Home > Cancer Types > Non-Hodgkin's Lymphoma > Primary CNS Lymphoma

Found this page useful?

Primary CNS Lymphoma

Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
CNS Tumours

Information Patients and the Public (8 links)

Information for Health Professionals / Researchers (8 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Cerqua R, Balestrini S, Perozzi C, et al.
Diagnostic delay and prognosis in primary central nervous system lymphoma compared with glioblastoma multiforme.
Neurol Sci. 2015; [PubMed] Related Publications
Glioblastoma multiforme (GBM) and primary central nervous system lymphoma (PCNSL) are malignant cerebral neoplasms associated with poor prognosis. Early diagnosis and subsequent planning of adequate treatment strategy are relevant to improve survival and reduce neurological deficit. Two groups of patients affected by GBM and PCNSL were compared to identify: (1) factors influencing the time necessary to obtain a correct diagnosis; (2) the influence of the interval time from clinical onset to diagnosis on the prognosis. Fifty-six patients (28 PCNSL and 28 GBM, 23 females and 33 males) referred to the same hospital setting were retrospectively evaluated. The mean age at diagnosis was 61 years. The two groups were comparable in terms of age, sex, clinical symptoms at onset and performance status. There was no relevant difference in time span from clinical onset to first neuroimaging examination, while time span from first neuroimaging to final morphological diagnosis was much longer in PCNSL patients (p = 0.008). Multivariate Cox regression analysis, including both PCNSL and GBM cases, showed a significant association of the overall survival with: time to diagnosis (HR 0.06), age at onset (HR 1.04). Our results show a significant diagnostic delay in PCNSL cases. Age at onset of disease and time to diagnosis emerge as clinical factors affecting overall survival in both groups. Stereotactic-guided biopsy should be chosen as routine method to early diagnose PCNSL. The clinical relevance of early diagnosis in GBM and PCNSL needs to be emphasized to maximize the overall survival in both neoplasms.

Bruno A, Alentorn A, Daniau M, et al.
TERT promoter mutations in primary central nervous system lymphoma are associated with spatial distribution in the splenium.
Acta Neuropathol. 2015; [PubMed] Related Publications

Liu J, Sun XF, Qian J, et al.
Immunochemotherapy for primary central nervous system lymphoma with rituximab, methotrexate, cytarabine and dexamethasone: Retrospective analysis of 18 cases.
Mol Clin Oncol. 2015; 3(4):949-953 [PubMed] Free Access to Full Article Related Publications
The incidence of primary central nervous system lymphoma (PCNSL) has increased in the last two decades and the clinical research regarding the treatment for PCNSL patients has also increased. However, the optimal induction chemotherapy has not been fully established. In the present retrospective study, the aim was to analyze the outcome in PCNSL patients treated with the combination of rituximab, methotrexate (MTX), cytarabine (Ara-C) and dexamethasone (R-MAD). Eighteen patients from Beijing Tiantan Hospital (Beijing, China) between January 2010 and March 2014 were newly diagnosed with PCNSL [diffuse large B-cell lymphoma (DLBCL) type] and received R-MAD as first-line treatment. The dosage was as follows: 375 mg/m(2) rituximab was administered on day 0, 3.5 g/m(2) MTX was administered on day 1, 1 g/m(2) Ara-C was administered on day 2 and 10 mg dexamethasone was administered on days 1-3, every 3 weeks. After 6 cycles, the overall response rate was 94.5%. Ten (55.6%) patients achieved complete response (CR), 7 (38.9%) achieved partial response (PR) and 1 (5.6%) had progressive disease (PD). Patients were followed up from the start of the treatment, median 24.2 months (range 6-48). The overall survival (OS) rate was 94.5% and progression-free survival rate was 94.5%. The median OS was 22 months (95% confidence interval, 19.4-24.6). The high level of serum lactate dehydrogenase (LDH) concentration was associated with a poor outcome. Among 5 patients with an abnormally high LDH concentration, 1 achieved CR, 3 had PR and 1 had PD. None of the patients experienced any grade 4 toxicity. These results indicated that the R-MAD immunochemotherapy regimen is effective in PCNSL patients without serious toxicity. A prospective investigation with more patients should be administered in order to understand the more accurate effect of the regimen.

