First report of the whole-genome sequence analysis of avian rotavirus A from Japanese chickens.

Rotavirus A infects many mammalian species, including humans and causes diarrhea and gastrointestinal diseases. The virus also infects various bird species, including chickens, although information of avian rotavirus A (ARVA) infection in chicken populations in Japan is scarce. In this study, we report for the first time the whole-genome sequences of ARVA strains from Japanese chicken populations. The virus strains were inoculated to MA104 cells and cultured viruses were used to obtain the sequences with the MiSeq system, and genetic analysis demonstrated the genotype constellation of G19-P[30]-I11-R6-C6-M7-A16-N6-T8-E10-H8 of the Japanese chicken ARVA isolates. Phylogenetic analyses demonstrated that the VP1, VP2, VP3, VP4, VP7, NSP2, and NSP4 coding gene sequences of the Japanese strains were closer to those of Korean than the European ARVA strains, although such relationship was not clear for other genes. The data suggest that the Japanese ARVA strains and the ones in Korea have genetically close relationship, although the origin is not clear at this point. Further information including the whole-genome sequences of the Korean strains and sequences of other Japanese chicken ARVA strains will be necessary for elucidation of their origin.

Status and prognostic value of immunological biomarkers of breast cancer.

The immune response to cancer serves an important role in disease progression and patient prognosis. For triple-negative breast cancer showing aggressive behavior, immunotherapy has a good efficacy because of the potent immunogenicity of this type of cancer. However, the dominant subtype, luminal human epidermal growth factor receptor-2 (HER2)-negative breast cancer, is less immunogenic. To determine whether luminal HER2-negative cancer reacts to the anticancer immune response, the present study analyzed the status and prognostic value of the principal immunological biomarkers of breast cancer, including tumor-infiltrating lymphocytes (TILs), CD8+ T lymphocytes, the major histocompatibility complex and programmed cell death ligand-1 (PD-L1). The biomarkers were compared between patients with luminal HER2-negative breast cancer and those with immunogenic subtypes including triple-negative and HER2-overexpressed breast cancer. A total of 71 patients with primary breast cancer were classified into the immunogenic non-luminal (n=23) and less immunogenic luminal HER2-negative groups (n=48) based on immunogenicity. In the luminal HER2-negative group, compared with patients with low TIL levels, those with high TIL levels were at an advanced stage of cancer (P=0.024) and showed worse relapse-free survival (P=0.057); however, the remaining biomarkers exhibited no association with cancer progression or prognosis. In the non-luminal group, patients with high TIL levels showed significantly better RFS than those with low TIL levels (P=0.014). Compared with non-luminal patients negative for PD-L1, those positive for PD-L1 exhibited better overall survival (P=0.064). Notably, TIL status was found to exhibit contrasting prognostic predictions based on immunogenicity. In conclusion, TILs are a strong candidate for prognostic prediction in breast cancer, regardless of the subtype. PD-L1 is a potential candidate for prognostic prediction in immunogenic breast cancers, but not in the luminal HER2-negative subtype.

[Efficacy of TS-1 as a Late-Line Treatment for Metastatic Breast Cancer].

We report 4 female patients with metastatic breast cancer who were administered TS-1 as a late-line treatment and showed favorable outcomes. Their average age was 66.3. The patients, all of whom had undergone prior treatment with both anthracyclines and taxanes, showed intrinsic Luminal A or B subtypes. After administration of TS-1 in the lines of 2 to 9 in metastatic settings, all patients showed a long progression-free survival with a favorable quality of life.

[Utility of Prophylactic Administration of Pegfilgrastim in Breast Cancer Chemotherapy].

Febrile neutropenia(FN)is a frequent adverse event observed in cancer patients undergoing chemotherapy that may cause life-threatening infections. However, reducing the dose of anti-cancer drugs for breast cancer in adjuvant settings to prevent FN has been reported to adversely affect patient survival. Therefore, it is important to administer therapeutic agents as per their prescheduled regimens without delays or reductions in the dosage. From April 2015 to September 2017, pegfilgrastim was administered to 24 patients with breast cancer(primary prevention in 11 patients and secondary prevention in 13 patients)to prevent FN during chemotherapy in either adjuvant or metastatic settings. We were able to reduce the incidence of FN through prophylactic administration of pegfilgrastim without encountering serious adverse events. The inclusion of pegfilgrastim is considered essential for the safe administration of chemotherapy according to a preplanned schedule. Here, we discuss the indications, efficacy, and safety of the drug.

