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Background: It is important to confirm CD30 expression in T-cell lymphoma cases, but immunohistochemical staining for CD30 is not commonly performed and no comparison has been done between the results of flow cytometry (FCM) and immunohistochemical staining for CD30. Therefore, we devised a notation that we termed proportion of immunoreactivity/expression for FCM (PRIME-F notation), based on the cellular proportion showing different antigen-antibody reactivity., Methods: We retrospectively compiled 211 cases of T-cell lymphoma, assessed via FCM, from major hospitals in Miyagi Prefecture from January 2012 to January 2019, and compared 52 of these cases with the immunohistochemical immunoreactive (IR) pattern of CD30 (PRIME-I notation). The PRIME-F notation was divided into five levels: notations starting with "-" followed by 3, 2, and 1 ">" correspond to level-I, level-II, or level-III; notations starting with "(dim)+" correspond to level-IV; and those starting with "+" or "(bright)+" correspond to level-V., Results: The 52 cases of PRIME-F notation with "+" included 16 cases of peripheral T-cell lymphoma (PTCL/NOS), 3 of follicular T-cell lymphoma (FTL), 3 of angioimmunoblastic T-cell lymphoma (AITL), 6 of extranodal NK/T-cell lymphoma/nasal type (ENKL), 18 of adult T-cell lymphoma (ATL), and 6 cases of anaplastic large cell lymphoma (ALCL). Eight of the 52 cases were immunohistochemically CD30-negative. In the PRIME-F level-I to III group (excluding false-positive cases), 21.7% (5 out of 23 cases) were < 10% positive for CD30 upon immunohistochemistry (IHC). Contrarily, in the level-IV & -V group, no CD30 positivity rate of < 10% upon IHC was found (0%) (p = 0.0497). In level-IV, 42.9% of cases presented a CD30 negative rate > 1/3 upon IHC, while in level-V, only 7.1% (one out of 14 cases) did. The CD30 negative rate tended to be low (p = 0.0877) in level-V., Conclusions: To our knowledge, this is the first report describing the correspondence between FCM and immunohistochemistry findings for CD30 through newly proposed notations. The PRIME-F and PRIME-I notations for CD30 showed a minor positive correlation. The PRIME notation is considered universally applicable to antibodies, and notations of both FCM and IHC show great potential for big data., (© 2021. The Author(s).)

Background: Nucleosomes consist of DNA wrapped around a histone octamer core like beads on a string so that DNA can be condensed as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death where chromatin is fragmentated and released as mononucleosomes into the blood. The Nu.Q™ H3.1 assay measures total nucleosome concentration in plasma of humans and has been used to detect and identify cancer even at early stages. The objectives of this study were to determine if nucleosome levels could be used to distinguish between healthy dogs and dogs with various stages of lymphoma (LSA) using the Nu.Q™ H3.1 assay. A total of 126 dogs diagnosed with LSA and 134 healthy controls were recruited for this study. Plasma was collected from each dog and stored in K2-EDTA tubes. The LSA patient samples were recruited from TAMU or purchased from various biobanks. All control cases were recruited from TAMU., Results: Dogs with LSA had an approximately 7-fold increase in their plasma nucleosome concentrations compared to controls (AUC 87.8%). Nucleosome concentrations increased with cancer stage and dogs with B cell lymphomas had significantly higher nucleosome concentrations than dogs with T cell lymphomas., Conclusions: The Nu.Q™ H3.1 assay was able to reliably detect elevated nucleosome concentrations in the plasma of dogs with LSA. Furthermore, it appears that nucleosomes are useful for differentiating cancer from healthy individuals in canines., (© 2021. The Author(s).)

Background: The programmed cell death protein 1 (PD-1) and its ligand 1 and 2 (PD-L1/PD-L2) regulate the immune system, and the checkpoint pathway can be exploited by malignant cells to evade anti-tumor immune response. Soluble forms (sPD-1/sPD-L1/sPD-L2) exist in the peripheral blood, but their biological and clinical significance is unclear., Method: Time-resolved immunofluorometric assay (TRIFMA) and enzyme-linked immunosorbent assay (ELISA) were used to measure sPD-1, sPD-L1, and sPD-L2 levels in serum from 131 lymphoma patients and 22 healthy individuals., Results: Patients had higher sPD-1 and sPD-L2 levels than healthy individuals. In diffuse large B-cell lymphoma, patients with high International Prognostic Index score had higher sPD-1 levels and sPD-L2 levels correlated with subtype according to cell of origin. Compared to other lymphoma types, follicular lymphoma displayed higher sPD-1 and lower sPD-L1 levels along with lower ligand/receptor ratios., Conclusion: This is the first study to simultaneously characterize pretherapeutic sPD-1, sPD-L1, and sPD-L2 in a variety of lymphoma subtypes. The relation between higher sPD-1 levels and adverse prognostic factors suggests a possible biological role and potential clinical usefulness of sPD-1. Moreover, the reverse expression pattern in follicular lymphoma and T-cell lymphoma/leukemia may reflect biological information relevant for immunotherapy targeting the PD-1 pathway., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study investigates the anticancer potential of methanolic extract of A. subulatum dry fruits (MEAS) in Dalton's Lymphoma Ascites (DLA) cells in vitro and on DLA induced ascitic and solid tumor-bearing mice. MEAS induced apoptosis in DLA cells and MEAS administration effectively reduced tumor burden, and increased life span via modulating pro-inflammatory cytokines and regulating NF-κB pathway. MEAS seemed to be much safer than the standard drug cyclophosphamide, as the latter was associated with adverse effects such as body weight loss, depletion of hemoglobin level and hepatotoxicity, suggesting A. subulatum as a potential nutraceutical against cancer.

Background: Angioimmunoblastic T cell lymphoma (AITL) is an infrequent hematological malignancy with variable and often atypical presentations. The presence of dysproteinemia, autoantibodies and systemic involvement in AITL has often led to a delay in diagnosis or even misdiagnosis in practice. We herewith present a case of AITL that primarily presented with acute kidney injury associated with type II Cryoglobulinemia, the underlying cause was only identified 8 months after the emergence of initial symptoms., Case Presentation: A 67-year old woman presented with 2-month history of intermittent joint pain and a 3-day history of bilateral lower limb edema and acute kidney injury. Initial laboratory investigations showed marked hypocomplementemia with positive autoantibodies of ANA, anti-cardiolipin-IgM and direct antiglobulin. The serum and urinary Immunofixation and serum cryoglobulin tests were negative, while the serum free κ to λ light chain ratio was 0.231. A renal biopsy showed a diffuse proliferative glomerulonephritis with intracapillary pseudothrombi formation. There were orderly arranged microtubular structures of 20-35 nm in diameter in the subendothelial and mesangial area on electron microscopy. Shortly afterwards, the patient developed tingling affecting her finger tips and weak hands and legs. A diagnosis of cryoglobulinemia complicated with cryoglobulinemic glomerulonephritis and polyneuropathy was made. She responded well to methylprednisolone, plasma exchange and rituximab. However, 3 months later, she presented with generalized pruritic rash, weight loss, and inguinal lymphadenopathy. A subsequent inguinal excisional lymph node biopsy at month 8 revealed AITL as the underlying disease., Conclusions: AITL and its associated B cell dysregulation can give rise to autoimmunity and cryoglobulinemia which may conceal itself as the underlying disorder. In various clinical scenarios of auto-immune diseases, it is advisable that the clinicians should take into consideration the multi-faceted lymphoma.

