Hodgkin's lymphoma:2023 update on treatment

Hodgkin's lymphoma(HL)is a common,malignant hematological tumor of the lymph nodes and lymphatic system,accounting for 10%of all lymphomas.HL comprises 2 main subtypes:classical HL(cHL)and nodular lymphocyte predominant HL.

Ataxia-telangiectasia complicated with Hodgkin's lymphoma:A case report

BACKGROUND Ataxia-telangiectasia(AT)is a rare,autosomal recessive,multisystem disorder.Because most clinicians have low awareness of the disease,only scarce reports of AT exist in the literature,especially of cases with lymphoma/leukemia.CASE SUMMARY A 7-year-old girl with a history of recurrent respiratory tract infections was referred to our department because of unstable walking for 5 years and enlarged neck nodes for 2-mo duration.Physical examination revealed scleral telangiectasia and cerebellar ataxia.Elevated alpha-fetoprotein,decreased serum immunoglobulin,and decreased T cell function were the major findings of laboratory examination.Histological analysis of cervical lymph node biopsy was suggestive of classical Hodgkin's lymphoma.Genetic examination showed heterozygous nucleotide variation of c.6679C>T and heterozygous nucleotide variation of c.5773 delG in the ATM gene;her parents were heterozygotes.The final diagnosis was AT with Hodgkin's lymphoma.CONCLUSION Clinicians should strengthen their understanding of AT diseases.Gene diagnosis plays an important role in its diagnosis and treatment.

Extranodal Imaging Manifestations of Non-Hodgkin's Lymphoma

A series of imaging features of extranodal, multi-systemic involvements in Non-Hodgkin's lymphoma (NHL) were investigated The clinical data and imaging findings of 16 patients with pathologically proved NHL were retrospectively analyzed The related literatures were reviewed Of the 16 cases of NHL, skeletal involvement was found in 4, nasal cavity and nasal sinuses were involved in 4, too Lesion in the thorax was seen in 3 patients, hepatic involvement occurred in one case, cerebral ventricle was affected in 3 cases, mesentery was involved in one case Even though extranodal involvement of NHL exhibited extremely variable patterns, there were some relatively typical imaging findings Emphasized in this report were the relatively specific imaging manifestations of different systems, which may mimic infectious or other neoplasms of different sites The importance of imaging studies lies in the availability for diagnosis, staging and follow-up of NHL Combined with the clinical and other related information, the diagnostic accuracy can be further improved, thus, providing reliable evidence in guiding clinical management

Composite diffuse large B-cell lymphoma and classical Hodgkin's lymphoma of the stomach:Case report and literature review

The combination of classical Hodgkin’s lymphoma(cHL)and non-Hodgkin lymphoma coexisting in the same patient is not common,especially in one extranodal location.Here we present a rare case of composite diffuse large B-cell lymphoma(DLBCL)and cHL occurring simultaneously in the stomach of a 53-year-old female who presented with upper abdominal discomfort and gas pain.Surgery was performed and the disease was diagnosed pathologically as composite lymphoma of DLBCL and cHL using hematoxylin-eosin and immunohistochemical staining.Epstein-Barr virus(EBV)infection was not detected by in situ hybridization for EBV-encoded RNA or immunohistochemistry for EBV latent membrane protein-1.Polymerase chain reaction analysis from the two distinct components of the tumor demonstrated clonal immunoglobulinκlight chain gene rearrangements.The patient died approximately 11 mo after diagnosis in spite of receiving eight courses of the CHOP and two courses of the rituximab-CHOP(RCHOP) chemotherapy regimen.This case report showed that the two distinct components,DLBCL and cHL,appeared to originate from the same clonal progenitor cell,and that EBV infection was not essential for transformation during the course of tumorigenesis.

