and a slightly irregular gallbladder wall. The serum alpha-fetoprotein level was 157,428 ng/mL. We initially suspected scirrhous hepatocellular carcinoma, sarcomatous hepatocellular carcinoma, biliary tract cancer, or pancreatic cancer. However, the hepatic tumor biopsy was histologically diagnosed as undifferentiated adenocarcinoma. Immunohistochemical analysis demonstrated that the tumor was positive for cytokeratin 19, focally positive for cytokeratin 7, but negative for hepatocyte paraffin 1 and cytokeratin 20, suggestive of biliary tract carcinoma. Although the patient received a course of hepatic arterial infusion chemotherapy with cisplatin, she died 2 months after admission. Histopathological examination at autopsy revealed that the hepatic tumor was adenoendocrine cell carcinoma of the gallbladder, which was positive for cytokeratin 19, focally positive for cytokeratin 7, chromogranin A, synaptophysin, and weakly positive for alpha-fetoprotein. Labeling index of Ki-67 was 28 %. Interestingly, this was the first case report of adenoendocrine cell carcinoma of the gallbladder that produced a high level of alpha-fetoprotein, which hampered correct diagnosis before autopsy.

Cytogenetic analysis of de novo CD5-positive diffuse large B-cell lymphoma.

AIMS: De novo CD5-positive diffuse large B cell lymphoma (CD5+DLBL) is a subtype of DLBL with poor clinical outcome. To investigate the cytogenetic pathogenesis of CD5+DLBL, we analyzed the chromosomal findings of 18 patients with CD5+DLBL. METHODS: Tumor cells were cultured and metaphase was captured by colchicine exposure. Using trypsin-Giemsa banding, the chromosomes were analyzed according to the International System for Human Cytogenetic Nomenclature. RESULTS: Metaphase was acquired from 12 patients. Normal karyotypes were seen in two patients and abnormal karyotypes in the remaining 10. The numbers of chromosomes ranged from 45 to 90. Gain, loss and rearrangements of various chromosomes were seen. Frequent breakpoints were located at chromosome 1 band p13, 3q27, 6q13, 7q32, 14q32, 18q21 and 19q13. There was no diagnosis-specific abnormality. A relationship between chromosomal findings and clinical outcomes such as involved site, relapse or survival, was not observed. CONCLUSION: Since previous and the present studies on the chromosomal analysis of CD5+DLBL are also contradictory, more detailed comprehensive genetic analysis appears to be needed to elucidate the biological mechanisms of CD5+DLBL.

Pure red cell aplasia caused by parvovirus B19 in two patients without chronic hemolysis.

Infection with human parvovirus B19 (PVB19) induces acquired pure red cell aplasia (PRCA). Chronic hemolytic anemia is well known as an underlying condition. However, additional factors have been recognized to accompany parvoviral PRCA; however, there are only limited reports on iron-deficiency anemia (IDA) and rituximab-induced B-cell dysfunction. We report two patients with PVB19-associated PRCA confirmed by positivity of viral DNA. Although they had no chronic hemolysis, patient 1 had IDA, and patient 2 had remitted small-lymphocytic lymphoma treated with rituximab-containing chemotherapy. Absence of reticulocytes in peripheral blood and marked depletion of erythroid precursors in bone marrow were observed both. Whereas patient 1 received only symptomatic therapy because anemia was not severe, patient 2 was treated with steroids, as PRCA etiology was at first uncertain, and immunological PRCA was not excluded. Both showed rapid increase of reticulocyte counts and recovery from anemia. Although immunoglobulin is considered effective for parvoviral PRCA, notable adverse reactions have been reported. When anemic symptom is not severe, reticulocyte observation only is recommended. The effects of steroids should also be re-evaluated. Optimal treatment according to disease severity remains to be established.

Relapse of hepatitis C in a pegylated-interferon-alpha-2b plus ribavirin-treated sustained virological responder.

A 41-year-old woman with chronic hepatitis C was treated with pegylated-interferon (PEG-IFN)-alpha-2b plus ribavirin for 24 weeks. She had hepatitis C virus (HCV) genotype 2a (1600 KIU/mL), and her liver histology showed mild inflammation and fibrosis. Four weeks after the start of the therapy, she achieved a rapid virological response (RVR) and then a sustained virological response (SVR). Serum alanine aminotransferase (ALT) levels remained within normal ranges and HCV RNA continued to be negative. However, ALT levels flared with the re-emergence of HCV RNA in the serum 1.5 years after discontinuation of therapy. HCV RNA obtained from sera before therapy and after relapse shared a 98.6% homology with the E2 region, and phylogenetic analyses indicated that they were the same HCV strain. These results eliminated the possibility of a re-infection and strongly indicated a late relapse of the disease. Therefore, follow-up is necessary for chronic hepatitis C patients after SVR, even if they respond well to therapy, including RVR.

