Primary central nervous system lymphoma in immunocompetent patients: a retrospective review of MRI features

Introduction: To define the features of primary central nervous system lymphoma (PCNSL) on MRI in immunocompetent patients. Methods: A retrospective review of the authors' institutional database was performed to identify histologically proven cases of PCNSL. Images were retrieved and reviewed with respect to location, lesion number, size, signal intensity, enhancement characteristics, oedema and necrosis. Results: Thirty‐one cases of histologically proven PCNSL had available imaging. One patient was excluded due to immunosuppression. Of the 30 remaining cases, the average age was 65.5 years, and males and females were equally represented. A total of 68 lesions (average of 2.5 per patient) were identified. With diffusion‐weighted imaging, all but two had restricted diffusion (40.3% mild and 55.6% marked) and all but one had enhancement (51.5% homogeneous, 42.6% heterogeneous and ring 4.4%). Most lesions were isointense to grey matter (75.8% on T2‐weighted image (WI) and 82.5% on T1‐WI). Oedema was mild in 43.4% and marked in 55.2%. Necrosis was seen in only five lesions (7.4%). On a per patient basis, 50% had bilateral lesions and 96.7% had lesions contacting a cerebrospinal fluid (CSF) surface. 16.7% of patients had posterior fossa involvement and 30% had lesions in the basal ganglia or thalami. Conclusion: The vast majority of cases of PCNSL in immunocompetent patients have lesions contacting a CSF surface, enhancement and restricted diffusion with no necrosis. These features should alert radiologists to the diagnosis of PCNSL.     

Hodgkin lymphoma: A review and update on recent progress

Hodgkin lymphoma (HL) is a unique hematopoietic neoplasm characterized by cancerous Reed‐Sternberg cells in an inflammatory background. Patients are commonly diagnosed with HL in their 20s and 30s, and they present with supradiaphragmatic lymphadenopathy, often with systemic B symptoms. Even in advanced‐stage disease, HL is highly curable with combination chemotherapy, radiation, or combined‐modality treatment. Although the same doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapeutic regimen has been the mainstay of therapy over the last 30 years, risk‐adapted approaches have helped de‐escalate therapy in low‐risk patients while intensifying treatment for higher risk patients. Even patients who are not cured with initial therapy can often be salvaged with alternate chemotherapy combinations, the novel antibody‐drug conjugate brentuximab, or high‐dose autologous or allogeneic hematopoietic stem cell transplantation. The programmed death‐1 inhibitors nivolumab and pembrolizumab have both demonstrated high response rates and durable remissions in patients with relapsed/refractory HL. Alternate donor sources and reduced‐intensity conditioning have made allogeneic hematopoietic stem cell transplantation a viable option for more patients. Future research will look to integrate novel strategies into earlier lines of therapy to improve the HL cure rate and minimize long‐term treatment toxicities. CA Cancer J Clin 2018;68:116‐132 . © 2017 American Cancer Society .     

Positron emission tomography at the end of first-line therapy and during follow-up in patients with Hodgkin lymphoma: a retrospective study

BackgroundRoutine positron emission tomography (PET) in follow-up of Hodgkin lymphoma (HL) after treatment is still controversial. The aim of this retrospective study was to analyze the clinical impact of routine PET examination during the follow-up for relapse detection in PET-negative HL patients at the end of therapy.Patients and methodsPET scans were carried out in 113 HL patients at the end of therapy and during the follow-up either in regular intervals or in a suspected relapse. Median follow-up of the group was 34 months.ResultsOverall 327 PET scans were evaluated in 113 patients (median three PET scans per patient). At the end of therapy, 94 (83.2%) patients were PET negative and 19 (16.8%) PET positive. Regular follow-up PET scans in 67 of 94 PET-negative patients correctly identified tumor in 6 of 155 PET scans (3.9%). In 27 of 94 patients with clinically suspected relapse, 5 of 27 PET scans (18.5%) confirmed tumor.ConclusionsOur analysis showed that there is no need for regular follow-up with PET scans in PET-negative patients at the end of therapy: the ratio of true-positive PET scans during the follow-up is low (3.9%). Positive PET at the end of therapy and during follow-up should be evaluated with caution.     

