bims-hodlyp Biomed News
on Hodgkin lymphoma: Pathology and Biology
Issue of 2023–11–05
thirteen papers selected by
Old Bear



  1. Zhonghua Bing Li Xue Za Zhi. 2023 Nov 08. 52(11): 1144-1150
      Objective: To investigate the clinicopathologic features of progressively transformed germinal center-like follicular T-cell lymphoma (PTGC-like FTCL). Methods: The clinicopathologic data of 14 PTGC-like FTCL cases that were diagnosed at the Beijing Friendship Hospital Affiliated to the Capital Medical University from January 2017 to January 2022 were retrospectively collected. Clinicopathological features, immunophenotype, and Epstein-Barr virus (EBV) infection status were analyzed in these cases. Polymerase chain reaction (PCR) was performed to detect the clonal gene rearrangements of T cell receptor (TCR) and the immunoglobulin (Ig) in 10 and 8 cases, respectively. Results: The male to female ratio was 5∶2. The median age was 61 years (range 32-70 years). All patients had lymphadenopathy at the time of diagnosis. By using the Ann Arbor system staging, seven cases were classified as stage Ⅰ-Ⅱ, and seven cases as stage Ⅲ-Ⅳ. Seven cases had B symptoms, four cases had splenomegaly, and two cases had skin rash and pruritus. Previously, three cases were diagnosed as classic Hodgkin's lymphoma, three cases as small B-cell lymphoma, two cases as atypical lymphoid hyperplasia unable to exclude angioimmunoblastic T-cell lymphoma (AITL), one case as EBV-associated lymphoproliferative disorder, and one case as peripheral T-cell lymphoma (PTCL) associated with the proliferation of B cells. All the 14 cases showed that the large nodules were composed of mature CD20+, IgD+B lymphocytes admixed with small aggregates of neoplastic cells with pale to clear cytoplasm. Moreover, hyperplastic germinal centers (GCs) and Hodgkin/Reed-Sternberg-like (HRS-like) cells were seen within these nodules in two and five cases, respectively. The neoplastic cells expressed CD3 (14/14), CD4 (14/14), PD1 (14/14), ICOS (14/14), CD10 (9/14), bcl-6 (12/14), CXCL13 (10/14), and CD30 (10/14). The HRS-like cells in five cases expressed CD20 (2/5), PAX5 (5/5), CD30 (5/5), CD15 (2/5), LCA (0/5), OCT2 (5/5) and BOB1 (2/5). Moreover, neoplastic T cells formed rosettes around HRS-like cells. EBV-encoded RNA (EBER) in situ hybridization showed scattered, small, positive bystander B lymphocytes in 8/14 cases, including 3/5 cases containing HRS-like cells. All tested cases (including five with HRS-like cells) showed monoclonal TCR gene rearrangement and polyclonal Ig gene rearrangement. Conclusions: PTGC-like FTCL is a rare tumor originated from T-follicular helper cells. It could be distinguished from angioimmunoblastic T-cell lymphoma by the formation of follicular structure, and lack of follicular dendritic cell proliferation outside the follicles and the polymorphous inflammatory background. In addition, it should be differentiated from lymphocyte-rich classical Hodgkin's lymphoma and low-grade B cell lymphoma.
    DOI:  https://doi.org/10.3760/cma.j.cn112151-20230205-00094
  2. Eur J Case Rep Intern Med. 2023 ;10(11): 004061
      Primary hepatic lymphoma (PHL) is extremely rare, accounting for less than 1% of all lymphomas, and is limited to the liver without extrahepatic involvement. A 30-year-old male was admitted in the Emergency Department complaining of weakness, fever, night sweats, significant weight loss, discrete ring alopecia, hepatomegaly, right axillary adenopathy and oedema of both legs. Laboratory evaluation showed normocytic normochromic anaemia, thrombocytosis, hyperbilirubinemia, cholestasis and increased international normalised ratio (INR). A computed tomography (CT) scan found an enlarged liver with a heterogeneous structure and moderate ascites. After admission in our ward further investigation revealed increased sedimentation velocity, ferritin and serum lactate dehydrogenase. A hepatic biopsy was performed which confirmed the diagnosis as a nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). The patient was transferred to a haematological ward and underwent chemotherapy with six cycles of R-CHOP. He is in complete remission after a year and half since the beginning of treatment. NLPHL, a very rare lymphoma, is more common in men between the third and fifth decades of life. Usually, the symptoms are very unspecific; a few patients have B symptoms at admission. This kind of presentation is also common in infectious, metabolic and autoimmune diseases, which were excluded in this case. Due to technical issues the final diagnosis was only possible due to the liver biopsy. Treatment with standard Hodgkin lymphoma protocols leads to complete remission in more that 95% of patients with NLPHL.
