Unusual variants of primary central nervous system lymphoma

Rare variants of primary central nervous system lymphoma (PCNSL) include unusual sites of presentation (eg, neurolymphomatosis and primary leptomeningeal lymphoma) and uncommon pathologic entities. Neurolymphomatosis involves peripheral nerves and nerve roots in addition to systemic and central nervous system (CNS) sites. Diagnosis requires a high index of suspicion, and treatment incorporates the principles of therapy for systemic and CNS lymphoma. Primary leptomeningeal lymphoma can present with symptoms of raised intracranial pressure or cranial or spinal polyradiculopathies. Diagnosis can be made by examining cerebrospinal fluid and incorporating immunophenotyping and molecular pathology techniques. Treatment options include irradiation and intrathecal or systemic chemotherapy. The features of PCNSL of T-cell origin and indolent B-cell PCNSL also are discussed.     

Meningitis with Burkitt like B-cell lymphoma in HIV infection

Malignant lymphoma with meningeal involvement was detected in 7 patients with stage IV HIV infection. The diagnosis of lymphoma was made at a maximum of four months before discovery of meningeal involvement. In our seven cases the lymphoma was B-cell type, one case expressed Kappa chains, four cases demonstrated Lambda chains and in two cases differentiation was not possible. A review of findings in all HIV positive patients treated in the same period revealed 10 non-Hodgkin lymphomas of the B-cell type, though meningeal and cerebral involvement was observed only in B-cell lymphoma of the Burkitt type.     

Clinical response following adjuvant Temozolomide in a patient with primary cerebral lymphoma

A 69-year-old female patient was treated for primary CNS-lymphoma (PCNSL) starting from August 2002. As her general condition allowed no high-dose methotrexate (MTX) therapy, radiotherapy was administered as a first-line treatment. CSF involvement could be managed by intrathecal Ara-C. Her general condition and cognitive status stabilized, but did not improve for 3 months. Therefore, oral chemotherapy with Temozolomide 200 mg/m2 was initiated. After two courses, which were tolerated without any problems, the patient's Karnofsky performance index had improved from 40% to 50%, the Mini-Mental Status rose from 16 to 27/30. The CSF-cell count was elevated again to 23 cells/l without signs of meningeal relapse. Unfortunately, the patient died unexpectedly from suspected pulmonary embolism. We conclude that adjuvant Temozolomide chemotherapy can improve the general condition and cognition in patients with PCNSL even when the general condition is poor. Long-term effects and neurotoxicity remain to be analysed in prospective trials, as well as the efficacy in leptomeningeal disease.     

原发性中枢神经系统淋巴瘤的诊断研究进展

 原发性中枢神经系统淋巴瘤（PCNSL）是一种临床上较为罕见的结外淋巴瘤,病理学分类多为弥漫性大B细胞淋巴瘤。WHO（2008）造血与淋巴组织肿瘤分类将"PCNSL"作为独立疾病实体列出。文章就近年PCNSL的临床诊断研究进展作一介绍。     

Primary Leptomeningeal Lymphoma

Primary leptomeningeal lymphoma is a rare disorder, and the neuroradiological characteristics or the complication of this rare disorder have not been well reported. We reported herein a patient with a primary leptomeningeal lymphoma who has complication with subdural hematoma. The patient complained of headache and vomiting. Neurological examination revealed progressive cranial nerve palsy. Cerebrospinal fluid examination disclosed monoclonal proliferation of atypical B-lymphocytes. Cranial computed tomographic scans showed a left frontal mass with convex form to the brain parenchyma. T1-weighted magnetic resonance (MR) images disclosed subacute subdural hematoma. However, proton-weighted MR images showed high signal intensity in subarachnoid space, which suggested leptomeningeal lymphoma. He underwent craniotomy, and the diagnosis of leptomeningeal lymphoma complicated with subdural hematoma was confirmed. Systemic examinations disclosed no lymphomatous lesions except for leptomeningus, and the diagnosis of primary leptomeningeal lymphoma was established. We suggested that subdural hematoma was associated with primary leptomeningeal lymphoma in this patient. Cerebrospinal fluid examination and proton-weighted MR imaging should be performed when progressive neurological abnormalities are found in patients with subdural hematoma.     