Acute myeloid leukemia following Hodgkin lymphoma: a population-based study of 35,511 patients

Treatments for Hodgkin lymphoma are associated with large relative risks of acute myeloid leukemia (AML), but there are few estimates of the excess absolute risk (EAR), a useful measure of disease burden. One-year Hodgkin lymphoma survivors (N = 35,511) were identified within 14 population-based cancer registries in Nordic countries and North America from January 1, 1970, through December 31, 2001. We used Poisson regression analysis to model the EAR of AML, per 10,000 person-years. A total of 217 Hodgkin lymphoma survivors were diagnosed with AML (10.8 expected; unadjusted EAR = 6.2; 95% confidence interval = 5.4 to 7.1). Excess absolute risk for AML was highest during the first 10 years after Hodgkin lymphoma diagnosis but remained elevated thereafter. In subsequent analyses, adjusted for time since Hodgkin lymphoma diagnosis and presented for the 5-9 year interval, the EAR was statistically significantly (P < .001) larger in patients diagnosed with Hodgkin lymphoma at age 35 years and older than in those diagnosed before 35 years of age. The EAR of AML declined statistically significantly after 1984 (7.0 to 4.2 and 16.4 to 9.9 in the < 35 and > or = 35 age groups, respectively), which may be associated with modifications in chemotherapy.     

肺霍奇金淋巴瘤一例并文献复习

目的 探讨肺霍奇金淋巴瘤(HL)患者的临床特点.方法 报道1例原发于肺的HL患者的临床表现、诊断治疗及随访,并进行相关文献复习.结果 经皮肺穿刺活组织病理检查,结合临床表现和影像学分析,有助于尽早明确诊断,治疗采用表柔比星+博来霉素+长春地辛+达卡巴嗪(ABVD)方案,疗效满意.结论 原发于肺的HL少见,影像学无特异性征象,临床不易判断,早期在CT引导下经皮肺穿刺,对确定诊断有明确作用.     

Primary localized non-Hodgkin's lymphoma of the thyroid: a retrospective clinicopathological review

Primary localized non-Hodgkin's lymphomas (NHL) of the thyroid are rare. The data presented are derived from 819 consecutive patients with NHL and six patients with anaplastic thyroid carcinomas of small cell type investigated and treated at our department between 1970 and 1981. The present analyses are based on the 19 patients, who were found to have localized primary thyroid lymphomas. Four of these patients were initially considered to have undifferentiated small cell carcinomas of the thyroid but revealed to be lymphomas at re-examination supplemented with immunohistopathologic staining. Prognosis has been evaluated with regard to initial stage, histopathology according to the Kiel classification and therapy. Median follow-up was 5 years. The crude survival was 77% 5 years after diagnosis. This was not significantly less (4.2%) than the overall-survival in an age- and sex-matched population, despite the majority of patients having tumours which were locally advanced, often with spread to regional lymph nodes, and in many cases a histology showing a high-grade malignancy according to Kiel classification. The excellent prognosis in the current study compared to other studies is probably mainly attributed to more extensive staging procedures. The biologic behaviour supports the hypothesis that these lymphomas represent lymphomas of mucosa associated lymphoid tissue (MALT). According to present results anaplastic thyroid carcinoma of small cell type must be extremely rare.     

Salvage radiotherapy in patients with relapsed and refractory Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Lymphoma Study Group.