Rationale: ALL is the most common form of leukemia (75% to 80%), it is characterized by clonal expansion of the lymphoid blasts in bone marrow, blood, and other tissues, which can be divided into T lineage and B lineage. Although relapse of acute leukemia is common, a change of immunophenotype at relapse only occurs rarely. Some of these cases have been labeled "lineage switch"., Patient Concerns: A 31-year-old man had multiple lymph nodes in the neck, and the lymph nodes on the right side adhered to the surrounding tissues. His lymphocytes ratio in blood was up to 86.3%. Flow cytometry of the bone marrow aspirate showed positive results for CD2, CD5, CD7, cCD3, TDT, CD4, CD8, and CD10, negative results for CD34, CD117, CD33, HLA-DR, CD19, and CD20. Twenty six months later, the patient felt pain in the neck and shoulder after touching. His lymphocytes of blood were 109.9×109 /L. 43 fusion genes and positive BCR/ABL was detected. Flow cytometry of the bone marrow aspirate showed pro B lymphocytes accounted for 85.54%, and positive expression of CD38, CD10, CD34, CD33, TDT, CD9, and HLA-DR. Moreover, the RT-PCR data showed the patient expressed high level of T cell and B cell development transcription factors., Diagnoses: Upon examination, the patient was initially diagnosed with T-lineage pro cell ALL. BM morphologic analysis presented complete remission (CR) after systemic chemotherapy. Twenty six months later, we discovered the patient was diagnosed with B-lineage acute lymphocytic leukemia., Interventions: Systemic chemotherapy is first given when a patient was diagnosed with T-cell acute lymphoblastic leukemia. After the patient happened linage switch, we adjusted the treatment plan, and the patient was complete remission after 1 course of treatment., Outcomes: Our case provides information of lineage switch from T-ALL to B-ALL in this report, which is never seen in our knowledge., Lessons: This lineage switch from T-ALL to B-ALL is never reported beforemoreover, the RT-PCR data showed the patient expressed high level of T cell and B cell development transcription factors. Its early recognition can let doctor provides appropriate therapy to patient.

Purpose: We assessed the frequency of triple-positive serology (viral capsid antigen [VCA]-immunoglobulin G [IgG], VCA-immunoglobulin M, Epstein-Barr nuclear antigen-IgG) for Epstein-Barr virus (EBV) in a small number of patients with angioimmunoblastic T-cell lymphoma (AITL) at disease onset., Methods: Nine patients with newly diagnosed AITL were retrospectively enrolled in the present study. For all of them, EBV serology data were available., Results: Of 9 patients, 7 (77.7%) had a triple-positive serology (VCA-IgG, VCA-IgM, EBNA-IgG ) for EBV. These patients were characterized by bone marrow involvement, high incidence of thrombocytopenia, and poor prognosis according to Revised International Prognostic Index and Prognostic Index for Angioimmunoblastic T-cell Lymphoma scores., Conclusion: Assessment of both viremia and serology for EBV could be useful in patients with clinical and laboratory data suggesting lymphoma diagnosis; furthermore, although our data need to be validated in a larger cohort of patients, triple positivity for EBV serology might help to direct the diagnosis toward AITL.

Recurrent hotspot (p.Gly17Val) mutations in RHOA encoding a small GTPase, together with loss-of-function mutations in TET2 encoding an epigenetic regulator, are genetic hallmarks of angioimmunoblastic T-cell lymphoma (AITL). Mice expressing the p.Gly17Val RHOA mutant on a Tet2 -null background succumbed to AITL-like T-cell lymphomas due to deregulated T-cell receptor (TCR) signaling. Using these mice to investigate therapeutics for AITL, we found that dasatinib, a multikinase inhibitor prolonged their survival through inhibition of hyperactivated TCR signaling. A phase I clinical trial study of dasatinib monotherapy in 5 patients with relapsed/refractory AITL was performed. Dasatinib was started at a dose of 100 mg/body once a day and continued until days 10-78 (median day 58). All the evaluable patients achieved partial responses. Our findings suggest that AITL is highly dependent on TCR signaling and that dasatinib could be a promising candidate drug for AITL treatment. SIGNIFICANCE: Deregulated T-cell receptor signaling is a critical molecular event in angioimmunoblastic T-cell lymphoma and can be targeted with dasatinib., (©2020 American Association for Cancer Research.)

In this study we aimed to identify a set of prognostic factors for angioimmunoblastic T-cell lymphoma (AITL) and establish a novel prognostic model. The clinical data of 64 AITL patients enrolled to the Fourth Hospital of Hebei Medical University (from 2012 Jan to 2017 May) were retrospectively analyzed. The estimated 5-year overall survival and progression-free survival of this cohort of patients were 45.8% and 30.8%, respectively. Univariate analysis showed that age > 60 years, performance status ≥2, Ann Arbor stage III/IV, lactate dehydrogenase > 250 U/L, serum albumin (ALB) < 30 g/l, Coombs test positive, and Ki-67 rate ≥ 70% were significantly associated with poor prognosis. Multivariate analysis demonstrated that age > 60 years, ALB < 30 g/l, Ki-67 rate ≥ 70%, and Coombs test positive were independent prognosis factors for AITL. Here a new prognostic model, named as AITLI, was constructed using the top 5 significant prognostic factors for AITL prognostic prediction. The AITL patients were stratified into 3 risk groups: low, intermediate, and high risk groups. The new prognostic model AITLI showed better performance in predicting prognosis than the International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) that were wisely used to predict the outcome for patients with other subtypes of lymphoma.

