Cases Of Hodgkin's Disease Research Articles

Epstein‐Barr virus (EBV) latent membrane protein‐1‐specific cytotoxic T lymphocytes targeting EBV‐carrying natural killer cell malignancies

Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP) 1 is a potential target for immunotherapy of some proportion of Hodgkin's disease cases, nasopharyngeal carcinomas, EBV-associated natural killer (NK)/T lymphomas, and chronic active EBV infection (CAEBV). Since it is unknown whether EBV-infected NK/T cells are susceptible to lysis by LMP1-specific cytotoxic T lymphohcytes (CTL), we here tested the ability of mRNA-transduced antigen-presenting cells (APC) to stimulate rare LMP1-specific CTL. A 43-amino acid N-terminal deletion mutant LMP1 (DeltaLMP1) could be efficiently expressed in dendritic cells and CD40-activated B cells upon mRNA electroporation. DeltaLMP1-expressing APC were found to stimulate LMP1-specific CTL from a healthy donor and a CTL clone recognized a peptide, IIIILIIFI, presented by HLA-A*0206 molecules. Processing and presentation of the antigenic peptide proved dependent on expression of an immunoproteasome subunit, low-molecular-weight protein-7, as confirmed by RNA interference gene silencing. Furthermore, an EBV-infected NK cell line derived from a patient with CAEBV, and another from an NK lymphoma with enforced HLA-A*0206 expression, were specifically lysed by the CTL. Overall, these data suggest that immunotherapy targeting LMP1 in EBV-associated NK lymphomas and CAEBV might serve as an alternative treatment modality.

CT diagnosis of 52 patients with lymphoma in abdominal lymph nodes

To assess CT manifestations and its diagnostic value for lymphoma in the abdominal lymph nodes (LALN). CT findings in 52 cases of LALN proved by surgery or biopsy, including Hodgkin's disease (HD) in 16 cases and non-Hodgkin's lymphoma (NHL) in 36 cases, were retrospectively analyzed. (1) CT manifestations based on distribution of the lesions of LALN: Solitary mass type was found in 10 cases, including solitary, round, uniform-density, enlarged lymph nodes in 3 cases; and multiple, enlarged lymph nodes fusing into singular lobular mass in 7 cases. Thirty-four cases of multiple-nodular type showed multiple, round, enlarged lymph nodes with uniform density and clear margins. Vessels-embedded signs, including mesenteric vessels, renal vessels, abdominal aorta or inferior vena cava, were seen in 6 cases, and duodenum-embedded signs were seen in 2 cases. Eight cases of diffuse type showed characteristic "cobblestone signs". (2) CT manifestations correlated with pathological type: CT manifestations of 12 cases of HD were different from those of 40 cases of NHL in distribution, size, quantity and fused lesion of enlarged lymph nodes. (3) Twenty-eight cases of 52 patients were accompanied with extra-nodal lymphoma in the abdomen, especially gastrointestinal lymphoma, which had characteristic CT findings. (4) In follow-up examinations, CT images showed uniform, heterogeneous or rim enhancement in 15 cases, and occasional calcifications accompanied with reduction of the lesion size and quantity in 12 cases, whereas the lesions disappeared in 3 cases after treatment. CT images show many characteristic manifestations valuable for qualitative diagnosis of LALN, and it is also helpful for pathological classification of LALN and therapeutic evaluation in follow-up of patients.

Rescue of Germinal Centre B Cells with Inactivated Immunoglobulin Genes by EBV In Vitro Suggests a Common Mechanism in the Pathogenesis of Post-Transplant Lymphoproliferative Disease and Hodgkin's Disease.