Han S, Wang M, Liu B, Yu J
Pemetrexed for primary central nervous system lymphoma in the elderly.
Clin Transl Oncol. 2015; [PubMed] Related Publications
OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of a consecutive series of elderly patients with primary central nervous system lymphoma (PCNSL) treated with single-agent pemetrexed without radiotherapy or intrathecal chemotherapy.
METHODS: Twelve histologically confirmed newly diagnosed PCNSL patients older than 65 years were studied between 2008 and 2013. An induction chemotherapy was initially given (pemetrexed 600 mg/m(2) on day 1, every 3 weeks). Patients achieving a complete, partial response or stable disease proceeded to a maintenance phase (up to 6 cycles). Patients with progressive/recurrent disease (PD) were treated with whole brain radiotherapy on an individual basis.
RESULTS: Four patients presented complete response, six patients showed partial response and two patients presented progressive disease. The median progression-free survival (PFS) was 9.0 months [95 % confidence interval (CI) 2.0-45.3] and the median overall survival was 19.5 months (95 % CI 5.0-45.3). Adverse events included leukocytopenia, anemia, fatigue, rash and vomiting. No neurotoxicity or treatment-related death was observed. The estimated 1-year and 2-year survival rate was 66.7 and 41.7 %, respectively.
CONCLUSIONS: Our efficacy results demonstrate that the single-agent pemetrexed was feasible, active and well tolerated in elderly patients with PCNSL. Furthermore, this single-agent regimen results in higher response rates and less toxicity comparable with other chemotherapy or radiotherapy regimens. Prospectively, controlled studies are warranted to confirm such results.

Korfel A
A focus on pharmacotherapy for primary central nervous system lymphoma.
Expert Rev Hematol. 2015; :1-4 [PubMed] Related Publications
The prognosis of primary central nervous system lymphoma (PCNSL) is still poor compared to other diffuse large B-cell lymphomas. High-dose methotrexate-based chemotherapy plays a central role in the management of PCNSL; however, the optimal regimen has not been established thus far. Consolidating whole-brain radiotherapy is currently not routinely being performed at most centers due to lack of survival advantage in a randomized Phase III trial and increased risk of cognitive impairment. Promising results with the combination of high-dose methotrexate-based chemotherapy with the CD20 antibody rituximab and consolidating the primary chemotherapy by other non-cross-resistant conventional chemotherapy or high-dose chemotherapy followed by autologous stem cell transplantation have been reported in non-comparative studies. Results of well-designed randomized trials must be awaited to better define the optimal management of PCNSL.

Sasaki T, Nakayama T, Kitamura M, et al.
Case of 55-year-old female with primary central nervous system lymphoma, presenting with brain and eye lesions and long-term relapsing/remitting course.
Rinsho Shinkeigaku. 2015; [PubMed] Related Publications
We report the case of a 55-year-old immunocompetent female with primary central nervous system lymphoma (PCNSL). Seven years previously, the patient presented with left facial dysesthesia, and a right thalamus lesion was revealed by brain MRI. Both her dysesthesia and the lesion disappeared spontaneously in six months. One year previously, she noted motor disturbance of the right limbs, and brain MRI revealed lesions in the bilateral basal ganglia and the left internal capsule which gradually increased in size. She was admitted to our hospital owing to the brain MRI findings of a white matter lesion in the left occipital lobe and bilateral optic neuritis. Previously, she had experienced two episodes of steroid-responsive uveitis in her left eye. An inflammatory disease such as multiple sclerosis was initially suspected because of the relapsing/remitting clinical course with a long time interval. Treatment with corticosteroids improved her clinical symptoms and decreased the size of the lesions, but the brain lesions and bilateral optic neuritis recurred within one month. At that time, the β2 microglobulin level in the cerebrospinal fluid was high and the left occipital lobe lesions showed increased (18)F-fluoro-deoxyglucose uptake in positron emission tomography and decreased Cho/NAA ratio in (1)H-MR spectroscopy. These findings suggested PCNSL. A brain biopsy confirmed the presence of diffuse large B cell lymphoma. Both uveitis and optic neuritis were considered to be caused by intraocular lymphoma associated with PCNSL. Although patients with PCNSL may experience temporary spontaneous remission, our present case suggests that the time interval from remission to relapse can be much longer than generally expected. We suggest that it is necessary to consider PCNSL and perform a brain biopsy on patients presenting with atypical clinical manifestations of an inflammatory disease, even in cases with a long clinical course.

Meng H, Zhou C, Hao Q, et al.
A rare case of Primary Central Nervous System Lymphoma initially diagnosed as demyelinating encephalopathy. Case Report.
Neuro Endocrinol Lett. 2015; 36(2):123-6 [PubMed] Related Publications
We report a case of histopathologically-confirmed primary central nervous system lymphoma who was initially diagnosed as demyelinating encephalopathy. A 58-year-old woman was admitted with confusion and left hemiparesis. Head MR showed abnormal flaky hypointense T1 and hyperintense T2 signals at right thalamus, splenium of corpus callosum, bilateral cerebral peduncle, pons, medulla oblongata, basal ganglia and right corona radiata. Her mental status improved a little and she was discharged from hospital after neuroprotective treatment. 10 days after her discharge, her confusion appeared again with hallucination and unsteady walking. Pathological examination revealed non-Hodgkin's lymphoma (WHO classification: DLBCL). The patient continued to deteriorate after the surgery and died 10 days later.

