Improving the Cyclic Reversibility of Layered Li-Rich Cathodes by Combining Oxygen Vacancies and Surface Fluorination.

Layered-type Li-rich cathode materials have attracted significant attention for next-generation Li-ion batteries, but the advantage of their high capacity is eclipsed by their poor reversibility upon cycling. Irreversible oxygen redox activity and surface degradation have been deemed as the root cause and direct cause for their poor performance, respectively. We attempted to suppress surface degradation by inserting fluoride ions up to some depth on the surface. By fluorination with NH4HF2 after introducing a significant amount of oxygen vacancies in layered Li1.2Ni0.2Co0.2Mn0.4O2 by using CaH2 as a reducing agent, the reversible capacity reached 268 mAh/g, and the capacity retention after 100 cycles was about 99%. The scanning transmission electron microscopy-electron energy loss spectroscopy (STEM-EELS) technique revealed that, in contrast to directly fluorinated samples, our materials exhibit deeper fluorine signals besides surface signals, and hard X-ray photoelectron spectroscopy (HAXPES) patterns show ionic and covalent fluorine coordination. These results indicate that the combination of oxygen deficiency introduction and surface fluorination allows some F- ions to occupy near-surface oxygen vacancy sites rather than forming only a LiF layer on the surface, suggesting a new strategy to modify cathode materials for lithium-ion batteries.

Unique Li deposition behavior in Li3PS4 solid electrolyte observed via operando X-ray computed tomography.

The problem of lithium dendrites must be addressed for practical lithium metal all-solid-state batteries. Herein, three-dimensional morphological changes within Li3PS4 electrolyte away from the anode were observed using operando X-ray computed tomography. We revealed that the electronic conduction of decomposition and the electrolyte/void interface cause the lithium deposition within the Li3PS4.

Challenges for fluoride superionic conductors: fundamentals, design, and applications.

Electronics, which harnesses the properties of electrons, has made remarkable progress since its inception and is a cornerstone of modern society. Ionics, which exploits the properties of ions, has also had a profound impact, as demonstrated by the award of the Nobel Prize in Chemistry in 2019 for achievements related to lithium-ion batteries (LIBs). Ionic conduction in solids is the flow of carrier ions through a solid owing to an electrical or chemical bias. Some ionic materials have been studied intensively because their ionic conductivities are higher than those of liquids, even though they are solids. Among various conductive species, fluoride ions are the most promising charge carriers for fluoride-ion batteries (FIBs) as post LIBs. Increasing fluoride-ion conductivity toward the superionic conductive region at room temperature would be a breakthrough for the room-temperature operation of all-solid-state FIBs. This review focuses on fluoride-ion conductors, from the general concept of ions to the characteristics of fluoride ions. Fluoride-ion conductors are classified according to material type and form, and our current understanding, identification of problems, and future directions are discussed from experimental and theoretical physics perspectives.

Clinical significance of oxidative stress for untreated patients with diffuse large B-cell lymphoma.

Oxidative stress serves an important role in carcinogenesis. The present study investigated the clinical significance of oxidative stress as a prognostic factor for diffuse large B-cell lymphoma (DLBCL). The participants comprised 55 consecutive patients with DLBCL. A commercially available derivatives of reactive oxygen metabolites (d-ROMs) test kit was used to assess oxidant levels. Similarly, a commercially available biological antioxidant potential (BAP) test was used to assess antioxidant levels. The antioxidative/oxidative stress ratio was calculated as d-ROMs/BAP. The median serum concentration of d-ROMs was 425 µM. The levels of d-ROMs were significantly higher in patients with DLBCL than in healthy volunteers (P<0.01). The complete remission (CR) rates in patients with d-ROMs <425 and ≥425 µM were 81.5 and 85.7%, respectively [not significant (NS)]. The 3-year overall survival (OS) rates for patients with d-ROMs <425 and ≥425 µM were 67.2 and 72.0%, respectively (NS). The median BAP was 2,002 µM. The CR rates of patients with BAP <2,002 and ≥2,002 µM were 77.8 and 88.9%, respectively (NS). The 3-year OS rates of patients with BAP <2,002 and ≥2,002 µM were 60.9 and 75.9%, respectively (NS). No significant difference in the d-ROMs/BAP ratio was observed between groups. Multivariate analysis revealed that d-ROMs were an independent prognostic factor for progression-free survival.

Spin polarization in the phase diagram of a Li-Fe-S system.

