scholarly journals Clonally-Related Composite Classic Hodgkin Lymphoma and Follicular Lymphoma

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S100-S101
Author(s):  
D P Larson ◽  
R P Ketterling ◽  
R He ◽  
M Shi ◽  
E D McPhail ◽  
...  
Keyword(s):  
Lymph Node ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Germinal Center ◽  
B Cell Lymphoma ◽  
Mediastinal Lymphadenopathy ◽  
Classic Hodgkin Lymphoma ◽  
History Of ◽  
Igh Rearrangement

Abstract Introduction/Objective Composite classic Hodgkin lymphoma and follicular lymphoma (CHLFL), defined as CHL and FL occurring simultaneously at the same site, is rare and poorly understood. While both Hodgkin/Reed-Sternberg (HRS) cells and FL are thought to be derived from germinal center B-cells, the relationship between CHL and FL when coexistent is unclear. Here, we present two cases of CHLFL and show that the CHL and FL components have a clonal relationship by FISH. Methods/Case Report Case #1 is a 50-year-old man with abdominal and mediastinal lymphadenopathy. An excised mesenteric lymph node showed two distinct components diagnostic for FL, grade 1-2 and CHL. Case #2 is a 63-year- old woman with a history of FL with transformation to diffuse large B-cell lymphoma. Cytogenetic studies showed a complex karyotype with an add(9p), del(10q), and trisomy 16. Post-treatment imaging revealed left axillary adenopathy. An excised axillary lymph node showed CHL with peripheral areas of FL, grade 3A. Both cases had areas of typical FL with BCL2-positive phenotype and no significant CD30/CD15 expression. HRS cells were CD45/CD20-negative, expressed CD30 (strong), CD15, and PAX5, and were present in a mixed inflammatory background. No EBV RNA was present by in situ hybridization. Interestingly, HRS cells in case #1 expressed both BCL6 and BCL2. FISH was performed in both cases. Case #1 had a BCL2 rearrangement in 48% of FL nuclei and in 100% of HRS cells. In case #2, targeted probes were used based on prior cytogenetic results. Here, 47% of FL nuclei and 44% of HRS cells had a 16p duplication; additionally, 32% of HRS cells had an unbalanced IGH rearrangement with loss of the IGH variable region, suggesting possible clonal evolution. No rearrangement of BCL2 or BCL6 was present. An additional 27 CHLFL cases from the literature were reviewed. CHLFL was mostly nodal and occurred in late adulthood in patients with or without a history of FL. It presented at advanced clinical stage, with a 5-year overall survival of 22%. BCL2 expression in HRS cells was common. Bone marrow involvement was 45% (5/11) and consisted of FL exclusively. Five of six tested cases demonstrated BCL2/IGH rearrangement in both FL and HRS cells. Results (if a Case Study enter NA) NA Conclusion Composite CHL and FL are often clonally related and may share a common progenitor B-cell origin – likely a germinal center B-cell – from which additional genetic abnormalities are acquired to develop two distinct lymphomas.

An Interesting Case Report of A Concurrent Classic Hodgkin Lymphoma and Gray Zone Lymphoma in the Mediastinum

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S110-S110
Author(s):  
B Mai ◽  
J Huddin ◽  
Z Hu
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Mediastinal Mass ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Gray Zone ◽  
Large B Cell Lymphoma ◽  
Classic Hodgkin Lymphoma ◽  
Atypical Cells ◽  
Large B Cell

Abstract Casestudy A 52-year-old female presented with night sweats, chills, anorexia, and weight loss. Computed tomography and positron emission tomography showed a soft tissue infiltration in the anterior mediastinum and hypermetabolic bilateral supraclavicular, mediastinal, right hilar, and left internal mammary lymph nodes. An anterior mediastinal mass resection and thymectomy was subsequently performed. Results Sections of the mediastinal mass showed Hodgkin/Reed-Sternberg cells (HRS) admixed with small lymphocytes, histiocytes, plasma cells, and eosinophils. The HRS cells are positive for CD30, CD15, and MUM1, faintly positive for PAX5, and negative for CD20, CD45, CD79a, and BCL6. The morphology and immunophenotype is diagnostic of nodular sclerosis classic Hodgkin lymphoma (CHL). Sections of the thymectomy specimen showed similar morphology, however, in an area that represents 10-20% of the specimen, there are nodular and diffuse lymphoid infiltrates consisting of small lymphocytes, histiocytes, and large atypical cells. The large atypical cells are positive for CD20, CD23, CD30, CD45, CD79a, BCL2, BCL6, MUM-1, and PAX5, and negative for CD1a, CD3, CD57, and Cyclin D1. The background small CD3-positive lymphocytes form a rosette around most of the large atypical cells. CD21 and CD23 stains highlight residual follicular structures. In situ hybridization for EBV-encoded RNA (EBER) is negative. The presence of residual follicular meshwork with an immunophenotype of large B cell lymphoma supports a diagnosis of a gray zone lymphoma (GZL). Overall, CHL is involving 80-90% and GZL is involving 10-20% of the thymic tissue. The patient was subsequently placed on ABVD chemotherapy and achieved remission. Conclusion An accurate diagnosis of GZL is challenging. GZL is a rare type of lymphoma with morphological features between CHL and diffuse large B-cell lymphoma (DLBCL). It is even rarer to encounter a CHL concurrently present with a GZL. The optimal therapeutic approach for cases with concurrent lymphoma diagnosed with CHL and GZL needs further investigation.