Zhu Y, Ye K, Zhan R, Tong Y
Multifocal lateral and fourth ventricular primary central nervous system lymphoma: case report and literature review.
Turk Neurosurg. 2015; 25(3):493-5 [PubMed] Related Publications
We report a 66-year-old man with 2-month history of dizziness and 1-month history of diplopia. Cranial magnetic resonance imaging (MRI) disclosed two solid masses, one in the right lateral ventricle and another in the fourth ventricle. A surgical biopsy was performed on the basis of safety. The diagnosis of large B-cell lymphoma was made postoperatively. The patient recovered without additional deficits and was then commenced on chemotherapy and remained well 6 months after the diagnosis. Primary B-cell lymphomas should always be included in the list of differential diagnosis of intraventricular tumors. Here we report an extremely rare case of primary central nervous system lymphoma with multifocal ventricular involvement.

Sakata A, Okada T, Yamamoto A, et al.
Primary central nervous system lymphoma: is absence of intratumoral hemorrhage a characteristic finding on MRI?
Radiol Oncol. 2015; 49(2):128-34 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Previous studies have shown that intratumoral hemorrhage is a common finding in glioblastoma multi-forme, but is rarely observed in primary central nervous system lymphoma. Our aim was to reevaluate whether intratumoral hemorrhage observed on T2-weighted imaging (T2WI) as gross intratumoral hemorrhage and on susceptibility-weighted imaging as intratumoral susceptibility signal can differentiate primary central nervous system lymphoma from glioblastoma multiforme.
PATIENTS AND METHODS: A retrospective cohort of brain tumors from August 2008 to March 2013 was searched, and 58 patients (19 with primary central nervous system lymphoma, 39 with glioblastoma multiforme) satisfied the inclusion criteria. Absence of gross intratumoral hemorrhage was examined on T2WI, and an intratumoral susceptibility signal was graded using a 3-point scale on susceptibility-weighted imaging. Results were compared between primary central nervous system lymphoma and glioblastoma multiforme, and values of P < 0.05 were considered significant.
RESULTS: Gross intratumoral hemorrhage on T2WI was absent in 15 patients (79%) with primary central nervous system lymphoma and 23 patients (59%) with glioblastoma multiforme. Absence of gross intratumoral hemorrhage could not differentiate between the two disorders (P = 0.20). However, intratumoral susceptibility signal grade 1 or 2 was diagnostic of primary central nervous system lymphoma with 78.9% sensitivity and 66.7% specificity (P < 0.001), irrespective of gross intratumoral hemorrhage.
CONCLUSIONS: Low intratumoral susceptibility signal grades can differentiate primary central nervous system lymphoma from glioblastoma multiforme. However, specificity in this study was relatively low, and primary central nervous system lymphoma cannot be excluded based solely on the presence of an intratumoral susceptibility signal.

Viaccoz A, Ducray F, Tholance Y, et al.
CSF neopterin level as a diagnostic marker in primary central nervous system lymphoma.
Neuro Oncol. 2015; [PubMed] Related Publications
BACKGROUND: The diagnosis of primary central nervous system lymphoma (PCNSL) can be challenging. PCNSL lesions are frequently located deep within the brain, and performing a cerebral biopsy is not always feasible. The aim of this study was to investigate the diagnostic value of CSF neopterin, a marker of neuroinflammation, in immunocompetent patients with suspected PCNSL.
METHODS: We retrospectively reviewed the characteristics of 124 patients with brain tumor (n = 82) or an inflammatory CNS disorder (n = 42) in whom CSF neopterin levels were assessed. Twenty-eight patients had PCNSL, 54 patients had another type of brain tumor (glioma n = 36, metastasis n = 13, other n = 5), and 13 patients had a pseudotumoral inflammatory brain lesion.
RESULTS: CSF neopterin levels were significantly higher in the patients with PCNSL than in those with other brain tumors (41.8 vs 5.1 nmol/L, P < .001), those with pseudotumoral inflammatory brain lesions (41.8 vs 4.3 nmol/L, P < .001), and those with nontumefactive inflammatory CNS disorders (41.8 vs 3.8 nmol/L, P < .001). In the 95 patients with space-occupying brain lesions, at a cutoff of 10 nmol/L, the sensitivity of this approach was 96% and the specificity was 93% for the diagnosis of PCNSL. The positive and negative predictive values were 84% and 98%, respectively.
CONCLUSION: Assessing CSF neopterin levels in patients with a suspected brain tumor might be helpful for the positive and differential diagnosis of PCNSL. A prospective study is warranted to confirm these results.

(P040) Radiosurgery for primary central nervous system lymphoma.
Oncology (Williston Park). 2015; 29(4 Suppl 1) [PubMed] Related Publications