    LEARNING POINTS: Differential diagnosis of fever, especially in young patients, is very complex and complete investigation takes time, which can delay the diagnosis of malignancies such as primary hepatic lymphoma (PHL).PHL is very rare, and overlapping symptoms with other liver diseases can make the diagnosis very challenging.When the suspicion of PHL is very high, only the hepatic biopsy can lead to the correct diagnosis because the disease has no extrahepatic involvement.
    Keywords:  Fever; cytocholestasis; nodular lymphocyte-predominant HL; primary hepatic lymphoma
    DOI:  https://doi.org/10.12890/2023_004061
  3. Rinsho Ketsueki. 2023 ;64(9): 1053-1065
      Information about genetic mutations that accumulate in each subtype of malignant lymphoma has been reported. Identification of mutations is predicted to become more crucial not only for a definitive diagnosis but also for selecting effective targeted therapies and analyzing detectable residual diseases. However, in the clinical environment of malignant lymphoma, DNA samples might be difficult to obtain, and longitudinal sample collection throughout disease development and/or remission is exceedingly difficult compared to leukemia sectors. Liquid biopsy is a new strategy of tumor biopsy that detects aberrant tumor-derived genes from a patient's plasma, cerebrospinal fluid, or other body fluids. With advances in genetic analysis methods, reports are accumulating on the usefulness of liquid biopsy in diffuse large B-cell lymphoma, central nerves system lymphoma, Hodgkin lymphoma, and other types of lymphoma. This method has the potential to significantly change the way of ML diagnosis and followed up in daily practice, and its development is a great deal of attention.
    Keywords:  Genetic alterations; Liquid biopsy; Malignant lymphoma; Measurable residual disease
    DOI:  https://doi.org/10.11406/rinketsu.64.1053
  4. Front Public Health. 2023 ;11 1261066
      The impact of nonbiological factors (NBF) on survival was investigated in a large cohort of adolescents and young adults (AYA) with lymphoma in the United States (US). We found that uninsured and Medicaid AYA beneficiaries with classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma (NHL) are at significantly increased risk of death when compared with their insured counterpart even after adjustment for other factors affecting survival. Increased risk of death was also noted for Non-Hispanic Black (NHB) patients with cHL and NHL when compared to Non-Hispanic White (NHW) patients, however, only Hispanic patients with NHL were found to have a significantly increased mortality risk while those with cHL were not. NHL AYA patients residing in lower-income counties are at increased risk of death. The strong association of NBF with survival indicates opportunities to improve the survival of AYA lymphoma patients by improving access/quality of care in the US.
    Keywords:  Hodgkin (cHL); adolescent and young adult (AYA) cancer; health disparities; lymphoma; non-Hodgkin’s lymphoma; socioeconomic
    DOI:  https://doi.org/10.3389/fpubh.2023.1261066
  5. Cancer Res Commun. 2023 Nov 01.
      The malignant Hodgkin and Reed Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) are scarce in affected lymph nodes, creating a challenge to detect driver somatic mutations. As an alternative to cell purification techniques, we hypothesized that ultra-deep exome sequencing would allow genomic study of HRS cells, thereby streamlining analysis and avoiding technical pitfalls. To test this, 31 cHL tumor/normal pairs were exome sequenced to ~1000x median depth of coverage. An orthogonal error-corrected sequencing approach verified >95% of the discovered mutations. We identified mutations in genes novel to cHL including: CDH5 and PCDH7, novel stop gain mutations in IL4R, and a novel pattern of recurrent mutations in pathways regulating Hippo signaling. As a further application of our exome sequencing, we attempted to identify expressed somatic single nucleotide variants (SNVs) in single nuclei RNA-seq (snRNA-seq) data generated from a patient in our cohort. Our snRNA analysis identified a clear cluster of cells containing a somatic SNV identified in our deep exome data. This cluster has differentially expressed genes that are consistent with genes known to be dysregulated in HRS cells (e.g., PIM1 and PIM3). The cluster also contains cells with an expanded B-cell clonotype further supporting a malignant phenotype. This study provides proof-of-principle that ultra-deep exome sequencing can be utilized to identify recurrent mutations in HRS cells and demonstrates the feasibility of snRNA-seq in the context of cHL. These studies provide the foundation for the further analysis of genomic variants in large cohorts of cHL patients.