Early onset post-transplant lymphoproliferative disease (PTLD) tumours resemble Epstein-Barr virus (EBV)-positive in vitro transformed lymphoblastoid cell lines (LCLs) both in cellular phenotype and in EBV latent gene expression. Here viral transformation appears to be sufficient for tumour growth. However, in cases of late onset PTLD and Hodgkin's disease (HD) where viral gene expression is more restricted and tumour evolution has involved additional cellular genetic changes, the role of EBV in pathogenesis is not certain. Many cases of PTLD and HD lack surface Ig and have functionally inactivated immunoglobulin (Ig) sequences. They appear to arise from atypical post-germinal centre (GC) B cells which have acquired crippling mutations in the Ig genes during GC transit. Such crippled GC cells normally die by apoptosis but if rescued may form a pool of cells particularly prone to tumour development. In the present work we investigated if EBV infection in vitro can transform crippled GC cells. GC cells isolated by FACS sorting CD10+ tonsillar B cells were infected with EBV (B95.8 strain) in vitro and seeded at limiting dilutions onto fibroblast feeders to establish cell lines. In parallel experiments, naïve and memory B cells, isolated from peripheral blood by FACS sorting of IgD+, CD27− and IgD−, CD27+ subsets respectively, were infected with EBV in vitro to establish LCLs. Over 100 GC-derived cell lines (GC-LCLs) and a similar number of peripheral blood-derived LCLs were established. All peripheral blood-derived LCLs consistently expressed surface Ig (predominantly IgM+, IgD+ co-expression in naïve and IgG+ or IgA+ expression in memory transformants). In comparison, whilst most GC-LCLs expressed surface Ig, we identified six lines that lacked surface Ig expression. Sequencing the variable regions of the IgH genes of the six surface Ig-negative GC-LCLs confirmed that three lines carried hypermutated but non-functional IgH genes. There was a 7 nucleotide insertion resulting in a frameshift of the downstream IgH sequence in one cell line, while the other two carried mutated Ig genes containing stop codons in the CDR1 and/or the CDR2 regions of the IgH sequence. In the three other surface Ig-negative GC-LCLs, the IgH reading frame was mutated but still intact. Sequence inactivation was not seen in any of the surface Ig-positive GC-LCLs analysed in parallel nor, in any of the peripheral blood derived LCLs. Interestingly, GC-derived transformants lost their original GC phenotype and acquired activation markers typical of conventional LCLs. Thus they were CD10−, CD23+, CD27+ and CD38+. Analysis of EBV gene expression showed that GC-LCLs including the six surface Ig-negative lines expressed EBNA1, EBNA2, LMP1 and LMP2 as seen in conventional LCLs. The present work provides strong evidence that EBV infection in vitro can rescue crippled GC cells, leading to the outgrowth of surface Ig-negative LCLs with functionally inactivated IgH alleles. These lines appear to be in vitro correlates of PTLD both in their cellular phenotype and in the expression of EBV latent proteins. Though the cellular phenotype and EBV latent antigen expression pattern is different in HD, it is possible that these tumours arise by different pathways from the same pool of atypical post-GC survivors.

Multicentric Primary Spinal Hodgkin??s Lymphoma: PET/CT and MR Imaging

Primary spinal Hodgkin lymphoma without classic nodal lesions or advanced systemic disease is uncommon. As a result of its rarity and nonspecific symptomatology, it may be inadequately evaluated at initial presentation and frequently mistaken for other pathologic processes. The authors present a case of Hodgkin disease with multiple vertebral lesions demonstrated by PET/CT and MR.

Primary spinal extranodal Hodgkin's disease at two levels

About 90% of Hodgkin's disease cases originate from lymph nodes whereas 10% from extranodal regions. Patients rarely present with spinal cord compression due to epidural Hodgkin's disease. Primary spinal extradural Hodgkin's disease which does not have any other organ involvement in the body is even rarer. A 39-year-old male patient who complained of lumbar pain had normal findings upon neurological examination. Radiological examination revealed a mass on the epidural space at level L3 and the involvement of the vertebral corpus accompanied by the involvement of C6 vertebral body. Primary focus could not be identified despite further investigation. The patient underwent L3 laminectomy and posterior decompression and biopsy was obtained from the lesion extending to epidural space. The pathological result was reported as lymphocyte dominant type Hodgkin's disease. Flow cytometry was performed to the lesion, also. The patient was evaluated as Stage 4A according to Ann Arbor classification. Postoperative radiotherapy was applied to lumbar and cervical region. In the literature we have not come across any case of primary spinal extranodal Hodgkin's disease with involvement at two levels. In conclusion, although it might be extremely rare, primary spinal extranodal Hodgkin's disease with involvement at two levels might be observed.

