CD30 Positivity Research Articles

Metanephric Adenoma in the Pediatric Population: Diagnostic Challenges and Follow-up

ObjectiveTo discuss the presenting features, imaging findings, and recommended management of patients with Metanephric adenoma (MA) focusing on the diagnostic challenges and indications for follow up. Materials and MethodsIn this case report, we present a case of a 10-year-old female with MA who eventually underwent nephron sparing surgery with a partial nephrectomy. We performed a literature review of previous cases of metanephric adenoma and their respective management and follow-up. ResultsRenal ultrasound demonstrated a heterogeneous, echogenic mass measuring 3.8 cm at the upper pole of the right kidney. Further investigations consisted of computed tomography scan, magnetic resonance imaging, and magnetic resonance angiography. The patient underwent robotic-assisted partial nephrectomy.The immunohistochemical staining pattern, gross, and microscopic appearance of the lesion were consistent with the diagnosis of MA. The combination of CK7, EMA, and S-100 negativity and WT1 and CD57 positivity is considered characteristic of metanephric adenoma as described in the literature. ConclusionMA is a rare benign tumor and especially in the pediatric population can cause significant concern over a possible malignant lesion. Although, no follow-up recommendations currently exist in cases of completely resected MA, we standardly perform postoperative surveillance. Although Metanephric Adenoma is difficult to diagnose preoperatively, given the advances in nephron sparing surgery and the utilization of nonionizing radiation modalities for follow up, we can manage these patients safely and with lower morbidity by preserving renal parenchyma.

Pathomorphological and Immunohıstochemical Evaluation of Unilateral Progressive Mooren’s Ulcer in a Cat

Background: Mooren’s ulcer is a chronic and painful ulceration of the cornea. It begins progressively in the periphery and spread centrally in cornea. In human, it is seen uniaterally in most of cases. Mooren ulcer has not been reported in any kind of animals up to now. Although its aetiology is not completely enlighted, it has been suspected of the inflammatoryreaction against injuries-microbiological and immun mediated effects. Immun response in presence of accumulation of immune complexes into the limbal vessels.As a result of the deficit in the regulatory mechanism because the number of suppressor cells control over B and T lymphocytes, These situations can result in a progressive tendancy to inflammationbecause the production of autoantibodies and/or lymphokine from cytotoxic T-lymhocytes creates an immune-mediated vasculitis. Numerous immigrant inflammatory cells and proteins are evaded from vessels. After triggering inflammatory cells and releasing of meditors, corneal vascularization, scar tissue and re-epithelization develop. This regenerative-reperative process plays an important role during post-inflammatory process.Case: In this case, it was aimed to detect pathomorphological structure and immunologic relations in progressive Mooren’s ulcer (MU). A 1 year-old mix breed cat was submitted to clinic with complaints of progressive painful and eyesight loss in left eye. There were 1 cm-ulceration, opacification and old haemorrhagic areas at peripheral cornea. Histopathologically, there was wide ulceration including all layers of corneal epithelium and particularly vacuolar degeneration at suprabasal cells. In corneal stroma, numerous neutrophiles and mononuclear cells were infiltrated. Neovascularisation and fibrosis beginning from limbus were also present. This fibrotic progress was confirmed by Masson’s trichrome staining method. Immunohistochemically, Cytokeratin 3 (CK3) and cytokeratin 12 (CK12) positivities showing regenerative activity of suprabasal and basal cells were not widespread. Epidermal Growth Factor (EGF) positivities were generally weak in epithelialcells. In stroma, moderate vimentin positivities were detected proliferated in fibrocytes originating from limbus. α1-antichymotrypsin (A1AC) was mildly reacted in neutrophiles. CD3 and CD4 confirmed the presence of regulatory and helper T lymphocytes. CD3 and CD8 marked cytotoxic T lymphocytes and CD20 marked B lymphocytes in inflammatory areas. CD34 were also positive in peripheral corneal stem cells derived from limbal basal epitheliums in partly regenerated area. CD57 positivity in T lymphocytes and NK cells and CD68 positivity in macrophages were attended to the area.Discussion: CD1a positivity in T lymphocytes proved mediating lipid and microbial origin glycolipid antigens. TUNEL reactions showing DNA in situ fragmentation were present in the destructive and aging epithelial cells at periphery. In conclusion, the case has been found as unique in terms of its immunohistochemical characterization. The markers show that CD1a and CD68 expressions follow different progress in animals unlike in humanbeings even though the ulcer of pathogenetic mechanism is found identical to humanbeings.. The roles of CD20 and CD57 markers have potential roles in this ulcer. It is also concluded that insufficient epithelial regeneration, fibrosis, inflammation and apoptosis showed progressive Mooren’s ulcers having possibly microbial origin.Keywords: Mooren’s ulcer, pathomorphology, immunohistochemistry, cat.

