Cancer, Central Nervous System Lymphoma


Article Author:
Keva Green


Article Editor:
Jeffery Hogg


Editors In Chief:
Kranthi Sitammagari
Mayank Singhal


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
8/18/2019 10:09:07 PM

Introduction

Lymphoma of the central nervous system, both primary and secondary, represents a rare subset of non-Hodgkin lymphoma. According to the World’s Health Organization definition, primary central nervous system lymphoma refers to those cases confined to the CNS parenchyma, dura, leptomeninges, cranial nerves, and spinal cord or the intraocular compartment in immunocompetent patients. On the other hand, secondary CNS lymphoma refers to systemic non-Hodgkin lymphoma that has disseminated to the CNS. Historically, the prognosis of primary central nervous system lymphoma has been very dismal, with overall survival of 1.5 months when untreated,[1] and a five (5) year survival rate of 30%.[2] Meanwhile, patients with aggressive systemic non-Hodgkin’s lymphoma have a 2 to 27% risk of developing secondary CNS disease, with a median survival of 2.2 months after diagnosis.[3] Due to the introduction of high-dose methotrexate based chemotherapy regimens, there has been substantial progress in treating patients with lymphomas of the CNS, leading to improved survival.

Etiology

Immunodeficiency, both primary and acquired, is a significant risk factor for lymphoma of the central nervous system.[4][3] Primary CNS lymphoma is seen in approximately 6% of patients with AIDS and is an AIDS-defining illness. It usually occurs when CD4 counts are very low, often in patients not on antiretroviral therapy. Meanwhile, 2 to 7% of cardiac, liver, and lung transplants patients, as well as up to 2% of renal transplant patients, ultimately develop the disease. The incidence is highest during the first year post-heart and lung transplant.[4] Primary immunodeficiency such as Wiskott Aldrich, ataxia telangiectasia, common variable, and severe combined immunodeficiency syndromes confers a 4% risk of developing primary central nervous system lymphoma.[3] The Epstein bar virus (EBV) highly correlates with CNS lymphoma in T cell immunodeficient states, such as patients on immunosuppressants post-organ transplant. EBV is also associated with 100% of primary CNS lymphoma in patients with AIDS.[3]

Epidemiology

Primary CNS lymphoma has an annual incidence of approximately 1400 cases in the United States.[5] It comprises 5% of all primary brain tumors and 1% of all cases of non-Hodgkin lymphoma. While CNS lymphoma is decreasing in the AIDS population due to the advent of highly active antiretroviral therapy (HAART), its incidence is rising in the elderly population. Rates are highest among the elderly and individuals with a compromised immune system, but the disease is rare in pediatric populations. Immunocompetent patients are often diagnosed between ages 50 to 70, while immunocompromised patients present earlier in their 30s and 40s.[4] Males are more frequently affected than females in both groups, but there is no gender predilection of CNS lymphoma in patients with post-transplant lymphoproliferative CNS lymphoma.[4][6]

Pathophysiology

The most commonly involved sites of primary central nervous system lymphoma are the frontal lobe and basal ganglia, with the brainstem, cerebellum, and spinal cord less commonly affected. Up to 25% of patients with primary central nervous system lymphoma develop intraocular lymphoma, and primary intraocular lymphoma ultimately disseminates to the CNS more than 80% of the time. Lesions of primary intraocular lymphoma tend to be found more often within the vitreous fluid and the retina.[6] However, it is uncommon for primary CNS lymphoma to disseminate systemically. On the other hand, secondary lymphoma of the CNS often has a predilection for the dura and leptomeninges, and the choroid in cases of intraocular involvement.