    DOI:  https://doi.org/10.1158/2767-9764.CRC-23-0140
  6. J Manag Care Spec Pharm. 2023 Nov 03. 1-9
      BACKGROUND: A 2010 study on the impact of cancer mortality on productivity costs found Hodgkin lymphoma to have the second largest productivity cost lost per death in the United States. The ECHELON-1 trial demonstrated that frontline brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) improves overall survival (OS) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in stage III/IV classical Hodgkin lymphoma (cHL), reducing the risk of death to 41% (hazard ratio = 0.59; 95% CI = 0.40-0.88; P = 0.009). OBJECTIVES: To assess the estimated impact of frontline treatment choice on mortality and productivity using an oncology simulation model informed by ECHELON-1 data. METHODS: Individual productivity was estimated using the human capital approach and reported via present value lifetime earnings (PVLE) estimates. Deaths avoided and lifeyears saved without and with A+AVD were calculated using a model informed by realworld treatment use, treatment-specific OS, and expert clinicians' opinions. A+AVD use in the base case was 27% (range: 0%-80%). Stage III/IV cHL prevalence over a 10-year period was estimated; downstream lifetime productivity costs were projected without and with A+AVD. RESULTS: In 2031, 3,645 patients were estimated to be newly diagnosed with stage III/IV cHL. Over 10 years with 27% A+AVD vs no A+AVD use, estimates predicted 14% fewer deaths (2,290 vs 2,650) and 14% less total PVLE losses ($1.438 vs $1.664 billion). Results from scenario analyses (40%-80% vs no A+AVD use) showed 20% to 32% decreases in PVLE losses ($1.331-$1.137 billion vs $1.664 billion), saving up to $527 million over 10 years. CONCLUSIONS: Productivity cost losses due to mortality in stage III/IV cHL are high. Increasing A+AVD use for patients with stage III/IV cHL would reduce productivity cost losses as deaths are avoided, based on ECHELON-1 OS results. DISCLOSURES: This study is sponsored by Seagen Inc. Dr. Phillips is a consultant to AbbVie, ADC, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Epizyme, Gilead, Lilly, Pharmacyclics, Regeneron, Seagen Inc., and Xencor, and he is on the boards of Epizyme, Genentech, and Merck. Dr. Liu is an employee of Seagen Inc. and owns stock in Seagen Inc. Mr. Bloudek, Ms. Migliaccio-Walle, and Ms. Reynolds are employees of Curta and are paid consultants to Seagen Inc. in connection with this study. Dr. Burke has been a member of the speaker's bureaus at Seagen Inc. and BeiGene, and he is a consultant to AbbVie, Adaptive Biotechnologies, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Epizyme, Foresight Diagnostics, Genentech/Roche, Kura, Kymera, Lilly, MorphoSys, Novartis, Nurix, Seagen Inc., TG Therapeutics, Verastem, and X4 Pharmaceuticals.
    DOI:  https://doi.org/10.18553/jmcp.2023.23101
  7. Cureus. 2023 Sep;15(9): e46032
      Classical Hodgkin lymphoma (cHL) has achieved high cure rates as a result of recent advancements in treatment. However, recurring or relapsed illness still poses a therapeutic challenge. Immune checkpoint inhibitor pembrolizumab, which targets PD-1, is now being commonly used as part of immunotherapy for recurrent and relapsed cHL. We found eight appropriate articles through systematic search and conducted in-depth analysis to find insights into the effectiveness and safety profiles of pembrolizumab by analyzing clinical trial data in patients with recurrent and relapsed cHL. Analysis of the studies shows that response rates, progression-free survival, and patient-reported quality of life have all significantly improved. However, immune-related consequences are among the adverse outcomes. The necessity for continued study is highlighted by the variation in reported adverse events and follow-up times. Clinicians, researchers, and other healthcare professionals can use this study as a resource to provide knowledgeable and individualized patient care in cHL.