FOXP3-positive T-cell lymphomas in non-HTLV1 carriers include ALK-negative anaplastic large cell lymphoma: expanding the spectrum of T-cell lymphomas with regulatory phenotype

Forkhead box P3 (FOXP3) is a specific marker for regulatory T-cells (Tregs). We report 6 cases of T-cell lymphomas with Treg phenotype based on diffuse positivity for FOXP3 in tumor cells. The patients showed a median age of 56 years with a male predominance. Sites of disease included lymph nodes (4), skin (2), subcutaneous tissue (1) and bone marrow (1). All cases showed monomorphic large cells, some with Hodgkin-like or anaplastic cells. All cases expressed pan T-cell markers and lacked cytotoxic markers; one case showed diffuse PD1 staining. Only one case harbored human T-lymphotrophic virus (HTLV)-1 DNA within tumor cells and was classified as adult T-cell leukemia/lymphoma (ATLL). Among 5 HTLV1-negative cases, 3 were classified as peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) and 2 fulfilled criteria for ALK-negative anaplastic large cell lymphoma (ALCL) with diffuse and strong CD30 positivity. We concluded that Treg phenotype may be rarely seen in HTLV1-negative cases, such as PTCL, NOS and ALK-negative ALCL. Our findings expand the spectrum of T-cell lymphomas with regulatory phenotype and suggest that consideration should be given to HTLV1 DNA testing in the appropriate clinical setting to rule out ATLL.

Blast Percentage of Bone Marrow Aspirate on Day 14 of Induction Chemotherapy Predicts Adult Acute Lymphoblastic Leukemia Treatment Outcomes

The prognosis of adult acute lymphoblastic leukemia is much worse than that of pediatric acute lymphoblastic leukemia, even when patients achieve complete remission. Early response to treatment can be an important alternative indicator of treatment outcomes. The purpose of our current study was to identify the prognostic value of the blast percentage of the induction interim bone marrow, which might predict relapse-free survival and overall survival in patients with adult acute lymphoblastic leukemia. A retrospective analysis was performed on 80 adult patients diagnosed with Philadelphia chromosome-negative acute lymphoblastic leukemia from 1994 to 2011. Complete remission was observed in 75 (93.8%) patients after induction chemotherapy. On multivariate analysis, a reduction of blasts to a level of 5% or less in the induction interim bone marrow and CD20 positivity were significant prognostic predictors of relapse-free survival (hazard ratio, HR = 2.88, p = 0.006, and HR = 2.67, p = 0.010) and overall survival (HR = 2.10, p = 0.033, and HR = 2.39, p = 0.013). The blast percentage of the induction interim bone marrow may be a useful prognostic factor to predict outcome.

Loss of 5-Hydroxymethylcytosine Is an Epigenetic Biomarker in Cutaneous T-CellLymphoma.