Several mutations in tumor suppressor and proto-oncogenes involved in B cell activation, differentiation, and apoptosis are believed to contribute to the development of primary CNS lymphoma. Somatic hypermutations in proto-oncogenes such as MYC, PAX5, Rho/TTF, and PIM1 as well as the tumor suppressor genes such as PRDM1 have been demonstrated in primary CNS lymphomas cases. NF-KB signaling is believed to play a role in the disease pathogenesis. The up-regulation of activators within the NF-KB pathway such as MYD88, CADR11, and CD79 as well as suppression of NF-KB inhibitors such as TNFAIP3 have presented in individuals with primary CNS lymphoma.[2] Expression of MYD88 and CD79B mutations in secondary CNS lymphoma is considerably lower than in primary CNS lymphoma, which suggests different pathogenesis.[7] Aberrant regulation of the JAK/STAT pathway is also implicated. Increased levels of IL-10, A JAK/STAT mediator is seen in CSF analysis of primary CNS lymphoma patients and is often associated with a worse prognosis. It is still unclear whether cells of primary CNS lymphoma first arise from within the CNS itself, or rather systemically then travel to the CNS via peripheral blood and further accumulates other mutations.[2]

Histopathology

About 95% of primary CNS lymphomas belong to the diffuse large B cell (DLBC) category, with low-grade B cell lymphoma, T cell lymphoma, and Burkitt lymphoma accounting for the rest.[2][8] There are two (2) histological variants of diffuse large B cell lymphoma: the germinal center subtype, often CD10 and BCL6 positive, and the activated B cell subtype which usually expresses MUM1. More than half of primary CNS lymphomas express both BCL6 and MUM1, suggesting that the tumor derives from B cells in the process of exiting the germinal center but that has not yet reached the post germinal center stage. While primary CNS lymphomas usually express the pan B cell markers CD19, CD20, CD22 and CD79a, the plasma cell markers CD38 and CD138 are often absent. Only 10% of cases are CD10 positive, but 80-90% of tumors are MUM1 positive, and 60-80% are BCL6 positive. While the prognostic value of these B cell differentiation markers is well elucidated in systemic diffuse large B cell lymphomas, their significance in primary CNS lymphoma remains unclear. Similarly, overexpression of the cell cycle regulator protein MYC, as well as the anti-apoptosis protein BCL2,  has prognostic implications in systemic DLBC lymphoma but is of uncertain significance in primary CNS lymphomas.[2]

Primary CNS lymphoma is a highly cellular and infiltrative tumor.   Cells often display a perivascular growth pattern called angiotropism, which has been shown to be associated with a worse prognosis. The lymphomatosis cerebri variant of diffuse large B cell lymphoma is rarely seen. A reactive perivascular infiltrate of T cells when present is associated with a better outcome. This antitumor T cell immune response is seen less in primary CNS lymphomas when compared to systemic DLBC lymphomas, which could in part account for its poorer prognosis.[2]

History and Physical

Up to 80% of patients with primary CNS lymphoma present with focal neurologic deficits and symptoms often correlate with the location of the lesion.[6][3] Behavioral and mental status changes present in 32% to 43% of patients, and 32% to 33% of patients present with signs of increased intracranial pressure. Seizures are uncommon and seen in only 11% to 14% of patients.[9] Central nervous system involvement by systemic lymphoma usually occurs early in the disease course, on average 5 to 12 months after diagnosis of systemic disease. Patients often present with headache as well as cranial or spinal neuropathy from leptomeningeal metastases.[10] Intraocular lymphoma usually presents with pain, decreased visual acuity, photophobia, blurry vision, and floaters. While symptoms rapidly improve with steroid administration, steroids often result in false-negative biopsies, so its use is not a recommendation until after making a definitive diagnosis.[8]