Candidate biomarkers predictive of anthracycline and taxane efficacy against breast cancer.

BACKGROUND: Since breast cancer shows diversity in clinical behaviors, a standard therapy does not always lead to favorable outcomes. MATERIALS AND METHODS: The expression statuses of candidate markers, including topoisomerase-II alpha (TOP2A), beta-tubulin (B-tub), and tissue inhibitor of metalloprotease-1 (TIMP-1), were immunohistochemically evaluated in 70 breast cancer tissues from 68 patients with advanced breast cancers receiving chemotherapy. RESULTS: The response rates to anthracycline and taxane were 70.5% and 67.2%, respectively. Overall, 25.1% ± 29.7%, 8.32% ± 10.1%, and 16.37% ±17.5% of cancer cells in the tumors studied were positive for B-tub, TOP2A, and TIMP-1 expressions, respectively. However, positive molecule expression did not differ between patients who did and did not exhibit clinical responses to treatment. The proportion of TOP2A-positive cancer cells was significantly higher among anthracycline responders than among nonresponders in HR-negative cancer (15.4% ±17.5% vs. 2.0% ± 2.4%, respectively, P = 0.048), whereas TOP2A and TIMP-1 expression statuses did not differ in HR-positive cancer. When patients were stratified according to B-tub, TOP2A, or TIMP-1 expression statuses (B-tub ≥10% vs. <10%, TOP2A ≥5% vs. <5%, TIMP-1 ≤20% vs. >20%, respectively), the proportion of patients with ≥10% B-tub-positive cancer cells was significantly higher in taxane responders than in nonresponders (72.4% vs. 37.5%, respectively, P = 0.016). Anthracycline responders showed a trend to have a higher proportion of patients with either ≥5% TOP2A-positive cancer cells or ≤20% TIMP-1-positive cancer cells compared to nonresponders (86.7% vs. 61.5%, respectively, P = 0.066). CONCLUSION: Immunohistochemical TOP2A, TIMP-1, and B-tub expression analyses are expected to be useful for predicting tumor responses to chemotherapy.

Indication of metronomic chemotherapy for metastatic breast cancer: Clinical outcomes and responsive subtypes.

The survival of patients with metastatic breast cancer (MBC) has not improved, despite recent advances in therapeutic strategies. This is mainly due to the fact that cytotoxic agents cannot be administered over a long period, even if they exhibit favorable activity, due to treatment-related side effects or acquisition of tumor resistance to the administered agents. Thus, the development of therapeutic strategies that may be used over a long time period is required to improve survival. We assessed the availability and clinical outcomes of metronomic chemotherapy, which is defined as continuous or frequent treatment with low doses of cytotoxic drugs. A total of 80 patients with MBC received chemotherapy in the metastatic setting, and the clinicopathological factors and clinical outcomes were retrospectively compared between 52 patients who received metronomic regimens and 28 patients who received other cytotoxic regimens. As regards clinical outcomes, the median time-to-treatment failure (TTF) and overall survival (OS) were significantly longer in the metronomic group compared with those in the non-metronomic group (TTF, 15 vs. 4 months, P=0.0001; and OS, 53 vs. 28 months P=0.0012, respectively). In the metronomic group, none of the 18 patients who responded to the regimen had triple-negative (TN) cancer (17 had luminal-type tumors and 1 had a human epidermal factor receptor 2-type tumor). Furthermore, TTF and OS were significantly longer in patients with non-TN cancer compared with those in patients with TN cancer in the metronomic group (TTF, 16 vs. 7 months, P=0.0014; and OS, 108 vs. 20 months, P=0.000007, respectively). The proportion of patients who experienced treatment-related adverse events was significantly lower in the metronomic group compared with that in the non-metronomic group (36.5 vs. 61.5%, respectively; P=0.038). In conclusion, metronomic chemotherapy is a viable option for luminal-type MBC in terms of effectiveness and minimal toxicity, regardless of metastatic sites or prior treatment. However, an alternative treatment is required for TN cancer.

Gradually-Deteriorating Liver Function due to Iron Overload Over Four Years after Allogeneic Stem Cell Transplantation.