    Keywords:  classical hodgkin lymphoma (chl); efficacy; immune checkpoint inhibitor; pembrolizumab; recurrent and relapsed chl; safety
    DOI:  https://doi.org/10.7759/cureus.46032
  8. Eur Rev Med Pharmacol Sci. 2023 Oct;pii: 34170. [Epub ahead of print]27(20): 9916-9927
       OBJECTIVE: The aim of the study was to evaluate the clinical importance and potential mechanisms of controlling nutritional status (CONUT) score as a prognostic tool for Hodgkin lymphoma (HL).
    PATIENTS AND METHODS: Diagnosed with HL, 307 patients were included in the study. Patients' demographic data, stages, B symptoms, extranodal involvement, presence of bulky disease, laboratory findings, treatments, treatment responses, nutritional status, and overall survival (OS) rates were evaluated from the hospital records. The primary endpoint of our study was to evaluate and classify newly diagnosed HL patients under the CONUT score. The secondary endpoint was to indicate any relationship between nutritional status, CONUT score, and other prognostic factors and OS.
    RESULTS: Of 307 patients (173 males, 134 females), the mean age was 41.58±16.26 (ranging between 18-82 years). The most common type of malignancy was nodular sclerosis (72.53%). To the receiver operating characteristic (ROC) curve analysis, the best cut-off point was 2.5 to predict mortality. Eigthy-five (27.7%) and 222 (72.3%) patients had ≥3 and ≤2 CONUT scores, respectively. Twenty-four (10.80%) and 23 (27.10%) cases were also mortal in the patients with ≤2 and ≥3 CONUT scores, respectively (p<0.001). Survival times were significantly lower in those with higher (≥3) CONUT scores (p<0.001) than among the other patients.
    CONCLUSIONS: Evaluation of nutritional status plays an important role in the response and survival of those with hematological malignancies. Malnutrition can reduce patients' tolerance to chemotherapy and increase the risk of secondary infections. In this study, undernutrition evaluated with the CONUT score was demonstrated to be a potential independent prognostic factor for OS in patients with HL.
    DOI:  https://doi.org/10.26355/eurrev_202310_34170
  9. Front Oncol. 2023 ;13 1288172
      Checkpoint inhibitor therapy has emerged as an effective therapeutic strategy for many types of malignancies, especially in solid tumors. Within the last two decades, numerous monoclonal antibody drugs targeting the CTLA-4 and PD-1/PD-L1 checkpoint pathways have seen FDA approval. Within hematologic malignancies, Hodgkin Lymphoma has seen the greatest clinical benefits thus far with more recent data showing efficacy in the front-line setting. As our understanding of checkpoint inhibition expands, using these pathways as a therapeutic target has shown some utility in the treatment of other hematologic malignancies as well, primarily in the relapsed/refractory settings. Checkpoint inhibition also appears to have a role as a synergistic agent to augment clinical responses to other forms of therapy such as hematopoietic stem cell transplant. Moreover, alternative checkpoint molecules that bypass the well-studied CTLA-4 and PD-1/PD-L1 pathways have emerged as exciting new therapeutic targets. Most excitingly is the use of anti-CD47 blockade in the treatment of high risk MDS and TP-53 mutated AML. Overall, there has been tremendous progress in understanding the benefits of checkpoint inhibition in hematologic malignancies, but further studies are needed in all areas to best utilize these agents. This is a review of the most recent developments and progress in Immune Checkpoint Inhibition in Hematologic Malignancies in the last decade.