PURPOSE: To evaluate treatment outcome and prognostic factors in patients with refractory or first relapsed Hodgkin's disease (HD) treated with salvage radiotherapy (SRT) alone. PATIENTS AND METHODS: From 4,754 patients registered in the database of the German Hodgkin Study Group from 1988 to 1999, 624 patients were identified with progressive disease (n = 202), or with early (n = 170) or late (n = 252) relapsed HD. At first treatment failure, SRT alone was given to 100 patients. Patient characteristics were: median age, 36 years; progressive disease, 47%; early relapse, 23%; late relapse, 30%; and "B" symptoms, 14%. Eighty-five percent of the patients relapsed after cyclophosphamide, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP/ABVD) -like regimens; 8% after bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) regimens, 7% after first-line radiotherapy alone. RESULTS: The volume irradiated was mantle field in 43% of patients, inverted-Y in 8%, total nodal irradiation in 12%, and involved-field in 37%. The median SRT dose was 40 Gy (range, 15 to 50 Gy). Seventy-seven patients achieved a complete remission and four patients achieved a partial remission. The 5-year freedom from treatment failure and overall survival (OS) rates were 28% and 51%, respectively. In multivariate analysis, significant prognostic factors for OS were B symptoms (P = .018) and stage at relapse (P = .014). For freedom from second failure (FF2F) Karnofsky performance status (P = .0001) was significant. In patients with limited stage at progression/relapse, duration of first remission was significant (P = .04) for FF2F. CONCLUSION: SRT offers an effective treatment for selected subsets of patients with relapsed or refractory HD.     

Central nervous system Hodgkin lymphoma: case report and review of the literature

Central nervous system (CNS) involvement by Hodgkin lymphoma (HL) is extremely rare, accounting for 0.5% or less of HL cases. In contrast, CNS involvement can occur in 5–30% of patients with non-Hodgkin lymphoma. CNS HL can present at any point in the course of HL, most commonly during relapsing disease, and has been described in both immunocompromised and immunocompetent patients. We describe a case of HL affecting the CNS and bone marrow on initial presentation in a 79-year-old immunocompetent female with a prior history of squamous cell carcinoma of the larynx and adenocarcinoma of the lung. Following the case report, a review of the literature on CNS HL is presented.     

Primary cerebral lymphoma: a retrospective study in 22 immunocompetent patients

AIMS AND BACKGROUND: Primary CNS lymphomas are uncommon tumors in immunocompetent patients. We describe the radiological features that should orient towards performing a biopsy and analyze the results in our series of patients. METHODS: We reviewed 22 immunocompetent patients with primary central nervous system lymphoma admitted in our Institute between 1977 and 1997. The follow-up period ranged from 2 months (patient deceased) to 69 months. Fourteen patients underwent surgical removal of the tumor and the remainder a biopsy. All patients received radiotherapy and 8 patients radiotherapy plus chemotherapy. RESULTS: Two of the 14 patients treated by surgical removal of the tumor died. There was no mortality related to biopsy procedures. Patients treated with radiotherapy had 1-year, 2-year and 5-year survival rates of 66%, 41.6% and 16.6%, compared to 87.5%, 62.5% and 50%, respectively, for patients who received radiotherapy and chemotherapy. CONCLUSIONS: At present, there is no definite treatment for these highly malignant brain tumors. The most favorable results seem related to biopsy followed by radiotherapy plus chemotherapy versus surgical removal, which is related to a high risk of severe postoperative deficit for both the deep location and infiltrating nature of these lesions.     

The dog as a possible animal model for human non‐Hodgkin lymphoma: a review

Lymphoma represents the most frequent hematopoietic cancer in dogs, and it shows significant overlap with the human disease. Several environmental factors have been associated with canine lymphoma, suggesting that they may contribute to lymphomagenesis. Canine lymphoma often presents in advanced stage (III–V) at diagnosis and, most commonly, has an aggressive clinical course requiring prompt treatment, which relies on the use of polychemotherapy. In this review, we will summarize the state‐of‐the‐art of canine lymphoma epidemiology, pathobiology, diagnostic work‐up and therapy, and will highlight the links to the corresponding human disease, providing evidence for the use of dog as an animal model of spontaneous disease. Copyright © 2012 John Wiley & Sons, Ltd.     