Divalent and trivalent states of Fe ions are known to be stable in inorganic compounds. We focus a novel LixFeS5 cathode, in which the Li content (x) changes from 2 to 10 by an electrochemical technique. As x increases from 2, a Pauli paramagnetic conductive Li2FeS5 phase changes into a superparamagnetic insulating Li10FeS5 phase. Density functional theory calculations suggest that Fe+ ions in a high-x phase are responsible for ferromagnetic spin polarization. Reaching the monovalent Fe ion is significant for understanding microscopic chemistry behind operation as Li-ion batteries and the original physical properties resulting from the unique local structure.

R-THP-COP versus R-CHOP in patients younger than 70 years with untreated diffuse large B cell lymphoma: A randomized, open-label, noninferiority phase 3 trial.

Pirarubicin (tetrahydropyranyl adriamycin [THP]) is an anthracyclin with less cardiotoxicity than doxorubicin (DOX). We previously reported the efficacy and safety of R-THP-COP consisting of rituximab (R), THP, cyclophosphamide (CPA), vincristine (VCR), and prednisolone (PSL) for diffuse large B cell lymphoma (DLBCL) in phase 2 studies. Here, we prospectively compared the efficacy and safety of the R-THP-COP and standard R-CHOP regimen (consisting of R, CPA, DOX, VCR, and PSL) in a noninferiority phase 3 trial. This prospective, randomized phase 3 study included patients younger than 70 years of age with previously untreated DLBCL. The regimen consisted of R (day 1), DOX, or THP (day 3), CPA (day 3), VCR (day 3), and PSL for 5 days every 3 weeks for 6 to 8 cycles. Between July 5, 2006 and June 11, 2013, 81 patients were randomly assigned to the treatment groups (R-CHOP group, 40 patients; R-THP-COP group, 41 patients). R-THP-COP was noninferior to R-CHOP, as assessed by the primary endpoint of complete response rate (85% vs 85% respectively). With a median follow-up of 75.2 months, the 5-year overall survival was 87% in the R-CHOP group and 82% in the R-THP-COP group (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.31-2.49; P = .82). The 5-year progression-free survival was 74% in the R-CHOP group and 79% in the R-THP-COP group (HR: 1.37, 95% CI: 0.56-3.55; P = .49). No grade 3 cardiac side effects were observed in either group. No serious late adverse reactions were observed in either group, with the exception of therapy-related acute myeloid leukemia in the R-THP-COP group. These data indicate that R-THP-COP is noninferior to R-CHOP with regard to clinical response, and has an acceptable safety profile. Thus, this regimen may be an alternative therapy to R-CHOP.

Association between increased serum GP88 (progranulin) concentrations and prognosis in patients with malignant lymphomas.

BACKGROUND: GP88 (progranulin; PGRN) is a secreted 88kDa glycosylated protein, with important functions, including inflammation and tumorigenesis. We assessed the significance of GP88 expression in survival outcomes of patients with malignant lymphoma (ML). METHODS: Serum samples from 254 previously untreated ML patients were examined to measure GP88 concentrations using a sandwich human GP88 ELISA kit. Immunohistochemical analyses were performed to examine GP88 tumor tissue expression. RESULTS: The median serum GP88 concentration of ML patients was 91.3ng/ml, and was significantly higher than that of the control group (median, 57.7ng/ml) (p<0.0001). Association between GP88 serum concentrations and overall survival (OS) was examined in patients with diffuse large B cell lymphoma (DLBCL) who had been stratified based on their serum GP88 concentrations. Kaplan Meier survival analysis showed that patients with serum GP88 concentrations of ≤116 and >116ng/ml, had 5-y OS rates of 70% and 50%, respectively (p=0.02). The immunohistochemical analyses of GP88 tumor expression revealed that DLBCL patients had lymphoma cells that were positive for GP88. CONCLUSIONS: High serum GP88 concentrations are associated with poor prognosis in patients with DLBCL.

Serum concentrations of l-kynurenine predict clinical outcomes of patients with peripheral T-cell lymphoma, not otherwise specified.