Hodgkin′s disease in an elderly patient with B-Cell chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia worldwide. It is an indolent disease, almost exclusively of B-cell origin. Some CLLs evolve into a more aggressive lymphoid malignancy. The most common of these is Richter's syndrome. Transformation to acute lymphoblastic leukemia, plasma cell leukemia, multiple myeloma, or Hodgkin's disease (HD) may also occur. CLL patients are also at a significantly increased risk of developing a second malignant neoplasm later in life. One of the most common of these is HD. Herein, we report a case of HD in an elderly man with a history of B-cell CLL.

Diagnostic accuracy of imprint cytology in the assessment of Hodgkin's disease in Japan

Our objective was to evaluate the usefulness of cytomorphologic assessment in the accuracy of diagnosis of Hodgkin's disease (HD), using imprint cytological preparations over a 18-yr period. Imprint materials from 34 HD cases were reviewed using cytomorphological and immunocytochemical studies. Twenty-six cases (76.5%) were diagnosed to be HD and 6 cases (17.6%) were suspected to be HD, but 2 cases (5.9%) were cytologically diagnosed as reactive lesions, because of an insufficient number of Reed-Sternberg (RS) cells. The 6 suspected cases were definitively diagnosed as HD, using immunocytochemistry. Immunophenotyping of RS cells in 32 cases (excluding the two cases of reactive lesions) showed CD30+ in 31 (96.9%) cases, CD15+ in 22 (68.8%) cases and CD20+ in 12 (37.5%) cases. RS cells were immunophenotypically classified into five groups: A, (CD 30+, 15+, 20-) 15 (46.9%); B, (CD30+, 15-, 20-) 5 (15.6%); C, (CD 30+, 15+, 20+) 6 (18.8%); D, (CD30+, 15-, 20+) 5 (15.6%); and E, (CD30-, 15+, 20+) 1 (3.1%). Cytomorphologic differences in RS cells were identified between group D and other groups (CD15+ and/ or CD20-). The former had a low polymorphic shape (like popcorn), and the latter had a more classical polymorphic shape. Epstein-Barr virus (EBV)-latent membrane protein-1(LMP-1) was identified in 16 (50%) cases. LMP-1 expression was found not only in classic RS cells, but also in smaller variants. These variants did not match the morphologic criteria of RS cells, but expressed the common phenotype (CD30+, CD15+/-) of RS cells, suggesting the same cellular origin as RS cells. This study demonstrated that imprint cytology from lymph node biopsies can be a useful tool for the diagnosis and the evaluation of the cellular biology of HD.

Primary multifocal osseous Hodgkin disease: a case report and review of the literature

Hodgkin disease (HD) typically involves the lymphatic system at one or more sites. Rarely, Hodgkin disease presents as an osseous lesion without involvement of lymph nodes. Therefore, the histologic diagnosis of osseous HD can be problematic. We present a rare case of multifocal osseous HD and a review the literature with special emphasis on treatment and prognosis. Osteomyelitis and lymphoma are the main differential diagnoses and can only be excluded histologically by the presence of Sternberg Reed cells or by immunohistochemical examinations. This case reports a 21-year old man with a Hodgkin lymphoma located at the proximal femur and the proximal tibia. Staging studies revealed no other tumor manifestations. Regarding the Ann Arbor classification, the presented case should be a stage IV disease. The patient is without evidence of disease 4 years after curettage, local radiation therapy, and systemic chemotherapy despite the poor prognosis considering the Ann Arbor classification. Reviewing the few reported cases, osseous HD must be distinguished from systemic HD with diffuse bone marrow involvement and from osseous metastases in advanced stage of disease because it seems to have a better prognosis.