Evaluation

In patients with suspected primary central nervous system lymphoma, MRI brain with contrast is the recommended first test in diagnosis. Lesions are often located centrally within the cerebral white matter as well as in the periventricular region. They are often isointense or hypointense on unenhanced T1 weighted imaging and isointense or hyperintense on T2. CT is not as sensitive as MRI but usually shows iso or hyperattenuating lesions with post-contrast enhancement. While lesions in immunocompetent patients are usually solitary with homogenous enhancement, 20% to 40% of cases report multiple lesions, and ring-like enhancement occurs in up to 13% of cases. Surrounding edema is often present but not to the extent seen in malignant gliomas or metastatic disease. Additionally, linear enhancement along perivascular space is highly associated with primary central nervous system lymphoma. In contrast, 30% to 80% of immunodeficient patients present with multiple lesions that usually have necrosis resulting in an irregular ring-enhancing pattern post-contrast.[3][6] In the primary dural subtype of primary CNS lymphoma, diffusely enhancing masses are usually visible on CT and MRI that can mimic a meningioma. While micro-hemorrhages often present in high-grade gliomas, hemorrhage and calcifications are uncommon in primary CNS lymphoma lesions except in AIDs related cases.

Conventional magnetic resonance imaging alone cannot reliably differentiate CNS lymphoma from other neoplastic lesions in the brain, so other sequences and imaging modalities are often helpful. Primary central nervous system lymphomas are highly cellular tumors, which makes them more hyperintense on diffusion-weighted MRI sequences than metastases and high-grade gliomas. Corresponding apparent diffusion coefficient (ADC) values are also lower and may be predictive of overall survival. However, AIDs related CNS lymphomas have similarly low ADC values when compared to cerebral toxoplasmosis and cannot be reliably differentiated based solely on ADC values. In this case, MR spectroscopy may offer some benefits as lymphoma and toxoplasmosis have different biochemical properties.

Additionally, CNS lymphomas are usually more hypermetabolic than gliomas, resulting in increased uptake on metabolic imaging such as methionine PET as well as FDG PET scans. The uptake area on PET imaging is often larger than the corresponding areas on conventional imaging, which reflects the infiltration of the tumor beyond the areas depicted on MR imaging. On the other hand, infectious lesions are generally hypometabolic, corresponding to lower thallium-201 uptake on SPECT and SPET as well as lower FDG uptake on PET imaging. This aids in the differentiation of primary central nervous system lymphomas in immunocompromised individuals from infectious etiologies.

MRI has a low sensitivity for detecting intraocular lymphoma, so a thin section protocol is required to reveal any nodular enhancing lesions on the macula or uvea.[10] While the preferred method for definitive diagnosis of primary vitreoretinal lymphoma is a vitreous aspiration or chorioretinal biopsy, a slit-lamp examination of both eyes is often done earlier in the workup process.[6][10][1] Flow cytometry can be used in the analysis of vitreous aspirate as well as in CSF analysis in cases of primary dural lymphoma, posterior fossa lesions or secondary CNS lymphoma.[3] Ultimately, a stereotactic needle biopsy allows for definitive diagnosis of intraparenchymal lesions, especially in patients without ocular or CSF involvement.[3][6]

Treatment / Management

Due to its high sensitivity to radiation, patients with newly diagnosed central nervous system lymphomas have traditionally received treatment with whole-brain radiotherapy (WBRT). While the initial responses were high, early relapse, as well as radiation-associated neurotoxicity, was common among survivors.[1] Moreover, the median overall survival was 12 to 18 months when WBRT was the sole treatment.[3] With the introduction of high-dose methotrexate (HD-MTX) chemotherapy regimens in the 1970s, improved survival occurred among individuals with CNS lymphoma. When used as a sole treatment, the median overall survival with high-dose methotrexate was 25 to 55 months. Investigations of surgical resection of PCNSL have shown no apparent benefit. The role for surgery with PCNSL is limited to stereotactic biopsy to establish the histopathologic diagnosis.[1]

