Equine Malignant Lymphomas: Morphologic and Immunohistochemical Classification

1998 ◽  
Vol 35 (4) ◽  
pp. 241-252 ◽  
Author(s):  
L. C. Kelley ◽  
E. A. Mahaffey

Gross lesions, microscopic appearance, and immunophenotyping are reported in a retrospective study of 31 cases of equine malignant lymphoma. Immunohistochemical studies were performed on archived formalin-fixed, paraffin-embedded tissues. Monoclonal antibodies to surface glycoprotein BLA.36 and intracytoplasmic domains of mb-1 and B29 were used to document the presence of B lymphocytes in the equine tumors. Polyclonal antibody to CD3 and monoclonal antibodies to T-lymphocyte markers CD3 and CD5 revealed the presence of variable numbers of T cells within the equine lymphomas. The neoplastic component of the equine lymphomas was determined through morphologic evaluation, immunophenotyping, and the use of proliferation markers Ki-67 and proliferating cell nuclear antigen. Equine malignant lymphomas were composed of a heterogeneous cell population. Most tumors contained B and T lymphocytes. Twenty-four horses had diffuse lymphomas derived from B lymphocytes. Thirteen of these lymphomas contained primarily neoplastic B lymphocytes. Eleven additional cases of diffuse large B-cell lymphoma contained from 40% to 80% nonneoplastic T lymphocytes and were classified as T-cell-rich, large B-cell lymphomas. This is the first description of T-cell-rich, B-cell lymphoma in the horse. Six tumors with a diffuse architecture were derived from T lymphocytes. Four T-cell tumors were large-cell tumors, 1 was a small-cell tumor, and in 1 tumor the size of the cells could not be determined accurately because of autolytic change in the tissues. One diffuse large-cell lymphoma did not react with either B- or T-cell markers.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4655-4655
Author(s):  
James A. Strauchen ◽  
David Burstein

Abstract X-linked inhibitor of apoptosis protein (XIAP) is an important regulator of apoptosis which binds to and inhibits caspases-3, -7 and -9, blocking the caspase 9-mediated apoptosis pathway. This pathway is activated by p53 and DNA damage and may be an important determinant of responsiveness to chemotherapy. Apoptosis also plays a major role in the regulation of follicle center B-cell proliferation and BCL2-mediated inhibition of apoptosis is a key factor in B-cell lymphomagenesis. In this study we examined the expression of XIAP in 65 reactive and neoplastic lymphoid proliferations utilizing a monoclonal antibody to XIAP (#610763 BD Biosciences, San Jose, CA) and immunohistochemistry with avidin-biotin-complex immunoperoxidase technique on formalin-fixed, paraffin-embedded sections. In reactive lymph nodes and tonsils, expression of XIAP was limited to large noncleaved cells in follicle centers (5 of 6 cases). XIAP was absent in plasmacytoma (3 cases) and small lymphocytic lymphoma/chronic lymphocytic leukemia (1 case). XIAP was expressed in follicular lymphoma, predominantly in large noncleaved cells (6 of 9 cases) and in diffuse large B cell lymphoma (11 of 16 cases), including cases of T-cell/histiocyte-rich diffuse large B cell lymphoma (2 cases), primary mediastinal large B cell lymphoma (1 case), and posttransplantation diffuse large B cell lymphoma (1 case). XIAP was consistently expressed in Burkitt and Burkitt-like lymphoma (3 of 3 cases) and anaplastic large cell lymphoma (3 of 3 cases) and in one case of adult T cell leukemia/lymphoma. XIAP was variably expressed in marginal-zone B cell lymphoma, predominantly in large blasts (2 of 4 cases) and in mantle cell lymphoma (2 of 3 cases). XIAP was not detected in peripheral T cell lymphoma, unspecified (1 case), extranodal NK/T cell lymphoma, nasal type (1 case), precursor B cell lymphoblastic leukemia (1 case), or granulocytic sarcoma (1 case). XIAP was consistently expressed in the Reed-Sternberg and mononuclear Reed-Sternberg-variant cells of classical Hodgkin disease (9 of 9 cases) and the L+H Reed-Sternberg-variant cells of nodular lymphocyte predominance Hodgkin disease (3 of 3 cases). XIAP is expressed across a broad range of lymphoproliferative disorders, including classical and nodular lymphocyte predominance Hodgkin disease, diffuse large B cell lymphoma, follicular lymphoma, Burkitt lymphoma, marginal-zone and mantle cell lymphoma, and anaplastic large cell lymphoma. XIAP appears to be selectively expressed in the proliferating elements of these lymphomas. The possible prognostic and therapeutic significance of XIAP expression needs to be determined.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17566-17566
Author(s):  
B. Beltran ◽  
A. Carrasco ◽  
L. Vera ◽  
E. Salinas ◽  
M. Ticona ◽  
...  