Cellina M, Fetoni V, Baron P, et al.
Unusual primary central nervous system lymphoma location involving the fourth ventricle and hypothalamus.
Neuroradiol J. 2015; 28(2):120-5 [PubMed] Related Publications
A previously healthy 65-year-old man presented with a two-week history of weight loss, headaches, blurred vision, asthenia and quickly worsening walking impairment. He denied photophobia, neck stiffness, fever, nausea or vomiting.Neurological examination showed global motor slowing, tendency to fall asleep during the clinical examination, generalized weakness against resistance to head and limbs, and osteotendon reflexes present in the upper limbs, but not evoked in the lower limbs. No sensitive deficit or focal neurologic sign was recognizable.Non-contrast multislice computed tomography (MSCT) of the head was performed in the emergency department, showing diffuse periventricular white matter and thalamic mild hyperdensity.Lumbar puncture, blood tests, including serology for HIV and other infections, were negative.On the third day the patient, showing decreased consciousness, underwent magnetic resonance imaging (MRI) with contrast medium injection. MRI revealed the presence of multiple pseudonodular avidly enhancing lesions, supra and infratentorial, crossing the midline, involving the ventricular system, including the fourth ventricle, with extension into the surrounding white matter, the corpus callosum, the thalamus and the hypothamalus.A stereotactic biopsy led to a diagnosis of diffuse large B-cell lymphoma, primarily located in the central nervous system (PCNSL).After the completion of the first phase of treatment (immunotherapy with intravenous Rituximab and corticosteroid), the MRI showed a marked regression of tumor masses.

She C, Tan L, Li P, et al.
[Clinical and prognostic analysis of 30 cases of primary central nervous system lymphoma].
Zhonghua Xue Ye Xue Za Zhi. 2015; 36(4):282-5 [PubMed] Related Publications
OBJECTIVE: To explore clinical characteristics, treatment and prognosis of primary central nervous system lymphoma(PCNSL).
METHODS: Retrospective analysis, Kaplan-Meier analysis and Log-rank test were conducted on 30 PCNSL patients from 2006 to 2014 in our hospital.
RESULTS: The median age of this cohort (14 males and 16 females) was 57.4 years old. 18 cases had single tumor, 12 cases multiple. 17 cases presentd with intracranial hypertension and 13 cases focal neurological deficits. 13 cases (62%) were diffuse large B cell lymphoma. About 60% patients received combination therapy including surgery, radiotherapy or chemotherapy. 63.3% complete remission rate (CR) was achieved for all patients. Kaplan-Meier analysis and Log-rank test showed the median overall survival (OS) was 24 months, the rates of 2-year survival, 5-year survival, 6-month progression-free survival(PFS) and 1-year free-progressed survival (PFS) were as of 46.7%, 13.3%, 60.0% and 43.3% respectively. The median OS of 11 patients received whole brain radiotherapy(WBRT)combined with chemotherapy was 48 months. The median OS of 7 patients treated with stereotactic radiosurgery(SRS) combined with chemotherapy had no significant difference when compared to the former (P=0.233). Survive analysis showed that age was prognostic factor for PCNSL patients(P=0.030).
CONCLUSION: Diffuse large B cell lymphoma was the main type of PCNSL, single or multiple location, presented with increased intracranial hypertension or focal neurological deficits. Age was the key prognostic factor for patients. Surgery was suitable for patients with supertentorial and superficial tumor or with acute intracranial hypertension syndrome. SRS was a feasible local therapy which alleviated the symptoms and led to less toxicity. PCNSL patients might benefit from multimode therapy.

Farhangi H, Sharifi N, Ahanchian H, Izanloo A
Autoimmune Hemolytic Anemia preceding the Diagnosis of Primary Central Nervous System Lymphoma.
Iran J Ped Hematol Oncol. 2015; 5(1):65-9 [PubMed] Free Access to Full Article Related Publications
In this study, a 2.5-year-old boy suffering from a febrile seizure with normal laboratory tests and a history of immune hemolytic anemia was examined. Brain MRI demonstrated some tumors in the frontal, parietal, and occipital lobe that corroborated the pathology results of primary central nervous system lymphoma for the patient. The patient was treated with high-dose of Methotrexate. Our result suggested regular and careful monitoring of patients with autoimmune hemolytic anemia in order to control the manifestations of concomitant disease such as lymphoma that may develop later.

Hirono S, Iwadate Y, Higuchi Y, et al.
Stereotactic radiosurgery in combination with up-front high-dose methotrexate as a first-line treatment for newly diagnosed primary central nervous system lymphoma.
J Neurooncol. 2015; 123(2):237-44 [PubMed] Related Publications
The efficacy of stereotactic radiosurgery (SRS) instead of whole brain radiotherapy (WBRT) following high-dose methotrexate (HD-MTX) for primary central nervous system lymphoma (PCNSL) is unclear. To clarify whether SRS in combination with up-front HD-MTX supplements the effect of HD-MTX in remaining or refractory lesions after initial HD-MTX treatment. The authors conducted a retrospective review for newly diagnosed PCNSL patients who underwent SRS after HD-MTX as a first-line treatment. The local control (LC), the progression-free survival (PFS), the recurrence patterns, the salvage treatments, the overall survival (OS), the Karnofsky Performance Status (KPS), the activities of daily living (ADL) were analyzed as well as radiosurgical parameters. Twenty patients underwent SRS for 51 lesions with the median volume of 0.45 cm(3). The median age at SRS was 67 (range 37-82). The median KPS at SRS was 90. The LC rate at 2 years was 86.0 %, the median PFS after SRS was 17 months, necessitating additional SRS and chemotherapy. The median OS was 52 months. No significant side effects related to SRS were observed. During follow-up period, the good ADL preservation was achieved for 13 months from SRS. Patients with KPS ≥ 90 at SRS demonstrated longer ADL preservation (32 months from SRS). SRS following up-front HD-MTX without WBRT provided excellent LC, acceptable OS and the long ADL preservation period. These benefits may be more emphasized especially in patients with good KPS, but should be validated in a large patient population.