Primary non-Hodgkin's lymphoma of the liver: sonographic and CT findings

BACKGROUND： A preoperative diagnosis of primary hepatic lymphoma（PHL） can have profound therapeutic and prognostic implications. Because of the rarity of PHL, however, there are few reports on diagnostic imaging. We reviewed the clinical and radiologic findings of 29 patients with PHL, the largest series to date, to evaluate the diagnostic features of this disease.METHODS： Clinical data and radiologic findings at presentation were retrospectively reviewed for 29 patients with pathologically confirmed PHL from January 2005 to June 2013. Imaging studies, including ultrasound（US）（n=29） and contrast-enhanced computed tomography（CECT）（n=24）, were performed within 2 weeks before biopsy or surgery.RESULTS： Among the 29 patients, 23（79%） were positive for hepatitis B virus（HBV） and 26（90%） had a significantly elevated level of serum lactate dehydrogenase（LDH）. There were two distinct types of PHL on imaging： diffuse（n=5） and nodular（n=24）. Homogeneous or heterogeneous hepatomegaly was the only sign for diffuse PHL on both US and CECT, without any definite hepatic mass. For the nodular type, 63%（15/24） of patients had solitary lesions and 38%（9/24） had multiple lesions. On US, seven patients displayed patchy distribution with an indistinct tumor margin and a rich color flow signal. CECT showed rim-like enhancement（n=3） and slightly homogeneous or heterogeneous enhancement（n=14） in the arterial phase and isoenhancement（n=5） and hypoenhancement（n=12） in the portal venous and late phases. Furthermore, in five patients, CT revealed that hepatic vessels passed through the lesions and were not displaced from the abnormal area or appreciably compressed.CONCLUSIONS： The infiltration type of PHL was associated with the histologic subtype. Considered together with HBV positivity and elevated LDH, homogeneous or heterogeneous hepatomegaly may indicate diffuse PHL, whereas patchy distribution with a rich color flow signal on US or normal vessels extending through the lesion on CECT may be the diagnostic indicators of nodular PHL.

Hepatitis C virus syndrome: A constellation of organ-and non-organ specific autoimmune disorders, B-cell nonHodgkin's lymphoma, and cancer

The clinical course of chronic hepatitis C virus(HCV)infection is characterized by possible development of both liver and extrahepatic disorders. The tropism of HCV for the lymphoid tissue is responsible for several immune-mediated disorders; a poly-oligoclonal B-lymphocyte expansion, commonly observed in a high proportion of patients with HCV infection, are responsible for the production of different autoantibodies and immune-complexes, such as mixed cryoglobulins. These serological alterations may characterize a variety of autoimmune or neoplastic diseases. Cryoglobulinemic vasculitis due to small-vessel deposition of circulating mixed cryoglobulins is the prototype of HCV-driven immune-mediated and lymphoproliferative disorders; interestingly, in some cases the disease may evolve to frank malignant lymphoma. In addition, HCV shows an oncogenic potential as suggested by several clinicoepidemiological and laboratory studies; in addition to hepatocellular carcinoma that represents the most frequent HCV-related malignancy, a causative role of HCV has been largely demonstrated in a significant percentage of patients with isolated B-cells nonHodgkin's lymphomas. The same virus may be also involved in the pathogenesis of papillary thyroid cancer, a rare neoplastic condition that may complicate HCVrelated thyroid involvement. Patients with HCV infection are frequently asymptomatic or may develop only hepatic alteration, while a limited but clinically relevant number can develop one or more autoimmune and/or neoplastic disorders. Given the large variability of their prevalence among patients' populations from different countries, it is possible to hypothesize a potential role of other co-factors, i.e., genetic and/or environmental, in the pathogenesis of HCV-related extra-hepatic diseases.