Purpose: Determine the frequency and prognostic value of circulating Epstein-Barr virus (EBV) DNA copy number in angioimmunoblastic T-cell lymphoma (AITL) patients who were treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) regimens., Materials and Methods: Sixty newly-diagnosed AITL patients were retrospectively enrolled in the present study. All patients were treated with DA-EPOCH regimen., Results: Twenty-two subjects (36.7%) had a EBV DNA-positive test at diagnosis. EBV DNA‒positive patients were associated with lower lymphocyte-monocyte ratio (p=0.024). Median follow-up was 40 months (range, 14 to 100 months). The overall response rate for all the 60 AITL patents were 71.7% (95% confidence interval [CI], 58.6 to 82.5) with 3-year progressive-free survival (PFS) rate of 30.9%±6.1% and overall survival (OS) rate of 60.1%±6.6%. Not only did PFS estimation differ between the EBV DNA‒positive and EBV DNA‒negative group (hazard ratio [HR], 2.24; 95% CI, 1.15 to 4.35; p=0.006), but also worse OS was observed in the pretreatment EBV DNA‒positive group than in the EBV DNA‒negative group (HR, 2.74; 95% CI, 1.22 to 6.19; p=0.006). EBV DNA test positivity was independent prognostic marker for both PFS (HR, 2.17; 95% CI, 1.17 to 4.00; p=0.014) and OS (HR, 3.24; 95% CI, 1.48 to 7.11; p=0.004) after adjusting International Prognostic Index and prognostic index for AITL score. Reduction in EBV copies was significantly associated with therapy-response., Conclusion: Circulating EBV DNA level was an important prognostic and monitoring marker for AITL patients who treated with DA-EPOCH regimens which cannot improve outcomes for AITL patients.

Aim: The aim of the study was to characterize quantitative and qualitative immunoglobulinopathies in patients with AITL at the onset of the disease., Materials and Methods: 55 patients with newly diagnosed AITL were enrolled in the study, the male/female ratio was 30/25; median age was 61 (29-81) years. Diagnosis was based on standard WHO criteria. Immunochemical studies of blood serum included serum protein electrophoresis/immunofixation, nephelometric quantification of total immunoglobulins, serum free light chain assay., Results: Quantitative and qualitative immunoglobulinopathies were determined in 49 (89,1%) of 55 pts. Quantitative immunoglobulinopathies were revealed in 47 (85.5%) of 55 cases, qualitative - in 14 (25,5%). Combination quantitative and qualitative immunoglobulinopathies was observed in 12 (21,8%) of 55 pts. The detected immunoglobulinopathies were divided into 4 groups: polyclonal hypergammaglobulinaemia, hypogammaglobulinaemia, oligoclonal gammapathy, and monoclonal gammapathy. Polyclonal hypergammaglobulinaemia was marked in 41 (74.5%) of 55 pts, elevated level of IgG was determined in 27 (49,15%) of 55 cases, IgM - in 18 (32,7%) and IgA - in 21 (38.2%). Interestingly, polyclonal IgE hypergammaglobulinaemia was detected in 12 (48,0%) of 25 cases of performed studies. Hypogammaglobulinaemia was detected in 8 (14,5%) of 55 cases. Oligoclonal gammapathy was determined in 4 (7.3%) of 55 pts. Monoclonal gammapathy was revealed in 11 (20,0%) of 55 cases. The amount of monoclonal immunoglobulin varied from 2.6 to 14.1 g/l. Monoclonal immunoglobulin Gk was detected in 5 of 11 pts, Gλ - in 2, Mλ - in 2, Mk - in 2. Monoclonal gammapathy was accompanied by polyclonal hypergammaglobulinaemia in 9 of 11 cases, hypogammaglobulinaemia - in 2., Conclusion: Quantitative and qualitative immunoglobulinopathies are observed in most patients at the onset of AITL. Quantitative abnormalities were determined more often than qualitative. Monoclonal gammapathy can be a manifestation of lymphoproliferation and other concomitant disorders. The prognostic value of immunochemical parameters is still unclear and requires dynamic observation and study.

Tuberculosis (TB) and Non-Hodgkins lymphoma (NHL) share similar clinical and radiological features, which make diagnosis a challenge. It is often difficult to rule out a diagnosis of extrapulmonary and/or disseminated TB because of its paucibacillary nature and difficulty in accessing the involved organs. In countries with high prevalence of TB like ours, empirical antitubercular treatment (ATT) is started, and the patient is followed up closely for response. We present a rare case of a 54-year old diabetic male who was suspected to be a case of disseminated TB but had a rapid downhill course despite ATT. A postmortem revealed features of a rare, aggressive T-cell NHL masquerading as disseminated TB., Competing Interests: There are no conflicts of interest

Background: Angioimmunoblastic T cell lymphoma is a rare malignancy, accounting for only 2% of all non-Hodgkin lymphomas, first described in the 1970s and subsequently accepted as a distinct entity in the current World Health Organization classification. Due to the paucity of this disease, there is still no identifiable etiology, no consistent risk factors, and the pathogenesis remains unclear., Case Presentation: An 83-year-old Caucasian man presented to an emergency department with palpitations and was found to have atrial fibrillation. During his hospitalization, he was found to have asymptomatic hypercalcemia with corrected calcium of 11.7. Ten days later while in rehabilitation, he started complaining of progressive fatigue and altered mental status was noted. He was found to have a calcium level of 15.5 and was admitted to the intensive care unit for management and further workup. He was found at that time to have, parathyroid hormone: < 1; 25 hydroxyvitamin D: 74; 1,25 dihydroxyvitamin D: 85.4; angiotensin-converting enzyme: 7; parathyroid hormone-related protein: < 2; and multiple myeloma workup was negative. Computed tomography of his chest and abdomen showed extensive retroperitoneal, pelvic, and mesenteric lymphadenopathy in addition to findings suggestive of peritoneal carcinomatosis. A right axillary lymph node biopsy showed immunohistochemical parameters consistent with angioimmunoblastic T cell lymphoma. After a lengthy discussion with his family, it was decided that no further treatment would be pursued. He had an aggressive course at the hospital during which he developed pleural effusions, ascites, and diffuse petechiae within 2 weeks; these were complications from his malignancy. Considering the poor outcomes of his aggressive disease, he decided to enroll in an out-patient hospice. He died within a few months as a result of cardiorespiratory arrest., Conclusions: This case illustrates a rare presentation of an extremely rare disease; that is, hypercalcemia in a patient who was later found to have angioimmunoblastic T cell lymphoma. Diagnosing angioimmunoblastic T cell lymphoma might be the most challenging part due to the wide array of clinical presentations, of which hypercalcemia accounts for only 1%. As seen in this case, most patients present in advanced stages of the disease with poor prognosis.