Indoleamine 2,3-dioxygenase exerts intense immunomodulatory effects due to enzymatic activities that catalyze the breakdown of the essential amino acid l-tryptophan. The activity of indoleamine 2,3-dioxygenase can be estimated by measuring serum l-kynurenine concentrations. Here, we aimed to determine the role of l-kynurenine as a prognostic factor for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in a retrospective analysis of data derived from 31 consecutive patients between June 2000 and March 2013 who were histologically diagnosed with PTCL-NOS according to the World Health Organization classification and treated with 6-8 cycles of cyclophosphamide, doxorubicin or pirarubicin, vincristine, and prednisolone. l-kynurenine concentrations in serum samples collected at admission were measured using high-performance liquid chromatography. The median serum concentration of l-kynurenine was 3.28 (range 0.92-8.16) µM. The l-kynurenine cutoff was set at 3.07 µM using receiver operating characteristics curves. The complete remission rates of patients with l-kynurenine <3.07 and ≥3.07 µM were 69% and 51%, respectively. The 5-year overall survival (OS) rates for patients with l-kynurenine <3.07 and ≥3.07 µM were 80.2% and 23.4%, respectively (p < 0.001). More advanced age, poor performance status, elevated lactate dehydrogenase, an unfavorable International Prognostic Index, and a poor prognostic index for T-cell lymphoma were significantly worse factors for OS. Multivariate analyses revealed only l-kynurenine as an independent prognostic factor for OS. In conclusion, serum concentrations of l-kynurenine might comprise a novel prognostic factor with which to determine the outcomes of treatment for PTCL-NOS. Copyright © 2016 John Wiley & Sons, Ltd.

A salvage chemotherapy of R-P-IMVP16/CBDCA consisting of rituximab, methylprednisolone, ifosfamide, methotrexate, etoposide, and carboplatin for patients with diffuse large B cell lymphoma who had previously received R-CHOP therapy as first-line chemotherapy.

We have reported the efficacy of the salvage chemotherapy P-IMVP16/CBDCA for patients with diffuse large B cell lymphoma (DLBCL) who had previously received CHOP before the availability of rituximab (R). Here, we confirmed the efficacy of R combined with P-IMVP16/CBDCA as a salvage chemotherapy for patients with DLBCL, who had previously received R-CHOP. We retrospectively analysed 59 patients with relapse or refractory DLBCL (38 male patients and 21 female patients) presenting between June 2004 and June 2013. The patients received R 375 mg/m2 on day 1, methylprednisolone 1000 mg/body for 3 days (from day 3 to day 5), ifosfamide 1000 mg/m2 for 5 days (from day 3 to day 7), methotrexate 30 mg/m2 on day 5 and day 12, etoposide 80 mg/m2 for 3 days (from day 3 to day 5), and carboplatin 300 mg/m2 on day 3 every 21 days. Patients aged 70 years or older were given 75% of the standard dose. The overall response rate (complete response + partial response) was 64.4%. The 2-year overall survival rate was 55.3%. The 2-year progression free survival rate was 34.7%. The 2-year overall survival rate was 61.5% for the relapse patients, and 15.6% for the refractory patients (p < 0.0001). One patient died because of sepsis related to the treatment regimen. Non-hematological adverse effects were mild and tolerable. The R-P-IMVP-16/CBDCA regimen displayed a significant activity in relapsed DLBCL, with acceptable toxicity, and should be considered a candidate for salvage chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd.

CHOP or THP-COP regimens in the treatment of newly diagnosed peripheral T-cell lymphoma, not otherwise specified: a comparison of doxorubicin and pirarubicin.

The CHOP regimen consisting of cyclophosphamide, doxorubicin (DOX), vincristine and prednisolone has been the most used regimen for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Pirarubicin [tetrahydropyranyladriamycin (THP)], a derivative of DOX, is an anthracycline with reportedly less cardiotoxicity than DOX. Here, we confirmed the efficacy of THP-COP using THP instead of DOX in the treatment of PTCL-NOS. The study protocol employed a retrospective, consecutive entry design. We retrospectively analysed 56 patients with PTCL-NOS who had received THP-COP or CHOP. These regimens were performed every 21 days. Twenty-nine patients received THP-COP, and 27 received CHOP. There were no significant differences in known prognostic factors, including in the International Prognostic Index (IPI) and the prognostic index for T-cell lymphoma (PIT), between the two groups. Complete remission rates in patients with THP-COP and CHOP were 52% in both groups; the 3-year overall survival (OS) rates were 67% and 52% (p = 0.074), and the 3-year progression-free survival (PFS) rates were 51% and 29% (p = 0.070), respectively. In patients with low IPI (low or low-intermediate), THP-COP had significantly better 3-year OS (100% vs. 64%; p < 0.001) and 3-year PFS (75% vs. 33%; p < 0.05) than CHOP. Similar differences between THP-COP and CHOP were observed in patients with a low PIT (groups 1 or 2). Our study showed that THP-COP produced results equivalent to CHOP regarding efficacy and safety in patients with PTCL-NOS. In patients with low IPI or PIT, THP-COP resulted in significantly better prognosis. Copyright © 2015 John Wiley & Sons, Ltd.