Shimada H, Dobashi H, Morimoto H, et al.
Primary central nervous system lymphoma in a rheumatoid arthritis patient treated with methotrexate: a case report.
BMC Res Notes. 2015; 8:88 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Rheumatoid arthritis is a systemic inflammatory disease characterized by synovitis and the destruction of articular structures in multiple joints. Methotrexate is recommended as an anchor drug for rheumatoid arthritis treatment to achieve the therapeutic goal of reducing damage to joints and improving clinical score. However, several studies have shown that methotrexate has been associated with the development of lymphoproliferative disorders, namely methotrexate-associated lymphoproliferative disorders. On the other hand, primary central nervous system lymphoma is an aggressive disease with poor prognosis. Both methotrexate-associated lymphoproliferative disorders and primary central nervous system lymphoma are reported to be associated with Epstein-Barr virus.
CASE PRESENTATION: A Japanese female patient of between 60 and 70 years of age with rheumatoid arthritis was admitted to our hospital because of sudden convulsion and impaired consciousness. Just before admission, she was treated with adalimumab and methotrexate. Contrast-enhanced computed tomography scan showed a densely stained mass with surrounding edema in both frontal lobes and the left nucleus basalis, and enlarged lymph nodes in the right supraclavicular fossa. We performed a biopsy of the right cervical lymph node, but could not establish a histopathological diagnosis. In situ hybridization showed the presence of Epstein Barr virus, therefore we diagnosed this case as methotrexate-associated lymphoproliferative disorders mediated by Epstein Barr virus after considering the drug history of the patient. After we discontinued methotrexate, patient symptoms gradually improved. The masses at both frontal lobes and the left nucleus basalis were gradually regressed.
CONCLUSION: Since the frequency of methotrexate use and the maximum dosage has been increasing, particular attention should be paid to the development of methotrexate-associated lymphoproliferative disorders in rheumatoid arthritis patients who are treated with methotrexate.

O'Neill A, Mikesch K, Fritsch K, et al.
Outcomes for HIV-positive patients with primary central nervous system lymphoma after high-dose chemotherapy and auto-SCT.
Bone Marrow Transplant. 2015; 50(7):999-1000 [PubMed] Related Publications

Fraser E, Gruenberg K, Rubenstein JL
New approaches in primary central nervous system lymphoma.
Chin Clin Oncol. 2015; 4(1):11 [PubMed] Related Publications
Primary central nervous system lymphoma (PCNSL) has long been associated with an inferior prognosis compared to other aggressive non-Hodgkin's lymphomas (NHLs). However, during the past 10 years an accumulation of clinical experience has demonstrated that long-term progression-free survival (PFS) can be attained in a major proportion of PCNSL patients who receive dose-intensive consolidation chemotherapy and avoid whole brain radiotherapy. One recent approach that has reproducibly demonstrated efficacy for newly diagnosed PCNSL patients is an immunochemotherapy combination regimen used during induction that consists of methotrexate, temozolomide, and rituximab followed by consolidative infusional etoposide plus high-dose cytarabine (EA), administered in first complete remission (CR). Other high-dose chemotherapy-based consolidative regimens have shown efficacy as well. Our goal in this review is to update principles of diagnosis and management as well as data regarding the molecular pathogenesis of PCNSL, information that may constitute a basis for development of more effective therapies required to make additional advances in this phenotype of aggressive NHL.

Deutsch MB, Mendez MF
Neurocognitive features distinguishing primary central nervous system lymphoma from other possible causes of rapidly progressive dementia.
Cogn Behav Neurol. 2015; 28(1):1-10 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
OBJECTIVE: Define the neurocognitive features of primary central nervous system lymphoma (PCNSL) presenting with dementia, and compare with other causes of rapidly progressive dementia (RPD).
BACKGROUND: PCNSL can present as an RPD. Differentiating PCNSL from other RPDs is critical because lymphomatous dementia may be reversible, and untreated PCNSL is fatal.
METHODS: We performed a meta-analysis of case reports of dementia from PCNSL (between 1950 and 2013); 20 patients (14 with lymphomatosis cerebri) met our criteria. We compared these patients to a case series of patients with RPD from Creutzfeldt-Jakob disease and other non-PCNSL etiologies (Sala et al, 2012. Alzheimer Dis Assoc Disord. 26:267-271).
RESULTS: Median age was 66 years (range 41 to 81); 70% were men. Time from symptom onset to evaluation was <6 months in 65%. No patients had seizures; 5% had headaches; 45% had non-aphasic speech difficulty. There was significantly more memory impairment in patients with PCNSL than other RPDs and significantly less myoclonus and parkinsonism. Behavioral changes and cerebellar signs were not significantly different. Significantly more patients with PCNSL than other RPDs had white matter changes; significantly fewer had atrophy. Elevated CSF protein and pleocytosis were more frequent in PCNSL; patients with other RPDs tended to have normal CSF±14-3-3 protein.
CONCLUSIONS: Unlike patients with RPD from other causes, those with PCNSL commonly present with impaired memory, apathy, and abnormal speech and gait, without headache, seizure, or myoclonus. White matter changes and CSF abnormalities predominate. Improved clinical awareness of PCNSL can prompt earlier diagnosis and treatment.