Positron emission tomography/computerized tomography in the evaluation of primary non-Hodgkin's lymphoma of prostate

Primary malignant lymphoma of the prostate is exceedingly rare.Here we report a case of a 65-year-old man who presented with increased urinary frequency,urinary urgency,and urinary incontinence for two years.Benign prostatic hypertrophy was suspected at primary impression.Ultrasound revealed a hypoechoic lesion of the prostate.The total serum prostate-specific antigen was within normal range.Positron emission tomography/computerized tomography(PET/CT)showed a hypermetabolic prostatic lesion.Prostate biopsy was consistent with a non-germinal center diffuse large B cell lymphoma.There was complete remission of the prostatic lesion following six cycles of chemotherapy as shown on the second PET/CT imaging.18F-fluoro-deoxy glucose PET/CT is not only a complement to conventional imaging,but also plays a significant role in the diagnosis and evaluation of treatment response of prostatic lymphoma.

Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma

AIM:To evaluate if indolent B cell-non Hodgkin's lymphoma(B-NHL) and diffuse large B-cell lymphoma(DLBCL) in hepatitis C virus(HCV) positive patients could have different biological and clinical characteristics requiring different management strategies.METHODS:A group of 24 HCV related B-NHL patients(11 indolent,13 DLBCL) in whom the biological and clinical characteristics were described and confronted.Patients with DLBCL were managed with the standard of care of treatment.Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed.The outcomes of the different approaches were compared.RESULTS:Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype.Five of the 9 patients with indolent HCV-relatedB-NHL treated with only antiviral therapy,achieved a complete response of their onco-haematological disease(55%).Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response(54%).CONCLUSION:HCV genotypes and duration of HCV infection differed between B-NHL subtypes.Indolent lymphomas can be managed with antiviral treatment,while DLBCL is not affected by the HCV infection.

Autologous peripheral blood stem cell mobilization following dose-adjusted cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy alone or in combination with rituximab in treating high-risk non-Hodgkin's lymphoma

Background: The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone(CHOP) is an eicient treatment of non-Hodgkin's lymphoma(NHL). This study aimed to assess the eicacy and toxicity of dose-adjusted CHOP alone or in combination with rituximab(R-CHOP) by examining the stem cell mobilization in NHL patients. Factors afecting the collection of CD34+ cells were also explored.Methods: Our retrospective study included 39 patients eligible for autologous stem cell transplantation: 14 patients who expressed CD20 and were inancially eligible received R-CHOP for autologous peripheral blood stem cell(APBSC) mobilization; the remaining 25 patients received CHOP.Results: The median CD34+ cell yield was 7.01 × 106 cells/kg body weight(range 1.49–28.39 × 106 cells/kg body weight), with only two patients failing to meet the target CD34+ cell harvest of ber of apheresis procedures per patient was 1(range 1–3). The≥2.0 APBS× 106 cells/kg body weight. The median numC mobilization yield of the CHOP group appeared to be higher than that of the R-CHOP group(P response(CR) rate in = 0.005), whereas the success rate was similar between groups. R-CHOP elevated the completeB cell lymphoma patients as compared with CHOP(P = 0.01). No signiicant diferences in toxicity or engraftment were observed between the two groups.Conclusion: The present study demonstrated that dose-adjusted CHOP chemotherapy efectively mobilized APBSCs in NHL patients and that the addition of rituximab to dose-adjusted CHOP chemotherapy elevated the CR rate for patients with B-cell lymphoma.

Simultaneous occurrence of a hepatocellular carcinoma and a hepatic non-Hodgkin's lymphoma infi ltration

To investigate the simultaneous occurrence of hepatocellular carcinoma and non-Hodgkin's lymphoma, we report the case of a 70 year old patient with a primary diagnosis of non-Hodgkin's lymphoma in 2002. In a routine follow up investigation of his chronic lymphocytic leukemia a newly detected mass in the Couinaud's segments 2 and 3 was found. No hepatitis C virus or hepatitis B virus infection or cirrhosis was evident. After laparoscopic segmentectomy the histological examination revealed a hepatocellular carcinoma. While the relation between liver parenchyma damages and hepatocellular carcinoma or non-Hodgkin's lymphoma is well known, only a few publications have focused on the coexistence of hepatocellular carcinoma and non-Hodgkin's lymphoma. With this case we demonstrate the coexistence of these diseases without having a pre- damaged liver parenchyma.