17566 Background: The clinicopathologic characteristics of malignant lymphomas vary according to geography. The aim of this study was to determine the relative frequency of cutaneous lymphomas and to examine the clinical relevance of the new WHO/EORTC classification in Peruvian cases of cutaneous lymphoma. Methods: We conducted a clinicopathologic retrospective study of a collection of 68 primary cutaneous lymphomas, diagnosed from 1997 to 2004 in a National General Hospital. The clinical records, haematoxylin & eosin-stained slides and immunohistochemical stains from 67 patients with malignant lymphomas of the skin were reviewed. HTLV-1 serology was made using ELISA and Western Blot methods. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: Mean age at presentation was 62 years and the female/male ratio 1.5:1. T cell lymphomas were 88.6% and 11.4% were B-cell lymphomas. The most frequent cutaneous lymphoma was mycosis fungoides (MF) 30/67 (44.7%), Adult T-cell leukemia/lymphoma (ATLL) 13/67 (19.4%), unspecified peripheral T-cell lymphoma 4/67 (6%), lymphomatoid papulosis 2/67 (3%), leg-type diffuse large B-cell lymphoma 2/67 (3%), diffuse large B-cell lymphoma 2/67 (3%), subcutaneous panniculitis-like T-cell lymphoma 2/67 (3%), anaplastic large cell lymphoma 1/67 (1.4%), Sézary síndrome 1/67 (1.4%), nasal type extranodal NK/T-cell lymphoma 1/67 (1.4%), marginal zone B-cell lymphoma 1/67 (1.4%), follicle center lymphoma 1/67 (1.4%), intravascular lymphoma 1/67 (1.4%) and unclassifiable 5/67 ( 7.4%). Clinical stages of MF were: 60% stage I; 30% stage II; 3% stage III and 7% stage IV. 5-year survival was 77%. In ATLL group, 3 had smouldering type and 10 had cutaneous type. 5-year survival was 18%. Conclusions: In this retrospective analysis, cutaneous T cell lymphomas were prevalent; both MF and ATLL had the most frequency among primary cutaneous lymphomas in our hospital. ATLL had a poor 5-year survival. No significant financial relationships to disclose.


Blood ◽  
2013 ◽  
Vol 122 (15) ◽  
pp. 2683-2693 ◽  
Author(s):  
Michela Boi ◽  
Andrea Rinaldi ◽  
Ivo Kwee ◽  
Paola Bonetti ◽  
Maria Todaro ◽  
...  

Key Points The commonest lesions in anaplastic large cell lymphomas are losses at 17p13 and at 6q21, concomitant in up to one-quarter of the cases. PRDM1 (BLIMP1) gene (6q21) is inactivated by multiple mechanisms and acts as a tumor suppressor gene in anaplastic large B-cell lymphoma.