Liu W, Xue J, Yu S, et al.
Primary central nervous system lymphoma mimicking recurrent depressive disorder: A case report.
Oncol Lett. 2015; 9(4):1819-1821 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma, which is limited to the central nervous system. Few studies are available reporting psychiatric symptoms as the initial and dominant presentation of PCNSL. The current study reports the case of a PCNSL patient with a history of major depressive disorder and coexisting rheumatoid arthritis (treated with methotrexate), who initially presented with recurrent depressive disorder that showed no response to antidepressant drug therapy. Magnetic resonance imaging revealed multiple mass lesions in the brain, and pathological examination of the biopsy confirmed the diagnosis of diffuse large B cell lymphoma of the central nervous system. The present case demonstrated that PCNSL may affect mood in the early stages of the disease and thus, clinicians must be aware of this manifestation in patients with depressive disorder co-existing with immunosuppressive conditions, as early detection and appropriate treatment are important prognostic factors for PCNSL.

Wang J, Guo Z, Ma E, et al.
Diagnosis and treatment of primary central nervous system lymphoma: A report of nine cases and literature review.
Oncol Lett. 2015; 9(4):1795-1801 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
Primary central nervous system lymphoma (PCNSL) is a rare, highly malignant tumor type of the nervous system and is associated with poor prognosis. To investigate the efficacy of current treatment strategies for PCNSL, the present study retrospectively analyzed the clinical and pathological features, imaging results, clinical management, and prognoses of nine patients with PCNSL. Postoperative pathological examination confirmed a diagnosis of lymphoma in all the patients and the adopted treatment regimens were as follows: Stereotactic biopsy in combination with methylprednisolone (MP) and methotrexate (MTX) and/or radiotherapy; craniotomy in combination with dexamethasone or MP and/or radiotherapy; and neuroendoscopic surgery in combination with MP and MTX. The follow-up period was 5-27 months with an average duration of 10.1 months. After the initial three months of follow-up, the clinical symptoms of all the patients were significantly improved, with the tumor disappearing in seven patients and evidently reducing in size in two patients. However, six patients exhibited tumor recurrence, three of whom eventually succumbed to the disease during the follow-up period. Currently, comprehensive treatment strategies based on a combination of stereotactic biopsy, chemotherapy and radiotherapy are recommended for the treatment of PCNSL. However, the effectiveness of these treatments remains unsatisfactory. Thus, future studies are required to investigate methods for improving the efficacy of PCNSL treatment strategies.

Canales Albendea MÁ
[Positron emission tomography in primary brain lymphoma: Diagnostic and prognostic significance].
Med Clin (Barc). 2015; 144(11):501-2 [PubMed] Related Publications

Patel B, Chacko G, Nair S, et al.
Clinicopathological correlates of primary central nervous system lymphoma: experience from a tertiary care center in South India.
Neurol India. 2015 Jan-Feb; 63(1):77-82 [PubMed] Related Publications
BACKGROUND: Primary central nervous system lymphomas (PCNSL) constitute a rare group of extranodal non-Hodgkin's lymphomas (NHLs).
AIM: To study the clinical and immunophenotypic profile of patients with a PCNSL who presented between the years 2000 and 2013 in a tertiary care center in South India.
MATERIALS AND METHODS: This was a retrospective study. Demographic and clinical data were obtained from the clinical case records.
INCLUSION CRITERIA: Cases of PCNSL involving brain.
EXCLUSION CRITERIA: Cases of PCNSL involving the spinal cord, meninges and orbit as well as intravascular large B-cell lymphoma, lymphomas with evidence of systemic disease or secondary lymphomas. Archived slides and tissue blocks were retrieved. All cases had hematoxylin and eosin stained sections and immunohistochemistry for CD20, CD3, and MIB-1. Additional immunohistochemistry was performed for CD10, BCL6, and MUM1 on paraffin blocks with sufficient tissue.
RESULTS: There were a total of 73 cases with the mean age of presentation being 45.9 years (range 8-71 years) and with a male predominance (male: female (M:F) = 2.3:1). Headache was the commonest presenting complaint. The mean duration of symptoms was 10.6 weeks. All patients were immunocompetent. Most tumors were supratentorial in location. Out of 73 cases, 70 presented with a diffuse large B-cell lymphoma (DLBCL), two with a Burkitt's lymphoma, and one with a lymphomatoid granulomatosis. Only 51 of the DLBCL cases had sufficient tissue for additional studies. Non-germinal center was the most common phenotype seen in 65.7% (33/51) of cases. Germinal center B-cell (GCB) phenotype was seen in 18/51 cases (34.3%).
CONCLUSION: DLBCL constituted the majority of PCNSLs and although non-germinal center was the predominant phenotype, more than a third of the cases were of the GCB phenotype. As the germinal center phenotype is known to have a better prognosis, further studies to explore its relevance in the Asian population are indicated.