Recent genetic studies identified that the disease-specific G17V RHOA mutation, together with mutations in TET2, DNMT3A, and IDH2, is a hallmark of angioimmunoblastic T cell lymphomas (AITL). The diagnostic value of these mutations is now being investigated. Circulating tumor DNAs (ctDNAs) may offer a non-invasive testing for diagnosis and disease monitoring of cancers. To investigate whether these mutations are useful markers for ctDNAs in AITL and its related lymphomas, we performed targeted sequencing for TET2, RHOA, DNMT3A, and IDH2 in paired tumors and cell-free DNAs from 14 patients at diagnosis. Eighty-three percent of mutations detected in tumors were also observed in cell-free DNAs. During the disease course, mutations were detectable in cell-free DNAs in a refractory case, while they disappeared in a chemosensitive case. These data suggest that the disease-specific gene mutations serve as sensitive indicators for ctDNAs and may also be applicable for non-invasive monitoring of minimal residual diseases in AITL.

Background: Primary central nervous system lymphomas (PCNSLs) are relatively rare brain tumors. Accurate diagnosis is usually made by surgical biopsy. In addition to surgical biopsy and decompression, treatment options include high-dose methotrexate and chemotherapy, radiation therapy, and stem cell therapy. Because of the rarity of this disease, guidelines for PCNSL diagnosis and treatment usually are formed from a large series of experiences., Methods: We retrospectively reviewed 79 patients in our tertiary referral center during a 13-year period. All patients with PCNSL underwent surgical or bone marrow biopsy procedures, and diagnoses were confirmed by hematologists or neuropathologists. At the time of diagnosis, 44 patients presented with a single lesion. Human immunodeficiency virus was confirmed positive in 1 patient. The standard therapy protocol included high-dose methotrexate (intravenous and intrathecal) and chemotherapy with cytosine arabinoside, followed by external irradiation of the brain., Results: Significant prognostic factors in these patients were low serum lactate dehydrogenase levels and radiation therapy. Multiplicity of lesions at time of diagnosis did not imply a worse outcome, and surgical resection and debulking did not show a significant survival benefit., Conclusions: PCNSL has a poor prognosis. Further clinical trials and diagnostic tools are needed to reveal the complexity of this disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In humans, multiple cytokines have been linked to the development of lymphoma, and are relevant biomarkers for response to chemotherapy and prognosis. In contrast, only a few circulating cytokines have been studied in dogs with lymphoma. We prospectively enrolled thirty-one dogs newly diagnosed with multicentric lymphoma. Immunophenotype was determined by flow cytometry in all dogs, separating them into 2 subgroups: B cell lymphoma (n=21) and T cell lymphoma (n=10). Nineteen healthy dogs were enrolled in the control group. Circulating cytokine concentrations were measured using a commercial canine multiplex magnetic bead-based assay which included Interleukin-2 (IL-2), IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF), Tumor Necrosis Factor-α (TNF-α), Interferon γ (IFN-γ), IFN-γ induced Protein-10 (IP-10), Keratinocyte Chemoattractant-like (KC-like), and Monocyte Chemoattractant Protein-1 (MCP-1). The serum levels of each cytokine were first compared between the lymphoma and control groups, and then between the B cell lymphoma, T cell lymphoma, and control groups. There was no significant difference between the lymphoma and healthy control groups regarding sex, age and weight. MCP-1, IL-6, and IL-10 were significantly higher in dogs with lymphoma compared to healthy dogs (p<0.01, p=0.01 and p=0.03, respectively). MCP-1 and IL-10 were significantly higher in the B cell lymphoma group than in the healthy group (p=0.01, p=0.01, respectively). MCP-1 and IL-6 levels were significantly higher in the T cell lymphoma group than in the healthy group (p=0.02, p<0.01, respectively). IL-6 was significantly higher in the T cell lymphoma group than in the B cell lymphoma group (p=0.03). Significant differences among the groups were found for IL-15 and KC-like, but they were affected by age and/or sex. There were no significant differences in serum IL-2, IL-7, IL-8, IL-18, GM-CSF, TNF-α, IFN-γ, and IP-10 between any of the groups. Significant differences in red blood cell, white blood cell, neutrophil, lymphocyte and monocyte counts were also found between the different groups of dogs. Our data showed different serum cytokine and peripheral blood cell profiles between dogs with lymphoma and healthy dogs, and between dogs with B cell and T cell lymphoma. Further study is necessary to investigate the role of these cytokines in lymphoma pathogenesis, response to treatment, and prognosis, and the influence of age, sex and blood cell counts on their expression., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Published studies, taken together, suggest the existence of a single canine lymphoma entity, with a small clear cell appearance by cytological evaluation, a histopathological T-zone pattern and an aberrant CD45-negative T-cell phenotype, mostly characterized by long-term survival. We describe clinical presentation and outcome in a retrospective case series of canine small clear cell/T-zone lymphoma. Despite the reported predisposition of Golden retriever, this breed was not represented in our case series. Most dogs presented with stage V disease, whereas only few had clinical signs or peripheral cytopenias. Blood was almost always more infiltrated than bone marrow. Median survival confirmed the favourable prognosis described in literature, but a few dogs died within a short time. Also, a subgroup of dogs developed second malignancies, eventually leading to death. We did not investigate possible prognostic factors because of the wide variety in treatments, and further studies are needed to identify high-risk animals., (© 2015 John Wiley & Sons Ltd.)

Background: T-cell malignancies are heterogeneous in their clinical presentation and pathology, and have a poor prognosis. New biomarkers are needed to predict prognosis and to provide insights into signal pathways used by these cells. The goal of this study was to evaluate pretreatment serum cytokines in patients with newly diagnosed T-cell neoplasms and correlate with clinical outcome., Patients and Methods: We evaluated 30 cytokines in pretreatment serum from 68 untreated patients and 14 normal controls. Significantly elevated cytokines were correlated with patterns of abnormalities, event-free survival (EFS) and overall survival (OS)., Results: Our data demonstrated significantly elevated levels (versus controls) of seven cytokines-epidermal growth factor (EGF), IL-6, IL-12, interferon gamma-induced protein (IP)-10, soluble interleukin (sIL)-2Rα, monokine induced by gamma interferon (MIG), and IL-1RA-in all T-cell neoplasms (P < 0.05). In the angioimmunoblastic subset, all seven cytokines except IP-10 and in the peripheral T-cell lymphoma (TCL)-not otherwise specified subset, only IP-10, sIL-2Rα, MIG, and IL-8 were statistically elevated compared with control. Of these, elevated cytokines all but EGF were predictive of an inferior EFS; IL-1RA, sIL-2Rα, and MIG predicted an inferior OS. In a multivariate analysis, sIL-2Rα [hazard ratio (HR) = 3.95; 95% confidence interval (CI) 1.61-8.38] and IL-1RA (HR = 3.28; 95% CI 1.47-7.29) levels remained independent predictors of inferior EFS. TCL cell lines secreted high levels of sIL-2Rα and expressed the IL-2Rα surface receptor., Conclusions: This report describes the cytokines relevant to prognosis in patients with untreated TCL and provides the rationale to include serum IL-1RA and sIL-2Rα as biomarkers in future trials. Inhibition of these cytokines may also be of therapeutic benefit., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We report the case of a 76-year-old man diagnosed with angioimmunoblastic T-cell lymphoma (AITL) with high serum vascular endothelial growth factor (VEGF) preceded by Remitting seronegative symmetrical synovitis with pitting edema syndrome. He suffered respiratory discomfort caused by large amounts of pleural effusion. Interestingly, changes in serum VEGF measured over time were similar to changes in pleural effusion. Whether VEGF is related to the pathological condition of AITL is a very important question.