Protein-losing enteropathy in a case of nodal follicular lymphoma without a gastrointestinal mucosal lesion.

Protein-losing enteropathy (PLE) is characterized by gastrointestinal loss of serum protein. It is usually caused by hypersecretion from a tumor, ulcer, or long standing lymphangiectasia. However, we report a 47-year-old man of peritoneal nodal follicular lymphoma who developed PLE with none of them. Oozing of whitish fluid from duodenal bulbar mucosa was endoscopically seen, resulting in continuous loss of protein. Chemotherapy was effective and PLE was rapidly diminished. Nodal lymphoma lesion was considered to disturb lymphatic flow and to regurgitate it to duodenal mucosa. To our knowledge, this is the second report of a lymphoma patient presenting PLE without a gastrointestinal mucosal lesion.

Non-prescription supplement-induced hepatitis with hyperferritinemia and mutation (H63D) in the HFE gene.

A 55-year-old Japanese woman was hospitalized because liver function tests showed an abnormality. Transaminases and biliary enzymes were markedly elevated with hyperferritinemia. Her imaging tests revealed no significant abnormality. She had been taking various non-prescription supplements for over approximately 6 months. After the supplements were discontinued her liver function gradually improved. This clinical course was suggestive of supplement-induced hepatitis. She had no history of taking supplements containing iron, so it was interesting that she had hyperferritinemia. We examined C282Y and H63D, which are important mutations in theiron-metabolizing gene, HFE. She was found to be heterozygous for the H63D mutation. The interaction between hyperferritinemia and supplements is unknown, but it can be speculated that some interaction between iron overload and supplements may have underlain the pathogenesis of her liver injury.

Clinicopathological analysis of a case with mesenteric solitary Castleman's disease: diagnostic value of radiological findings.

We report a case with rare solitary mesenteric Castleman's disease (CD). A 45-year-old woman complaining of nausea was presented. A round-shaped, smooth margin, and hypoechoic mass was seen on screening abdominal ultrasonography. Computed tomography showed a markedly enhanced tumor anterior to the left iliopsoas muscle. Selective jejunal arteriography revealed an extreme hypervascularity without vascular invasion. These results retrospectively seem to differ from those of malignant lymphoma or sarcoma. The tumor was surgically resected, and hyaline-vascular type CD was pathologically diagnosed. We postulate that these radiological findings might suggest hyaline-vascular type CD as one of the differential diagnoses in similar cases, although more clinical data should be evaluated.

[A case of recrudescent groove pancreatitis, which was in remission by proximal gastrectomy with vagotomy for gastric cancer].

This report describes our experience with a 60 year old male who suffered from a recrudescence of groove pancreatitis. He had been treated by conservative medication therapy by proton pump inhibitor used for therapy of duodenal ulcer, and was in remission. During a follow-up one year later, endoscopy revealed gastric cancer, for which a proximal gastrectomy and vagotomy were performed. The patient continues to remain in remission for the groove pancreatitis. Our experience with the clinical course of this disease, in which treatment for duodenal ulcer was used effectively, offers new insights into the progression and therapy of groove pancreatitis.

Simultaneous complication of multiple myeloma with Sjögren syndrome.

We report a 72-year-old female case of IgG-kappa type multiple myeloma (MM) simultaneously complicated with Sjögren syndrome (SS). She also presented marked hyperamylasemia of salivary-type isozyme. Although she had received sequential chemotherapy completed with high-dose therapy with autologous hematopoietic stem cell transplantation, she died of relapse fifteen months after the initial diagnosis. Various autoantibodies indicated that her sicca symptoms were due to true SS and not caused by MM cell infiltration to exocrine glands. MM cells appeared to produce amylase that fluctuated correspondingly to the disease status of MM. To our knowledge, this is the first English report of simultaneous complication of SS and MM referring to hyperamylasemia. Accumulation of this rare clinical manifestation is important to elucidate the pathogenesis of MM under condition of immunological disorder caused by SS.

Relapse of idiopathic thrombocytopenic purpura caused by influenza A virus infection: a case report.

We report a patient with idiopathic thrombocytopenic purpura (ITP) in remission, who relapsed as a result of an influenza A virus infection. A 41-year-old woman presented with fever elevation, coughing, and generalized petechiae. Her platelet count had decreased to 1 x 10(9)/l. She had been diagnosed with ITP at age 23, and continuous complete remission had followed steroid therapy and splenectomy. Influenza A antigen was positive in her pharyngeal aspirate, and oseltamivir was effective for her symptoms. Findings of a bone marrow smear were typical for ITP. Steroid therapy resulted in a second complete remission. Although the development of ITP caused by influenza infection and a relapse caused by an influenza vaccination have been previously described, a relapse caused by a sporadic infection has never been documented to our knowledge. Physicians should carefully monitor the hematological data of influenza patients, especially those with ITP, even in remission.