Acquisition of potential N-glycosylation sites in the immunoglobulin variable region by somatic mutation is a distinctive feature of follicular lymphoma

Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2562-2568 ◽  
Author(s):  
Delin Zhu ◽  
Helen McCarthy ◽  
Christian H. Ottensmeier ◽  
Peter Johnson ◽  
Terry J. Hamblin ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Somatic Mutation ◽  
Germinal Center ◽  
Variable Region ◽  
B Cell Lymphoma ◽  
Single Chain ◽  
Single Chain Fv ◽  
Glycosylation Sites ◽  
Vh Genes

Most patients with follicular lymphoma (FL) have somatically mutated V genes with intraclonal variation, consistent with location in the germinal center site. Using our own and published sequences, we have investigated the frequency of potential N-glycosylation sites introduced into functional VH genes as a consequence of somatic mutation. FL cells were compared with normal memory B cells or plasma cells matched for similar levels of mutation. Strikingly, novel sites were detected in 55 of 70 (79%) patients with FL, compared to 7 of 75 (9%) in the normal B-cell population (P < .001). Diffuse large B-cell lymphoma (DLCL) showed an intermediate frequency (13 of 32 [41%] patients). Myeloma and the mutated subset of chronic lymphocytic leukemia showed frequencies similar to those of normal cells in 5 of 64 (8%) patients and 5 of 40 (13%) patients, respectively. In 3 of 3 random patients with FL, immunoglobulin was expressed as recombinant single-chain Fv inPichia pastoris, and glycosylation was demonstrated. These findings indicate that N-glycosylation of the variable region may be common in FL and in a subset of DLCL. Most novel sites are located in the complementarity-determining regions. VH sequences of nonfunctional VH genes contained few sites, arguing for positive selection in FL. One possibility is that the added carbohydrate in the variable region contributes to interaction with elements in the germinal center environment. This common feature of FL may be critical for tumor behavior.

Nodular Lymphocyte Predominant Hodgkin Lymphoma: A Rare Case with Fan Pattern E

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S107-S107
Author(s):  
E Ozluk ◽  
E Wei
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Atypical Cells ◽  
Large B Cell

Abstract Introduction/Objective Growth patterns of nodular lymphocyte predominant Hogdkin lymphoma (NLPHL) has been further described by Fan et all. Pattern E is T cell/histiocyte rich large B-cell lymphoma-like and is quite rare. The treatment usually may follow large B cell lymphoma protocol instead of Hodgkin lymphoma regimen. Methods Here we report a patient with NLPHL pattern E. Patient was a 25 years-old African American man who initially presented with generalized lymphadenopathy. Results Biopsy of the axillary lymph node revealed effaced lymph node architecture by a malignant neoplasm in a diffuse and vaguely nodular pattern. In the background of a diffuse infiltrate, there were small to medium sized lymphocytes, numerous atypical large cells with irregular, basophilic nucleoli, and variable cytoplasm. The large cells focally sheeted out. Many histiocytes were also seen in the background. The large atypical cells were positive for CD20, BOB-1, OCT2, BCL-2 (focally), BCL-6, PAX5, and MUM-1, and IgD, whereas negative for BCL-1, CD10, CD15, CD30. CD2, CD3, CD4, CD5, CD7, CD8 highlighted numerous T cells with mild cytological atypia, forming rosettes around the large atypical cells. T cells were negative for ALK-1, CD1a, TdT with increased Ki-67 proliferation index around 35%. Although the surrounding T cells appear atypical in morphology, flow cytometric analysis showed predominantly reactive T-cells with no loss of T-cell associated antigens. PCR analysis showed a producible peak in a single IgH reaction. However, the fragment size of the peak observed did not meet the criteria. T-cell gene rearrangement by TCR gamma and TCR beta PCR was negative for monoclonal T-cells. BCL-1, BCL-2, and BCL-6 FISH panel were negative for gene rearrangements. Based on these findings the diagnosis was made at stage IV. Patient started treatment with R-CHOP therapy with subsequent relapse. Patient has been placed on RICE chemotherapy with partial response. Conclusion NLPHL Pattern E type should be differentiated from classical Hodgkin lymphoma, diffuse large B-cell lymphoma and peripheral T cell lymphoma because the treatment greatly differs from those with higher stage and tendency for recurrence. It is the pathologist role to lead the clinician and render a correct histopathologic diagnosis.