Hepatitis C virus and non-Hodgkin's lymphomas:Metaanalysisof epidemiology data and therapy options

Hepatitis C virus(HCV) is a global health problem affecting a large fraction of the world's population: This virus is able to determine both hepatic and extrahepatic diseases. Mixed cryoglobulinemia, a B-cell "benign" lymphoproliferative disorders, represents the most closely related as well as the most investigated HCVrelated extrahepatic disorder. Since this virus is able to determine extrahepatic [non-Hodgkin's lymphoma(NHL)] as well as hepatic malignancies(hepatocellular carcinoma), HCV has been included among human cancer viruses. The most common histological types of HCV-associated NHL are the marginal zone, the lymphoplasmacytic and diffuse large cell lymphomas. The role of the HCV in the pathogenesis of the B-cell lymphoproliferative disorders is confirmed also by the responsiveness of the NHL to antiviral therapy. The purpose of this review is to provide an overview of the recent literature and a meta analysis of the epidemiology data, to explain the role of HCV in the development of NHL's lymphoma. Furthermore, the possibility to treat these HCV-related NHL with the antiviral therapy or with other therapeutic options, like chemotherapy, is also discussed.

HCV infection, B-cell non-Hodgkin's lymphoma and immunochemotherapy: Evidence and open questions

There is plenty of data confirming that hepatitis C virus (HCV) infection is a predisposing factor for a B-cell non-Hodgkin's lymphoma (B-NHL) outbreak, while relatively few reports have addressed the role of HCV in affecting B-NHL patients' outcome. HCV infection may influence the short-term outcome of B-NHL because of the emergence of severe hepatic toxicity (HT) during immunochemotherapy. Furthermore, the long term outcome of HCV-related liver disease and patients' quality of life will possibly be affected by Rituximab maintenance, multiple-lines of toxicity during chemotherapy and hematopoietic stem cell transplantation. In this review, data dealing with aggressive and low-grade B-NHL were separately analyzed. The few retrospective papers reporting on aggressive B-NHL patients showed that HCV infection is a risk factor for the outbreak of severe HT during treatment. This adverse event not infrequently leads to the reduction of treatment density and intensity. Existing papers report that low-grade B-NHL patients with HCV infection may have a more widespread disease, more frequent relapses or a lower ORR compared to HCV-negative patients. Notwithstanding, there is no statistical evidence that the prognosis of HCV-positive patients is inferior to that of HCV-negative subjects. HCV-positive prospective studies and longer follow-up are necessary to ascertain if HCV-positive B-NHL patients have inferior outcomes and if there are long term sequels of immunochemotherapies on the progression of liver disease.

Hepatitis viruses and non-Hodgkin's lymphoma: A review

Non-Hodgkin's lymphoma(NHL) is among the haematological malignancies with high prevalence worldwide, causing estimated 355 900 new cases and 191 400 deaths in 2008. High prevalence of NHL is documented in economically more developed areas while low prevalence is observed in less developed areas of the globe. A wide array of environmental factors have been reported to be either directly involved or in modifying the risk of NHL development. In addition to these factors, a number of infectious agents, chiefly viruses have also been implicated in the development of NHL. This article reviews the available literature to discuss the role of hepatitis viruses in NHL development, possible mechanisms of lymphomagenesis and also identify the areas in which further research is required to better understand this disease. A brief discussion on the clinical aspects such as classification, staging, treatment approaches have also been included in this article.

Hodgkin's lymphoma coexisting with liver failure secondary to acute on chronic hepatitis B

Acute on chronic liver failure(ACLF) is rarely the initial manifestation of a malignant process or precipitated by the initiation of anti-viral treatment with a nucleoside or nucleotide agent. We report an unusual case of ACLF temporally associated with initiation of Entecavir for treatment of chronic hepatitis B. Early Hodgkin's lymphoma(HL) was unmasked with initiation of the antiviral treatment which may have exacerbated ACLF. To the best of our knowledge, this has not been described in the literature. In reviewing our patients clinical course and liver autopsy, he developed a severe acute exacerbation of his chronic hepatitis B virus coinciding with the institution of antiviral therapy and the underlying HL perhaps modulating the overall degree of hepatic injury.

