The oncogene Ahi-1 was recently identified through provirus insertional mutagenesis in murine leukemias and lymphomas. Its involvement in human leukemogenesis is demonstrated by gross perturbations in its expression in several leukemic cells lines, particularly in cutaneous T-cell lymphoma (CTCL) cell lines (Hut 78 and Hut 102). Hut 78 is derived from a patient with Sezary syndrome, a common leukemic variant of the human CTCL mycosis fungoides. Aberrant expression of AHI-1 mRNA and protein has been found in CD4⁺CD7⁻ leukemic Sezary cells from patients with Sezary syndrome. Moreover, stable suppression of AHI-1 using retroviral-mediated RNA interference in Hut 78 cells inhibits their transforming activity in vitro and in vivo. In an effort to identify genes involved in AHI-1-mediated leukemic transformation in CTCL, microarray analysis was performed to compare six RNA samples from AHI-1 suppressed Hut 78/sh4 cells to five samples from Hut 78 control cells. Limma and dChip analyses identified 218 and 95 differentially expressed genes, respectively, using a fold change criteria of > or < 2 and a p-value threshold of ≤ 0.01. After evaluation of both analyses, 21 genes were selected based upon interesting structural and functional information, specificity to hematopoietic cells or T-cells, and previous connections to cancer. Expression patterns of these 21 genes were validated by qRT-PCR with p-values < 0.05 ranging from 1.97 x 10⁻¹⁰ to 6.55 x 10⁻³, with the exception of BRDG1 at 5.88 x 10⁻². The observed up-regulation of both BIN1 and HCK in AHI-1 suppressed Hut 78/sh4 cells as compared to control cells further confirmed at the protein level. The tumor suppressor BIN1 is known to physically interact with c-MYC, which also exhibits differential protein expression in these cells. Characterization of BIN1 identified 4 isoforms all of which contain exon 10 and demonstrate alternative splicing of exons 12A and 13. Additionally, qRT-PCR results from primary Sezary samples indicate there is clinical significance in the expression changes detected for BIN1, HCK, REPS2, BRDG1, NKG7 and SPIB. These findings identify several new differentially expressed genes that may play critical roles in AHI-1-mediated leukemic transformation of human CTCL cells. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

Orientadores: Andre Deeke Sasse, Carmen Silvia Passos Lima / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T04:20:53Z (GMT). No. of bitstreams: 1 Santos_LucasVieirados_M.pdf: 843952 bytes, checksum: bd8daf1913e68951fafe63ae91e9b070 (MD5) Previous issue date: 2013 / Resumo: Introdução: O linfoma não-Hodgkin é o sexto grupo de neoplasias em mortalidade no mundo. Quando em estágio precoce, o linfoma não-Hodgkin pode ser curado com quimioterapia. A radioterapia tem sido utilizada para se reduzir a recorrência local, entretanto o seu impacto nos desfechos de sobrevivência é desconhecido. Vários estudos tentaram responder a esta questão, mas com resultados conflitantes. Frente a resultados controversos derivados de estudos randomizados, uma revisão sistemática da literatura faz-se necessária para determinar se a radioterapia, acrescentada ao tratamento sistêmico, traz ganhos reais para o paciente. Objetivos: Comparar os desfechos do paciente com linfoma não-Hodgkin agressivo e localizado tratado com quimioterapia seguido de radioterapia, com os da quimioterapia isoladamente. Métodos: Revisão sistemática da literatura com meta-análise. Estudos clínicos randomizados no tratamento do linfoma não-Hodgkin foram identificados, através de busca nas bases de dados Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, e LILACS. Referências de artigos encontrados, Resumos de apresentações em congressos e bases de dados de estudos em andamento também foram utilizados para localizar estudos pertinentes. Critérios de inclusão: estudos controlados randomizados que compararam radioterapia adicionada ao tratamento sistêmico com tratamento sistêmico isoladamente em pacientes com linfoma não-Hodgkin agressivo e localizado. Dois revisores extraíram independentemente os dados dos artigos utilizando formulários de extração de 10 dados. Quando possível, para cada desfecho clínico foi feita meta-análise com os dados extraídos, com o fim de calcular o efeito dos tratamentos entre os estudos. Os resultados da meta-análise são expressos como Risco Relativo (RR), e Hazard Ratio (HR), com o correspondente intervalo de confiança (IC) de 95%. Os desfechos clínicos avaliados foram sobrevida global, sobrevida livre de progressão, resposta radiológica e toxicidade. O modelo de efeito fixo foi usado para se calcular as variáveis de interesse. Resultados: De um total de 7020 estudos identificados por meio da