Assessing Immunoglobulin Heavy Chain Rearrangements in Pediatric CD20-Positive and CD20-Negative Classic Hodgkin's Diseas

Approximately 15% of all cases of childhood classical Hodgkin's disease (HD) express CD20, a B-cell marker associated with immunoglobulin heavy chain rearrangements. Immunoglobulin heavy chain rearrangements in Reed-Sternberg cells could be used to assess minimal residual disease (MRD), as was shown with immunoglobulin heavy chain patient-specific primers (PSPs) in non- Hodgkin's lymphoma. The aim of this study was to analyze pediatric HD for future design of immunoglobulin heavy chain PSP for MRD detection. DNA was extracted from paraffin-embedded tissue from unstained slides of 8 pediatric CD20+ nodular sclerosis HD cases and 10 CD20− nodular sclerosis HD cases. Immunoglobulin heavy chain polymerase chain reaction and sequencing were performed on 16 of 18 cases, which had adequate DNA for further analysis. Sequence analysis from 3 cases (19% of HD cases) demonstrated unique V(D)J regions, which could potentially be used to design PSP. Unique PSPs could be used to assess MRD in advanced-stage HD specimens. Future studies should focus on improved detection and analysis of more cases to identify appropriate specimens in assessing clinical implications of MRD detection.

Human T‐cell lymphotropic virus type 1 (HTLV‐1) and lymphoid malignancies in Dominica: A seroprevalence study

Human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in certain regions of the world where it is associated with lymphoid malignancies. Herein we aim to describe the seroprevalence of HTLV-1 in lymphoid malignancies in Dominica. We carried out a 10-year retrospective study of histologically proven hematologic malignancies and HTLV-1 seropositivity at the Princess Margaret Hospital, Dominica. Ninety-eight cases were reviewed (59% males, 41% females), ranging in age from 3 to 91 years. HTLV-1 was seropositive in 38.6% (31/80) of all hematologic malignancies. Three of 6 cases of Hodgkin disease (50%), 16 of 36 (44.4%) of non-Hodgkin lymphoma, and 3 out of 8 unclassified lymphomas (37.5%) were seropositive; all 6 cases (100%) of acute adult T-cell leukemia/lymphoma (ATLL) were seropositive. One case each of chronic lymphocytic leukemia and myeloproliferative disorder was seropositive. HTLV-1-seropositive lymphomas presented at a younger age than did seronegative cases. Thus, HTLV-1 is significantly associated with lymphoid malignancies in Dominica, and further studies are needed before a causal relationship with Hodgkin disease can be established.

Differential Effects of Three Small Molecules Blocking Phosphatidylinositol-3 Kinase or AKT in Hodgkin Disease Cell Lines: Induction of Apoptosis and Cell Cycle Arrest.

Several types of tumor cells utilize the phosphatidylinositol 3 Kinase (PI3K)/AKT pathway to support their growth and survival, and blockade of this pathway has been shown to have an antiproliferative effect in these cells. The significance of this survival pathway in Hodgkin disease (HD), and in particular, the neoplastic Hodgkin and Reed-Sternberg (H/RS) of Hodgkin disease (HD) is unknown. We studied routinely processed tissue sections of 42 cases of primary HD (n=42, 35 classical HD and 7 nodular lymphocyte predominant) for the expression of the active phosphorylated form of AKT. We also studied AKT expression in a panel of 4 well-characterized HD-derived cell lines (HD-MyZ, HD-LM2, L-428, and KM-H2). 27 of 42 (64.3%) cases of primary HD sections expressed phospho AKT (23/35 classical and 4/7 nodular lymphocyte predominant). Cultured H/RS cells also showed constitutive phosphorylation of AKT on Ser473. CD30 ligand (CD30L), CD40L and RANKL, increased the phosphorylation of AKT and downstream molecules as early as 1 hour. The effect of 3 small molecule inhibitors of PI3K/AKT pathway (PI3K inhibitor LY294002; AKT inhibitors QLT0394 and QLT0395 from QLT Inc, Vancouver, Canada) on cell proliferation and survival of cultured H/RS cells was examined by the MTS assay. The PI3K inhibitor LY294002 showed antiproliferative activity in a time and dose dependent manner in all cell lines tested. This antiproliferative effect was primarily due to cell cycle arrest in G0/G1 phase, as determined by propidium iodide staining, and to a less extent due to induction of apoptosis, as determined by the Annexin-V binding assay. However, when the AKT inhibitors QLT0394 and QLT0395 were used, they primarily induced apoptosis even at nanomolar doses. Apoptosis was mediated by caspase 8 activation as determined by western blot and was partially reversed by the pancaspase inhibitor ZVAD-FMK. Both AKT inhibitors alteredf AKT phosphorylation within 24 hours, and reduced phosphorylation of downstream molecules, such as 4E-BP1. Moreover, the AKT inhibitor QLT0395 showed downregulation of MDM2 and cyclin D1 within 24 hours, and increased ERK1/2 phosphorylation with subsequent decrease of total ERK1/2 levels at the same time frame, but had no effect in BCL-2, cFLIP or Bax. Importantly, both AKT inhibitors (QLT0394 and QLT0395) maintained their killing activity even in the presene of CD30L, CD40L, and RANKL. These preclinical data suggest that small molecules hitting different targets within PI3K/AKT pathway may have different effects on proliferation and apoptosis and that blockade of this pathway may be of therapeutic value in the treatment of patients with HD.