Primary intestinal non-Hodgkin's lymphoma:A clinicopathologic analysis of 81 patients

AIM:To analyze the clinicopathologic features and the prognosis of primary intestinal lymphoma.METHODS:Patients were included in the study based on standard diagnostic criteria for primary gastrointesti-nal lymphoma,and were treated at Sun Yat-sen Univer-sity Cancer Centre between 1993 and 2008.RESULTS:The study comprised 81 adults.The most common site was the ileocaecal region.Twenty-two point two percent patients had low-grade B-cell lym-phoma.Fifty-one point nine percent patients had high-grade B-cell lymphoma and 25.9% patients had T-cell lymphoma.Most patients had localized disease.There were more patients and more early stage diseases in the latter period,and the origin sites changed.The ma-jority of patients received the combined treatment,andabout 20% patients only received nonsurgical therapy.The wverall survival and event-free survival rates after 5 years were 71.6% and 60.9% respectively.The mul-tivariate analysis revealed that small intestine and ileo-caecal region localization,B-cell phenotype,and normal lactate dehydrogenase were independent prognostic factors for better patient survival.Surgery based treat-ment did not improve the survival rate.CONCLUSION:Refined stratification of the patients according to the prognostic variables may allow indi-vidualized treatment.Conservative treatment may be an optimal therapeutic modality for selected patients.

STUDIES OF THE CHARACTERISTIC FEATURES OF KI-1 POSITIVE NON-HODGKIN'S LYMPHOMA

The clinical histopathological and immuno-phenotypic features in 5 patients with Ki-1 positive non-Hodgkin's lymphoma (NHL) were studied. When firstseen, 4 patients presented enlargement of superficiallymph nodes, with skin lesions in 2 patients. Two patientsin stage Ⅳ with fever, hepato-splenomegaly and bonemarrow invasion, died. Histologically, the tumor cellsshowed diffused or patchy hyperplasia. The cells wererelatively large in size, rich in basophilic or slightlyeosinophilic cytoplasm with irregular-shaped nuclei,prominent nucleoli, and distinct anaplasia andpleomorphism. Some of the cells looked very much likethe Reed-Sternberg cells. Multinucleated giant cells wereseen. Immunophenotypically, all the cells were CD30 (Ki-1) and CD25 (IL-2 receptor) positive but CD15 (Leu M1)negative. Thus, the 5 patients with Ki-1 positive NHLwere all of T cell type.

Tuberculosis versus non-Hodgkin's lymphomas involving small bowel mesentery:Evaluation with contrast-enhanced computed tomography

AIM: To evaluate the specific computed tomography (CT) imaging criteria for differentiating tuberculosis involving the small bowel mesenteric lymph nodes from lymphomas. METHODS: We retrospectively reviewed the anatomic distribution,CT enhancement patterns of lymphoma in 18 patients with mesenteric tuberculosis and 22 with untreated non-Hodgkin’s lymphomas (NHL) involving small bowel mesentery (SBM). Of the 18 patients with tuberculosis,9 had purely mesenteric tuberculous lymphadenopathy (TL),and 9 had mesenteric TL accompanied with tuberculous mesenteritis (TLM). RESULTS: CT showed that tuberculosis and NHL mainly affected lymph nodes in the body and root of SBM. Homogeneously enhanced lymph nodes in the body and root of SBM were found more often in the NHL (P < 0.05). Homogeneously mixed peripheral enhanced lymph nodes in the body of SBM were found more often in mesenteric TL and TLM (P < 0.05). Peripheral enhanced lymph nodes in the root of SBM were found more often in mesenteric TL and TLM (P < 0.01). "Sandwich sign" in the root of SBM was observed more often in NHL (P < 0.05). CONCLUSION: Anatomic lymph node distribution,sandwich sign and specific enhancement patterns of lymphadenopathy in SBM on CT images can be used in differentiating between tuberculosis and untreated NHL involving SBM.