estratégia de busca, cinco foram selecionados. Destes, um estudo foi excluído. Quatro estudos, compreendendo 1796 pacientes foram incluídos na meta-análise. A adição de radioterapia trouxe incremento na sobrevivência livre de progressão [HR 0,81; IC95% 0,67-0,98; p=0,03], sem, entretanto trazer impacto na taxa de resposta ou em sobrevivência global. As diferenças em como os dados foram reportados não permitiu que os dados de segurança fossem combinados. Conclusão: Até o presente momento, não há evidência de que a radioterapia traga ganhos em sobrevivência global em pacientes com linfoma não-Hodgkin agressivo e localizado. Investigações adicionais, com a incorporação dos agentes biológicos à quimioterapia, são necessárias / Abstract: Background: Non-Hodgkin lymphoma is the sixth group of neoplasms in mortality in the world. Aggressive and localized non-Hodgkin lymphoma can be cured by chemotherapy. Radiotherapy has been used to reduce local recurrence, however its impact on survival outcomes is unknown. Several studies have attempted to answer this question, but with conflicting results. Thus, a systematic literature review is needed to determine whether radiation therapy added to systemic treatment enhances the efficacy in non-Hodgkin lymphoma treatment. Objectives: To compare outcomes of patients with aggressive and localized non- Hodgkin lymphoma treated with chemotherapy followed by radiotherapy with chemotherapy alone. Methods: This is a systematic review with meta-analysis. Randomized clinical trials were identified the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and LILACS. Inclusion criteria: randomized controlled trials that compared the addition of radiotherapy to systemic therapy versus systemic therapy alone in patients with aggressive and localized lymphoma. Two reviewers independently extracted data from articles using data extraction forms. When possible, for each clinical outcome was performed meta-analysis of the extracted data in order to calculate the effect of treatments across studies. The results of the meta-analysis are expressed as relative risk (RR) and hazard ratio (HR) with corresponding confidence interval (CI) of 95%. The main outcomes were overall 12 survival, progression-free survival, radiologic response and toxicity. The fixed-effect model was used to estimate the effect size. Results: A total of 7,020 studies identified through the search strategy, five were selected. Of these, one study was excluded. Four studies comprising 1,796 patients were included in the meta-analysis. The addition of radiotherapy increased the progression-free survival [HR 0.81, 95% CI 0.67 to 0.98, p = 0.03]. There were no differences in response rate or overall survival. The differences in how data was reported did not allow us to combine toxicity data Conclusion: To date, there is no evidence that radiotherapy will increase overall survival in patients with aggressive and localized non-Hodgkin lymphoma. Further investigations, with the incorporation of biologic agents to chemotherapy, are needed / Mestrado / Clinica Medica / Mestre em Clinica Medica

Cancer is the second leading cause of death in the United States, and it results from genetic alterations that promote the survival and proliferation of neoplastic cells. One of the most commonly disrupted cancer gene networks is the ARF-Mdm2-Tip60-p53 pathway. Inactivation of the ARF, Tip60 and p53 tumor suppressors and/or overexpression of the Mdm2 oncogene occurs in most, if not all, human cancers. An improved molecular understanding of that pathway, especially how it becomes activated, is expected to advance the development of innovative therapeutics aimed at restoring its function in tumors. Our group originally discovered NIAM (Nuclear Interactor of ARF and Mdm2) as a novel binding partner of ARF that has several functional ties to Mdm2 and p53. Early studies showed that NIAM is negatively regulated by Mdm2, can collaborate with ARF to block cell proliferation, and is a new activator of p53-mediated transcription. NIAM could also act independent of those factors to suppress cell proliferation and promote chromosomal stability, and microarray studies suggested its expression is significantly reduced in many human cancers. Those findings led us to speculate that NIAM is a tumor suppressor that functions in both the ARF-Mdm2-p53 pathway as well as other undefined anti-cancer pathways. My thesis research explored two different aspects of that hypothesis: 1) how does NIAM activate p53, and 2) is NIAM a tumor suppressor? Initial work showed that NIAM could stimulate p53 independently of ARF, the major activator of p53, indicating that other factors must be required. My studies revealed that NIAM