Primary primitive neuroectodermal tumors (PNETs) are extremely rare in the lung and especially in adult women. We describe a case of PNET of the lung with aggressive behavior in 31-year-old woman. Diagnosis was based on histopathological and immunohistochemical studies, and confirmed by molecular genetic analysis of chromosome rearrangements in the EWSR1 gene region. Clinical follow-up, post-mortem findings, and differential diagnosis are also discussed.Electronic supplementary materialThe online version of this article (doi:10.1186/1477-7819-12-374) contains supplementary material, which is available to authorized users.
The basic principles of lymphoma classification(s) in general have been widely evolving in a course of decades of years wiht the use of contemporary resources and recent cutting edges in hematooncology on a clinical, morphological and molecular level bring new possibilities not only in improvements of diagnostic and prognostic algorithms and also bear new opportunities in so called targeted and tailored strategies of lymphoma therapy. The pathogenesis and biologic behavior of lymphoproliferations and even lymphomas should be studied in a context of lymphocytic and (neoplastic) lymphoid stage and chronologic development. In a current more complex insight into lymphoproliferations we would like to describe huge heterogeneity of diffuse large B-cell lymphoma in relationship to mandatory WHO classification since 2008 and the next development of knowledge in this field with potential new influence on an advancement of both classification and therapy.
2671 Introduction: Primary mediastinal diffuse large B-cell lymphoma (PMBCL) is an uncommon disease with an aggressive clinical course and potential curability. Growing evidence suggests that host antitumor immunity suppression may play a role in resistant cases. The most studied candidate molecules are ligands PD-L1 (CD 274) and PD-L2 (CD 273) expressed by lymphoma cells, which effectively suppress host T cells. The PD ligand genes are located on chromosome 9p24.1 close to Janus kinase 2 (JAK2) gene. The clinical impact of PD-L1/PD-L2 protein expression has not been described in PMBCL. Methods: Tumor samples of 27 previously untreated patients were analyzed. Clinical characteristics were as follows: median age at diagnosis 35 years (20–74), female-to-male ratio 1.7:1, most patients (70%) had limited mediastinal disease and a mean tumor diameter of 10.7 cm. The IPI and aaIPI scores were low in 67% and 37%, intermediate-low in 26% and 41% and intermediate-high in 7% and 22%, respectively. No patients were assigned to a high risk group. All patients were treated with anthracycline-based chemotherapy 15% with CHOP and 85% with third-generation intensive regimen. Therapy was intensified in 70% of the cases with high-dose therapy and autologous stem cell transplantation. Most of the patients (70%) received rituximab and 15% were also treated with IF radiotherapy. Formalin-fixed and paraffin-embedded tissues were processed in routine tissue sections (approx. 5 micrometers) and placed on plus slides. After antigen retrieval with the use of the enzymatic or microwave oven processes, indirect immunohistochemistry with commercially available primary antibodies in optimized dilution was performed: CD20 clone L27, CD23 clone 1B12, CD30 clone Ber-H2, CD10 clone G27-P, Bcl-2 clone 100, Bcl-6 clone PGB6p, MUM1/IRF4 clone MUM1p, CD274 polyclonal, CD273 polyclonal, and HLADR clone TAL.1B5. For visualization, a secondary antibody with the standard avidin-biotin (ABC) method was applied. Results were expressed as a percentage of positive tumor cells and H-score (product of percentage of positive cells and staining intensity). Cytogenetic analysis with a locus-specific FISH probe (9p24) and arrayCGH was carried out in 15 (56%) of the patients. Results: Final treatment response was assessed in 26 (96%) patients (1 patient did not passed restaging procedures yet), CR was achieved in 22 (85%), PR in three and one patient progressed. After a median follow-up of 73 months (6.1 yrs), 22/26 (84%) patients are alive in the 1st CR, and only three patients died. Five-year PFS was 82.6% (95% CI 0.67–0.98) and five-year overall survival was 90.9% (95% CI 0.79–1.00). All samples expressed PD-L2 in (a median of) 80% of