In allogeneic hematopoietic stem cell transplantation (allo-SCT) recipients with liver dysfunction, it is often difficult to determine the cause. Several cases of liver dysfunction may be interpreted as chronic graft versus host disease without a definitive diagnosis, resulting in continued immunosuppressive therapy for longer periods. Allo-SCT recipients commonly require frequent red blood cell transfusions during the course of treatment and transplantation, leading to significant iron overload, which could be one of causes of liver dysfunction. Here we report an allo-SCT recipient with chronic deteriorating liver dysfunction due to iron overload, despite maintaining transfusion independence for more than four years. Using magnetic resonance-based liver iron concentration (MR-LIC), iron overload-related liver dysfunction was diagnosed. It drastically improved with monthly phlebotomy and has not recurred following its termination. The observations from our case suggested that iron overload should be recognized as a cause of chronic liver dysfunction even in patients who remain transfusion-independent for several years and that MR-LIC analysis is a useful and reliable method for detecting iron overload and monitoring the effect of iron-reduction therapy.

Primary cerebral lymphomatoid granulomatosis progressing to methotrexate-associated lymphoproliferative disease under immunosuppressive therapy.

Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive lymphoproliferative disease involving extranodal sites. Although LYG cerebral lesions are usually located adjacent to LYG pulmonary lesions, few reports have described the occurrence of primary cerebral LYG. We herein discuss a case of a 40-year-old Japanese woman with primary cerebral LYG that caused various neurological symptoms for more than five years and progressed to methotrexate-associated lymphoproliferative disease under treatment with immunosuppressive therapy. This case suggests that primary cerebral LYG should be considered a lymphoid neoplasm manifesting as a primary brain tumor and a component of the differential diagnosis of chronic neuroinflammatory disorders.

Factors responsible for long-term survival in metastatic breast cancer.

BACKGROUND: Although survival of patients with metastatic breast cancer (MBC) has been significantly prolonged over the past decade due to improvement of anti-cancer therapeutics, only a few patients survive for more than 10 years. It has not been determined which patients can have long-term survival with treatment. METHODS: To determine prognostic factors responsible for long-term survival, we retrospectively compared clinicopathologic factors of patients with MBC who survived for 50 months or more after diagnosis with patients who did not. Of 70 patients with MBC who received chemotherapy between November 2005 and September 2011, 23 patients who survived for 50 months or more after diagnosis and 28 patients who died within 50 months after diagnosis were assessed for their clinicopathologic factors and outcomes. RESULTS: The proportion of patients with hormone receptor-positive (HR+) tumors was significantly higher and the proportion of patients with triple negative tumors (TN) was lower in long-term survivors than in non-long-term survivors (HR+: 87% versus 28.6%, P=0.000037; TN: 13.1% versus 53.6%, P=0.0028). Metastatic site, number of disease sites, prior chemotherapeutic regimens and human epidermal growth factor receptor-2 (HER2) status did not differ between the two groups. The proportion of patients who received metronomic regimens was significantly higher in long-term survivors than in non-long-term survivors (65.2% versus 35.7%, P=0.034) when the most effective regimen among regimens that were received in metastatic settings was compared between the two groups. Overall response rate was significantly higher (82.6% versus 17.9%, P<0.00001) and time to treatment failure after receiving the most effective regimen was longer in long-term survivors than in non-long-term survivors (26 versus 5 months, P=0.0001). The number of chemotherapeutic regimens for breast cancer and that for MBC did not differ between the two groups. CONCLUSIONS: Patients with luminal-type MBC who benefit at least once from chemotherapy including metronomic regimens, or patients who continued to receive the most effective regimen for more than two years can be expected to have long-term survival after diagnosis of MBC, regardless of the number of chemotherapeutic regimens they had received.

Successful treatment of Philadelphia chromosome-positive mixed phenotype acute leukemia by appropriate alternation of second-generation tyrosine kinase inhibitors according to BCR-ABL1 mutation status.