2020 ◽  
Author(s):  
Yangyang Xu ◽  
Zhenchuan Liu ◽  
Lixin Lv ◽  
Ping Li ◽  
Aibin Liang

Abstract Background: CD8+ tumor-infiltrating T lymphocytes (T-TILs) in the tumor microenvironment (TME) play an important role in tumor development, and miRNAs regulate tumor cell interactions with the microenvironment. T-TIL-based tumor immunotherapy provides a promising treatment strategy in diffuse large B-cell lymphoma (DLBCL). MiRNAs tend to be attractive targets for novel antitumor interventions.Methods: Weighted gene coexpression network analysis (WGCNA), CIBERSORT analysis and Cox regression analysis were used to identify CD8+ T-TIL-related miRNAs. RT-PCR, western blotting, immunohistochemistry (IHC), luciferase reporter assay, coimmunoprecipitation and ubiquitination analyses were used to detect miRNA, mRNA and protein expression and their combination. The viability and function of CD8+ T cells after stimulation were evaluated by enzyme-linked immunosorbent assay (ELISA), cytotoxicity assay, functional avidity assessment, flow cytometry and Cell Counting Kit-8 (CCK-8) assay. DLBCL cell lines, primary cells and a murine xenograft model established with A20 cell injection were used as in vitro and in vivo experimental models.Results: MiR-340-5p was positively correlated with CD8+ T-TILs in DLBCL patients, and KMT5A was a direct target gene of miR-340-5p. CD8+ T-cell function was significantly enhanced by miR-340-5p mimics both in vitro and in vivo, which was reversed by KMT5A overexpression. We demonstrated that COP1/CD73 was involved in the downstream mechanism of the miR-340-5p/KMT5A axis involving ubiquitination. In vivo, we validated an improved CD8+ T-TIL infiltration rate and tumor suppression with miR-340-5p treatment. Furthermore, miR-340-5p directly regulated the biological activity of DLBCL cells without CD8+ T-cell participation.Conclusions: MiR-340-5p promoted CD8+ T-TIL infiltration and antitumor function by regulating KMT5A and COP1 and further activating CD73 ubiquitination. MiR-340-5p is potentially a novel target for DLBCL immunotherapy.


2012 ◽  
Vol 03 (06) ◽  
pp. 1060-1065
Author(s):  
Lakshmi Rajappannair ◽  
Elaine Lam ◽  
Don Benson ◽  
Frederick Racke ◽  
Steven Devine ◽  
...  

2020 ◽  
Author(s):  
Yangyang Xu ◽  
Zhenchuan Liu ◽  
Lixin Lv ◽  
Ping Li ◽  
Bing Xiu ◽  
...  

Abstract Background: CD8+ tumor-infiltrating T lymphocytes (T-TILs) in the tumor microenvironment (TME) play an important role in tumor development, and miRNAs regulate tumor cell interactions with the microenvironment. T-TIL-based tumor immunotherapy provides a promising treatment strategy in diffuse large B-cell lymphoma (DLBCL). MiRNAs tend to be attractive targets for novel antitumor interventions. Methods: Weighted gene coexpression network analysis (WGCNA), CIBERSORT analysis and Cox regression analysis were used to identify CD8+ T-TIL-related miRNAs. RT-PCR, western blotting, immunohistochemistry (IHC), in situ hybridization (ISH), luciferase reporter assay, coimmunoprecipitation and ubiquitination analyses were used to detect miRNA, mRNA and protein expression and their combination. The viability and function of CD8+ T cells after stimulation were evaluated by enzyme-linked immunosorbent assay (ELISA), cytotoxicity assay, functional avidity assessment, flow cytometry and Cell Counting Kit-8 (CCK-8) assay. DLBCL cell lines, primary cells and a murine xenograft model established with A20 cell injection were used as in vitro and in vivo experimental models. Results: MiR-340-5p was positively correlated with CD8+ T-TILs in DLBCL patients, and KMT5A was a direct target gene of miR-340-5p. CD8+ T-cell function was significantly enhanced by miR-340-5p mimics both in vitro and in vivo, which was reversed by KMT5A overexpression. We demonstrated that COP1/CD73 was involved in the downstream mechanism of the miR-340-5p/KMT5A axis involving ubiquitination. In vivo, we validated an improved CD8+ T-TIL infiltration rate and tumor suppression with miR-340-5p treatment. Furthermore, miR-340-5p directly regulated the biological activity of DLBCL cells without CD8+ T-cell participation. Conclusions: MiR-340-5p promoted CD8+ T-TIL infiltration and antitumor function by regulating KMT5A and COP1 and further activating CD73 ubiquitination. MiR-340-5p is potentially a novel target for DLBCL immunotherapy.