Familial risk for non-Hodgkin lymphoma and other lymphoproliferative malignancies by histopathologic subtype: the Swedish Family-Cancer Database

Blood ◽  
2005 ◽  
Vol 106 (2) ◽  
pp. 668-672 ◽  
Author(s):  
Andrea Altieri ◽  
Justo Lorenzo Bermejo ◽  
Kari Hemminki
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Familial Risk ◽  
B Cell Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Swedish Family ◽  
History Of ◽  
Large B Cell

Abstract Non-Hodgkin lymphoma (NHL) consists of a heterogeneous group of tumors. Population-based data on the familial risk for specific histopathologic subtypes have not been established. Such data are useful for clinical counseling and for searching tumor subtypes sharing common genetic pathways. We used the Swedish Family-Cancer Database to calculate standardized incidence ratios (SIRs) for histopathology-specific subtypes of NHL in 4455 offspring with NHL whose parents or siblings were affected with different types of lymphoproliferative malignancies. A familial history of NHL significantly increased the risk for NHL (SIRparent = 1.8; SIRsibling = 1.9) and for diffuse large B-cell lymphoma (SIRparent = 2.3), follicular lymphoma (SIRsibling = 2.3), and B-cell lymphoma not otherwise specified (NOS) (SIRsibling = 3.4). For a parental history of histopathology-specific concordant cancer, the risks were significantly increased for diffuse large B-cell lymphoma (SIR = 11.8), follicular NHL (SIR = 6.1), plasma cell myeloma (SIR = 2.5), and chronic lymphocytic leukemia (SIR = 5.9). Familial clusters for NHL seemed stronger in females and in siblings. Our study provides the first quantification of the familial risks for NHL by histopathology. The present findings give evidence for a strong familial association of NHL, with little differences in the magnitude of risks for various histopathologic subtypes. The patterns of risks in parents and siblings support the hypothesis of an autosomal-dominant component for diffuse large B-cell NHL and a recessive one for follicular NHL. (Blood. 2005;106:668-672)

CD40L Modulates TRAIL-Induced Apoptosis in Germinal Center Derived B Cell Lymphomas.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4630-4630
Author(s):  
Marion Travert ◽  
Patricia Ame-Thomas ◽  
Thierry Fest ◽  
Céline Pangault ◽  
Gilbert Semana ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lines ◽  
Germinal Center ◽  
B Cell Lymphoma ◽  
B Cell Lymphomas ◽  
Lymphoma Cells ◽  
Over Expression ◽  
Induced Apoptosis ◽  
Transformed Cell Lines

Abstract Follicular lymphoma are characterized by the rearrangement of the bcl-2 gene, present in more than 90% of patients. Over-expression of the bcl-2 protein resulting from this translocation is associated with the inability to eradicate the lymphoma, by inhibiting apoptosis. Despite the median survival ranges from 8 to 15 years, leading to the designation of indolent lymphoma, patients with advanced-stage follicular lymphoma are not cured with current therapeutic options. Numerous reports have shown that Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in a wide variety of transformed cell lines of diverse lineage, but does not appear to kill normal cells, even though TRAIL mRNA is expressed at significant levels in most normal tissues. As cell death induced by TRAIL occurs almost exclusively in tumor cells, it suggests that this drug is safe to use as an antitumor therapy. We therefore investigated the efficiency of this cytokine to induce apoptosis in germinal center derived B cell lymphoma, despite bcl-2 over-expression. Our study was also designed to evaluate the role of CD40L, one of the main differentiation signal involved in B cell maturation during the germinal center reaction, on the regulation of TRAIL-induced apoptosis. This study was performed on three germinal center derived tumor cell lines (BL2, VAL and RL), and on normal and tumor primary cells obtained from human tonsils and lymph nodes. Our data show that normal B lymphocytes obtained from tonsil biopsies are resistant to TRAIL-mediated apoptosis, when B lymphoma cells issued from lymph node of numerous patients are significantly sensitive to the cytokine. When we treat these lymphoma cells with trimeric huCD40L, we partly rescue these cells from spontaneous apoptosis which naturally occurs after few days of culture, and reverse by 50% TRAIL-mediated apoptosis when cells were co-treated with huCD40L for 16 hours. Similar results were reproduced on some germinal center derived cell lines. BL2 was indeed found highly sensitive to TRAIL-induced apoptosis following a 24 hour exposure. On the opposite, VAL and RL were almost insensitive. We have demonstrate that apoptosis is exclusively mediated by TRAIL-R1 in BL2. Analysis of signalling pathways revealed that the protection to TRAIL-induced apoptosis by CD40L is due to some specific anti-apoptotic molecules that will be described. Genes encoding these molecules are targets of the NFκB signalling pathway activated by CD40L. Our results suggest that activation of NFκB and induction of anti-apoptotic molecules by CD40L play an important role in the protection of germinal center derived B cell lymphomas against apoptosis. Then, NFκB inhibitors may be wise to use in clinical trials in conjunction with TRAIL against follicular lymphomas.