Philadelphia chromosome-positive mixed phenotype acute leukemia (Ph(+)MPAL) is a rare type of acute leukemia having myeloid and lymphoid features. In the present study, we describe the successful treatment of a 71-year-old Japanese female patient with Ph(+)MPAL by the alternation of second-generation tyrosine kinase inhibitors according to BCR-ABL1 mutations. The patient survived in her third complete remission (CR) for over 4 years. In her first CR, the patient was treated with multiple-agent chemotherapy and underwent maintenance therapy with imatinib and monthly vincristine and prednisolone (VP). At the first relapse, an examination of the bone marrow revealed a transformation into acute lymphoblastic leukemia and an F317L mutation in BCR-ABL1 gene, which responded preferentially to nilotinib over dasatinib. She achieved second CR, and nilotinib with VP therapy was selected for maintenance treatment. At second relapse, BCR-ABL1 mutational analysis revealed Y253H mutation instead of F317L mutation, resulting in resistance to nilotinib. The patient achieved third CR with dasatinib and VP therapy, and maintained CR with this treatment. This suggests that appropriate alternation of TKIs may contribute to long-term survival in elderly patients with Ph(+)MPAL.

Successful diagnosis of type II enteropathy-associated T-cell lymphoma using flow cytometry and the cell block technique of celomic fluid manifesting as massive pyoid ascites that could not be diagnosed via emergency laparotomy.

Enteropathy-associated T-cell lymphoma (EATL), an intestinal tumor of intraepithelial T lymphocytes, is a rare and highly aggressive disease. We herein describe a case of type II EATL with massive pyoid ascites in which a histological examination could not be performed despite emergency laparotomy that was successfully diagnosed using flow cytometry and the cell block technique to analyze the celomic fluid. This case suggests that EATL should be included in the differential diagnosis of pyoid ascites of unknown origin and that flow cytometry and the cell block technique of assessing celomic fluid are useful procedures for diagnosing EATL, especially in cases in which conducting a histological examination is impossible.

Secondary neurolymphomatosis detected by whole-body diffusion-weighted magnetic resonance imaging: a case report.

Neurolymphomatosis (NL) is a rare clinical entity defined as peripheral nervous system infiltration by lymphoma. The diagnosis is difficult and often elusive. Whole-body diffusion-weighted magnetic resonance imaging (DW MRI) was developed to enhance the detection of vaguely delineated tumors. Here, we describe the case of a 71-year-old male with secondary NL of diffuse large B-cell lymphoma (DLBCL) that was successfully detected by whole-body DW MRI. The patient was diagnosed with DLBCL extending from the ethmoidal sinus to the nasal cavity, orbital cavity, and anterior cranial fossa. Although he was administered R-THP-COP chemotherapy and the tumor remarkably decreased in size, he developed painful paresthesia and weakness in the left upper and bilateral lower extremities during treatment. Because lymphoma cells were detected in his spinal fluid, high-dose methotrexate (MTX) and weekly intrathecal MTX and cytarabine injections were administered. Test results for lymphoma cells in the spinal fluid became negative ; however, the neurological disorders progressed. Whole-body DW MRI was performed as whole-body screening and could localize NL at the left cervical and bilateral lumbar nerve roots. Both cervical spine plain MRI and enhanced computed tomography performed around the same time could not detect the cervical lesion. Our case report suggests that whole-body DW MRI is a useful diagnostic imaging procedure, especially as whole-body screening in facilities where PET/CT is not available.

Relationship between severity of footpad dermatitis and carcass performance in broiler chickens.

The relationship between the severity of footpad dermatitis (FPD) and growth performance parameters (live weight, condemnation rate, leg meat yield and breast meat yield) was investigated in a total of 63 million broiler chickens that were processed over a period of 1,053 days between 2008 and 2012 at a full-scale processing plant in Kagoshima Prefecture, Japan. FPD scores and carcass data were summarized daily and analyzed to determine their correlations. It was found that FPD severity was positively correlated with the condemnation rate and negatively correlated with the live weight and leg meat yield. These results indicate that controlling FPD may play an important role in reducing condemnations while improving live weight and leg meat yields.

