Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diagnosis of classic Hodgkin lymphoma requires immunohistochemical confirmation in most cases and one can argue for these studies as standard-of-care in the diagnostic workup. The authors propose a panel of studies for primary identification of CHL to include: CD3, CD20, CD15, CD30 and PAX5. When pattern discordances are identified, additional assessment is recommended. In the case of overexpression of B lineage markers by Hodgkin/Reed-Sternberg cells, or a differential diagnosis that includes large B-cell lymphoma or variants, additional markers recommended are: CD45, OCT2, BOB1, CD79a and MUM1/IRF4. If primary mediastinal large B cell lymphoma is considered in the differential diagnosis, suggested additional markers include: P63, CD23, CD45 and CD79a. When considering a differential diagnosis that includes anaplastic large cell lymphoma we suggest: ALK, CD45, pan T cell antigens (such as CD2, CD5, CD7, and CD43), and cytotoxic markers (granzyme, perforin, and TIA1). If peripheral T cell lymphoma or T cell lymphomas of follicular helper origin are considered in the differential diagnosis, the following panel is recommended: pan T cell antigens, CD4, CD8, one or more follicular dendritic cell markers, and assessment for Epstein-Barr virus (EBV) infection, preferably EBV encoded RNA (EBER) as assessed by in situ hybridization When the differential diagnosis includes nodular lymphocyte predominant Hodgkin lymphoma, recommended additional studies include OCT2, CD21 and/or CD23, PD1, and assessment for EBV infection. The authors recognize that these panels may not be adequate to completely characterize other lymphomas, but these panels will usually be sufficient to distinguish classic Hodgkin lymphoma from other lymphoma types.
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PMID:American Registry of Pathology Expert Opinions: Immunohistochemical evaluation of classic Hodgkin lymphoma. 3080 9

We report a fulminant case of classical Hodgkin lymphoma (CHL). The patient died only approximately 2 months after the onset of subjective symptoms. Autopsy specimens revealed atypical cells resembling Hodgkin and Reed-Sternberg (HRS) cells in a rich inflammatory background in various organs. There were marked, characteristic angiodestructive lesions from infiltrating HRS-like cells and numerous macrophages. The HRS-like cells were infected with Epstein-Barr virus (EBV), immunohistochemically positive for PAX5 and CD30, and negative for CD3, CD20, and ALK. Most B-cell markers other than PAX5 were negative, and the HRS-like cells also expressed cytotoxic molecules. Monoclonal rearrangement of immunoglobulin heavy chain was detected by PCR analysis. According to the 2016 WHO classification, we diagnosed mixed cellularity CHL. However, EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified and EBV-positive B-cell lymphoma, unclassifiable with features intermediate between DLBCL and CHL were considered as differential diagnoses because both tumors are aggressive EBV-positive large B-cell neoplasms with reactive inflammatory cells and sometimes contains HRS-like cells. The clinical condition of the current case was closer to these two entities than to CHL. A diagnosis of EBV-positive large B-cell neoplasms was difficult because of overlapping morphological and immunohistochemical characteristics, but should be considered for prognosis.
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PMID:A fulminant case of classical Hodgkin lymphoma: A diagnostic dilemma of Epstein-Barr virus-positive large B-cell neoplasms. 3121 9

Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) represents less than 1% of non-Hodgkin lymphomas and 2%-3% of brain tumors. Primary CNS DLBCL occurs sporadically in healthy patients. Tumor development and progression have been associated with reduced/absent expression of human leukocyte antigen class I and II proteins; increased expression of CXCR4, CXCL12, CXCR5, and CCR7; mutations of VH4/34, BCL6, MYC, and PAX5 genes; and rearrangement of immunoglobulin heavy and light chain genes. Generally, DLBCL is a single supratentorial lesion (60%-70%), and stereotactic biopsy and intraoperative examination are the main diagnostic methods. Distinctive histologic features are a diffuse growth pattern and angioinvasiveness. Most neoplastic cells resemble centroblasts and exhibit positive CD20, CD22, PAX5, CD79a, and MUM1 expression. The prognosis of primary CNS DLBCL is less favorable than that of nodal DLBCL, and DLBCL subtype, strong FOXP1 immunoreactivity, MYC and BCL2 overexpression, and BCL6 translocations are associated with poor prognosis.
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PMID:Primary Intra-Axial Diffuse Large B-Cell Lymphoma in Immunocompetent Patients: Clinical Impact of Molecular Analysis and Histogenetic Evaluation. 3160 45

Although several reports have highlighted neoplastic PD-L1 (nPD-L1) expression in classic Hodgkin lymphoma (CHL), some have addressed associations between its expression and detailed histopathologic features. Here we describe four cases of syncytial variant of CHL (SV-CHL), with and without Epstein-Barr virus (EBV) association, and highlight the diagnostic utility of PD-L1 (clone SP142) immunohistochemistry. The patients were a 61-year-old male, 45-year-old male, 85-year-old female, and 89-year-old female. All presented with cervical or axillary lymphadenopathy, which on biopsy had the established histopathologic features of SV-CHL with a biphasic pattern of cohesive sheets of large tumor cells and typically scattered distribution of Hodgkin and Reed-Stenberg (HRS) cells. These tumor cells showed identical immunophenotypic findings for CD15, CD30, Fascin, PAX5, OCT2, BOB1 and EBV harboring, regardless of location. The exception was absent or decreased expression of nPD-L1 from tumor cells in the confluent sheets, contrasting with HRS cell positivity in typical areas of CHL. These findings offer the first suggestion of possible downregulation of nPD-L1 expression in association with the histopathologic progression of CHL. The results may be relevant for recognizing 'confluent' sheets in the diagnostic workup for SV-CHL.
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PMID:Syncytial variant of classic Hodgkin lymphoma: Four cases diagnosed with the aid of CD274/programmed cell death ligand 1 immunohistochemistry. 3189 92