Childhood Crowding, Atopy and Risk of Non-Hodgkin Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4648-4648
Author(s):  
Wendy Cozen ◽  
Engels A. Eric ◽  
James R. Cerhan ◽  
Martha Linet ◽  
Leslie Bernstein ◽  
...  
Keyword(s):  
Immune Response ◽  
Los Angeles ◽  
Follicular Lymphoma ◽  
Hodgkin Lymphoma ◽  
Health Care Financing ◽  
B Cell Lymphoma ◽  
Cancer Registries ◽  
Non Hodgkin Lymphoma ◽  
Increased Risk ◽  
History Of

Abstract Subtle differences in immune response may play a role in non-Hodgkin lymphoma (NHL) etiology. Because adult immune response may be influenced by early childhood exposures, we examined the role of childhood crowding, history of atopic disease, and other childhood immune-related exposures on the risk of non-Hodgkin lymphoma in a multi-center case-control study. Interviews were completed with 1,321 cases ascertained from population-based cancer registries in Seattle, Detroit, Los Angeles and Iowa, and with 1,057 frequency-matched controls, selected by random-digit dialing and from the Health Care Financing Administration (HCFA) database. The association between NHL risk in relation to atopy and other exposures was assessed using multivariable logistic regression methods. Most types of allergy were associated with protection from NHL, with hay fever especially protective against all NHL combined (Odds Ratio [OR] = 0.71, 95% confidence interval [CI]= 0.54–0.94), diffuse large B-cell lymphoma [DLBCL] (OR=0.61, 95% CI=0.41–0.91), and follicular lymphoma (OR=0.70, 95% CI=0.45–1.09). A history of eczema increased risk of follicular lymphoma (OR=1.92, 95% CI= 1.08–3.41) but not DLBCL (OR=1.06, 95% CI= 0.55.2.04). Asthma in childhood was not associated with risk of NHL. Risk of DLBCL (OR =1.72, 95% CI=1.17–2.52), but not follicular lymphoma (OR=1.15, 95% CI=0.75–1.76) was elevated for the youngest compared to the oldest of siblings. Neither number of siblings nor years between births of siblings were significantly associated with risk. These results suggest that some immune-related exposures may affect NHL risk.

The Emergence of Clonally Related Hodgkin Lymphoma Following B-Cell Malignancies Treated with Rituximab.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3664-3664
Author(s):  
Catherine H Burton ◽  
Sheila J.M. zsnO'Connor ◽  
Roger G Owen ◽  
Andrew S Jack
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
B Cell Lymphoma ◽  
Tumour Cells ◽  
Classical Hodgkin Lymphoma ◽  
Composite Lymphoma ◽  
Original Diagnosis ◽  
B Cell Malignancy ◽  
Cell Malignancy