Case History: A 5-year-old male neutered Poodle cross presented with a 2-week history of non-specific gastrointestinal signs including vomiting, inappetence and lethargy (Case 1). A 14-year-old male neutered Staffordshire Bull Terrier presented with a 6-week history of progressive inappetence and lethargy (Case 2)., Clinical Findings: On presentation, Case 1 was dehydrated and had repeatable cranial abdominal pain. Mild hypoproteinemia with hypoalbuminemia, and electrolyte disturbances were found on biochemistry profile. Abdominal ultrasonography showed moderate diffuse small intestinal wall irregularity and moderate local lymphadenopathy. Haematology was repeated 2 days after initial presentation and showed a marked leucocytosis associated with an elevated circulating neoplastic cell population. On presentation, Case 2 was dehydrated, had palpable hepatomegaly and a mild generalised lymphadenopathy. A low number of large, atypical lymphocytes were found on haematology. Sonographically there was hepatomegaly with diffuse parenchymal changes and severe mesenteric lymphadenopathy., Laboratory Findings: Aspirates from the abdominal lymph nodes (Cases 1 and 2) and liver (Case 2), and blood smears revealed atypical neoplastic lymphoid populations, predominantly comprising large lymphocytes. Immunocytochemistry failed to determine the lymphoid phenotype in Case 1 but supported a T cell phenotype in Case 2. Immunohistochemistry of formalin-fixed paraffin-embedded (FF-PE) blood clots was able to identify a T cell phenotype in both cases. PCR for antigen receptor rearrangement results from both cases were consistent with an expanded T cell population., Diagnosis: In both cases, immunohistochemistry on FF-PE blood clots revealed a circulating T cell lymphocyte population, consistent with T cell lymphoproliferative neoplasia., Clinical Relevance: Immunohistochemistry on FF-PE blood clots offers clinicians a reliable, inexpensive and minimally invasive method of phenotyping neoplastic cells in circulation. Compared to other available methods, prolonged sample stability allowing for transport and retrospective examination is a distinct advantage. This technique should be considered a useful adjunct to the currently available methods for the phenotypic evaluation of lymphoid leukaemia in dogs.

Extracorporeal photopheresis (ECP) is accepted as a second-line therapy for the treatment of acute and chronic steroid-refractory graft versus host disease (GvHD), cutaneous T-cell lymphoma and solid organ transplantation. ECP should be validated: we compared in parallel apoptosis and proliferation analysis of patient lymphocytes treated with 8-MOP ECP using respectively Annexin V/7-aminoactinomycin D (7-AAD) and CFSE with a tetrazolium salt (WST-1) method. Using WST-1 assay we found a significant decrement (p < 0.01) of metabolic activity at 4 days between ECP-treated and untreated cells. This finding was confirmed by the significant decrease of cell proliferation and increase of cell death observed by CFSE and 7AAD-Annexin V, respectively. Accordingly, once validated against a reference method, WST-1 could represent a rapid and easy assay for routinely quality control of ECP., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Cancer cells have distinct metabolomic profile. Metabolic enzymes regulate key oncogenic signaling pathways and have an essential role on tumor progression. Here, serum metabolomic analysis was performed in 45 patients with T-cell lymphoma (TCL) and 50 healthy volunteers. The results showed that dysregulation of choline metabolism occurred in TCL and was related to tumor cell overexpression of choline kinase-α (Chokα). In T-lymphoma cells, pharmacological and molecular silencing of Chokα significantly decreased Ras-GTP activity, AKT and ERK phosphorylation and MYC oncoprotein expression, leading to restoration of choline metabolites and induction of tumor cell apoptosis/necropotosis. In a T-lymphoma xenograft murine model, Chokα inhibitor CK37 remarkably retarded tumor growth, suppressed Ras-AKT/ERK signaling, increased lysophosphatidylcholine levels and induced in situ cell apoptosis/necropotosis. Collectively, as a regulatory gene of aberrant choline metabolism, Chokα possessed oncogenic activity and could be a potential therapeutic target in TCL, as well as other hematological malignancies with interrupted Ras signaling pathways.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of non-Hodgkin lymphoma and displays an aggressive clinical course with poor outcome. To identify prognostic factors for AITL, we retrospectively analyzed 36 patients with AITL. The median age was 74 years with 83% of the patients having advanced stage. Eighty-three percent received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-like chemotherapies, resulting in an overall response rate of 63%. With a median follow-up of 9 years, the estimated overall survival at 5 years was 33.3%. Median serum level of soluble interleukin-2 receptor (sIL-2R) was 5615 U/mL at diagnosis, and over 10 000 U/mL of sIL-2R was identified as a significant poor prognostic factor, independent of the International Prognostic Index, Prognostic Index for peripheral T-cell lymphoma and Prognostic index for AITL (hazard ratio [HR], 4.42; 95% confidence interval [CI], 1.49-13.11; log-rank, p < 0.01). Our study shows that an ultra-high level of serum sIL-2R at diagnosis is a significant poor prognostic biomarker for AITL.