Latent-Membrane 2a Specific CTL's but Not Latent-Mebrane 1 Specific CTL's Lysis Efficiently Hodgkin Lymphoma Cells.

Relapse is the leading cause of treatment failure after allogeneic SCT of Hodgkin Disease (HD). As Ebstein-Barr infection (EBV) is associated with 60% of all HD cases, adoptive immunotherapy with donor derived EBV-specific T-cells lines has resulted in disease control of allogeneic SCT. Potential targets for the adoptively transferred T-cells are the type II latency protein LMP-1 and LMP-2a, which are both homogenously expressed by HD cells. In healthy individuals, both LMP-1 and LMP-2a elicits subdominant CD8+ T-cell responses with frequencies of less than 1:10000. LMP-1 and LMP-2a specific T-cells from 1x108 PBMC derived from HLA A*0201+healthy donors were stimulated with the HLA A*0201 LMP1-epitopes YLLEMLWRL and YLGQNWWTL and the HLA A*0201 LMP-2a epitope CLGGLLTM. Activated T-cells were selected by the cytokine secretion assay and expanded for 10 days. In 85% of donors 1.7 x106 (range 0.7 –4.5 x106; n=13) LMP-1 or LMP-2a specific CD8+ T-cell could be generated with an average purity of 83% as determined by tetramer staining. LMP1- and LMP2a-specific CD8+ T-cells were then expanded 3000 x in 14 d by the rapid expansion protocol and evaluated functionally for cytokine production and specific lysis. Both LMP-1 and LMP-2a specific CD8+ T-cells retained specific cytokine production if stimulated with peptide pulsed targets, efficiently lysed peptid pulsed targets. Surprisingly, if LMP-1 was presented endogenously by EBV positive targets or by targets cells transduced with LMP-1, no cytokine production or specific lysis was detected despite protein expression of LMP-1 in all targets. In contrast, IFN-γ production could be readily detected in LMP-2a-specific CD8+ T-cells after stimulation with target cells processing endogenously the LMP-2a antigen as well as specific lysis of EBV positive target cells. Furthermore, LMP2a specific CD8+ demostrated also specific lyse of Hodgkin-cells expressing the LMP2a (30:1 E/T ratio; 29,3%) where as LMP-1-specific CD8+ T-cells could not lyse HD-cells. In summary, LMP-1 and LMP-2a specific T-cells, although present at undectable levels in healthy donors, can be readily selected and expanded to up to 6x109 antigen-specific T-cells in less than 4 weeks starting from 1x108 PBMC. Based on this data, adoptive immunotherapy of relapsed EBV positive HD after allogeneic SCT should be preferentially performed with LMP-2a specific CD8+ T-cells rather than with LMP-1 specific CD8+ T-cells.

Hodgkin Disease Associated With T-Cell Non-Hodgkin Lymphomas

Non-Hodgkin lymphoma (NHL) is more likely to develop in patients with Hodgkin disease (HD) than in the general population. Although reports of synchronous or metachronous HD and NHL are not uncommon in the literature, the biologic relationship of these 2 malignant neoplasms often is unclear. A larger-than-expected fraction of NHLs occurring in patients with HD are of the T-cell phenotype. We report 1 synchronous and 3 metachronous cases of HD and T-cell NHL. In 2 cases, the 2 tumors are unlikely to be related clonally. In the other 2 cases, however, T-cell receptor rearrangement studies demonstrated the presence of the same rearranged clone in both tumor specimens, suggesting that they share a common precursor or that one arose by transformation of the other. These observations imply that, similar to the observations in B-cell NHLs occurring with HD, a subset of synchronous and metachronous T-cell NHLs and HD may be related clonally.