DNA hydroxymethylation at the 5 position of cytosine (5-hmC) is a product of the TET family of DNA hydroxylases. Accumulating evidence shows that loss of 5-hmC is critical for various biological and pathological processes. However, its level in cutaneous T-cell lymphoma (CTCL) remains largely unknown. Here, we report that the loss of 5-hmC is an epigenetic hallmark of CTCL, with diagnostic and prognostic implications. Immunohistochemistry staining on 90 mycosis fungoides (MF) samples showed a significant decrease of 5-hmC staining in CD4+ T cells in patch and tumor stages, especially in MF with large cell transformation, compared with benign inflammatory dermatoses. The 5-hmC staining level decreased with disease progression and showed remarkable loss in the large cells of large cell transformed MF samples, regardless of the CD30 positivity. Furthermore, 5-hmC decrease was correlated to poor overall survival in our patient cohort. Pharmacological augments of global 5-hmC with l-ascorbic acid in CTCL cell lines led to remarkable 5-hmC accumulation and promoted apoptosis in CTCL cell lines, as well as in patient-derived CTCL cells. In conclusion, 5-hmC is an epigenetic mark of predictive value in MF prognosis. Restoration of 5-hmC levels in MF may serve as a therapeutic regimen in CTCL.

197 Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of disease progression in cutaneous T cell lymphoma

DNA hydroxymethylation at the 5 position of cytosine (5-hmC) is a product of the ten-eleven translocation (TET) family of DNA hydroxylases. Accumulating pieces of evidence showed that loss of 5-hmC is critical for various biological and pathological processes. However, its expression and function in cutaneous T cell lymphoma remain largely unknown. Here, with a large cohort of patients, we report that loss of 5-hmC is an epigenetic hallmark of cutaneous T cell lymphoma, with diagnostic and prognostic implications. Immunohistochemistry staining on 91 mycosis fungoides (MF) cases display a significant decrease of 5-hmC staining in CD4+ T cells, compared to benign inflammatory dermatoses, including lupus erythematosus (N=15), lichen planus (N=15), and psoriasis (N=12). 5-hmC staining level is further decreased with disease progression and demonstrates remarkable loss of staining in the large cells of large cell transformed MF cases, regardless of the CD30 positivity. Furthermore, 5-hmC decreases are correlated with poorer overall survival in our patient cohort. Compared to healthy CD4+ T cells, 5-hmC levels also decreased in 9 CTCL cell lines. Pharmacological augment of global 5hmC with L-ascorbic acid [L-AA] and 2-phospho-L-ascorbic acid (P-AA) in CTCL cell lines lead to a remarkable 5-hmC accumulation and induce specific apoptosis in CTCL cell lines, as well as primary CTCL cells. In conclusion, 5-hmC is an epigenetic marker of disease progression in MF. Reversing 5-hmC levels in MF may serve as a novel therapeutic regimen in cutaneous T cell lymphoma.

CD30 expression and its correlation with MYC and BCL2 in de novo diffuse large B-cell lymphoma

AimCD30+ diffuse large B-cell lymphoma (DLBCL) has emerged as a new immunophenotypic variant of de novo DLBCLs. However, the prevalence of CD30 positivity is variable according to different studies, and...

Small cell lymphocytic variant of marginal zone lymphoma: A distinct form of marginal zone lymphoma derived from naïve B cells as a cutaneous counterpart to the naïve marginal zone lymphoma of splenic origin.

Abstract Primary cutaneous marginal zone lymphoma most commonly represents an indolent form of cutaneous B cell lymphoma. However, epidermotropic marginal zone lymphoma, blastic marginal zone lymphoma and B cell dominant variants without isotype switching can be associated with extracutaneous dissemination. The presumptive cell of origin is a post germinal center B cell with plasmacytic features. In the extracutaneous setting, however, a naive B cell origin has been proposed for a subset of marginal zone lymphomas, notably splenic marginal zone lymphoma. The author encountered 11 cases of atypical lymphocytic infiltration of the skin primarily occurring in older individuals with an upper arm and head and neck localization; there was a reproducible pattern of diffuse and nodular infiltration by small monomorphic-appearing B cells. Phenotypically, the infiltrate was one predominated by B cells exhibiting CD23 and IgD positivity without immunoreactivity for CD38 and there were either no plasma cells or only a few without light chain restriction. In cases presenting with a solitary lesion complete excision and/or radiation led to successful disease remission in all cases without recurrence or metastatic disease. Of three cases with multiple initial lesions, evidence of extracutaneous disease was seen in two cases and recurrence occurred in one case. No patients have died of lymphoma. Longer term follows up and additional cases are needed to determine if this subset of marginal zone lymphoma is associated with a worse prognosis.