indirectly promotes p53 activation through functional interactions with two other p53 regulators, Tip60 and Mdm2. Tip60 is an acetyltransferase that activates p53 through direct association on p53 target promoters as well as acetylation of p53 at lysine 120 (K120). I found that NIAM can induce K120 acetylation of p53; however, NIAM's association with Tip60 (not the acetylation of p53) was essential for maximal p53 transcriptional activation. Mdm2, the major antagonist of p53, is an E3 ubiquitin ligase that promotes p53 ubiquitylation and degradation. I found that NIAM disrupts Mdm2-p53 complexes and blocks p53 ubiquitylation, thereby interfering with p53 inhibition by Mdm2. Thus, NIAM regulates two critical pathways that control p53 function and are altered in human cancers, implying an important role for NIAM in tumorigenesis. To test that idea directly, we generated NIAM gene-trap knockout mice (hypomorphs) that expressed greatly reduced yet detectable levels of NIAM in all tissues. Fifty percent of the NIAM knockout mice developed benign and early stage cancers, including B-cell lymphoma, whereas all age-matched control animals were tumor-free. These results showed that NIAM loss causes increased susceptibility to tumorigenesis. In sum, my work suggests a significant role for NIAM in p53 control and tumor biology. Additional studies will be needed to determine which physiological or pathological signals normally engage NIAM to promote p53 function and suppress tumor development. It is anticipated that the NIAM knockout mice will provide an outstanding platform to interrogate NIAM's biological role in cancer, particularly in ARF-Mdm2-Tip60-p53 signaling as well as other pathways affecting genome maintenance. Ultimately, insights gained from such studies may justify novel therapies that seek to restore NIAM activity in tumors.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare type of lymphoid malignancy with most affected patients presenting in their late 60’s with nonspecific symptoms, laboratory signs and advanced stage disease. 78 year old female with history of hypertension presented to the hospital with complaints of dyspnea, dry cough and fatigue of one week duration. She denied having fever, chills, night sweats or recent weight loss. Labs on admission were significant for leukopenia with lymphocytopenia, thrombocytopenia, hyponatremia and hyperglobulinemia. Computer tomography chest and abdomen showed bilateral multifocal lung infiltrates, large left side pleural effusion, diffuse lymphadenopathy and splenomegaly. She was started on empiric antibiotics for community acquired pneumonia. Sputum culture did not identify any offending organism and although thoracentesis was consistent with exudative fluid, microbiology and pathologic studies also did not offer a diagnosis. Fine needle aspiration of a suspicious lymph node was also negative. She was discharged home to complete treatment for pneumonia but over the next two months, she presented on three different occasions with the same respiratory symptoms. Serial thoracentesis thereafter showed chylous fluid that was fast re-accumulating. A repeat flow cytometry of the pleural fluid was concerning for a lymphoproliferative process and subsequent excisional biopsy with molecular studies performed on rearrangement of T-cell receptors resulted in eventual diagnosis of Angioimmunoblastic T-cell lymphoma stage IV due to associated lung involvement. She declined aggressive management and opted for palliative care. Lymphoma presenting with chylothorax is not common due to early diagnosis of most lymphoma but it can be the initial presentation of AITL because most patients present with nonspecific symptoms and lab findings that make diagnosis difficult and delayed. In our patient, eventual diagnosis was three months from initial presentation. This is not ideal because most patients who succumb to the disease tend to do so from progressive worsening nutritional status and immunosuppression that ensues as the disease advances. The recurrent chylothorax seen in our patient is likely a result of tumor burden that obstructed chyle drainage through the thoracic duct and may have resolved with adequate treatment of the disease. Multiple laboratory abnormalities and B-type symptoms in a patient with unclear primary process should prompt workup for a possible neoplastic disease, particularly lymphoma. Clinicians who suspect a lymphoproliferative process in patients with diffuse lymphadenopathy and pulmonary symptoms of unclear etiology should consider getting an excisional tissue biopsy for further diagnostic studies. PCR based studies that assess for cell locality is also helpful in particularly difficult cases.