Schmitz N
Treatment of primary CNS lymphoma.
Blood. 2015; 125(9):1360-1 [PubMed] Related Publications
In this issue of Blood, Omuro et al report the results of a phase 2 study for patients with newly diagnosed primary central nervous system lymphoma (PCNSL) using induction immunochemotherapy (rituximab, high-dose methotrexate [MTX], vincristine, procarbazine) followed by a novel consolidation high-dose chemotherapy (thiotepa, busulfan, cyclophosphamide) and autologous stem cell transplantation (HDC-ASCT).

Korfel A, Thiel E, Martus P, et al.
Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma.
Neurology. 2015; 84(12):1242-8 [PubMed] Related Publications
OBJECTIVE: This is the final report of a phase III randomized study to evaluate whole-brain radiotherapy (WBRT) in primary therapy of primary CNS lymphoma (PCNSL) after a median follow-up of 81.2 months.
METHODS: Patients with newly diagnosed PCNSL were randomized to high-dose methotrexate (HDMTX)-based chemotherapy alone or followed by WBRT. We hypothesized that the omission of WBRT would not compromise overall survival (OS; primary endpoint), using a noninferiority design with a margin of 0.9.
RESULTS: In the per-protocol population (n = 320), WBRT nonsignificantly prolonged progression-free survival (PFS) (median 18.2 vs 11.9 months, hazard ratio [HR] 0.83 [95% confidence interval (CI) 0.65-1.06], p = 0.14) and significantly PFS from last HDMTX (25.5 vs 12.0 months, HR 0.65 [95% CI 0.5-0.83], p = 0.001), but without OS prolongation (35.6 vs 37.1 months, HR 1.03 [95% CI 0.79-1.35], p = 0.82). In the intent-to-treat population (n = 410), there was a prolongation by WBRT of both PFS (15.4 vs 9.9 months, HR 0.79 [95% CI 0.64-0.98], p = 0.034) and PFS from last HDMTX (19.4 vs 11.9 months, HR 0.72 [95% CI 0.58-0.89], p = 0.003), but not of OS (32.4 vs 36.1 months, HR 0.98 [95% CI 0.79-1.26], p = 0.98).
CONCLUSION: Although the statistical proof of noninferiority regarding OS was not given, our results suggest no worsening of OS without WBRT in primary therapy of PCNSL.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in PCNSL HDMTX-based chemotherapy followed by WBRT does not significantly increase survival compared to chemotherapy alone. The study lacked the precision to exclude an important survival benefit or harm from WBRT.

Kasenda B, Ferreri AJ, Marturano E, et al.
First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)-a systematic review and individual patient data meta-analysis.
Ann Oncol. 2015; 26(7):1305-13 [PubMed] Related Publications
BACKGROUND: To investigate prognosis and effects of first-line therapy in elderly primary central nervous system lymphoma (PCNSL) patients.
PATIENTS AND METHODS: A systematic review of studies about first-line therapy in immunocompetent patients ≥60 years with PCNSL until 2014 and a meta-analysis of individual patient data from eligible studies and international collaborators were carried out.
RESULTS: We identified 20 eligible studies; from 13 studies, we obtained individual data of 405 patients, which were pooled with data of 378 additional patients (N = 783). Median age and Karnofsky Performance Score (KPS) was 68 years (range: 60-90 years) and 60% (range: 10%-100%), respectively. Treatments varied greatly, 573 (73%) patients received high-dose methotrexate (HD-MTX)-based therapy. A total of 276 patients received whole-brain radiotherapy (median 36 Gy, range 28.5-70 Gy). KPS ≥ 70% was the strongest prognostic factor for mortality [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.41-0.62]. After a median follow-up of 40 months, HD-MTX-based therapy was associated with improved survival (HR 0.70, 95% CI 0.53-0.93). There was no difference between HD-MTX plus oral chemotherapy and more aggressive HD-MTX-based therapies (HR 1.39, 95% CI 0.90-2.15). Radiotherapy was associated with an improved survival, but correlated with an increased risk for neurological side-effects (odds ratio 5.23, 95% CI 2.33-11.74).
CONCLUSIONS: Elderly PCNSL patients benefit from HD-MTX-based therapy, especially if combined with oral alkylating agents. More aggressive HD-MTX protocols do not seem to improve outcome. WBRT may improve outcome, but is associated with increased risk for neurological side-effects. Prospective trials for elderly PCNSL patients are warranted.