Secondary primary malignancy presence and related factors in chronic lymphocytic leukemia

Objective: The secondary primary malignancy frequencies have seen increased in chronic lymphocytic leukemia (CLL) regardless of therapy. The aim of this study was to investigate the frequency of secondary primary malignancy in patients followed with the diagnosis of chronic lymphocytic leukemia. Materials and Methods: The 183 patients with diagnosed of CLL were enrolled into this study. The data of the patients were evaluated retrospectively. Patients diagnosed with CLL were categorized according to age, gender and presence or absence of additional malignancy. Patients with CLL and concomitant malignancy were compared with other patients. Results: Fifty four patients (29.5%) were female and 129 (70.5%) were male. Secondary primary malignancy was detected in 9 (%4,9) patients. CD5 positivity was found in all of the patients with malignancy and in 91% of whole patients. 5.4% of males and 3.7% of females had solid organ tumors with CLL. Although the proportion of solid tumors was higher in males, this difference was not statistically significant (p = 0.847). The mean age of cases with secondary malignancy was statistically significantly higher than that without secondary malignancy (p <0.05). Conclusion:  In our study, all of the patients with the second primary malignancy were CD5 positive. BCL2 proto-oncogene levels were found increased in CD5-positive CLL cells, not in normal B cells those were positive for CD5. In vitro studies showed that, B-CLL cells with higher BCL2 levels survive is longer than cells with lower BCL2 levels. Presence of the secondary malignancy except CLL may be related with BCL2 increment as well as CD5 positivity. We need more comprehensive studies to determine the relationship between the presence of BCL2, CD5 positivity and  secondary malignancies.

Case Report: A Woman with Fever, Acute Changes in Mental State, and Progressive Neurological Degeneration

Introduction: Anaplastic large cell lymphoma (ALCL), which was first described by Stein in 1985 as a feature of CD30 positivity, is now acknowledged as a distinct subset of T-cell non-Hodgkin lymphomas (NHL). It accounts for approximately 3% of adult NHL while constitutes as many as 30%–40% of pediatric large-cell lymphomas. It is rarely metastasized to other sites, especially to the central nervous system (CNS). Case Report: We present a case of a 73-year-old woman hospitalized for fever, acute behavioral changes, and progressive neurological degeneration; a rare case of systemic ALCL which metastasized to the brain. There are very few case reports of this matter in the literature. Conclusion: In the management of patients with neurological impairment, cognitive, and behavioral changes, we suspect the presence of lymphomas associated with the CNS still suspicious of other primary causes. Keywords: Anaplastic large-cell lymphoma, anaplastic lymphoma kinase gene, primary central nervous system lymphoma, non-Hodgkin lymphoma, T-cell lymphoma, lymph node enlargement.

Isolated central nervous system post-transplant lymphoproliferative disorder in a pediatric patient: a case report with pathobiological perspective

Isolated central nervous system post-transplant lymphoproliferative disorder (ICNS-PTLD) in pediatric patients is a distinctly rare entity without accepted diagnostic criteria or treatment recommendations. We present a case of an 8-year-old male with a prior history of a kidney transplant who developed and ICNS-PTLD. We highlight the pathobiology and diagnostic features with a brief review of the literature on these rare cases. There is a complex interplay between CD30, Epstein Barr Virus and MYC as part of lymphocyte transformation leading to PTLD. In the appropriate clinical setting, CD30 and EBV positivity along with normal MYC expression are highly predictive of CNS-PTLD over a Primary CNS lymphoma. ICNS-PTLD has only been rarely reported in children. The faithful diagnosis is necessary for prognostication and to accrue data for treatment recommendations.