Ocular involvement in patients with primary CNS lymphoma

To describe the demographics, clinical characteristics, and treatment outcomes in patients with primary CNS lymphoma (PCNSL) with ocular involvement. A retrospective chart review was conducted on 61 patients who were diagnosed with PCNSL from January 2000 to October 2008 at the Asan Medical Center, Seoul, Korea. Among 46 patients who underwent ophthalmologic examination, 13 (28%) showed intraocular involvement. Mean age at diagnosis was 52.8 years, and 54% of patients were female. Diagnosis of PCNSL was made by vitrectomy (1 patient) or brain biopsy and/or CSF cytology (12 patients). In 4 (31%) patients, ocular symptoms preceded CNS symptoms. The most common ocular symptom was decreased visual acuity. Nine patients showed bilateral involvement. Intraocular findings included retinal infiltrative lesions (3 eyes), vitritis/vitreous opacity (5 eyes), or both (14 eyes). In addition to systemic chemotherapy and/or radiotherapy, vitrectomy and/or intravitreal methotrexate was utilized in 8 patients. Mean survival duration was 32.2 months (range 2–120 months). Although rare, the number of patients with PCNSL seems to be increasing in Korea. Early detection and dedicated treatment of intraocular lymphoma may result in improved visual outcome.     

Aggressive treatment with complete remission in primary diffuse leptomeningeal gliomatosis: A case report

Primary leptomeningeal gliomatosis is rare, and the diffuse form (PLDG) is even more unusual. The following report is an example. A 17 year-old man developed a syndrome characterized by extensive basal and chronic spinal meningitis. Routine biological tests showed elevated levels of CSF proteins, and moderate mononuclear pleocytosis, with no direct evidence of neoplasia, leading to a diagnosis of chronic meningitis. A second meningeal biopsy, guided by MRI and performed in the left frontal region, led to the specific diagnosis of primary diffuse leptomeningeal gliomatosis. Treatment including ventricular and lumbar shunting, a course of cortico-spinal radiation, and three courses of an eight-drug systemic chemotherapy with intrathecal methotrexate lead to complete remission over 15 months. We believe that this is the first report of such a remission in the literature.     

Primary adrenal lymphoma

Primary adrenal lymphoma is a rare extranodal lymphoma with characteristic clinical features including a high incidence of bilateral involvement, predominantly diffuse large B-cell histology, and a low incidence of extra-adrenal disease at diagnosis. Patients are most commonly older men presenting with fever, lumbar pain, and/or symptoms of adrenal insufficiency. Prolonged disease-free survival appears uncommon, which may reflect a publication bias and/or the presence of additional adverse prognostic factors at diagnosis in most patients. Given the rarity of this disease, no prospective chemotherapy studies have been reported. Unresolved therapeutic issues include the optimal chemotherapy regimen (with vs. without monoclonal antibody), the role of bilateral adrenalectomy and/or adjuvant radiation therapy, and the need for central nervous system prophylaxis, given recent reports raising the possibility of a high risk of parenchymal or meningeal relapse. Multicenter collaborative retrospective reviews and prospective trials are needed to address these issues.     

Varicella-zoster viral meningitis mimicking lymphoma

We report the case of a 30-year-old HIV-infected man admitted for a meningeal syndrome and a zoster rash. The CSF had cytological features suggesting a primary CNS lymphoma (PCNSL). The large lymphoid cells had a fine chromatin with nucleoli, a basophilic cytoplasm with azurophilic granules and high mitotic activity. Several arguments demonstrated the viral origin of the meningitis: the large lymphoid cells were of T origin with no evidence of clonal TCR γ gene rearrangement. The PCR was positive for Varicella-Zoster Virus (VZV) and EBV DNA. Clinical evolution was favorable under acyclovir. We should be cautious in the differential diagnosis between viral meningitis and PCNSL.     

Primary meningeal lymphoma of T-cell origin: a rare presentation of primary central nervous system lymphomas

Primary meningeal lymphoma is a rare clinical entity. Central nervous system infiltration by systemic lymphoma should always be excluded. Diagnosis can be difficult, and prognosis is usually poor. Most are of B-cell origin. We present the case of a young man with a primary meningeal lymphoma of T-cell origin. He was treated with systemic chemotherapy with high-dose methotrexate and cytarabine and intraventricular chemotherapy. He had a clinical improvement and a complete remission, with a long overall survival. There is no standard treatment for this rare disease. Traditionally, treatment has been based in craniospinal radiation therapy and intrathecal chemotherapy, with poor overall results. More recently, systemic chemotherapy with high-dose methotrexate has been advocated, which could avoid the long-term toxicity of craniospinal radiation therapy, and could improve the prognosis of these patients.     