The purpose of our study was to assess the gonadal function in male survivors of childhood lymphoma. We studied 171 male survivors of childhood lymphoma (83 with B-cell non-Hodgkin lymphoma [B-NHL], 32 with T-cell non-Hodgkin lymphoma [T-NHL], 50 with Hodgkin lymphoma [HL], and 6 with anaplastic large-cell lymphoma [ALCL]), measuring follicle-stimulating hormone [FSH] and luteinizing hormone [LH] levels at a median age of 21.1 (17-30.4) years after a median delay of 9.3 (2-22.4) years from treatment. FSH levels were above normal range (≥10 IU/L) in 42.1% and LH levels ≥8 IU/L in only 8.9% of survivors. In multivariate analysis, only the following chemotherapeutic agents were associated with higher FSH or LH levels: cyclophosphamide (P < .0001, .04), lomustine (CCNU; P = .002, 0.04), and procarbazine (P < .0001, .07). No significant correlation was found between FSH or LH levels and age or pubertal status at diagnosis. Mean FSH level was significantly lower in NHL survivors treated more recently: 6 ± 5.1 IU/L in B-NHL survivors treated since 1986 versus 12.3 ± 5.4 IU/L for those treated before 1981 (P = .0001), and 6.8 ± 9.6 IU/L in T-NHL survivors treated since 1989 versus 9.4 ± 5.7 IU/L for those treated before 1989 (P = .035). In HL, mean FSH level was 12.4 ± 9.9 IU/L following procarbazine containing chemotherapy versus 3.4 ± 1.9 IU/L in the absence of procarbazine and increased significantly with the number of MOPP/OPPA (mechlorethamine, Oncovin [vincristine], procarbazine, and prednisone/Oncovin, procarbazine, and prednisone, and Adriamycin [doxorubicin]) courses received, from 6.8 ± 5.7 IU/L for 1-2 MOPP/OPPA to 12.6 ± 7.5 for 3-4 MOPP/OPPA and 19.6 ± 13.3 for more than 4 MOPP/OPPA (P for trend = .006). Testicular toxicity of alkylating agents on childhood lymphoma survivors is dose dependent and not correlated to diagnosis, age, or pubertal status at diagnosis.

The serum immunoglobulin free light chain (FLC) assay quantitates free kappa (κ) and lambda (λ) light chains. FLC elevations in patients with diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL), and chronic lymphocytic leukemia (CLL) are associated with an inferior survival. These increases in FLC can be monoclonal (as in myeloma) or polyclonal. The goal was to estimate the frequency of these elevations within distinct types of B-cell and T-cell non-Hodgkin lymphoma (NHL) and whether the FLC measurements are associated with event-free survival (EFS). We studied serum for FLC abnormalities using normal laboratory reference ranges to define an elevated κ or λ FLC. Elevations were further classified as polyclonal or monoclonal. Four hundred ninety-two patients were studied: 453 B-cell and 34 T-cell NHL patients. Twenty-nine % (142/453) of patients had an elevated FLC of which 10% were monoclonal elevations. Within B-cell NHL, FLC abnormalities were most common in lymphoplasmacytic (79%), mantle cell (68%), and lymphomas of mucosa associated lymphoid tissue (31%); they were least common in follicular (15%). The hazard ratio (HR) for EFS in all patients was 1.41 (95% CI; 1.11-1.81); in all B-cell NHL the HR was 1.44 (95% CI 1.11-1.96); in all T-cell NHL the HR was 1.17 (95% CI 0.55-2.49). FLC abnormalities predicted an inferior OS (HR = 2.75, 95% CI: 1.93-3.90, P < 0.0001). The serum FLC assay is useful for prognosis in both B-cell and T-cell types of NHL. In B-cell NHL further discrimination between a monoclonal and polyclonal elevation may be helpful and should be analyzed in prospective clinical trials., (© 2014 Wiley Periodicals, Inc.)

Peripheral T cell lymphomas (PTCL) account for 10-15 % of non-Hodgkin's lymphomas and are associated with poor prognosis. Although many prognostic factors for PTCL have been proposed, the heterogeneity of PTCL seems to be an obstacle in the establishment of clinically useful prognostic system, such as the International Prognostic Index (IPI) in diffuse large B cell lymphoma. PTCL with nodal manifestation include the HTLV-I-negative histologic subtypes of PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL). As PTCL-NOS encompasses a group of similar tumors and mostly shares their clinical pictures, we retrospectively analyzed clinical data from 77 patients diagnosed with ALCL, AITL, and PTCL-NOS at Kobe City Medical Center General Hospital from May 1994 to February 2012 to identify the prognostic factor for nodal PTCL. The median age of patients was 64 years, ranging from 23 to 83 years. With a median follow-up of 50 months, 5-year overall survival (OS) was 43 %. Multivariate analysis identified high-risk IPI (hazard ratio (HR), 4.04; P = 0.015), absolute monocyte count > 0.8 × 10(9)/L (HR, 3.44; P = 0.001), and serum concentration of IgA > 410 mg/dL (HR, 2.31; P = 0.013) as poor prognostic factors for OS. Thus, we have identified novel prognostic factors of monocyte count and serum IgA level for nodal PTCL. Although conventional prognostic models mainly reflect both tumor characteristics and host factors, the present model indicates the importance of host immune response as the unfavorable prognosis.

Angioimmunoblastic T cell lymphoma (AITL) belongs to the subgroup of mature T cell lymphomas according to the World Health Organization and is one of the common T cell lymphomas in Western countries. Particularly in cases in which histological confirmation cannot be easily achieved, immunophenotyping of peripheral blood can give important information for the differential diagnosis of AITL. sCD3⁻ CD4⁺ T cells are a typical feature of AILT in flow cytometry of peripheral blood. In this retrospective study, the diagnostic value of flow cytometry for the diagnosis 'AITL' was assessed by comparing the frequency of sCD3⁻ CD4⁺ T cells in leukemic AITL patients and in patients with other leukemic CD4⁺ T cell lymphomas. Immunophenotyping of peripheral blood by flow cytometry was performed in a lymphocyte gate using fluorochrome-labelled antibodies against CD3, CD2, CD4, CD5, CD7, CD8, CD10, CD14, CD16, CD19, CD56, CD57 and T cell receptor. In 17/17 leukemic AITL patients, a small but distinct population of sCD3⁻ CD4⁺ T cells was detected (mean percentage of sCD3⁻ CD4⁺ T cells in the lymphocyte gate: 11.9 ± 15.4%, range 0.1-51.8%). In contrast, sCD3⁻ CD4⁺ T cells were found in only 1/40 patients with other leukemic CD4⁺ T cell lymphomas (one patient with mycosis fungoides). sCD3⁻ CD4⁺ T cells have a high positive predictive value (94%) for the diagnosis 'AITL'. Flow cytometry is particularly useful in the differential diagnosis of AITL, even if the aberrant T cell population has a very low frequency. Further biological characterization of this subfraction of lymphoma cells is warranted., (Copyright © 2013 John Wiley & Sons, Ltd.)