Unmutated IGHV and Double Negative CD38/CD49d Predict Good Prognosis and Long Treatment Free Survival (TFS) in Chronic Lymphocytic Leukaemia; Regardless of Genetic Mutations

Background: Most patients do not need treatment at the time of diagnosis; however group of patients progress rapidly and respond poorly to conventional treatments (Parikh, Semin Oncol, 2016) . Mutation in IGHV genes (mutated CLL) is predictor for better disease outcomes compared with IGHV genes (unmutated (Hamblin, Blood, 1999)). Targeted next-generation sequencing (Targeted NGS) has proven to be accurate and reproducible technique when validated against the gold standard Sanger sequencing (Lesley-Ann Sutton, Haematologica, 2014). Both CD38 a surface molecule and CD49d an alpha-chain of the integrin heterodimer VLA-4 are involved in cell migration, adhesion and homing to secondary lymphoid organs. CD38 and CD49d are poor prognostic factors in (Gentile, Br J Haematol, 2005; Gattei, Blood, 2008). There is physical and functional association between CD49d and CD38 expression (Zucchetto, Leukemia, 2012) Aim: We aim to investigate the impact of IGHV status, CD49d and CD38 expression on treatment free survival (TFS) and time to first treatment (TTFT) in CLL. Methods: We enrolled 23 patients with confirmed diagnosis of (WHO criteria). cells were extracted from whole blood by negative selection using RosetteSep Human B Cell Enrichment Cocktail. Immunophenotyping was performed using Beckman Coulter FC500 Flowcytometer. cells were identified by co- expression of CD5 and CD19. We checked the expression of CD38 and CD49d and we used cut off of 7% or more for CD38 positivity and 30% or more for CD49d positivity as per previous studies (Gentile, Br J Haematol, 2005; Gattei, Blood, 2008). Targeted NGS was performed and reported using the ERIC (European Research Initiative on CLL) panel that includes: ATM, BIRC3, MYD88, NOTCH1, SF3B1, TP53, EGR2, POT1, NFKBIE and XPO1 [www.ericll.org]. IGHV mutational analysis was performed and patients with no or limited somatic hyper mutation burden (germline identity (GI) ≥ 98%) constituted unmutated CLL (U-CLL), whereas patients with GI Results: Sixteen patients were treatment naive while 7 patients received one or more lines of treatment (Table-1). Treatment naive patients had variable time since diagnosis that ranged between 17 and 225 months (Median: 91 months) and half of them had not required treatment for more than 10 years. Our data showed that CD38 expression is dynamic and can increase, decrease or stay the same over the disease course (Table-1). We found that the level of CD38 was significantly higher in patients who required treatment compared to patients who did not require treatment (p=0.031) There was also significant increase in CD 49d expression in patients who required treatment compared to patients who did not require treatment (p=0.023). All patients who needed treatment and tested for both CD38 and CD49d (N: 4) showed strong double expression of both antigens. In stark contrast, only 15% (2/13) of the patients who never required treatment showed double expression of both CD38 and CD49d. IGHV was in 23.5% (4/17) of patients. All the patients with IGHV required one or more lines of treatment, while only 7.6% (1/13) patients with mutated IGHV required treatment. Targeted NGS showed that 42.8% (6/14) of the patients carried mutation (Table-1). We did not find any correlation between genetic mutations by NGS and treatment free survival (TFS). Only one patient with mutation (XPO1) needed treatment. The remaining 5 patients with mutations including high risk mutations like TP53 and ATM have so far not required treatment. None of the patients with both mutated IGHV and double negative CD38/CD49d required treatment. Conclusion: patients with mutated IGHV and double negative CD38/CD49d have good prognosis and long treatment free survival regardless of their genetic mutations. We suggest that combining IGHV mutational analysis with high risk immunophentotypic markers like CD38 and CD49d may offer enhanced prognostic tool beyond that offered by genetic mutations in isolation in predicting treatment free survival (TFS) and time to first treatment (TTFT). Disclosures No relevant conflicts of interest to declare.