Surveillance imaging of Hodgkin lymphoma patients in first remission

BACKGROUND:

The majority of patients with Hodgkin lymphoma (HL) achieve disease remission after primary therapy. To the best of the authors' knowledge, no consensus exists for postremission surveillance imaging.

METHODS:

Retrospectively analyzed were 192 adult patients with classic HL in first remission. Events were defined as recurrent HL or secondary malignancies. Primary outcome was positive predictive value (PPV) of surveillance positron emission tomography/computed tomography (PET/CT) and CT scans in event detection. Secondary outcomes were costs and radiation exposures of surveillance scans.

RESULTS:

Sixteen events (12 recurrent HL cases and 4 secondary malignancies) were detected during a median follow‐up of 31 months. The PPV of surveillance PET/CT was 22.9% compared with 28.6% for CT (P = .73). Factors that were found to significantly improve the PPV of scans in detecting recurrent HL included PET and CT concordance, involvement of a prior disease site, or the occurrence of a radiographic abnormality within 12 months. There were too few events to determine whether event detection by PET/CT versus CT or the presence of symptoms at the time of event detection affected overall outcomes. The cost to detect a single event was approximately $100,000. Radiation exposure to detect a single event was 146.6 millisieverts per patient for each of 9 patients.

CONCLUSIONS:

For patients with HL in first disease remission, surveillance radiography appears to be expensive, with limited clinical impact. Surveillance CT is generally adequate. Cancer 2010. © 2010 American Cancer Society.     

Survival after second primary lung cancer: a population-based study of 187 Hodgkin lymphoma patients

BACKGROUND:

Lung cancer accounts for the largest absolute risk of second malignancies among Hodgkin lymphoma (HL) survivors. However, no population‐based studies have compared overall survival (OS) between HL survivors who developed nonsmall cell lung cancer (HL‐NSCLC) versus patients with first primary NSCLC (NSCLC‐1).

METHODS:

The authors compared the OS of 178,431 patients who had NSCLC‐1 and 187 patients who had HL‐NSCLC (among 22,648 HL survivors), accounting for sex, race, sociodemographic status, calendar year, and age at NSCLC diagnosis, and NSCLC histology and stage. All patients were reported to the population‐based Surveillance, Epidemiology, and End Results Program. Hazard ratios (HRs) were derived from a Cox proportional hazards model.

RESULTS:

Although the NSCLC stage distribution was similar in both groups (20% localized, 30% regional, and 50% distant), HL survivors experienced significantly inferior stage‐specific OS. For patients with localized, regional, and distant stage NSCLC, the HRs (95% confidence interval [CI]) for death among HL survivors were 1.60 (95% CI, 1.08‐2.37; P < .0001), 1.67 (95% CI, 1.26‐2.22; P = .0004), and 1.31 (95% CI, 1.06‐1.61; P = .013), respectively. Among HL‐NSCLC patients, significant associations were observed between more advanced NSCLC stage and the following variables: younger age at HL diagnosis (P = .003), younger age at NSCLC diagnosis (P = .048), and longer latency between HL and NSCLC diagnoses (P = .015).

CONCLUSIONS:

Compared with patients who had de novo NSCLC, HL survivors experienced a significant 30% to 60% decrease in OS after an NSCLC diagnosis. Further research is needed to not only elucidate the clinical‐biologic underpinnings of NSCLC after HL, including the influence of previous HL treatment, but also to define the role of lung cancer screening in selected patients. Cancer 2011;. © 2011 American Cancer Society.     