2013 ◽  
Vol 2013 ◽  
pp. 1-7
Author(s):  
Kristin La Fortune ◽  
Dahua Zhang ◽  
Gordana Raca ◽  
Erik A. Ranheim

Posttransplant lymphoproliferative disorder (PTLD) comprises a spectrum ranging from polyclonal hyperplasia to aggressive monoclonal lymphomas. The majority of PTLDs are of B-cell origin while T-cell PTLDs and Hodgkin lymphoma-like PTLDs are uncommon. Here, we report a unique case of a 56-year-old man in whom a lymphoma with two distinct components developed as a duodenal mass seventeen years following a combined kidney-pancreas transplant. This PTLD, which has features not previously reported in the literature, consisted of one component of CD20 positive and EBV negative monomorphic diffuse large B-cell lymphoma. The other component showed anaplastic morphology, expressed some but not all T-cell markers, failed to express most B-cell markers except for PAX5, and was diffusely EBV positive. Possible etiologies for this peculiar constellation of findings are discussed and the literature reviewed for “composite-like” lymphomas late in the posttransplant setting.


Author(s):  
Yangyang Xu ◽  
Zhenchuan Liu ◽  
Lixin Lv ◽  
Ping Li ◽  
Bing Xiu ◽  
...  

Abstract Background CD8+ tumor-infiltrating T lymphocytes (T-TILs) in the tumor microenvironment (TME) play an important role in tumor development, and miRNAs regulate tumor cell interactions with the microenvironment. T-TIL-based tumor immunotherapy provides a promising treatment strategy in diffuse large B-cell lymphoma (DLBCL). MiRNAs tend to be attractive targets for novel antitumor interventions. Methods Weighted gene coexpression network analysis (WGCNA), CIBERSORT analysis and Cox regression analysis were used to identify CD8+ T-TIL-related miRNAs. RT-PCR, western blotting, immunohistochemistry (IHC), in situ hybridization (ISH), luciferase reporter assay, coimmunoprecipitation and ubiquitination analyses were used to detect miRNA, mRNA and protein expression and their combination. The viability and function of CD8+ T cells after stimulation were evaluated by enzyme-linked immunosorbent assay (ELISA), cytotoxicity assay, functional avidity assessment, flow cytometry and Cell Counting Kit-8 (CCK-8) assay. DLBCL cell lines, primary cells and a murine xenograft model established with A20 cell injection were used as in vitro and in vivo experimental models. Results MiR-340-5p was positively correlated with CD8+ T-TILs in DLBCL patients, and KMT5A was a direct target gene of miR-340-5p. CD8+ T-cell function was significantly enhanced by miR-340-5p mimics both in vitro and in vivo, which was reversed by KMT5A overexpression. We demonstrated that COP1/CD73 was involved in the downstream mechanism of the miR-340-5p/KMT5A axis involving ubiquitination. In vivo, we validated an improved CD8+ T-TIL infiltration rate and tumor suppression with miR-340-5p treatment. Furthermore, miR-340-5p directly regulated the biological activity of DLBCL cells without CD8+ T-cell participation. Conclusions MiR-340-5p promoted CD8+ T-TIL infiltration and antitumor function by regulating KMT5A and COP1 and further activating CD73 ubiquitination. MiR-340-5p is potentially a novel target for DLBCL immunotherapy.


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