Currently, the mainstay of treatment for individuals with CNS lymphoma is induction chemotherapy that aims for a complete radiographic response (CR), followed by consolidative therapy. The goal of consolidative therapy is to eradicate residual disease and improve overall survival.[1] Induction chemotherapy usually involves some combination of high-dose methotrexate (HD-MTX) with other chemotherapy agents, including temozolomide, cytarabine, etoposide, vincristine, carmustine, ifosfamide, thiotepa, and cyclophosphamide. Options for consolidation include high-dose radiation (45 Gy), low dose radiation (23.4 Gy), and dose-intensive chemotherapy with agents such as carmustine, thiotepa, cyclophosphamide, busulfan, cytarabine, and etoposide. While studies with reduced-dose WBRT as consolidative therapy have shown good progression-free and overall survival rates, a longer follow-up period is required to determine the long-term neuropsychological effects of the radiation. Importantly, in studies that omitted WBRT from consolidative therapy, no survival compromise was shown, and patients had a better neurological outcome[1][3]

In one study, cytarabine was added to HD-MTX for induction, followed by WBRT for consolidation, with the overall survival at 3 years 46% compared to 32% with HD-MTX monotherapy. In another, thiotepa and rituximab were added to HD-MTX during induction followed by WBRT for consolidation and overall survival was 69% vs. 42% with HD-MTX alone. When using HD-MTX along with procarbazine, vincristine, and rituximab for induction followed by cytarabine and reduced-dose consolidative radiotherapy, the overall survival rate at 3 years was 87% in patients who achieved a complete response (CR) to induction. Also, the median overall survival was not reached at 6 years[1] The CALGB 50202 trial investigated the use of HD-MTX with oral temozolomide and rituximab (MT-R) for induction, followed by etoposide and cytarabine (EA) for consolidation. 66% of patients achieved a complete response to induction therapy (CR), and the progression-free survival rate was 0.57 at two years[3] Similarly, the median overall survival was not reached at the 5-year follow-up.

Myeloablative therapy and autologous stem cell transplant are also options for consolidation. In one study, HD-MTX along with cytarabine, thiotepa, and rituximab for induction was followed by myeloablative therapy with high-dose carmustine and thiotepa with autologous stem cell transplant. The overall survival rate at 2 years was 87%. In a similar study, after an HD-MTX based induction regimen, conditioning therapy was achieved with thiotepa, busulfan, and cyclophosphamide followed by stem cell transplant. The overall survival rate at 2 years was 81%, and progression-free survival rate was 79%. At 10 years, the overall survival rate in a similar study was 35%, suggesting that this might be an effective consolidative option especially for younger patients[1] The CALGB 51101 was initiated based on the successes of the CALGB 50202 trial and is currently investigating consolidative therapy with etoposide and cytarabine versus myeloablative therapy with carmustine and thiotepa followed by stem cell transplant following, high-dose methotrexate, temozolomide and rituximab (MT-R) based induction.

Unfortunately, more than half of patients with CNS lymphoma experience a relapse, with an average survival of 2 months at that time.[9][1] It is not uncommon for relapses to happen up to 10 years after initial treatment, even though most are seen within 5 years. While the optimal salvage regimen remains investigational, additional HD-MTX, if previously sensitive, along with other central nervous system penetrants such as thiotepa, cytarabine, cytarabine liposome injection, etoposide, and ifosfamide have shown promising results.[3] Additionally, myeloablative therapy followed by stem cell transplant is a good option in younger patients. WBRT if not previously used, remains an effective salvage option with a median overall survival rate of 11 to 19 months.[1] Several new therapeutic agents such as lenalidomide, ibrutinib, buparlisib, nivolumab, pemetrexed, pomalidomide, temsirolimus, and pembrolizumab are currently being investigated.

For the treatment of intraocular lymphoma, one study recommended an HD-MTX and rituximab based induction, followed by consolidation with cytarabine and etoposide. Intraocular lymphoma also responds well to binocular external beam radiation. Intravitreal rituximab and MTX remains an effective option in unilateral disease. But, systemic chemotherapy is the reocmmendation if the disease is suspected elsewhere within the neuraxis.