男性乳腺霍奇金淋巴瘤一例并文献复习

目的 探讨乳腺霍奇金淋巴瘤(HL)的临床特征、诊断、治疗及影响预后的因素.方法 回顾性分析1例男性乳腺HL患者的临床资料、诊治经过及预后,并进行相关文献复习.结果 该例患者为71岁男性,临床主要表现为乳腺无痛性包块,生长较快,伴全身多处淋巴结肿大、皮肤瘙痒、盗汗,病理结果为经典型HLⅢE期B组.化疗后患者病情进展,最终死亡,生存时间7个月.结论 乳腺HL罕见,临床表现不具特异性,术前诊断困难,确诊依靠组织病理学及免疫组织化学检查.目前尚无标准治疗方案,化疗联合放疗可能有效,但预后欠佳.     

Enteroviral infection in patients treated with rituximab for non‐Hodgkin lymphoma: a case series and review of the literature

In recent years, anti‐CD20 antibodies have been increasingly used to treat lymphoproliferative and immune disorders. Chronic viral infections are infrequently reported in patients receiving these therapies. Enteroviral infection can cause life‐threatening meningoencephalitis and other systemic chronic syndromes in immune deficient patients. We describe the clinical courses and outcomes of 6 patients from 2 tertiary care institutions who developed chronic enteroviral infection with neurological manifestations, after combined chemoimmunotherapy with rituximab for B‐cell lymphoma. We review the literature that includes 10 sporadic reported cases of chronic enteroviral meningoencephalitis attributed to rituximab therapy. It is a rare disease, and its diagnosis is often elusive. We propose that low immunoglobulin G levels are the main risk factor for developing chronic enteroviral infection and emphasize the need for a high index of suspicion, early diagnosis, and intervention in this iatrogenic and potentially fatal complication.     

Disparities in survival after Hodgkin lymphoma: a population-based study

Survival after Hodgkin lymphoma (HL) is generally favorable, but may vary by patient demographic characteristics. The authors examined HL survival according to race/ethnicity and neighborhood socioeconomic status (SES), determined from residential census-block group at diagnosis. For 12,492 classical HL patients ≥15 years diagnosed in California during 1988–2006 and followed through 2007, we determined risk of overall and HL-specific death using Cox proportional hazards regression; analyses were stratified by age and Ann Arbor stage. Irrespective of disease stage, patients with lower neighborhood SES had worse overall and HL-specific survival than patients with higher SES. Patients with the lowest quintile of neighborhood SES had a 64% (patients aged 15–44 years) and 36% (≥45 years) increased risk of HL-death compared to patients with the highest quintile of SES; SES results were similar for overall survival. Even after adjustment for neighborhood SES, blacks and Hispanics had increased risks of HL-death 74% and 43% (15–44 years) and 40% and 17% (≥45 years), respectively, higher than white patients. The racial/ethnic differences in survival were evident for all stages of disease. These data provide evidence for substantial, and probably remediable, racial/ethnic and neighborhood SES disparities in HL outcomes.     

Cranial vault lymphoma: a systematic review of five patients

Bone involvement is a common finding in many types of lymphoma (Clin Oncol 9(3): 195–196, 1997). However, cranial vault affliction has been regarded as an exceedingly rare presentation, particularly in the case of primary lymphoma (J Neurosurg 108(5): 1018–1020, 2008). Our objective is to describe a series of five immunocompetent patients with histologically confirmed cranial vault lymphoma (CVL), and to conduct a systematic review of the current literature. Our review points out identical imaging patterns in most of the lesions for all reported CVL cases, despite their different histological subtypes. This typical pattern can be seen on computed tomography (CT) scans and magnetic resonance imaging (MRI) as an expansive tumor that affects all three compartments of the cranial vault, including the scalp, skull bone, and pachymeninges, even in the absence of osteolysis. We argue that the absence of osteolysis might enhance diagnostic capability. In the appropriate clinical setting, these features represent important disease characteristics that may help with an earlier diagnosis. Large B-cell lymphoma was the most common subtype of primary CVL.