Outcomes among North American patients with diffuse large B-cell lymphoma are independent of tumor Epstein-Barr virus positivity or immunosuppression.

The prevalence, presenting clinical and pathological characteristics, and outcomes for patients with diffuse large B-cell lymphoma that is Epstein-Barr virus positive remain uncertain as does the impact of congenital or iatrogenic immunosuppression. Patients with newly diagnosed diffuse large B-cell lymphoma with available tissue arrays were identified from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource. Patients infected with human immunodeficiency virus or who had undergone a prior organ transplant were excluded. Epstein-Barr virus-associated ribonucleic acid testing was performed on all tissue arrays. A history of significant congenital or iatrogenic immunosuppression was determined for all patients. At enrollment, 16 of the 362 (4.4%) biopsies were positive for Epstein-Barr virus. Thirty-nine (10.8%) patients had a significant history of immunosuppression. Patients with Epstein-Barr-positive diffuse large B-cell lymphoma had no unique clinical characteristics but on pathology exhibited a higher frequency of CD30 positivity (25.0% versus 8.1%, respectively; P<0.01), and non-germinal-center subtype (62.5% versus 34.1%, respectively; P<0.01). No baseline clinical characteristics were associated with a history of immunosuppression. With a median follow up of 59 months, and after adjustment for International Prognostic Index, there was no association of Epstein-Barr virus positivity or immunosuppression with event-free survival at 24 months (odds ratio=0.49; 95% confidence interval: 0.13–1.84 and odds ratio=0.81; 95% confidence interval: 0.37–1.77) or overall survival (hazard ratio=0.86; 95% confidence interval: 0.38–1.97 and hazard ratio=1.00; 95% confidence interval: 0.57–1.74). In contrast to non-Western populations, our North American population had a low prevalence of Epstein-Barr virus-positive diffuse large B-cell lymphoma that did not convey an adverse prognosis. A history of immunosuppression, while known to be a risk factor for the development of diffuse large B-cell lymphoma, did not affect subsequent prognosis.

Double CD38−/CD138− negative multiple myeloma

The standard diagnosis of multiple myeloma by flow cytometry is based on selection of population of CD38+/CD138+ positives cells. As the result treatment with proteasome inhibitors, CD138 may be underexpressed on atypical plasma cells. Thus, in order to improve this strategy, recently new CD138-independent method, based on CD38 positivity of plasma cells was developed. We present an unusual case of CD138− negative multiple myeloma which had become double CD138−/CD38− negative after treatment with daratumumab by which we would like to illustrate potential pitfalls of both strategies.

Brentuximab vedotin exerts profound antiproliferative and pro-apoptotic efficacy in CD30-positive as well as cocultured CD30-negative germ cell tumour cell lines.

Prognosis in patients suffering from high‐risk, refractory and relapsed germ cell tumours (GCT) often comprising of CD30‐positive embryonal carcinoma (EC) components remains poor. Thus, novel treatment strategies are warranted. The antibody‐drug conjugate (ADC) brentuximab vedotin delivers the potent antimitotic drug monomethyl auristatin E (MMAE) to CD30‐expressing tumour cells. After CD30 binding, internalization and intracellular linker cleavage cytotoxic MMAE can efflux and eradicate neighbouring CD30‐negative cells. To analyse cytotoxicity and a potential bystander effect of brentuximab vedotin in GCT, we established an in vitro coculture model mimicking GCT of heterogeneous CD30 positivity and measured cell viability, proliferation and apoptosis after exposure to brentuximab vedotin and unbound MMAE by MTS‐ and flow cytometry‐based CFSE/Hoechst assay. CD30 expression being assessed by quantitative RT‐PCR and immunohistochemistry was apparent in all EC cell lines with different intensity. Brentuximab vedotin abrogates cell viability of CD30‐positive GCT27 EC line exerting marked time‐dependent antiproliferative and pro‐apoptotic activity. CD30‐negative JAR cultured alone barely responds to brentuximab vedotin, while in coculture with GCT27 brentuximab vedotin induces clear dose‐dependent cytotoxicity. Cellular proliferation and cell death are significantly enhanced in CD30‐negative JAR cocultured with CD30‐positive GCT27 compared to JAR cultured alone in proof of substantial bystander activity of brentuximab vedotin in CD30‐negative GCT. We present first evidence that in an in vitro model mimicking GCT of heterogeneous histology, brentuximab vedotin exerts potent antiproliferative and pro‐apoptotic activity against both CD30‐positive as well as CD30‐negative GCT subsets. Our results strongly support translational efforts to evaluate clinical efficacy of brentuximab vedotin in high‐risk GCT of heterogeneous CD30 positivity.