Primary Central Nervous System Mucosa-Associated Lymphoid Tissue Lymphoma: Case Report and Literature Review

Primary presentation of intradural non-Hodgkin lymphoma is rare. Recently, B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) have been recognized as an important pathologic subtype. When MALT lymphomas present in the central nervous system (CNS), they are distinguishable from primary high-grade CNS lymphomas. We present the clinicopathologic features of 5 patients with primary CNS MALT lymphoma treated at our institution from 1999 to 2006. Four out of 5 patients were women, and all patients presented with headaches, focal motor deficits, or cranial nerve palsy. Radiologic studies demonstrated ill-defined dural masses in 3 and well-defined masses in 2 patients. Pathology revealed small to medium-sized cells with a moderate amount of cytoplasm and irregular nuclear borders, expressing pan B-cell markers (CD19, CD20, and CD79a) but lacking CD10, CD23, and cyclin D1, confirming low-grade MALT lymphoma. Plasma cells were encountered in all the biopsies with variable reactive T-cell infiltration. δ chain restriction was seen in 3 patients. Therapy consisted of either surgical resection, whole-brain radiation, or systemic or intrathecal chemotherapy. There was no evidence of recurrence or systemic relapse in 4 patients at 4 years of follow-up. One patient died in 2 months, unrelated to CNS lymphoma. This case series illustrates the rare occurrence of low-grade dural B-cell lymphoma and the need to consider this entity in the differential diagnosis of CNS lesions.     

Involvement of the appendix in a relapsed case of primary nasal NK/T-cell lymphoma

We report here a 20-year-old man presenting with primary nasal NK/T-cell lymphoma which showed an aggressive clinical course spreading to the spleen and skin despite various treatments. Eight months after high dose chemotherapy followed by autologous peripheral blood stem cell transplantation, acute appendicitis with perforation occurred and the patient underwent appendectomy. The histopathological diagnosis was NK/T-cell lymphoma of the appendix. Lymphoma of the appendix is extremely rare and the majority of appendiceal lymphomas are of B-cell origin. This is the first report of involvement of appendix by nasal NK/T-cell lymphoma.     

Primary meningeal CNS lymphoma treated with intra-arterial chemotherapy and blood-brain barrier disruption

Diffuse large B-cell lymphoma of the meninges is a particularly rare form of primary CNS lymphoma. We report a case of a 63-year-old woman found to have primary meningeal lymphoma (PML) with dural and leptomeningeal involvement whom we treated with multiple cycles of intra-arterial (IA) methotrexate, intravenous (IV) etoposide phosphate, and IV cyclophosphamide after reversible osmotic blood-brain barrier disruption (BBBD). Improvement was evident on gadolinium-enhanced brain MRI one month into therapy. At 67 months post-diagnosis there is no evidence of CNS disease. After completing her therapy regimen, she remained disease-free for 34 months, when stage IV diffuse large B-cell lymphoma was discovered in her left adrenal gland and right thigh. Following six cycles of rituximab and CHOP treatment, she is presently in complete remission. IA methotrexate and reversible osmotic BBBD without radiation therapy may be an effective therapy for treating PML.     

The CSF IL-10 concentration is an effective diagnostic marker in immunocompetent primary CNS lymphoma and a potential prognostic biomarker in treatment-responsive patients

IntroductionWe aimed to confirm the diagnostic value and to evaluate the pre- and post-therapeutic prognostic value of cerebrospinal fluid (CSF) concentrations of interleukin (IL)-10 and IL-6 in patients with diffuse large B-cell primary central nervous system lymphoma (PCNSL).Patients and methodsIL-10 and IL-6 concentrations were measured in 79 patients with PCNSL at diagnosis and in 40 control individuals. Fifty-four PCNSL patients underwent repeat assessments starting at diagnosis.ResultsThe IL-10 concentration distinguished PCNSL from other neurologic diseases with a sensitivity of 88.6% and a specificity of 88.9% with a cutoff of 4 pg/ml. In a multivariate analysis of PCNSL patients, CSF involvement was associated with a higher IL-10 concentration (mean log (IL-10) of 4.4 versus 2.5 pg/ml, respectively, p = 0.0004). The pre-therapeutic IL-10 concentration had no prognostic impact on outcome. The IL-10 concentration decreased after treatment for most patients tested. Among patients with complete remission or partial remission, as evaluated by magnetic resonance imaging (MRI), a persistent detectable IL-10 level in the CSF at the end of treatment was associated with a negative impact on progression-free survival (PFS) (1-year PFS: 15%, 95% confidence interval [CI]: 2.5–38% versus 59%, 95% CI: 32–78%, respectively, p = 0.0004).ConclusionOur study confirmed that IL-10 is a useful biomarker for the diagnosis of PCNSL. We highlight new findings showing that the IL-10 level in the CSF could be used as a surrogate marker for CSF involvement and that the post-treatment IL-10 concentration could complement standard MRI for therapeutic response assessment in PCNSL.     