Prophylaxis with HD-MTX can be considered for those patients with high-risk systemic non-Hodgkin’s lymphoma to prevent CNS dissemination. High-risk features in these patients include a high international prognostic index score and the presence of extranodal disease, particularly in the testes.[3]

Differential Diagnosis

The differential diagnosis of central nervous system lymphoma is broad. High-grade gliomas, meningioma, granulomatous and demyelinating diseases, as well as vasculitis, should all merit consideration. Metastatic disease from systemic malignancies as well as infections within the neuraxis can also present similarly and must be ruled out with a careful history and diagnostic work-up. Additionally, infectious etiologies such as cerebral toxoplasmosis must be considered possibilities in immunocompromised patients, especially those with AIDs.[8]

Toxicity and Side Effect Management

Up to 5% of patients develop nephropathy related to high-dose methotrexate use. Adequate hydration, urinary alkalinization, avoidance of penicillin, and other drugs that interact with methotrexate are ways to mitigate this toxicity. Recommendations are to observe a two-day gap between iodinated contrast use for imaging and high-dose methotrexate administration. Leucovorin rescue with escalated dosing strategies, as well as the use of the enzyme carboxypeptidase G2 to facilitate methotrexate clearance via the kidneys, are also effective options.[3]

Staging

Approximately 4% to 12% of patients originally thought to have primary CNS lymphoma is found to have systemic disease. MRI spine, CT chest, abdomen and pelvis, bone marrow biopsy, PET imaging, and testis ultrasound in select cases, can be done in the staging process.[1][3] PET imaging can be more sensitive for detecting systemic disease than conventional CT chest, abdomen and pelvis, and bone marrow biopsy can detect disease not evident on other imaging modalities in the staging process.[1] Baseline levels of LDH, HIV, as well as hepatitis B, and C serology are often done. Also, since 15 to 25% of patients with CNS lymphoma also have intraocular involvement, an ophthalmologic slit-lamp examination is standard. MRI brain with contrast along with CSF evaluation should also be obtained in patients diagnosed with intraocular lymphoma since 80% of these patients ultimately develop lymphoma in other areas of their central nervous system.[3] Optical coherence tomography and fluorescence angiography can also be options in the diagnosis and staging of intraocular lymphoma.

Prognosis

Overall survival for untreated primary CNS lymphoma is approximately 1.5 months.[1] Several variables are known to correlate with prognosis, including serum lactate dehydrogenase levels, Eastern Cooperative Oncology Group (ECOG) score greater than 1, age greater than 60, CSF protein level and the presence of lesions within deep brain structures that are difficult to access. While age has been a reproducible prognostic index in the past, newer studies have shown that the relationship between prognosis and age is treatment dependent.[3] Primary CNS lymphoma often has a more favorable response to chemotherapy and radiation when compared to other primary brain tumors, but the prognosis can be poor in those patients that relapse. While low-grade B cell lymphomas have a more favorable long-term outcome, T cell lymphomas and intravascular large B cell lymphomas are often very aggressive and poorly responsive to chemo-radiation therapy.[6] The use of high-dose methotrexate in CNS lymphomas has been reliably shown to improve prognosis.[3][1]

Complications

Several neuropsychological complications, such as gait impairments, memory losses, as well as incontinence, can arise in patients treated with WBRT. These most commonly occur in individuals older than 60 years.[3] Reports also exist of post-traumatic stress disorders in individuals post-treatment. The risk of developing second malignancy increases in long-term CNS lymphoma survivors, particularly in the younger age groups. Patients with secondary CNS lymphoma would be at an increased risk for radiation-associated cardiovascular disease if applying radiation to the chest. The use of anthracyclines such as doxorubicin has demonstrated cardiotoxicity, and the use of rituximab is associated with an increased risk of progressive multifocal leukoencephalopathy. In post-transplant CNS lymphoma patients, allograft failure is a risk, particularly if the immunosuppressant gets reduced or halted to reconstitute immune function.