Burkitt lymphoma is a highly aggressive B cell non-Hodgkin lymphoma characterized by the translocation t(8,14) and deregulation of the MYC gene on chromosome 8. The endemic (African) form presents classically as an expanding mass in the jaw. The nonendemic (European/North American) form often presents with an abdominal mass. We present an interesting case of Burkitt’s Lymphoma with atypical features. A thirty-five-year-old lady with no significant medical history presented to the hospital with a three week complaint of vaginal bleeding and lower abdominal pain/cramps associated with night sweats and chills. She underwent gynecologic workup with an ultrasound revealing endometrial thickening followed by a hysteroscopic Dilatation and Curettage procedure. Laboratory workup revealed direct hyperbilirubinemia and elevated liver enzymes. MRCP showed gallbladder wall thickening but no biliary obstruction. A diagnosis of acalculous cholecystitis was considered and she underwent a laproscopic cholecystectomy and liver biopsy. Her initial complete blood count revealed mild leukocytosis. Follow up lab work revealed worsening leukocytosis and a hematology consultation was sought. A peak WBC of 81,000 with peripheral blood blasts as high as 31% was noted. Peripheral smear exam revealed moderate sized immature wbc precursors/blasts with high nuclear-cytoplasmic ratio. Further hematological work up including bone marrow aspirate and biopsy was expedited. Pathology resulted positive for Burkitt's lymphoma/leukemia, positive molecular studies, t(8,14), involving bone marrow, gallbladder, liver and endometrium. Patient was emergently treated with dexamethasone and nitrogen mustard as elevated bilirubin levels precluded standard treatment. She was started on Rituxan as this neoplasm is a CD 20+ B cell malignancy but could not tolerate it. HyperCVAD multi-agent chemotherapy was subsequently initiated along with intrathecal chemotherapy (cytarabine and methotrexate). CSF cytology remained negative for lymphoma. Patient’s clinical condition has improved after 2 cycles of chemotherapy and she is currently receiving on going therapy. Burkitt’s lymphoma is one of the most aggressive neoplasms with a tumor doubling time of a few days. The usual presentation is with constitutional symptoms and adenopathy or a mass lesion, and sometimes may manifest solely in the peripheral circulation as an L3 variant of acute lymphoblastic leukemia. Hepatic parenchymal involvement is rare, but reported. Gallbladder involvement with endoluminal deposits is even rarer. Simultaneous hepatic, gallbladder, uterine, nodal and leukemic involvement at presentation is unique. Treatment is primarily with systemic chemotherapy and multi agent regimens effective in acute lymphoblastic leukemia and/or aggressive lymphomas have been used successfully in this condition with a complete response rate of 80%-90% with a long-term survival rate of approximately 60%. Therapy is fraught with risks of fatal tumor lysis syndrome, pancytopenia, infection/sepsis, and bleeding. Potential progression/relapse in the CNS with the CSF serving as a sanctuary site has been well documented necessitating prophylactic intra thecal chemotherapy administration as in our patient. Aggressive biology of this disease required urgent treatment, as delay in institution of combination chemotherapy could result in poor outcome. This case highlights the need to maintain an open mind while evaluating apparently routine symptoms and the importance of rapid diagnosis and treatment of a hematologic-oncologic emergency.