Background: Canine T-cell lymphoma (TCL) is conventionally considered an aggressive disease, but some forms are histologically and clinically indolent. CD4 TCL is reported to be the most common subtype of TCL. We assessed flow cytometric characteristics, histologic features when available, and clinical outcomes of CD4+ TCL to determine if flow cytometry can be used to subclassify this group of lymphomas., Objective: To test the hypothesis that canine CD4+ T-cell lymphoma (TCL) is a homogeneous group of lymphomas with an aggressive clinical course., Animals: Sixty-seven dogs diagnosed with CD4+ TCL by flow cytometry and treated at 1 of 3 oncology referral clinics., Methods: Retrospective multivariable analysis of outcome in canine CD4+ TCL including patient characteristics, treatment, and flow cytometric features., Results: The majority of CD4+ TCL were CD45+, expressed low class II MHC, and exhibited an aggressive clinical course independent of treatment regimen (median survival, 159 days). Histologically, CD4+ TCL were classified as lymphoblastic or peripheral T cell. Size of the neoplastic lymphocytes had a modest effect on both PFI and survival in this group. A small number of CD4+ TCL were CD45- and class II MHC high, and exhibited an apparently more indolent clinical course (median survival not yet reached)., Conclusions and Clinical Importance: Although the majority of CD4+ TCL in dogs had uniform clinical and flow cytometric features and an aggressive clinical course, a subset had a unique immunophenotype that predicts significantly longer survival. This finding strengthens the utility of flow cytometry to aid in the stratification of canine lymphoma., (Copyright © 2014 by the American College of Veterinary Internal Medicine.)

Toll-like receptor (TLR) mediated recognition of pathogen associated molecular patterns allows the immune system to rapidly respond to a pathogenic insult. The "danger context" elicited by TLR agonists allows an initially non-immunogenic antigen to become immunogenic. This ability to alter environment is highly relevant in tumor immunity, since it is inherently difficult for the immune system to recognize host-derived tumors as immunogenic. However, immune cells may have encountered certain TLR ligands associated with tumor development, yet the endogenous stimulation is typically not sufficient to induce spontaneous tumor rejection. Of special interest are TLR5 agonists, because there are no endogenous ligands that bind TLR5. CBLB502 is a pharmacologically optimized TLR5 agonist derived from Salmonella enterica flagellin. We examined the effect of CBLB502 on tumor immunity using two syngeneic lymphoma models, both of which do not express TLR5, and thus do not directly respond to CBLB502. Upon challenge with the T-cell lymphoma RMAS, CBLB502 treatment after tumor inoculation protects C57BL/6 mice from death caused by tumor growth. This protective effect is both natural killer (NK) cell- and perforin-dependent. In addition, CBLB502 stimulates clearance of the B-cell lymphoma A20 in BALB/c mice in a CD8(+) T cell-dependent fashion. Analysis on the cellular level via ImageStream flow cytometry reveals that CD11b(+) and CD11c(+) cells, but neither NK nor T cells, directly respond to CBLB502 as determined by NFκB nuclear translocation. Our findings demonstrate that CBLB502 stimulates a robust antitumor response by directly activating TLR5-expressing accessory immune cells, which in turn activate cytotoxic lymphocytes.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of non-Hodgkin lymphoma characterized by aggressive symptoms and various abnormal laboratory test results. One of the rare immunologic abnormalities in AITL is exuberant polyclonal plasmacytosis, but its clinical significance has not been evaluated. This report concerns three AITL cases with exuberant polyclonal plasmacytosis and investigates its clinical impact by comparison with 12 patients without plasmacytosis. Our study found that the performance status (PS) of the former was significantly worse and their serum immunoglobulin levels were significantly higher. All other parameters, including B symptoms, various prognostic scores, blood cell counts other than plasmacyte, and serum levels of lactate dehydrogenase, C-reactive protein and soluble interleukin-2 receptor, showed no significant differences. More importantly, although the diagnosis of AITL with plasmacytosis was not straightforward in our series, outcomes of treatment with conventional chemotherapy or immunosuppressive therapy with cyclosporine A were favorable. To conclude, AITL should be considered a candidate underlying disease of exuberant polyclonal plasmacytosis. Provided a correct diagnosis is made early and is followed by adequate treatment, the prognosis for AITL with plasmacytosis may not be worse than that for those without plasmacytosis despite the severe exhaustion at first presentation.

In this retrospective study we evaluated the prognostic impact of peripheral blood monocytosis in patients with T-cell non Hodgkin lymphomas with "aggressive-typically nodal presentation". In this dataset monocytes >0.8 × 10(9)/L had a strong and statistically significant negative impact on overall survival (OS). In univariate analysis several parameters, including age >60 years, advanced stage, bone marrow involvement, ECOG PS >1, high LDH level, monocytes >0.8 × 10(9)/L, hemoglobin<120 g/L, albumin<35 g/L) had a negative influence on outcome, but in multivariate analysis, monocytosis alone had a stronger association with poor OS., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Previously we demonstrated that intraperitoneal (IP) inoculation of Rev-2-T-6 mouse lymphoma into syngeneic Balb/c hosts resulted in brain metastasis, migration along the optic nerve sheath, and ocular infiltration. In a second model: intravitreal inoculation of Rev-2-T-6 cells, the developing lymphoma was largely confined within the eye, seldom breaching the retinal pigment epithelium to reside in the choroid and sclera. There was no retrograde infiltration into the brain. Here, we describe a third, complementary model, whereby intravitreal inoculation of Rev-2-T-6 cells into Balb/c mice, followed by repeated IP inoculations of anti-LFA-1/CD11a monoclonal antibodies, results in extensive infiltration of the choroid, sclera, conjunctiva, eyelids and orbit. Furthermore, the lymphoma cells metastasize along the optic nerve sheath into the brain, and through the contralateral optic nerve tract into the contralateral eye. There is no systemic involvement of the lymphoma. Furthermore, anti-LFA-1 treatment results in elevated levels of serum anti-Rev-2-T-6 antibodies. Inoculation of Rev-2-T-6 cells into the vitreous of severe combined immune deficient mice demonstrates a course of clinical signs and histopathological findings similar to those in immune-competent mice treated with anti-LFA-1 antibodies, including invasion of the contralateral eye. Taken together, these findings suggest that confinement of Rev-2-T-6 lymphoma cells to the eye depends on active immune surveillance using a population of effector cells expressing the cell surface integrin LFA-1. Impairing this protection enhances tumor aggressiveness within the eye, and the likelihood of early retrograde lymphoma metastasis into the brain and the contralateral eye.