Deterrence and Patient Education

Patients require education regarding their disease process as well as potential pitfalls to avoid while undergoing therapy. Methotrexate, when given in high doses, can precipitate in renal tubules as well as cause direct tubular injury. This risk is increased in volume-depleted states as well as with acidic urine. Adequate hydration is of paramount importance. Also, certain drugs such as NSAIDs, penicillins, probenecid, phenytoin, ciprofloxacin, proton-pump inhibitors, and levetiracetam interfere with methotrexate renal clearance, and so should be avoided when possible.

Enhancing Healthcare Team Outcomes

Successful treatment of central nervous system lymphomas requires a collaborative multidisciplinary team approach to enhance the patient’s quality of life before, during, and after treatment; this often includes a team of experts in various subspecialties such as:  

  • Medical oncologists
  • Neurologists
  • Neuroradiologists
  • Pain management specialists
  • Physical and occupational therapists
  • Psychiatrists
  • Neurosurgeons
  • Neuropathologists
  • Radiation oncologists
  • Ophthalmologist
  • Social workers
  • Spiritual care leaders
  • Oncology nurses
  • Palliative care specialists

In addition to those listed above, nursing and pharmacy will play crucial roles in the management of CNS lymphoma. Nursing will be administering the chemotherapy, which should have input from an oncology specialist pharmacist, who will verify agent selections and verify all dosing while checking against drug-drug interactions, many of which can later therapeutic results, as has been discussed. The nurse should be alert to adverse reactions, as well as noting therapeutic efficacy, reporting any concerns to the ordering physician. In this way, all these various disciplines can contribute to the collaborative interprofessional team approach to disease management to optimize outcomes. [Level V]

CNS lymphoma has a guarded prognosis; every treatment has major side effects which add to the morbidity. Even in patients who do respond to treatment, relapse is common. Because of the grim prognosis, a palliative team should have involvement early in the care of these patients. Comfort care and quality of life should not get sacrificed with exhaustive tests and procedures which do not change the prognosis.


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Cancer, Central Nervous System Lymphoma - Questions

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A 55-year-old male presents with new-onset worsening headache and left arm weakness over the past 2 months. He has a past medical history of primary biliary cirrhosis requiring a liver transplant a few years ago. Magnetic resonance imaging with gadolinium contrast shows a circumscribed solitary homogenously enhancing periventricular lesion within the right frontal lobe. The lesion is hypointense on T1 and hyperintense on T2 and diffusion-weighted imaging. Corresponding apparent diffusion coefficient values are low. Stereotactic biopsy shows malignant lymphocytes accumulating around blood vessels. His disease is confined to the central nervous system. Which of the following is the most common histological variant of this tumor?



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A 54-year-old African American male presents with progressive ataxia and left hemiparesis. He has a past medical history significant for focal segmental glomerulonephritis. Family history is notable for sarcoidosis in his mother as well as breast cancer in his sister. MRI brain shows a solitary homogenously enhancing lesion within the right internal capsule that is hyperintense to gray matter on T2 with restricted diffusion on diffusion-weighted imaging. Brain biopsy reveals a diffuse large B cell lymphoma. Which of the following is the next best step in management?



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Which of the following variants of primary central nervous system lymphoma do not manifest in both immunocompetent and immunocompromised patients?



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A 29-year-old male with HIV for the past 8 years complains of a 2-month history of visual changes. He has been having transient flashes together with a distortion of a portion of his left visual field. Routine electroencephalography (EEG) identifies a seizure focus within the right occipital lobe. Magnetic resonance imaging (MRI) shows a 3 cm right occipital lobe lesion that shows rim enhancement post-contrast. Cerebrospinal fluid polymerase chain reaction analysis is positive for Epstein-Barr virus. The patient is scheduled for a stereotactic biopsy. Which of the following is the most likely diagnosis?