32例原发性中枢神经系统恶性淋巴瘤临床分析及文献复习

背景与目的:原发性中枢神经系统淋巴瘤(primarycentralnervoussystemlymphoma,PCNSL)发病率上升且预后很差。本研究目的是探讨免疫正常的中国人PCNSL的临床特征,评价大剂量甲氨蝶呤(HD-MTX)治疗PCNSL的疗效。方法:回顾性分析经病理证实的32例(中位年龄50岁)PCNSL患者的临床资料和治疗效果。2001年11月以前采用以CHOP方案为主、单用或联合全脑放疗的治疗方法,2001年12月以后采用以HD-MTX为主、单用或联合全脑放疗的治疗方法。结果:32例PCNSL患者中25例(78.1%)45岁以上;24例(75%)主要表现为颅内高压;25例(78.1%)单发病灶;32例患者均未见脑脊液细胞学阳性表现;28例(87.5%)为B细胞淋巴瘤,其中19例为弥漫性大B细胞淋巴瘤。32例中位随访期13.5个月(1～84个月),Kaplan-Meier分析总中位生存期26个月,2年生存率45.7%;HD-MTX联合放疗组患者完全缓解率61.1%,中位生存期在26个月以上,2年生存率65.1%,疗效明显优于非HD-MTX联合放疗组;log-rank检验显示乳酸脱氢酶正常、状态评分在0～1的患者生存期较长。结论:PCNSL多发于中老年人,颅内高压为主要表现,B细胞亚型占绝对优势。HD-MTX联合全脑放射治疗PCNSL有效和可行。     

Autoimmune hemolytic anemia with myelodysplastic features followed by bilateral adrenal non-hodgkin lymphoma: a case report and review of the literature

Primary adrenal lymphoma is a rare entity characterized mainly by bilateral involvement, presenting predominantly diffuse large B-cell histology, adrenal insufficiency and poor prognosis. Approximately 85 cases have been described in the literature. We report here a case of a 77-year-old man who presented with autoimmune hemolytic anemia (AIHA), which preceded the diagnosis of lymphoma by more than 2 years. An ultrasound guided biopsy revealed diffuse, large B-cell, lymphoma; subsequent staging revealed no other disease site, and the patient was considered to have primary adrenal lymphoma. The patient had adrenal insufficiency at diagnosis. He received hormonal replacement and chemotherapy, but he succumbed to his disease because of sepsis and multi-organ failure a few days post diagnosis. To our knowledge, this is the first case in the literature in which AIHA preceded bilateral adrenal lymphoma. We also provide a summary of the current data for the clinical features, diagnosis and treatment of primary adrenal lymphoma.     

Management of primary intraocular lymphoma

Primary intraocular lymphoma (PIOL) is a subset of primary central nervous system lymphoma (PCNSL) in which malignant lymphoid cells invade the retina, vitreous body, or optic nerve head. It is usually a large B-cell non-Hodgkin’s lymphoma. PIOL typically presents as a vitritis that is unresponsive to corticosteroid therapy. Diagnosis of PIOL requires pathologic confirmation of malignant cells in specimens of the cerebrospinal fluid, vitreous, or chorioretinal biopsies. The optimal therapy for PIOL has yet to be determined. It is generally believed that PIOL should be treated with a combination of systemic chemotherapy, including high-dose methotrexate and radiotherapy. However, several new developments for PIOL with central nervous system involvement have been reported, including intrathecal therapy and autologous stem-cell transplantation. In addition, intravitreal methotrexate has been successful in the treatment of isolated recurrent ocular disease. This article provides an overview of treatment modalities for initial, recurrent, and relapsed PIOL.     

Primary central nervous system anaplastic large-cell lymphoma mimicking lymphomatosis cerebri

Primary central nervous system lymphoma (PCNSL) is usually diffuse large B-cell lymphoma. Anaplastic large-cell lymphoma (ALCL) rarely occurs in the central nervous system. PCNSL always presents as single or multiple nodular contrast-enhancing mass lesions within T2-hyperintense areas on magnetic resonance imaging (MRI). Infrequently, diffuse infiltrating change with little contrast enhancement called lymphomatosis cerebri can be seen in PCNSL. In this report, we describe a 75-year-old immunocompetent man who had progressive dementia. On MRI, diffuse white matter lesions with little contrast enhancement were observed to gradually progress, which was clinically consistent with his worsening condition. A biopsy specimen revealed non-destructive, diffusely infiltrating, anaplastic large CD30-positive lymphoma, indicating a diagnosis of ALCL. After the biopsy, he was treated by whole brain irradiation (total 46 Gy) and focal boost irradiation (total 14 Gy). However, his performance status worsened and there was no symptom improvement. The patient died 8 months after symptom onset. The clinical course, diagnostic workup, pathologic correlates, and treatment outcomes are described herein.