Factors influencing treatment recommendations in early-stage Hodgkin’s disease: a survey of physicians

The aim of this study was to explore variation in practice patterns and identify factors associated with physicians' treatment decisions for early-stage Hodgkin's disease. We conducted a one-time mail survey of oncologists randomly selected from directories of national oncology societies (n = 207) and Hodgkin's disease experts (n = 147). The survey included questions on (i) physician factors, (ii) preferred treatment choices for six case scenarios of early-stage Hodgkin's disease that varied by patient factors, and (iii) thresholds for changing treatment recommendations. The response rate was 50%. For non-bulky Hodgkin's disease, 69% of respondents chose combined modality therapy (CMT). On multivariate analysis, physician factors that independently predicted for choice of CMT included a high Hodgkin's disease case load (P = 0.02) and a high percentage of patients enrolled in clinical trials (P = 0.05). Radiation oncologists had a lower threshold for adding radiation therapy (P = 0.02). More experience with second malignancy cases and longer time in practice were associated with a higher threshold for adding radiation therapy (P = 0.04 and P = 0.008, respectively). In stratified analyses, treatment decisions of non-experts were significantly influenced by physician factors, but not by patient factors. Conversely, choices of Hodgkin's disease experts were insensitive to all physician factors, but experts were significantly more likely to select chemotherapy alone in young women and CMT in older patients. Our results indicate that physician factors including practice type and experience may in part explain variation in practice pattern for Hodgkin's disease therapy. Hodgkin's disease experts are more likely to tailor therapy according to individual patient factors.

Primary colonic Hodgkin’s lymphoma masquerading as Crohn’s disease

Primary gastrointestinal (GI) Hodgkin's disease (HD) is rare, representing less than 0.5% of cases of HD. This is a case of primary colonic HD that was treated as Crohn's disease (CD) for 3 years until the diagnosis of lymphoma was made. A 32 year-old man presented in 1999 with diarrhea and melena. He was diagnosed with CD based on colonoscopy with biopsies. He was managed medically, and did well for a year when he had increased diarrhea. Colonoscopy showed worsened colitis. The patient did not tolerate immunosuppressants, and on Pentasa, his diarrhea improved. In early 2002, he complained of fatigue, abdominal distention and anorexia. CT scan demonstrated small bowel and colonic wall thickening. He was treated for iron and B12 deficient anemia. In June 2002, his symptoms worsened and he was referred to our institution. Exam revealed a cachectic, afebrile male with marked abdominal distention and a large tender palpable mass in the mid abdomen. There was no lymphadenopathy. Laboratory data included WBC 20, HCT 16.6, Platelets 680, albumin <1, and normal liver enzymes. Bone marrow biopsy was negative for lymphoma, and HIV test was negative. CT showed a large mass defining the wall of the ascending colon and terminal ileum with bulky mesenteric lymphadenopathy. Colonoscopy revealed a normal left colon and a 20cm long area in the right colon that was markedly dilated with irregular, erythematous mucosa with ulceration and areas of necrosis. Biopsies demonstrated numerous large, atypical cells, and scattered Reed-Sternberg cells, staining positive for CD 15 and 30. The diagnosis of Hodgkin's lymphoma was made. The patient underwent hemicolectomy and was found to have a mass involving the terminal ileum and right colon. The mesentery was replaced completely by tumor. Pleural fluid contained Reed-Sternberg cells and he was treated for stage IV HD with chemotherapy. He never achieved complete remission, and 8 months after diagnosis was found to have progression of disease. Retrospective review of biopsies from the patient's initial colonoscopies shows nonspecific colitis with mild chronic changes. Deeper sections show rare Reed-Sternberg cells, making HD the patient's primary diagnosis. There are few reports in the literature of primary HD mimicking inflammatory bowel disease (IBD). In our case, we were able to demonstrate that HD was present all along. Primary colonic lymphoma is rare, but should be considered in the differential of IBD, especially with atypical or refractory behavior.