Cytokeratin-positive fibroblastic reticular cell tumor with follicular dendritic cell features: a case report and review of the literature.

Fibroblastic reticular cell (FRC) neoplasms, which are one of the histiocyte tumor types, are very rare. Here we report a cytokeratin (CK)-positive FRC neoplasm having features of follicular dendritic cells in a 54-year-old woman with right axillary lymph node swelling. The resected lymph node showed multiple nodular aggregations simulating and replacing normal follicles. The tumor cells had a uniform, large and oval to polygonal shape, abundant cytoplasm, and various sizes of nuclei with central eosinophilic nucleoli and coarse nuclear chromatin. They were positive for CK AE1/AE3+CAM5.2, CK7, tenascin C, l-caldesomone, and CD21, weakly positive for S100, and negative for CD1a. Ultrastructurally, the tumor cells had long interdigitating microvillus-like cell processes and oval to elongated vesicular nuclei. In addition, the intercellular spaces contained accumulations of collagen, and some tumor cells had desmosomal-like junctions. These findings suggest that the present case is a CK-positive FRC tumor with follicular dendritic cell features.

Pathogenesis of Morquio A syndrome: an autopsied case reveals systemic storage disorder.

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase, which results in systemic accumulation of glycosaminoglycans (GAGs), keratan sulfate and chondroitin-6-sulfate. Accumulation of these GAGs causes characteristic features as disproportionate dwarfism associated with skeletal deformities, genu valgum, pigeon chest, joint laxity, and kyphoscoliosis. However, the pathological mechanism of systemic skeletal dysplasia and involvement of other tissues remain unanswered in the paucity of availability of an autopsied case and successive systemic analyses of multiple tissues. We report here a 20-year-old male autopsied case with MPS IVA, who developed characteristic skeletal features by the age of 1.5 years and died of acute respiratory distress syndrome five days later after occipito-C1-C2 cervical fusion. We pathohistologically analyzed postmortem tissues including trachea, lung, thyroid, humerus, aorta, heart, liver, spleen, kidney, testes, bone marrow, and lumbar vertebrae. The postmortem tissues relevant with clinical findings demonstrated 1) systemic storage materials in multiple tissues beyond cartilage, 2) severely vacuolated and ballooned chondrocytes in trachea, humerus, vertebrae, and thyroid cartilage with disorganized extracellular matrix and poor ossification, 3) appearance of foam cells and macrophages in lung, aorta, heart valves, heart muscle, trachea, visceral organs, and bone marrow, and 4) storage of chondrotin-6-sulfate in aorta. This is the first autopsied case with MPS IVA whose multiple tissues have been analyzed pathohistologically and these pathological findings should provide a new insight into pathogenesis of MPS IVA.

Serum level of soluble tumor necrosis factor receptor 2 is associated with the outcome of patients with diffuse large B-cell lymphoma treated with the R-CHOP regimen.

BACKGROUND: Serum soluble tumor necrosis factor receptor 2 (sTNFR2) concentration predicted the clinical outcome of patients with aggressive non-Hodgkin's lymphoma including diffuse large B-cell lymphoma (DLBCL) treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) in our previous study. However, after rituximab (R) was introduced in clinical practice, R-CHOP replaced CHOP as the standard therapy for DLBCL. PATIENTS AND METHODS: In this study, we re-evaluated the prognostic significance of serum sTNFR2 in 154 patients with DLBCL treated with R-CHOP. RESULTS: Five-yr overall survival (5-yr OS) rates with sTNFR2 ≥20 ng/mL and <20 ng/mL were 29.2% and 83.3% (P < 0.0001), respectively, and the corresponding 5-yr progression-free survival (5-yr PFS) rates were 26.9% and 76.4% (P < 0.0001), respectively. A multivariate analysis revealed that serum sTNFR2 and complete remission (CR) were independent prognostic factors for both OS (CR: P < 0.0001, sTNFR2: P = 0.0001) and PFS (CR: P < 0.0001, sTNFR2: P = 0.0001). The prognosis of patients with poor risk groups according to the revised International Prognostic Index who also had high serum sTNFR2 was especially poor. CONCLUSION: Serum sTNFR2 might be a powerful prognostic factor for patients with DLBCL in the rituximab era.