Hodgkin’s lymphoma (HL) is a disease that represents approximately 10% of lymphomas with bimodal age distribution. It is curable in approximately 75 percent of patients worldwide. ABVD regimen (doxorubicin, bleomycin, vinblastine, and dacarbazine) was originally developed for patients with disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, and prednisone), but subsequently became the gold standard initial chemotherapy for patients with HL. Anthracyclines remain as a backbone for combination regimens and in patients with systolic dysfunction MOPP regimen has been used as initial chemotherapy. In patients with relapsed or refractory HL, the goal of treatment should be to achieve long-term disease control and requires salvage regimens to reduce disease burden beforehand followed by autologous hematopoietic cell transplantation (HCT) in curative intent. There are no randomized trials that directly compare the various salvage regimens for relapsed HL. Brentuximab Vedontin (BV) and nivolumab are currently approved for the treatment of refractory disease in patients who have failed two or more first-line treatments or who have failed HCT. Little literature exists regarding the efficacy and overall survival of patients who receive BV with or without nivolumab for refractory disease in patients who are ineligible or refuse HCT. We report a case of a 24-year-old refractory nodular sclerosing Hodgkin’s disease with a lengthy progression-free survival on BV and Nivolumab and without HCT. The patient was diagnosed with stage IV HL due to bone marrow involvement and was started on the MOPP regimen due to an ejection fraction of 45-50% and given a history of transposition of great vessels. The first surveillance PET scan after 6 cycles of MOPP chemotherapy showed new hypermetabolic widespread adenopathy and new multifocal abnormal FDG uptake within the liver and spleen suggestive of early relapse. Salvage chemoimmunotherapy with RICE was then started with the intention to reduce the disease burden prior to HCT. Despite starting salvage chemoimmunotherapy, the patient’s liver function tests (LFT) continued to rise along with progressively worsening pancytopenia. Due to concern for refractoriness and worsening LFT’s, he was started on third-line single-agent nivolumab and showed tremendous response after 4 cycles. BV was added to nivolumab to further improve responses based on phase 2 data. Despite considerable efforts in counseling regarding smoking cessation, he continued to smoke and refused HCT. The patient received 4 cycles of Nivolumab every 2 weeks and then a combination of BV and Nivolumab for 17 cycles. Subsequently had progressive disease. Right, mandibular gingiva biopsy was consistent with high-grade large B cell lymphoma with concern for Richter's transformation from Hodgkin’s to non-Hodgkin’s lymphoma (NHL). He has received a course of radiation therapy to the involved facial area for symptom control and was later started on CEOP (vincristine, etoposide, cyclophosphamide, prednisone) regimen with intrathecal methotrexate. This case provides unique clinical data of durability results of a patient treated with BV in combination with nivolumab in relapsed or refractory HL patients who are ineligible or refuse HCT. Our patient likely had Richter's transformation of HL to the NHL, which has rarely been reported in the literature.

This is a report of a case of Ki-1-positive large-cell anaplastic lymphoma in an 87-year-old man diagnosed on pleural and peritoneal fluids by cytomophologic and immunohistochemical examination. Papanicolaou-stained smears revealed many single, large neoplastic cells containing one or two nuclei with occasional multinucleated cells having a wreath-like nuclear arrangement. The tumor cells expressed Ki-1 antigen and epithelial membrane antigen. This is the first known report of Ki-1 lymphoma diagnosed initially on cytologic examination of pleural and peritoneal fluids.

Marginal zone B-cell lymphomas (MZBL) constitute 7% of all non-Hodgkin lymphomas, being the third most common subtype after diffuse large B-cell lymphoma(DLBCL) and follicular lymphoma. Extranodal MZBL (ENMZBL) most commonly arise from the mucosa-associated lymphoid tissue (MALT lymphoma), with stomach being the most common site. ENMZBL involving the dura is anatomically unusual and very rare. A 54 year old female presented to the hospital with worsening headaches and new onset generalized tonic clonic seizures. Complete blood counts and chemistry were unremarkable. No constitutional symptoms, new / progressive lymphadenopathy reported. Magnetic resonance Imaging( MRI) brain showed an enhancing right subdural soft tissue lesion overlying the right frontotemporal lobe suggestive of meningioma versus metastasis. Computed Tomography (CT) chest/abdomen/pelvis revealed no mass or lymphadenopathy. Lumbar Puncture cerebrospinal fluid cytology was negative for malignancy. She underwent brain biopsy. Pathology revealed diffuse infiltrate of small to medium-sized lymphoid cells, Immunohistochemical stains positive for CD 20, PAX5, CD 79a, Ki-67 at 5-10%, weakly positive for MUM1 and BCL2, negative for CD3, CD5, CD10, BCL6, cyclin D1, consistent with ENMZBL. Bone marrow biopsy and aspiration negative for involvement with lymphoma. Patient received local/regional therapy with radiation (XRT), total dose 24 Gy in 12 fractions. She presented six months later with worsening neck pain. MRI cervical spine revealed diffuse thick dural based enhancement within the spinal canal at C1-C4 levels leading to moderate-to-severe spinal canal stenosis at C2-C3 level with significant soft tissue extension. Repeat labs, systemic imaging, and bone marrow biopsy continued to show no evidence of systemic disease. She received low dose XRT to the entire craniospinal axis (dose-4Gy). Patient developed profound pancytopenia secondary to craniospinal XRT. After count recovery she initiated daily oral Ibrutinib (560 mg) with plans for a treatment duration of one year. Dural based ENMZL usually present as solitary masses, mimicking meningioma's. Marked female predilection is seen with median age of onset 50 years. Very few cases have been reported in literature with no standard therapy being described. ENMZL are usually indolent requiring less aggressive therapy. In contrast, primary CNS lymphoma (PCNSL) of diffuse large B cell histology is usually aggressive with high tendency to relapse, requiring treatment with high dose methotrexate based regimes. Dural based ENMZL therapy entails local treatments such as surgery and radiation therapy (relatively low dose radiation usually effective with prolonged durable responses). Systemic treatment with single agent Rituximab or with Tyrosine Kinase inhibitors like Ibrutinib with CNS penetration can also be considered. Long-term follow-up is recommended even in those patients who achieved complete remission as relapses may occur.

While CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), the current standard of care for non-Hodgkin lymphoma (NHL), kills tumor cells, the accumulation of tumor cell “debris” can stimulate inflammation and tumor growth. Thus, cytotoxic cancer therapies are a double-edged sword. Previous studies have shown that apoptotic debris stimulates tumor growth. We hypothesize that (1) CHOP-generated tumor cell debris can promote lymphoma progression via release of pro-inflammatory cytokines; (2) blocking phosphatidylserine (PS), which is presented on the surface of apoptotic cells, may inhibit debris-stimulated cancer progression. METHODS: Lymphoma EL4 debris was generated by treating tumor cells with CHOP chemotherapy. EL4 debris was isolated via Ficoll gradient and co-injected with living EL4 tumor cells into immunocompetent C57BL/6 mice. Macrophage-secreted cytokines were measured via array analysis. RESULTS: Flow cytometry confirmed CHOP chemotherapy generated apoptotic/necrotic debris. Vincristine-, mafosfamide-, and prednisolone-generated lymphoma EL4 debris stimulated tumor growth by over 100-fold in a dose-dependent manner. Debris alone did not induce tumors, even at 250 days post-injection. Doxorubicin-generated EL4 debris stimulated tumor growth at low dose (1x105), but inhibited growth at high dose (9x105). Systemic administration of doxorubicin-generated EL4 debris or blocking PS in the cell debris generated by doxorubicin using annexin V or an anti-PS neutralizing antibody inhibited doxorubicin-generated debris-stimulated tumor growth. Therapy-generated debris stimulated macrophage pro-inflammatory cytokine production. CONCLUSIONS: CHOP chemotherapy-generated debris regulates tumor growth via cytokine production. Thus, harnessing the anti-tumor activity of inhibitory debris or neutralizing PS on stimulatory debris may be a novel anti-cancer approach. / 2018-07-11T00:00:00Z

Background: The aim of this study was to describe the morphological signs of the central nervous system lymphoma (CNSL) in magnetic resonance imaging (MRI). We compared morphological characteristics of primary CNSL (PCNSL) and secondary CNSL (SCNSL) and also of PCNSL and glioblastoma (GBM). Methods: We included 64 patients with PCNSL (ten of them were immunocompromised), 21 patients with SCNSL and 54 patients with GBM. The diagnosis was confirmed histologically in all patients. We evaluated morphological signs on the first MRI examination. Additionally, in patients with PCNSL, we evaluated the development of the disease on follow-up examination before histological confirmation of the diagnosis, if available. Results: In most patients with PCNSL (62.5%) the tumor was localized supratentorially and presented as multiple lesions (53.1%) or as a diffuse infiltrative lesion (23.4%). In 87.5% of the patients the lesions reached the brain surface. Infiltration of ependyma was seen in 56.3%, infiltration of meninges in 39.1% and infiltration of cranial nerves in 48.5% of patients. Restriction of diffusion in some part of the tumor was apparent in nearly all patients (97.6%) with PCNSL. After administration of contrast media, marked enhancement was usually seen. In immunocompetent patients, homogenous...