Abstract Abstract 3664 Poster Board III-600 Classical Hodgkin lymphoma in association with another type of B-cell malignancy is a well recognised entity. In at least some of these composite lymphoma cases, a clonal relationship between the lymphoma sub-types can be demonstrated by the presence of common cytogenetic abnormalities or mutational patterns within the IGH locus. There is little known of possible mechanisms of clonal divergence in these cases. It is possible that treatment or the tumour micro-environment could, in some circumstances, favour the outgrowth of Reed Sternberg cells. These cells having lost many central phenotypic characteristics of mature B-cells may have an advantage over clonal tumour cells that remain under the control of normal regulatory pathways. In such a model, treatment with rituximab could add selective pressure favouring the development of a composite lymphoma. We have recently identified three male patients who relapsed with classical Hodgkin lymphoma after treatment for another form of B-cell malignancy. Patient 1, aged 76 years, had stage 3, asymptomatic follicular lymphoma, and was treated with rituximab alone. Eight months from the original diagnosis he developed new submental lymphadenopathy. Patient 2, aged 49 years, had stage four, symptomatic follicular lymphoma, treated with R-CVP. He developed biopsy proven high grade transformation at the end of his treatment and proceeded to two cycles of R-DHAP. At the end of treatment, twelve months from the original diagnosis, he developed inguinal lymphadenopathy. Patient 3, aged 70 years, had stage four, diffuse large B-cell lymphoma, treated at presentation with R-CHOP. Two years after initial diagnosis, he developed cervical lymphadenopathy. In all three presenting cases, CD20 was strongly expressed on the lymphoma cells and a t(14;18) was identified in the biopsy. In all three relapsed cases the biopsy showed morphologically typical classical Hodgkin lymphoma with CD30/IRF4 co-expression and absence of Oct2, Bob1 and CD20 expression within the Reed Sternberg cells. A t(14;18) was detected by FISH in the Reed Sternberg cells, demonstrating clonal identity with the underlying lymphoma. There was no evidence of the preceding lymphoma and complete absence of a normal B-cell population in the biopsy. Epstein Barr Virus was not detectable by EBER in situ hybridisation. All patients have been treated for Hodgkin lymphoma. Patient 1 has subsequently died, patient 2 is awaiting a stem cell transplant and patient 3 is currently receiving treatment. Treatment with rituximab is associated with the development of CD20 negative phenotypic change. In some cases this may be due to the selection of tumour cells that have epigenetically silenced the expression of CD20. Epigenetic silencing of key transcription factors may also be the mechanism of loss of the B-cell phenotype, including CD20, in Reed Sternberg cells. The relatively frequent occurrence of composite lymphoma suggests that this may occur regularly with neoplastic B-cell populations and the outgrowth of these cells would be strongly favoured by rituximab treatment. The cases presented here highlight the need for a more systematic approach to the collection of data from patients with relapsed lymphoma. An association between rituximab treatment and the development of composite lymphoma has practical consequence but may also provide a unique insight into the pathogenesis of Hodgkin lymphoma. Disclosures: No relevant conflicts of interest to declare.

Age-related Epstein-Barr virus (EBV)–associated B-cell lymphoproliferative disorders: comparison with EBV-positive classic Hodgkin lymphoma in elderly patients

Blood ◽  
2009 ◽  
Vol 113 (12) ◽  
pp. 2629-2636 ◽  
Author(s):  
Naoko Asano ◽  
Kazuhito Yamamoto ◽  
Jun-Ichi Tamaru ◽  
Takashi Oyama ◽  
Fumihiro Ishida ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
Age At Onset ◽  
B Cell Lymphoma ◽  
Female Ratio ◽  
Barr Virus ◽  
Age Related ◽  
Classic Hodgkin Lymphoma ◽  
Epstein Barr

Abstract Age-related Epstein-Barr virus–associated B-cell lymphoproliferative disorder (aEBVLPD) is a disease group characterized by EBV-associated large B-cell lymphoma in elderly without predisposing immunodeficiency. In nearly one- third of cases, aEBVLPD occurs as a polymorphous subtype with reactive cell-rich components, bearing a morphologic similarity to classic Hodgkin lymphoma (cHL). The aim of this study was to clarify clinicopathologic differences between the polymorphic subtype of aEBVLPD (n = 34) and EBV+ cHL (n = 108) in patients aged 50 years or older. Results showed that aEBVLPD was more closely associated with aggressive clinical parameters than cHL, with a higher age at onset (71 vs 63 years); lower male predominance (male-female ratio, 1.4 vs 3.3); and a higher rate of involvement of the skin (18% vs 2%), gastrointestinal tract (15% vs 4%), and lung (12% vs 2%). aEBVLPD was histopathologically characterized by a higher ratio of geographic necrosis, greater increase (> 30%) in cytotoxic T cells among background lymphocytes, higher positivity for CD20 and EBNA2, and absence of CD15 expression. As predicted by the clinical profile, aEBVLPD had a significantly poorer prognosis than EBV+ cHL (P < .001). The polymorphous subtype of aEBVLPD constitutes an aggressive group with an immune response distinct from EBV+ cHL, and requires the development of innovative therapeutic strategies.

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