Diagnosis of the jejunoileal lymphoma by double-balloon endoscopy.

AIM: To investigate the feasibility of double-balloon endoscopy (DBE) to detect jejunoileal lymphoma, compared with fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Between March 2004 and January 2011, we histologically confirmed involvement of malignant lymphoma of the jejunoileum in 31 patients by DBE and biopsy. In 20 patients of them, we performed with FDG-PET. We retrospectively reviewed the records of these 20 patients. Their median age was 64 years (range 50-81). In the 20 patients, the pathological diagnosis of underlying non-Hodgkin's lymphoma (NHL) comprised follicular lymphoma (FL, n = 12), diffuse large B cell lymphoma (DLBCL, n = 4), mantle cell lymphoma (MCL, n = 2), enteropathy associated T cell lymphoma (ETL, n = 1) and anaplastic large cell lymphoma (ALCL, n = 1). RESULTS: Ten cases showed accumulation by FDG-PET (50%). FDG-PET was positive in 3 of 12 FL cases (25%) while in 7 of 8 non-FL cases (88%, P < 0.05). Intestinal FL showed a significantly lower rate of positive FDG-PET, in comparison with other types of lymphoma. Cases with endoscopically elevated lesions (n = 10) showed positive FDG-PET in 2 (20%), but those with other type NHL did in 8 of 10 (80%, P < 0.05). When the cases having elevated type was compared with those not having elevated type lesion, the number of cases that showed accumulation of FDG was significantly smaller in the former than in the latter. CONCLUSION: In a significant proportion, small intestinal involvement cannot be pointed out by FDG-PET. Especially, FL is difficult to evaluate by FDG-PET but essentially requires DBE.

Clinical significance of jejunoileal involvement of non-Hodgkin's lymphoma detected by double-balloon enteroscopy.

Jejunoileal involvement of non-Hodgkin's lymphoma (NHL) is an important diagnostic factor in determining optimal treatment strategies. Here, we used double-balloon enteroscopy (DBE) to detect jejunoileal involvement of NHL and studied its clinical significance in a series of patients with NHL. Adults aged between 18 and 85 years with infiltration of the stomach, duodenum, or colon confirmed by gastrointestinal endoscopy or colonoscopy, suspected jejunoileal involvement determined by CT or FDG-PET, or any other gastrointestinal symptoms, were eligible for inclusion in the study. Among 428 patients with histologically confirmed NHL between 2004 and 2011, 83 were eligible for DBE, but 20 patients were excluded due to rejection or poor clinical status. Thus, 63 underwent DBE. The 3-year overall survival rate was significantly lower in patients with (n = 33), than without (n = 30) jejunoileal involvement of NHL confirmed by DBE (49 vs. 92 %, p < 0.005). Four participants developed aspiration pneumonia, but recovered after treatment with antibiotics.

Lactobacillus acidophilus strain L-92 induces CD4(+)CD25(+)Foxp3(+) regulatory T cells and suppresses allergic contact dermatitis.

The anti-allergic mechanism of heat-killed Lactobacillus acidophilus strain L-92 has not been fully investigated. Recent studies have reported that CD4(+)CD25(+)Foxp3(+) (forkhead box P3) T regulatory (Treg) cells play important roles in controlling allergic diseases. Hence, we examined the effect of orally administered L-92 on CD4(+)CD25(+)Foxp3(+) cell populations. BALB/c mice were supplemented daily with L-92 by gavage for 5 weeks. 2,4-Dinitrofluorobenzene (DNFB) was used to induce allergic contact dermatitis (ACD) in mice. Fluorescent-activated cell sorter (FACS) analysis was used to determine CD4(+)CD25(+)Foxp3(+) T cell populations in spleen and cervical lymph nodes (CLN). Interleukin-10 (IL-10), transforming growth factor-ß (TGF-ß), and Foxp3 mRNA expressions in mouse ear skin were investigated by real-time reverse transcription-polymerase chain reaction (RT-PCR). The percentage of CD4(+)CD25(+)Foxp3(+) T cell populations were significantly increased in both spleen and CLN of L-92-fed group than vehicle and control. In addition, L-92 produced higher levels of Foxp3, IL-10 and TGF-ß compared to control mice. These results suggest that L-92 can up-regulate the number of Treg cells to suppress the progression of DNFB-induced contact dermatitis in mice.

Serum soluble CD27 level is associated with outcome in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone.