Successful treatment by azacitidine therapy of intestinal Behçet's disease associated with myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell diseases. It has been reported that several autoimmune diseases are associated with MDS. Recently, the co-occurrence of MDS with trisomy 8 and rare disorders of the immune system, such as Behçet's disease (BD), has been described. Prognosis in the older-onset group of MDS-associated BD is unfavorable. Here, we report a case of MDS-associated intestinal BD treated successfully by azacitidine therapy. A 59-year-old Japanese male suffering from recurrent high fever, melena, and oral and genital ulcerations was diagnosed with MDS with trisomy 8 and intestinal BD by endoscopic and bone marrow examinations. Immunosuppressive therapies, including infliximab, were ineffective. Due to his severe emphysema, the patient was considered ineligible for stem cell transplantation, and azacitidine therapy was initiated. With the exception of fever, the symptoms of intestinal BD improved, and severe malnutrition and anemia were ameliorated. Fluorescence in situ hybridization analyses of the bone marrow before the eighth cycle revealed that the trisomy 8 had not decreased. To our knowledge, this is the first report of azacitidine therapy for MDS-associated BD. We suggest that azacitidine may control intestinal BD by mechanisms other than those responsible for its effect in MDS.

Metronomic chemotherapy for metastatic breast cancer to prolong time to treatment failure to 12 months or more.

The objective of treatment for metastatic breast cancer (MBC) is to control the disease or disease-related symptoms. Prolonged survival has also often been achieved by chemotherapeutic regimens in this setting. Long-term administration of one therapeutic regimen is essential for prolonging survival as well as for maintaining quality of life in these patients. In this study, we focused on time to treatment failure (TTF) as a parameter that predicts patient survival and we retrospectively compared clinical outcomes of patients with MBC who showed TTF of ≥12 months (26 patients) and <12 months (29 patients). The proportion of hormone receptor-positive tumors and the number of prior chemotherapy regimens for MBC were significantly higher and tumor grade was lower in patients with TTF ≥12 months compared to those with TTF <12 months. With regard to clinical outcomes, the objective response rate (ORR) in patients with TTF ≥12 months was significantly higher and median time to progression (TTP) and overall survival (OS) were longer compared to those with TTF <12 months. Of note, the proportion of patients who received metronomic regimens was significantly higher in patients with TTF ≥12 months compared to those with TTF <12 months (80.8 vs. 24.1%, P=0.00003). To assess the clinical benefit of metronomic regimens, the efficacy in patients receiving metronomic and those receiving non-metronomic regimens was compared. Although there was no difference in ORR between the two groups, median TTP and OS were significantly longer in the metronomic compared to the non-metronomic group (TTP: 30 vs. 4 months, P=0.0017; OS: 68 vs. 28 months, P=0.0005). The results suggested that metronomic chemotherapy is useful for palliative care and also improved clinical outcomes as a regimen for which long-term administration may be expected.

Clinical usefulness of human epidermal growth factor receptor-2 extracellular domain as a biomarker for monitoring cancer status and predicting the therapeutic efficacy in breast cancer.

We assessed the clinical usefulness of human epidermal growth factor receptor-2 extracellular domain (HER2ECD) as a biomarker for detecting cancer and monitoring disease status and for predicting the efficacy of anticancer treatment in breast cancer. Five-hundred and eighty serum samples from 252 patients with breast cancer were examined for the concentration of HER2ECD to compare with conventional tumor markers (CEA, CA15-3, NCC-ST439 and BCA225). Also, in 19 patients with HER2-overexpressed advanced or recurrent breast cancer who were treated with trastuzumab, clinical outcomes were evaluated retrospectively to determine whether their serum HER2ECD levels predict clinical responses. The proportion of patients with elevated HER2ECD levels was 15.1%, which was compatible with those with elevated conventional marker levels. In patients with HER2-overexpressed breast cancer, the positive rate of HER2ECD was significantly higher (24.1%) than those of conventional markers (7.4-12.9%), suggesting the usefulness of HER2ECD for detecting cancer in this population. HER2-overexpressed patients responding to trastuzumab (12 of 19 patients) showed significantly higher serum HER2ECD level (p = 0.033) and longer time to progression (TTP) (p = 0.039) and overall survival (OS) (p = 0.031) than did patients not responding (seven patients). Furthermore, higher response rates were observed in patients with elevated HER2ECD levels than in patients without elevated HER2ECD levels (91.3% vs. 14.3%, p = 0.032), whereas there was no difference in survival between the two groups. The results suggest that HER2ECD is a useful biomarker not only for detecting breast cancer recurrence but also for predicting tumor responses to trastuzumab.

Occurrence of lymphoplasmacytic lymphoma 6 years after amelioration of primary cold agglutinin disease by rituximab therapy.

Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia, classified into primary and secondary types. Secondary CAD accompanies infection or malignant disease, most often lymphoma, whereas primary CAD frequently represents a lymphoproliferative bone marrow disorder characterized by clonal expansion of B cells. Here, I describe a case of lymphoplasmacytic lymphoma (LPL) developed 6 years after amelioration of primary CAD by rituximab monotherapy. A 54-year-old Japanese woman was diagnosed with primary CAD characterized by a small fraction of B lymphocytes and kappa laterality in the peripheral blood. M-protein was not detected by immuno-electrophoresis. The patient achieved remission following two courses of rituximab monotherapy. The level of IgM was specifically decreased, although levels of IgG and IgA were slightly increased. Six years after rituximab monotherapy, she developed LPL without CAD recurrence. Flow cytometry performed on bone marrow specimens revealed that lymphoma cells were positive for CD19 and CD20 with kappa laterality. The lymphoma may have transformed from clonal B lymphocytes at presentation of CAD. Rituximab monotherapy induced remission of CAD by specific decrease of IgM level, but did not eliminate the clonal B lymphocytes that may have progressed to LPL. This experience may provide clues toward the understanding of the pathophysiology of primary CAD with clonal lymphoproliferative disease of the bone marrow.

Hepatitis B reactivation in a multiple myeloma patient with resolved hepatitis B infection during bortezomib therapy : case report.

It has recently been reported that hepatitis B virus (HBV) reactivation in patients with hepatitis B surface antigen (HBsAg)-negative lymphoma during or after cytotoxic therapy occurs after the use of rituximab and stem cell transplantation for hematologic malignancies. However, clinical data on HBV reactivation in multiple myeloma patients have not been extensively reported. This is the first reported case of HBV reactivation in an HBsAg-negative myeloma patient treated with bortezomib (BOR) as salvage therapy and not stem cell transplantation. By closely monitoring HBV-DNA and early administration of entecavir, severe hepatitis was avoided and BOR therapy was continued. We suggest the importance of close monitoring of HBV-DNA for transplant-ineligible myeloma patients treated with BOR as salvage therapy.

Leukemic presentation of ALK-negative anaplastic large cell lymphoma in a patient with myelodysplastic syndrome.

A 50-year-old woman with a history of aplastic anemia developed cervical lymphadenopathy and atypical lymphocytosis. Atypical cells of lymph nodes were positive for CD3 and CD30 but negative for anaplastic lymphoma kinase (ALK). Bone marrow examination showed trilineage myelodysplasia. She was diagnosed with ALK-negative anaplastic large cell lymphoma (ALCL) with leukemic transformation and myelodysplastic syndrome (MDS) which presumably developed from aplastic anemia. The lymphoma was resistant to intensive chemotherapies, ultimately leading to death. Leukemic presentation of ALK-negative ALCL as an initial manifestation is extremely rare, and the progression of the disease may be influenced by MDS through alteration of immune functions.

Double-hit lymphoma at second relapse of Burkitt-like lymphoma: a case report.

Double-hit lymphoma (DHL) is a rare and extremely unfavorable type of lymphoma with concurrent chromosomal translocations of BCL2 and MYC. It is considered that BCL2 translocation precedes MYC events in lymphomagenesis of DHL. In fact, most cases of DHL arise de novo or following FL. We describe a very rare case of DHL arising from Burkitt-like lymphoma according to the revised European-American classification of lymphoid neoplasms. A 67-year-old Japanese male presented with persistent fever. [(18)F]-fluorodeoxyglucose positron emission tomography revealed multiple abnormal accumulations in the bone marrow, pancreas, and periphery of the left kidney. The patient was diagnosed with Burkitt-like lymphoma according to a bone marrow biopsy. At the disease onset and the first relapse, chemotherapy was effective and the patient experienced sustained and complete remission. At the second relapse, however, the clinical presentation and morphology of lymphoma cells were nearly identical, but a high level of chemoresistance was acquired, and the patient succumbed almost 1 month after hospitalization. Chromosomal analyses revealed a complex karyotype with concurrent t(14;18) and t(8;22) translocations, which have not been previously detected. It is therefore important to note that DHL cannot be diagnosed without chromosomal analysis. Cytogenetic analyses should thus be performed for patients with high-grade B-cell lymphoma and who experience a recurrence of this lymphoma.