CD20 positivity and white blood cell count predict treatment outcomes in Philadelphia chromosome-negative acute lymphoblastic leukemia patients ineligible for pediatric-inspired chemotherapy.

The efficacy of conventional chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been controversial as post-remission therapies for adult Philadelphia chromosome-negative acute lymphoblastic leukemia patients. We retrospectively analyzed 96 adolescent and adult cases of Philadelphia chromosome-negative acute lymphoblastic leukemia to evaluate whether allo-HSCT should be performed after first complete remission (1CR). In total, 34 patients received chemotherapy followed by allo-HSCT (HSCT group) and 62 received chemotherapy alone (chemotherapy group). No significant differences in the event-free survival (EFS) or overall survival were observed between the two groups. In the chemotherapy group, use of pediatric regimens was significantly associated with favorable EFS, while high white blood cell (WBC) count and CD20 positivity were associated with poor outcome. In patients who received pediatric regimens, subsequent allo-HSCT did not influence EFS. In patients who received conventional chemotherapy (adult regimen), subsequent allo-HSCT did not improve EFS. High WBC count and CD20 positivity were also significantly associated with poor EFS in patients who received adult regimens. Patients with low WBC count and absence of CD20 who received adult regimens did not benefit from allo-HSCT. Allo-HSCT may not be required in the pediatric regimen-eligible patients; however, pediatric regimen-ineligible patients with either CD20 positivity or high WBC count should receive allo-HSCT after achieving 1CR. This study was registered at http://www.umin.ac.jp/ctr/ as #C000016287.

Are There Any Differences Between the Distribution of Placental Bed Leukocyte Subtypes and Plasma Cytokine Levels of Preeclamptic and Healthy Pregnants?

Objectives: Preeclampsia (PE) is associated with impaired decidual leukocyte and plasma cytokine balance compared with normal pregnancy. We aimed to investigate maternal plasma levels of Interferon-gamma (IFN-g), Tumor Necrosis Factor-alpha (TNF-a), Transforming Growth Factor-beta (TGF-b), Interleukin-4 (IL4), IL6, IL10, IL17, IL35, suppressor of Cytokine Signalling-3 (SOCS3) and placental bed leukocytes in preeclamptic and healthy pregnants.Materials & Methods: This study was conducted with 40 preeclamptic and 40 normotensive pregnants. Cytokine levels were studied with enzyme-linked immunosorbent assay. CD8, CD56 and CD163 antigens were analysed by immunohistochemical study on placental bed biopsies. Results: In preeclamptic women; IFN-g and TGF-b levels were significantly higher and IL-35 levels were significantly lower than those of controls. CD8, CD56 and CD163 positivity of preeclamptic group were not significantly higher than those of controls. CD8 staining showed negative correlation with plasma IL17 levels. CD163 staining showed negative correlation with TNF-a/IL4 ratio. TNF-a/IL4 ratio showed minimal influence on placental bed CD163 staining.Conclusion: Slightly increased placental bed CD8, CD56 and CD163 positive leukocytes and increased plasma IFN-g, TGF-b and decreased plasma IL35 levels of preeclamptic pregnants indicate an aberrant cell mediated immunity in PE. We could not say yet that this condition is whether result or reason. New studies are needed to discuss our results.