Since the introduction of rituximab (R), the prognosis for diffuse large B-cell lymphoma (DLBCL) has markedly improved. We evaluated the prognostic significance of serum soluble CD27 (sCD27) in 143 patients with DLBCL treated with cyclophosphamide, doxorubicin, vincristine and prednisolone plus rituximab (R-CHOP). Five-year overall survival rates for patients with sCD27≥213 U/mL or <213 U/mL were 38.7% and 76.8%, respectively (p =0.0005). Multivariate analysis revealed that serum sCD27 was significantly correlated with OS (p =0.047). Immunohistochemical staining for CD27 in lymphoma tissues revealed positive lymphoma cells in 22 cases (18.5%) and positive microenvironment T-cells in 62 cases (52.1%) and was negative in the remaining patients. In these three subgroups, median sCD27 levels were 336 U/mL, 242.6 U/mL and 109.9 U/mL, respectively (p =0.004). Thus, serum sCD27 level is associated with CD27 expression on lymphoma cells, and may be a powerful prognostic factor for DLBCL.

Serum soluble interleukin-2 receptor (sIL-2R) level is associated with the outcome of patients with diffuse large B cell lymphoma treated with R-CHOP regimens.

Serum concentration of soluble interleukin-2 receptor (sIL-2R) predicts the clinical outcome of patients with aggressive non-Hodgkin's lymphoma treated with the cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen without rituximab. In the present study, we aim to re-assess the prognostic significance of serum sIL-2R for diffuse large B cell lymphoma (DLBCL) patients treated with CHOP plus rituximab and to assess sIL-2R with subtype of DLBCL, such as GCB type and non-GCB type. Two hundred and thirty-three patients with DLBCL were enrolled between December 2002 and March 2008. To evaluate serum levels of sIL-2R, venous blood samples were drawn from patients immediately before initiation of treatment. Serum sIL-2R was determined by sandwich enzyme-linked immunosorbent assay. The 5-year overall survival (OS) rates for patients with sIL-2R levels of ≥2,000 (110 cases) and <2,000 U/mL (123 cases) were 54.2% and 89.0% (P < 0.0001), respectively. Multivariate analysis using the proportional-hazards model revealed that serum sIL-2R (P = 0.0099) and extranodal involvement sites (P = 0.0392) were independent prognostic factors for OS and that clinical stage (P = 0.0168), performance status (P = 0.0181), sIL-2R (P = 0.0232), and LDH (P = 0.0316) were independent prognostic factors for progression-free survival in sIL-2R and every factor of the International Prognostic Index. Serum sIL-2R might be a useful prognostic factor for DLBCL patients in the rituximab era.

Endoscopic ultrasound-guided fine needle aspiration biopsy for diagnosis of lymphoproliferative disorders: feasibility of immunohistological, flow cytometric, and cytogenetic assessments.

OBJECTIVES: In addition to morphology, immunophenotype and genetic abnormalities should be assessed during diagnosis and subclassification of lymphoproliferative disorders. The objective of this study was to evaluate the yield of endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) using a standard 19-gauge needle for diagnosis and subclassification of lymphoma, assessing the feasibility of immunohistological, flow cytometric, and cytogenetic assessments. METHODS: Two hundred forty patients with suspected lymphoma were referred for EUS-FNAB to our quaternary EUS center between June 2005 and December 2010. EUS-FNAB using a conventional 19-gauge needle was attempted for all patients, followed by histological assessments including immunohistological staining, flow cytometry, and cytogenetic analysis (G-band karyotyping). Among the patients, 152 were ultimately diagnosed with lymphoma. The primary outcome measure of this study was the sensitivity of histological assessment, including immunohistological staining, flow cytometry, and G-band karyotyping, for diagnosis and subclassification of lymphoma. RESULTS: Among the 152 patients ultimately diagnosed with lymphoma, 147 patients (96.7%) were diagnosed by EUS-FNAB, and classification in accordance with the WHO (World Health Organization) system was also possible for 135 patients (88.8%) on the basis of histological findings, including immunohistological staining. Flow cytometry showed abnormal or unusual cell populations in 121 (79.6%) of the 152 patients diagnosed with lymphoma, and in 114 (90.5%) of the 126 patients diagnosed with B-cell lymphoma. Specific cytogenetic abnormalities were detected in 21 (13.8%) of the lymphoma patients. CONCLUSIONS: EUS-FNAB using a standard 19-gauge needle has high diagnostic value for lymphoma. Immunophenotyping is usually possible, while cytogenetic abnormalities can be identified in a relatively limited number of patients.