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Total Registration of Non-Hodgkin's Lymphoma and Hodgkin's Disease in Scotland: Effect of Deprivation and Caseload on Outcome

All cases ≥16 years of age with a histological diagnosis of non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) presented in Scotland between 1 January 1994 and 31 December 1996 were registered prospectively in the Scotland and Newcastle Lymphoma Group database by a process of total registration. The census population of Scotland in 1996-1997 was 5.1 million.One thousand seven hundred and sixty three patients were registered with NHL and 350 patients with HD. These patients have been followed up for a median of 47 months in the case of NHL and 51 months for HD cases. Actuarial 5-year survival for adult NHL was 35% and for HD, 75%. Outcome for both NHL and HD was particularly poor in the population over 60 years with median survival of 18 months for NHL and 27 months for HD. When analysis of survival was related to degree of material deprivation using the Carstairs score a significantly poorer survival was seen for NHL with increasing deprivation that could not be explained by a different pattern of age or stage at presentation. Deprivation had no impact on incidence or survival in HD. Analysis of impact of caseload of the physician initiating therapy showed no significant difference in 5-year survival.

Partially successful treatment of a patient with chronic lymphocytic leukemia and Hodgkin's disease: Case report and literature review

Chronic lymphocytic leukemia (CLL) is rarely associated with Hodgkin's disease (HD). We report a case of nodular sclerosis HD in a patient previously diagnosed with CLL. Reed-Sternberg cells were CD15(+) and CD30(+). He was treated with dose-escalated CHOP and at relapse, mitoxantrone, vinblastine, and CCNU (MVC) with partial response to the former and complete response to the latter, although the patient died 15 months later. Data from 88 other similar cases published in the English language were analyzed. Based on the histological and clinical features at the time of transformation, these patients were divided into distinct categories for analysis. Prognosis was found to be poorer in patients with continued active CLL when compared with those with CLL in remission at the time of transformation to HD. It is suggested that these two presentations may derive from different pathogenic mechanisms.

Comparison of Fascin Expression in Anaplastic Large Cell Lymphoma and Hodgkin Disease

Diagnostic difficulties sometimes arise in distinguishing anaplastic large cell lymphoma (ALCL) from Hodgkin disease (HD), especially the syncytial variant. Study of the biologic features of diagnostic Reed-Sternberg cells in HD, in search of specific markers for Reed-Sternberg cells, has suggested fascin as a relatively specific and sensitive marker. We studied the frequency of fascin expression in 30 ALCLs and 34 cases of classic HD, including 17 cases of the syncytial variant. Staining with CD30 and anaplastic lymphoma kinase (ALK)-1 also was performed in all cases. All ALCL and HD cases showed membranous and Golgi zone CD30 positivity. Fascin stained all HD cases but also stained 67% (20/30) of the ALCLs in a cytoplasmic pattern. Fascin positivity was observed in 59% (10/17) of T-cell ALCLs and 77% (10/13) of null-cell ALCLs; ALK-1–positive ALCLs, regardless of origin, were usually fascin-positive (91% [10/11]). In conclusion, fascin shows strong positivity in all cases of classic HD but also is positive in the majority of ALCLs, including ALK-1–positive and ALK-1–negative cases. Positive staining for fascin is not useful for distinguishing ALCL from HD. In some cases, fascin negativity may help rule out classic HD.

New Candidate Virus in Association with Hodgkin's Disease

Epidemiologic and molecular investigations of Hodgkin's disease (HD) suggest a strong infectious association. The Epstein-Barr virus (EBV), together with its viral proteins, is expressed in Hodgkin-Reed-Sternberg (HRS) cells in the lymph nodes involved by HD. EBV is more likely to be related to childhood and older adult cases of HD and is much less frequently expressed in young adult HD patients, the group most expected to be associated with an infectious agent. In addition, the "hit and run" theory of EBV infection remains speculative and no other lymphotropic viruses studied to date seem to satisfy the quest for a new candidate virus in young adults with HD. We have recently found preliminary evidence suggesting a possible association between the measles virus (MV) and HD. This evidence is the subject of the present review.