ABCG2 and CD200 define patients at high risk of relapse in ELN favorable subgroup of AML.

Overexpression of ABCG2 and CD200 has been independently associated with poor outcome in acute myeloid leukemia (AML). However, no data are available on the role of these two factors in patients with core-binding factor (CBF)-positive or FLT3-negative/NPM1-mutated cytogenetically normal (CN) AML. We analyzed 65 adult AML patients with CBF+ (n=16) or FLT3-/NPM1+ CN (n=49), evaluating clinical and biological factors associated with complete remission attainment, leukemia-free survival (LFS) and overall survival (OS). ABCG2 was expressed in 36 (55%) cases, and CD200 was positive in 33 (51%) cases, six at high levels. Both ABCG2 and CD200 positivity have a negative impact on relapse risk: 3-year LFS was 51% vs 82% in ABCG2+ cases (RR 3.3), 49% vs 82% in CD200+ patients (RR=4.4), and 25% in CD200- high cases (RR=17.1). ABCG2 and CD200 affected also OS with 3-year OS of 39% in ABCG2+ (compared to 71% in ABCG2-; RR=2.6) and CD200+ (compared to 68% in CD200-; RR=2.5) patients. Our data confirm a negative impact of ABCG2 and CD200 overexpression also in AML patients considered at favorable risk according to ELN cytogenetic/molecular classification.

Adult intussusception: unusual cause

Adult intussusception is a rare entity which accounts for 1-5% of intestinal obstructions in adults and just 5% of all cases of intussusception. The basic pathology and management of intussusception in adults differs from paediatric intussusception. Here we present an interesting case of adult intussusception with an unusual cause. A 33-year-old female presented with features of intestinal obstruction. Colonoscopy was done outside our institution which reported a smooth polypoidal mass in the terminal ileum, biopsy report was pending at that time. CT abdomen revealed dilated small bowel with narrowing in the ileo caecal junction. We proceeded with laparotomy. Intraoperatively dilated ileum with intussusception of the ileocecal junction into the ascending colon was found. Right hemicolectomy with ileotransverse colon anastomosis was done. Histopathology revealed Polyp with intussusception, 5cm from ileocecal junction, with sheets of lymphoid cells showing moderate pleomorphism, infiltrating submucosa, muscularis propria, and serosa, margins uninvolved with lymph node- 3/32 positivity. Immunohistochemistry suggested B- cell lymphoma with CD20 positivity and Bcl 2 focal positivity. Routine treatment of Lymphoma after confirming with biopsy have been Chemotherapy. Role of surgeon in lymphoma is presently limited to biopsy, but there are situations like obstruction and perforation, where surgeon should take the lead role

Clinicopathological analysis of primary splenic diffuse large B-cell lymphoma.

Splenic infiltration is often seen in diffuse large B-cell lymphoma (DLBCL). However, primary splenic DLBCL is rare and studies on its clinicopathological features are limited. We assessed 66 cases of primary splenic DLBCL and 309 control DLBCL, not otherwise specified. Hepatitis C virus antibody prevalence, B symptoms, poor performance status and CD5 positivity differed significantly between the primary splenic DLBCL and control DLBCL groups. Primary splenic DLBCL cases were classified histopathologically into two groups [white pulp pattern (n=46), red pulp pattern (n=20)]. Survival analysis showed no difference in overall survival between the primary splenic DLBCL and the control group, but the former had a more favourable progression-free survival. In the examination of primary splenic DLBCL, the white pulp pattern was statistically associated with a lower performance status (2-4), and a lower CD5 positivity than the red pulp pattern. In the survival analysis, the red pulp pattern demonstrated poorer overall survival. Multivariate analysis of overall survival in primary splenic DLBCL cases identified CD5 positivity as an indicator of poor prognosis. Classifying primary splenic DLBCL into white and red pulp patterns was useful in terms of clinicopathological features and overall survival.