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A 40-year-old male presents with worsening memory problems over the past few weeks. He has noticed mild right-sided lower extremity weakness along with increased lethargy. Further review of systems is positive for recent seizures. He has been HIV positive for 15 years and has never been on HAART. His last CD4 count was 44/mm3. An MRI shows multiple ring-enhancing lesions in the left frontal lobe and basal ganglia that are hypointense on T1 weighted sequences and hypointense to grey matter on T2. CSF PCR is negative for toxoplasma antigens but positive for EBV antigens, with cytology and flow cytometry pending. The lesions are hypermetabolic on thallium-201 SPECT imaging as well as on methionine PET imaging. What is the most likely diagnosis?



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A 43-year-old female presents with increasing blurred vision in her left eye for four weeks. A review of systems is positive for floaters in her left eye, decreased visual acuity, and headaches. She has a past medical history of idiopathic pulmonary fibrosis for which she underwent a lung transplant in her 30’s. Ophthalmologic slit-lamp examination reveals a widening of the optic nerve as well as vitreous debris. Pars plana vitrectomy with cytology shows atypical lymphoid cells along with many reactive lymphocytes. What is the next best step in the management of this patient?



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A 65-year-old male presents with worsening headaches, double vision, along with left facial numbness and tingling for the past 3 weeks. Further review of systems is positive for a right-sided hemiparesis and testicular swelling. He has a past medical history of non-Hodgkin’s lymphoma for which he is currently in remission after completing treatment 8 months ago. He was recently diagnosed with bronchogenic adenocarcinoma for which he is undergoing treatment. An unenhanced head CT shows a high-density mass. Which of the following is needed to obtain a definitive diagnosis?



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A 45-year-old male presents to the clinic complaining of progressive gait instability, paresthesias of his right upper extremity, and left-sided facial weakness for about 4 weeks. He has a past medical history of chronic bronchitis, HIV, congenital hydronephrosis of his right kidney, hepatitis C and Kaposi sarcoma. Further review of systems is positive for a productive cough and shortness of breath over the past few days. On examination, he is mildly tachypneic. A 3/5 weakness of his left facial musculature and right lower extremity is appreciated. The patient is given antibiotics and a 2-week follow up is scheduled. What is the next best step in the management of the patient?



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Cancer, Central Nervous System Lymphoma - References

References

Han CH,Batchelor TT, Diagnosis and management of primary central nervous system lymphoma. Cancer. 2017 Nov 15;     [PubMed]
Yang XL,Liu YB, Advances in Pathobiology of Primary Central Nervous System Lymphoma. Chinese medical journal. 2017 Aug 20;     [PubMed]
Wang CC,Carnevale J,Rubenstein JL, Progress in central nervous system lymphomas. British journal of haematology. 2014 Aug;     [PubMed]
Bathla G,Hegde A, Lymphomatous involvement of the central nervous system. Clinical radiology. 2016 Jun;     [PubMed]
Giannini C,Dogan A,Salomão DR, CNS lymphoma: a practical diagnostic approach. Journal of neuropathology and experimental neurology. 2014 Jun;     [PubMed]
Lukas RV,Stupp R,Gondi V,Raizer JJ, Primary Central Nervous System Lymphoma-PART 1: Epidemiology, Diagnosis, Staging, and Prognosis. Oncology (Williston Park, N.Y.). 2018 Jan 15;     [PubMed]
Rubenstein JL,Gupta NK,Mannis GN,Lamarre AK,Treseler P, How I treat CNS lymphomas. Blood. 2013 Oct 3;     [PubMed]
Chiavazza C,Pellerino A,Ferrio F,Cistaro A,Soffietti R,Rudà R, Primary CNS Lymphomas: Challenges in Diagnosis and Monitoring. BioMed research international. 2018;     [PubMed]
Grommes C,DeAngelis LM, Primary CNS Lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2017 Jul 20;     [PubMed]
Haldorsen IS,Espeland A,Larsson EM, Central nervous system lymphoma: characteristic findings on traditional and advanced imaging. AJNR. American journal of neuroradiology. 2011 Jun-Jul;     [PubMed]

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