tumor cells with a median H-score of 90. PD-L2 protein expression was very low - six cases were negative and in positive cases, median expression was only 5% (H-score 5). HLA-DR expression was detected in all cases with a median positivity of 70% (H-score 140). Cytogenetic analysis detected amplification of 9p24.1 in 8/15 (53%) of the cases. When analyzing clinical characteristics, only correlation of high HLA-DR expression with limited clinical stage (p=0.04) and low IPI (p<0.01) was found. There was no correlation between treatment response quality and HLA-DR or PD-L2 expression, but high PD-L1 expression (above the median) correlated with non-CR status after treatment (p=0.07). Due to a low number of relapses, there was no relationship between protein expression and survival. No difference was found between cases with or without JAK-2 copy gain in terms of PD-1L expression (71% vs. 73%, p=0.92) or PD-L1 H-score (80 vs. 73, p=0.55); expression of PD-2L was higher (4% vs. 9%, p=0.19) in cases with JAK-2 amplification. Conclusion: Frontline intensive therapy is very effective in PMBCL patients. This is why no clear prognostic impact of protein expression of PD ligands or HLA expression was observed. There was constant high PD-L1 protein expression in PMBCL, low PD-2L expression and a high proportion of cases with JAK-2 gene amplification. Preliminary data show relationship between tumor immunogenicity (HLA-DR expression) and lymphoma aggressiveness. High PD-1L protein expression may probably influence treatment response quality. Further analyses are needed to clarify correlation between 9p24.1 amplification and PD-L protein expression. Supported by grants: MZ ÈR IGA NT 11103, LF-2012-007 and MSM 6198959205. Disclosures: Prochazka: Roche: Travel grants Other.
Objective: Neoplastic milieu is an integral part of all malignant diseases including multiple myeloma and plays variable role in their development, retention/adhesivity, resistency or sensitivity to therapeutic approach, homing and also paraneoplastic manifestations. Relatively genetically stable milieu may play an important role in new specific molecular therapeutic approaches and therefore should be contextually studied with neoplastic cells as complex neoplastic tissues. The expressions of 15 proteins with close relation to the development of myeloma bone disease (MBD) were analysed in consecutive multiple myeloma specimens. Methods: Bone marrow trephine biopsy specimens (n=57) with multiple myeloma were included in our prospective study. FFPE tissues were processed in app. 5microm sections and placed on charged slides. The indirect immunohistochemical staining was applicated after antigen retrieval and commercial primary antibodies were used for the detection of observed proteins. Standard secondary antibody and ABC method were included in visualisation. We analysed the expressions of MIP1alfa, Annexin A2, TRAP, DKK-1, RANK, RANKL, OPG, Sclerostin, Activin A, NFkappaB proteins (p50, p52, p65), p62 (sequestosome 1), MMP9 and RUNX2. Results: Bone marrow multiple myeloma specimens showed variable positivity of MIP1alfa in 60% (cut-off point 20%), Annexin A2 in 42% (myeloma cells, cut-off point 30%) and in 74% (stromal cells, cut-off point 5%), TRAP in 28% (cut-off point 5%), DKK-1 in 23% (cut-off point 30%), RANK in 53% (cut-off point 30%), RANKL in 70%, OPG in 39% (cut-off point 5%), Sclerostin in 95% (cut-off point 90%), Activin A in 35% (cut-off point 30%), cytoplasmic positivity of p50 in 5% (cut-off point 10%), p52 in 86% (cut-off point 10%), p62 in 91% (cut-off point 10%), p65 in 89% (cut-off point 10%), positivity of MMP9 in 22% (cut-off point 30%) and positivity of RUNX2 in 56% (cut-off point 30%). Conclusion: Our study showed variable expression of proteins related to MBD in multiple myeloma and its bone marrow microenvironment that imply biological heterogeneity, different development and stromal plasticity in this complex hemato-oncological disease. The exact and contextual knowledge of the engaged signaling pathways may suggest more specific or tailored therapeutic approaches (e.g. anti-RANKL, anti-DKK-1, anti-Sclerostin, anti-Activin A). Supported by the grant NT 14393. Disclosures No relevant conflicts of interest to declare.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.