Kuusisto ME, Haapasaari KM, Remes AM, et al.
Antithrombin III is probably not a suitable biomarker for diagnosis of primary central nervous system lymphoma.
Ann Hematol. 2015; 94(7):1167-74 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
Antithrombin III (AT III) in cerebrospinal fluid (CSF) has been suggested to have high specificity and sensitivity in separating primary central nervous system (CNS) lymphoma from other neurological conditions. We measured with ELISA CSF and serum AT III and albumin levels in 12 lymphoma patients with CNS involvement, 30 lymphoma patients without CNS involvement, and 41 patients with non-neoplastic neurological diseases. AT III immunostaining was also carried out, in lymphoma patients. Both CSF AT III and albumin levels were higher in lymphoma patients with CNS involvement. AT III/albumin ratio in CSF was the most sensitive and specific measure for diagnosis. Lowest it was in patients with known CNS lymphoma. Serum AT III levels were lower both in CNS lymphoma and systemic lymphoma. CSF AT III levels were shown to be higher in lymphoma patients with CNS involvement, when AT III/albumin ratios were lower. This was probably a result of lowered serum AT III levels, indicating that high levels of AT III in CSF might reflect only leakage of the blood-brain barrier. Thus, AT III fails to be a specific marker for diagnosis of lymphoma CNS involvement.

Shin SH, Jung KW, Ha J, et al.
Population-based Incidence and Survival for Primary Central Nervous System Lymphoma in Korea, 1999-2009.
Cancer Res Treat. 2015; [PubMed] Related Publications
Purpose: Primary central nervous system lymphoma (PCNSL) is an uncommon brain tumor accounting for 2%-5% of all primary brain tumors. Few population-based analyses of survival for patients with PCNSL have been conducted, particularly in Asian countries.
Materials and Methods: Using the Korea National Cancer Incidence Database, 1,062 cases of PCNSL newly diagnosed from 1999 to 2009 were analyzed. The crude rate, age-standardized rate (ASR), and annual percent change were calculated. To estimate the observed survival, we restricted the data to between 1999 and 2007 and followed the cases until December 2010. The overall survival was estimated using the Kaplan-Meier method, and piecewise Poisson regression model.
Results: The ASR for PCNSL between 1999 and 2009 was 0.17 per 100,000, and the annual percent change from 1999 to 2009 was 8.8% (p < 0.001). The ASR of males was higher than that of females, and the older groups (60s or over) showed the largest increase in incidence rates. For all ages, the five-year survival from PCNSL was 29.9% between 1999 and 2007. Survival from PCNSL is known to show strong association with age at diagnosis.
Conclusion: These results are similar to those of previous studies. Our findings may be helpful to clinicians and patients in determining long-term prognoses for PCNSL.

Liu HL, Liu T, Ma C, et al.
[Clinical characteristics and prognosis of 20 cases of primary central nervous system lymphoma].
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015; 23(1):111-8 [PubMed] Related Publications
OBJECTIVE: This study was to investigate the clinical and pathological characteristics, curative effect and prognosis of primary central nervous system lymphoma (PCNSL).
METHODS: The clinical and pathological features, diagnosis and treatment, curative efficacy and survival rate of 20 cases of primary central nervous system lymphoma were retrospectivaly analyzed.
RESULTS: The indicated that the clinical manifestations included headache, paralysis, seizures, dizziness and mental acuity, etc. There were 7 cases with single focus of lesion, 13 cases with multiple foci of lesions. The pathologic examimation showed 1 case of peripheral T-cell lymphoma and 19 cases of diffuse large B cell lymphoma, they all were from non-germinal center. Out of 20 cases, 11 cases with Ki-67>75%,6 cases with Ki-67 50%-75%, 2 cases with Ki-67 25%-50% and 1 case with Ki-67 10%. Therapeutic evaluation were as follows: 10 cases with CR, 2 cases with PR, 6 cases with PD in 18 patients recieved treatment. The use of ritusimab in treatment or no use and number of lesion foci in cranium were related to survival time (P < 0.05) . The survival time in group with Ki-67(+)<75% was longer than that in group with Ki-67(+)>75% (P = 0.042). Age and CSF-TP level were related to curative effect (P < 0.05) .
CONCLUTION: There is no specific clinical manifestation. The physical examination and imageological diagnosis of PCNSL, as well as pathological biopsy are necessary for diagnose of PCNSL. The factors for poor prognosis include age > 60 years, CSF-TP > 600 mg/L, multiple lesions and Ki-67(+)>75%. PCNSL has high malignancy and poor prognosis. The chemotherapy based on high dose of MTX (among which MTX combined with rituximab) and HSCT after CR are the best treatment regimen for DLBCL.

Poulain S, Boyle EM, Tricot S, et al.
Absence of CXCR4 mutations but high incidence of double mutant in CD79A/B and MYD88 in primary central nervous system lymphoma.
Br J Haematol. 2015; 170(2):285-7 [PubMed] Related Publications

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

[Home]    Page last updated: 06 August, 2015     © CancerIndex, Established 1996