    Keywords:  LAG-3; TIGIT; cd47; checkpoint inhibitors; hematologic malignancies; immunotherapy; leukemia; lymphoma
    DOI:  https://doi.org/10.3389/fonc.2023.1288172
  10. Leuk Lymphoma. 2023 Oct 28. 1-9
      Hodgkin lymphoma (HL) affects older and younger patients and includes multiple options for initial treatment. We sought to examine the decision processes of practicing oncologists caring for patients with newly diagnosed HL. Through semi-structured interviews, we explored their perspectives about treatment decisions. We completed thematic analysis using the Anderson Behavioral Model of Health Services framework to identify factors associated with initial decisions. We completed 22 interviews, grouping findings into contextual factors, individual characteristics, and physician preferences. Paternalism was widely cited, along with collaboration between community and academic colleagues. Participants used sequential therapy but not geriatric assessment in care for older patients. Physicians had varied responses about use of frontline brentuximab vedotin (Bv)-based therapy based on perceptions about benefit versus toxicity. Our work suggests a need to further understand the heterogeneity of clinical practices, especially in the post-approval setting of new therapies.
    Keywords:  Lymphoma and Hodgkin disease; cancer care delivery; neoplasia; qualitative research
    DOI:  https://doi.org/10.1080/10428194.2023.2256913
  11. Lab Invest. 2023 Oct 26. pii: S0023-6837(23)00210-6. [Epub ahead of print] 100267
      The study was performed to assess the feasibility of integrating state-of-the-art sequencing techniques and flow cytometry into diagnostic workup of pediatric lymphoma. RNA sequencing (RNAseq), whole exome sequencing (WES) and flow cytometry were implemented into routine diagnostic workup of pediatric biopsies with lymphoma in the differential diagnosis. Within one year, biopsies from 110 children (122 specimens) were analyzed because of suspected malignant lymphoma. The experience with a standardized workflow combining histology and immunohistochemistry, flow cytometry, and next-generation sequencing technologies is reported. Flow cytometry was performed with fresh tissue in 83% (102/122) of specimens and allowed rapid diagnosis of T- and B-cell non-Hodgkin lymphomas (NHL). RNAseq was performed in all NHL biopsies and in 42% (19/45) of Hodgkin lymphoma (HL) samples. RNAseq detected all but one of the translocations found by FISH and PCR. RNAseq and WES identified additional genetic abnormalities not detected by conventional approaches. Finally, three cases are highlighted to exemplify how synergy between different diagnostic techniques and specialists can be achieved. This study demonstrates the feasibility and discusses the added value of integrating modern sequencing techniques and flow cytometry into a workflow for routine diagnostic workup of lymphoma. The inclusion of RNA and DNA sequencing not only supports diagnostics but will also lay the ground for the development of novel research-based treatment strategies for pediatric lymphoma patients.
    DOI:  https://doi.org/10.1016/j.labinv.2023.100267
  12. Case Rep Oncol. 2023 Jan-Dec;16(1):16(1): 628-633
      A 71-year-old man with slight fever and dull abdominal pain was referred to our hospital. He had been receiving methotrexate (MTX) to treat his rheumatoid arthritis for more than 6 years but stopped taking MTX after admission due to the rapid aggravation of his liver function. Computed tomography (CT) showed multiple liver lesions with late enhancement, highly suggesting them to be cholangiocarcinomas. Tumor marker levels were normal except for a slightly elevated PIVKA-II level, i.e., 45 mAU/mL (range 0-40 mAU/mL). We did a biopsy to the largest lesion and endoscopic biliary drainage to make a definitive diagnosis of the hepatic lesions and treat jaundice, respectively. Pathological study showed round, polygonal, and spindle-shaped epithelial atypical cells growing in a sarcomatoid fashion. Atypical cells were positive for CD31, CD34, vimentin, and TFE3, and some of them had intracellular vacuoles, leading to the diagnosis of epithelioid hemangioendothelioma (EHE) of the liver. The patient got well 4 weeks after the endoscopic biliary drainage. CTs showed marked regression of the EHE lesions 3 months after biliary drainage and complete regression in 12 months. The patient further developed Hodgkin lymphoma in the para-aortic lymph nodes 23 months after the biliary drainage and is now under chemotherapy for the malignant lymphoma. We, however, have not detected any EHE lesions in the liver or distant organs for at least 16 months after the confirmation of complete regression of the EHE lesions. Oncologists should note the spontaneous regression of the EHE and investigate the correlation between MTX cessation and EHE regression.
    Keywords:  Epithelioid hemangioendothelioma; Liver; Methotrexate; Spontaneous regression
    DOI:  https://doi.org/10.1159/000531133