Expression of hepatitis B virus surface antigen in 120 Hodgkin's lymphoma patients

Background and Objective: Little is known about the incidence of hepatitis B virus (HBV) infection in Hodgkin's lymphoma patients. This study was to evaluate the impact of HBV infection on the survival of Hodgkin's lymphoma patient. Methods: Clinical data of 120 Hodgkin's lymphoma patients treated at the Sun Yat-sen University Cancer Center between January 2004 and October 2007 were collected. The impact of prognostic factors including HBV infection on survival was examined by univariate and multivariate analyses. A log-rank test was used for univariate analysis and the Cox proportional hazards regression model was used for multivariate analysis. Results: Of the 120 patients, 18 (15.0%) were hepatitis B virus surface antigen (HBsAg)-positive. The HBsAg-positive patients had lower 5-year survival rate than did the HBsAg-negative ones (66.9% vs. 91.3%, P = 0.006). When the patients were divided into early-stage (Ⅰ+Ⅱ) and advanced-stage (Ⅲ+Ⅳ) groups, the 5-year survival rate was significantly different between the HBsAg-positive and -negative patients in early-stage group (64.8% vs. 96.0%, P < 0.001), while not significantly different in advanced-stage group (75.0% vs. 84.8%, P=0.667). Both univariate and multivariate analyses showed that radiotherapy and HBV infection were independent prognosis factors for the patients with early-stage Hodgkin's lymphoma (P=0.006 and 0.014, respectively). Conclusions: The incidence of HBV infection is similar between Hodgkin's lymphoma patients and normal population. HBV infection is an independent prognosis factor for survival in the patients with early-stage Hodgkin's lymphoma.

Primary non hodgkin's lymphoma of lacrimal sac presented as recurrent acute dacryocystitis: A case report

Primary non Hodgkin's lymphoma of the lacrimal sac is uncommon but potentially delay in diagnosis as it may mimic the presentation of primary post saccal nasolacrimal duct obstruction. In this article, we reported a case of primary non Hodgkin's lymphoma of the lacrimal sac presented with recurrent acute dacryocystitis in a young lady. A 28 years old Malay lady had history of persistent epiphora on left eye for 4 years. Prior to presentation to our clinic, it was preceded by progressive recurrent painful medial canthal swelling for 6 months duration. Clinical diagnosis of post saccal naso lacrimal duct obstruction was made and otorhinolaryngology assessment revealed intranasal mass. Endoscopic excision was done showed diffuse large B cell lymphoma on histology. The patient was started on 6 cycles of chemotherapy which subsequently result in no recurrence of the tumour post chemotherapy. Any case of post saccal nasolacrimal duct obstruction should be investigated thoroughly as it may become as a presentation of other sinister pathology.

Clinical characteristics of the patients with Hodgkin's lymphoma involving extranodal sites

Differences between Hodgkin's lymphoma (HL) patients in China and Western countries are known to exist, but data on Chinese patients with HL are limited. It is not clear whether there are clinical and histological differences in patients with HL involving different extranodal sites. This is the first study to analyze Chinese patients with HL involving different extranodal sites. We selected 22 HL patients with extranodal involvement from more than 250 previously untreated HL patients. Most patients were young males, and 20 of the 22 patients had stage IV disease. The major pathologic types were nodular sclerosis classical HL (NSCHL) and mixed cellularity classical HL(MCCHL). At diagnosis, the most commonly involved extranodal sites were the liver and lung, followed by the bones. There was no significant association between the international prognostic score(IPS) and survival in patients with different extranodal sites. Our data showed the overall survival (OS) and disease-free survival (DFS) rates of low-risk group (IPS = 0-2) were relatively higher than those of high-risk group (IPS ≥ 3), but the IPS did not show predictive power for survival. Although HL with extranodal involvement is rare, it should be considered as a unique form of HL.