Objective: HBV infection may cause damage to the immune system and induce lymphomas as a result. Some scholars have indicated that HBsAg(+) reflecting HBV infection may have a relationship with lymphoma development. This study was designed to find out the specific stage of HBV infection which may be related to lymphoma., Methods: HBV serum markers, including HBsAg, HBsAb, HBeAg, HBeAb, HBcAb were tested among 100 lymphoma patients and 100 other patients who were diagnosed with non-lymphoma diseases in the First Hospital of Jilin University from 2010.1.1 to 2012.12.31. Three subgroups were established depending on different combinations of HBV serum markers. Subgroup 1 was HBsAg(+) representing the early stage of HBV infection. Subgroup 2 was HbsAb(+) representing convalescence and Subgroup 3 was "HbsAg and HbsAb negative combined with other positive markers" representing the intermediate stage of HBV infection. Chi square tests were used to compare the rates of three subgroups in lymphoma and control groups., Results: The rates of Subgroup were 13% and 5% respectively, an association between HBsAg and lymphoma being found (P<0.05). There was no difference between rate of Subgroup 2 of lymphoma group (15%) and that of control group (16%). In lymphoma group and control group , the rate of Subgroup 3 was different (12% vs 4%). This evidence was not specific to T cell lymphoma, B cell lymphoma or Hodgkin's lymphoma., Conclusions: Among serum markers of HBV, the combination of serum markers representing the early stage and intermediate stage of HBV infection have a relationship with lymphoma. Convalescence from HBV infection appears to have no relationship with lymphoma.

Objective: To explore the diagnostic value of serum levels of BamHI-W fragment, latent membrane protein-1 (LMP-1), BZLF1 and ZEBRA protein in patients with natural killer (NK)/T-cell lymphomas (NKTCLs), and to evaluate their relationship with clinical features., Methods: A total of 144 cases were analyzed in this study, including 48 NKTCLs patients, 48 other types of non-Hodgkin's lymphomas (NHL) patients and 48 healthy individuals as controls. Fluorescent quantitative real-time polymerase chain reaction (RQ-PCR) was used to measure the copy number of BamHI-W, LMP-1 and BZLF1 in serum. Enzyme linked immunosorbent assay (ELISA) was applied to measure the serum levels of ZEBRA protein. The relative operating characteristic (ROC) curve was applied in the evaluation of the tested markers in diagnosis of NKTCL patients, and the correlations among the tested markers and clinical feature were analyzed., Results: Compared with the controls, NKTCL group showed significantly higher levels of all the tested markers (P < 0.01). The median values of serum BamHI-W, LMP-1 and BZLF1 DNAs level were 1870, 394 and 499 copies/ml, respectively. And the median value of ZEBRA protein level was 73.3 µg/L. Furthermore, the ROC curves analysis revealed that all the area under curve (AUC) of LMP-1, BZLF1 and ZEBRA were more than 0.70, which were probably helpful in the diagnosis of NKTCL. To predict the presence of NKTCL, BamHI-W showed a high sensitivity of 81.3%, while BZLF1 showed a high specificity of 81.2%. Untreated patients seemed to have a significantly higher level of serum LMP1 DNA than that of treated patients (median value 898 copies/ml vs 0 copies/ml, P = 0.050). Correlation analysis showed that serum BamHI-W DNA level was correlated with the presence of B symptoms. All the three genes expressed in 94.4% of the untreated cases. On the other hand, none of them expressed in treated cases., Conclusions: It suggested that combined measurements of BamHI W, LMP1 and BZLF1 DNA levels might be helpful to the diagnosis and therapeutic monitor of NKTCL.

A 70-year-old man was admitted to our hospital with fever, generalized lymphadenopathy and hypoxia in October 2009. Blood examination demonstrated leukocytosis, anemia, thrombocytopenia and hyper γ-globulinemia. Peripheral blood and bone marrow smear showed marked plasma cell proliferation mimicking plasma cell leukemia. However, flow cytometric analysis showed that plasma cells were of polyclonal origin and M-protein was not detected by immunofixation of serum protein. Elevations of soluble interleukin 2 receptor and serum IL-6 were observed. A heavy Epstein-Barr viral load was detected in serum by real-time PCR. Biopsy was obtained from the right inguinal lymph node. The pathological diagnosis was angioimmunoblastic T-cell lymphoma (AITL) and rearrangement of the T-cell receptor Cβ1 gene was detected. The patient was treated with CHOP therapy, and all clinical manifestations, including fever, lymphadenopathy, anemia, thrombocytopenia, hyper γ-globulinemia, plasmacytosis and hypoxia, were improved. Only a few reported cases have demonstrated AITL with marked polyclonal plasmacytosis. Although pathological mechanisms of plasmacytosis in AITL patients have not been fully elucidated, it is suggested that IL-6 and IL-10 were involved in its pathogenesis in the present case.

Two dogs presented with suspected renal disease and polycythemia. Abdominal ultrasound examinations performed on both dogs revealed coalescing masses causing bilateral renomegaly. Serum erythropoietin (EPO) concentrations were physiologically inappropriate. Postmortem examinations revealed renal T-cell lymphoma in both dogs. One of the two dogs also had involvement of the liver and mesentery. EPO-immunohistochemistry on tissue samples demonstrated positive staining in tumor cells and occasional normal renal cells. This report illustrates that paraneoplastic EPO production may induce polycythemia. The pattern of EPO-immunohistochemistry staining suggested that the mechanism of production was due to tumor production of EPO and local hypoxia-induced EPO production from compression of normal renal cells and vasculature.

Background: extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a heterogeneous entity with poor survival, requiring risk stratification in affected patients. We proposed absolute lymphocyte count (ALC) as a new prognostic factor in ENKL., Patients and Methods: we retrospectively analyzed 128 patients newly diagnosed with ENKL. Independent prognostic factors of survival were determined by Cox regression analysis., Results: patients with low ALC (<1.0 × 10(9)/l) at diagnosis tended to have more adverse clinical features. Patients with high ALC (≥1.0 × 10(9)/l) at diagnosis had better overall survival (OS; P < 0.0001) and progression-free survival (PFS; P<0.0001), and achieved higher complete remission rates (P=0.001). Multivariate analysis with known prognostic factors showed that ALC, B symptoms and advanced stage were independent predictors for OS and PFS. Using the International Prognostic Index, Prognostic Index for Peripheral T-cell lymphoma unspecified, or Korean Prognostic Index for nasal NK/T-cell lymphoma, the majority of patients were in the low-risk category (with no or one adverse factor). ALC was helpful to differentiate the low-risk patients with different survival outcomes (P < 0.0001)., Conclusions: our data suggest that ALC at diagnosis is a novel, powerful predictor of prognosis in ENKL. Immune status at diagnosis might have an important influence on survival in patients with ENKL.