RSK2 is a serine/threonine kinase downstream signaling mediator in the RAS/ERK signaling pathway and may be a therapeutic target in mantle cell lymphoma (MCL), an almost incurable disease subtype of non-Hodgkin lymphoma. In this study, serine-227 (RSK2Ser227 ) in the N-terminal kinase domain (NTKD) of RSK2 was found to be ubiquitously active in five MCL-derived cell lines and in tumor tissues derived from five MCL patients. BI-D1870, an inhibitor specific to RSK2-NTKD, caused RSK2Ser227 dephosphorylation, and thereby, induced dose-dependent growth inhibition via G2 /M cell cycle blockade and apoptosis in four of the five cell lines, while one cell line showed only modest sensitivity. In addition, RSK2 gene knockdown caused growth inhibition in the four BI-D1870-sensitive cell lines. Comparative gene expression profiling of the MCL-derived cell lines showed that inhibition of RSK2Ser227 by BI-D1870 caused downregulation of oncogenes, such as c-MYC and MYB; anti-apoptosis genes, such as BCL2 and BCL2L1; genes for B cell development, including IKZF1, IKZF3, and PAX5; and genes constituting the B cell receptor signaling pathway, such as CD19, CD79B, and BLNK. These findings show that targeting of RSK2Ser227 enables concomitant blockade of pathways that are critically important in B cell tumorigenesis. In addition, we found favorable combinatory growth inhibitory effects of BI-D1870 with inhibitors of BTK (ibrutinib), AKT (ipatasertib), and BCL2 (venetoclax) in cell characteristic-dependent manners. These results provide a rationale for RSK2Ser227 in the NTKD as a potential therapeutic target in MCL and for future development of a novel bioavailable RSK2 NTKD-specific inhibitor.
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PMID:Serine-227 in the N-terminal kinase domain of RSK2 is a potential therapeutic target for mantle cell lymphoma. 3242 Jun 99

NOTCH1 and PAX5 participate in the proliferation and differentiation of B and T lymphocytes. Their expression can be modified by activation of NOTCH1, induced by the Epstein-Barr (EBV) viral proteins identified as LMP1 and LMP2. To identify whether PAX5, NOTCH1, and EBV latency genes participate in the oncogenic process of pediatric patients with classical Hodgkin lymphoma (cHL), the present study aimed to identify the variable expression of NOTCH1 among disease subtypes and to assess its effect on PAX5 expression. A total of 41 paraffin-embedded tissues from Mexican pediatric patients with cHL were analyzed. The expression of CD30, CD20, NOTCH1, PAX5, and LMP1 was evaluated by immunohistochemistry and immunofluorescence. EBV detection was performed by in situ hybridization. Out of all cases, 78% (32/41) of the cHL cases were EBV positive. NOTCH1 expression was detected in 78.1% (25/32) of EBV-positive cases, nodular sclerosis being the most frequent subtype (11/25, 44%). In cases where the expression of both genes was identified, double immunofluorescence assays were conducted, finding no colocalization. We found that Reed-Sternberg cells had aberrant expression compared to their cells of origin (B lymphocytes) due to the molecular mechanisms involved in the loss of expression of PAX5 and that the identification of NOTCH1 could be considered as a candidate diagnostic/prognostic marker and a therapeutic target in pediatric cHL.
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PMID:Variable Expression of Notch1 and Pax5 in Classical Hodgkin Lymphoma and Infection with Epstein-Barr in Pediatric Patients. 3260 37

The case of 70-year-old man with mantle cell lymphoma (MCL) carrying t(11;14) translocation that relapsed as nodal lymphoma combining MCL and classic Hodgkin lymphoma (cHL) 9 years after autologous peripheral blood stem cell transplant (auto-PBSCT) is reported. Lymph nodes contained two separate areas of MCL and cHL-like components. Hodgkin and Reed-Sternberg (HRS)-like cells were accompanied by a prominent histiocyte background. HRS-like cells were CD5- , CD15+ , CD20- , CD30+ , PAX5+ , Bob.1- , Oct2- and EBER+ . The MCL component expressed cyclin D1 and SOX11, whereas cyclin D1 and SOX11 expressions were reduced and lost, respectively, in HRS-like cells. Polymerase chain reaction results showed a single clonal rearrangement of the IGH gene in MCL and cHL-like components. CCND1 break apart fluorescence in situ hybridization showed split signals in both MCL and HRS-like cells, suggesting that MCL and cHL-like components were clonally related. Acquisition of p53 expression and Epstein-Barr virus (EBV)-positivity was seen in HRS-like cells. The patient died of disease progression with elevated hepatobiliary enzymes. The autopsy showed both MCL and cHL-like components around the bile ducts, splenic white pulp and bone marrow. The two components were phenotypically distinct, but genetically related, suggesting that transformation of MCL to HRS-like cells during the course of MCL in association with EBV infection.
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PMID:Mantle cell lymphoma with EBV-positive Hodgkin and Reed-Sternberg-like cells in a patient after autologous PBSCT: Phenotypically distinct but genetically related tumors. 3307 23


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