CASE ILLUSTRATIONMEDICINA 2018, Volume 49, Number 1: 59-62

P-ISSN.2540-8313, E-ISSN.2540-8321

59

CrossMark

ABSTRACT

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal lymphoma found within brain, leptomeningens, eyes, or spinal cord, without any lymphoma in other site. Primary central nervous system lymphoma represents 1-6% of intracranial tumors and 1-2% of extranodal lymphoma. A 45-year-old man complained of left side headache and weakness of right-side body since 1.5 months ago. The contrast computed tomography scan revealed solid mass sized 2.4 x 2 cm in left parietal lobe, suspected of primary brain tumor (glioblastoma multiforme or

high-grade astrocytoma). Tumor resection was performed and the result is non-Hodgkin’s lymphoma. There were no other systemic manifestations. The patient had received 20 times whole brain radiotherapy and physiotherapy. Three months after operation, the patient’s condition improved although he still complained of right hemiparesis without other problems. In conclusion, PCNSL is a rare disease in immunocompetent patient. Brain tumor resection and radiotherapy can improve patient’s quality of life and activity of daily living.

Keywords: primary brain non-Hodgkin’s lymphoma, brain tumor, treatmentCite This Article: Irawan, H., Maliawan, S. 2018. Primary brain non-hodgkin’s lymphoma: a case report in sanglah general hospital denpasar. Medicina 49(1): 59-62. DOI:10.15562/medi.v49i1.264

ABSTRAK

Limfoma sistem saraf pusat primer adalah bentuk yang jarang dari limfoma ekstranodal seperti di dalam otak, leptomeningens, mata, atau sumsum tulang belakang, tanpa limfoma di tempat lainnya. Limfoma sistem saraf pusat primer menyusun sekitar 1-6% dari tumor intrakranial dan 1-2% dari limfoma ekstranodal. Seorang pria 45 tahun dengan mengeluh sakit kepala sisi kiri dan kelemahan tubuh sisi kanan sejak 1,5 bulan lalu. Computed tomography scan kontras menunjukkan massa solid berukuran 2,4 x 2 cm di lobus parietal kiri, kemungkinan tumor otak primer

(glioblastoma atau astrositoma derajat tinggi). Dilakukan reseksi tumor pada pasien dan hasilnya adalah limfoma non-Hodgkin. Tidak ada manifestasi sistemik lain. Pasien telah menerima 20 kali radioterapi seluruh otak dan fisioterapi. Setelah 3 bulan operasi, kondisi pasien membaik dan masih mengeluh hemiparesis kanan tanpa masalah lain. Jadi, limfoma sistem saraf pusat primer adalah penyakit langka pada pasien imunokompeten. Reseksi tumor otak dan radioterapi dapat meningkatkan kualitas hidup pasien dan aktivitas hidup sehari-hari.

Kata kunci: limfoma non-Hodgkin otak primer, tumor otak, pengobatanCite Pasal Ini: Irawan, H., Maliawan, S. 2018. Primary brain non-hodgkin’s lymphoma: a case report in sanglah general hospital denpasar. Medicina 49(1): 59-62. DOI:10.15562/medi.v49i1.264

Primary brain non-hodgkin’s lymphoma: a case report in sanglah general hospital denpasar

Hendry Irawan,1 Sri Maliawan2

INTRODUCTION

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal lymphoma found within brain, leptomeningens, eyes, or spinal cord, without any lymphoma in other site.1-3 Primary central nervous system lymphoma represents 1-6% of intracranial tumors and 1-2% of extranodal lymphoma.4 The major predispos-ing factors are patient with congenital or acquired immunodeficiencies, such as acquired immunode-ficiency syndrome (AIDS), autoimmune diseases, and after organ transplantation.1-4 However, the incidence in immunocompetent patient is

increasing due to improved investigative modalities (stereotactic brain biopsies of deep-seated lesions), greater clinical and neuropathological awareness, and widespread availability of immunohistochem-istry.5 The disease is also rare in Sanglah General Hospital Denpasar and this case report is a primary brain non-Hodgkin’s lymphoma.

CASE ILLUSTRASION

A fully alert 45-year-old man complained of throbbing headache primarily of left side since 1.5 months ago. He also presented a gradual weak-ness of right-side body since 1.5 months ago. The

1Department of Surgery and 2Neurosurgery Udayana University Medical School / Sanglah General Hospital Denpasar Bali

*Correspondence to:

Diterima: 2018-01-01 Disetujui: 2018-01-25

Volume No.: 49

Issue: 1

First page No.: 59

P-ISSN.2540-8313

E-ISSN.2540-8321

Doi: http://dx.doi.org/10.15562/medicina.v49i2.264

CASE ILLUSTRATION

60 Medicina 2018; 49(1): 59-62 | doi: 10.15562/Medicina.v49i2.264

CASE ILLUSTRATION

pain decreased after taking paracetamol. Patient had a shuffling gait, blurred vision, vomiting episodes, facial asymmetry, and unclear voice, which coin-cided with weakness of right-side body. There was no history of trauma, prolonged or bloody cough, hypertension, diabetes, heart disease, immune problems, and other chronic diseases. He also expe-rienced loss of appetite.

His vital signs and physical examinations were normal. Neurological examinations revealed supra-nuclear right facial nerve palsy, supranuclear right hypoglossal nerve palsy, right spastic hemiparesis with muscle power of right limbs was 4, and there were neither meningeal signs nor pathological reflexes.

Blood examinations showed leukocytosis, hypo-albuminemia, hyponatremia, and non-reactive on toxoplasma IgG and IgM. Chest x-ray and abdomi-nal ultrasound revealed normal result. Figure 1, the non-contrast and contrast multi sliced computed tomography (CT) scan revealed solid mass, slight hyperdense (36 Hounsfield units), clear margin, sized 2.4 x 2 cm in left parietal lobe, rim contrast enhancement, edema around the mass, and 0.8 cm right midline shift. The result pointed towards primary brain tumor (glioblastoma multiforme or high-grade astrocytoma).

We performed brain tumor resection and anatomic pathology examination. The pathological examinations were brain parenchyma with diffuse tumor mass and perivascular infiltration, tumor mass contained anaplastic lymphoid cells prolif-eration, dominant large cells with size 3-4 times greater than mature lymphocyte, narrow cytoplasm

with ovoid round core, rough granular chromatin, mitotic index 29/10 HPF (high-power field), apop-totic bodies, and necrotic tissue, as well as reactive glial cells. The final pathology was morphologically appropriate for non-Hodgkin’s lymphoma, diffuse large cell, and intermediate grade.

There was no other systemic manifestation of the disease through physical examinations, chest x-ray, and abdominal ultrasonography. Figure 2, the non contrast and contrast multi sliced CT scan one month after operation revealed solid mass, hetero-geneous density, unclear margin, irregular edge, edema around the mass, heterogeneous contrast enhancement, and 0.8 cm right midline shift. Thus, it was clear there was residual mass post operation. The patient received 20 times whole brain radio-therapy and physiotherapy.

Figure 3, three months after operation, the patient’s condition improved although he still complained of right hemiparesis without other problems. Current treatment was symptomatic drug and vitamins B1, B6, and B12. The patient refused chemotherapy.

DISCUSSION

Primary brain non-Hodgkin’s lymphoma is a rare form of extranodal lymphoma, which represents 1-6% of intracranial tumors and 1-2% of extran-odal lymphoma.1-4 Previously, PCNSL was regarded as the tumor of immunodeficient individuals, such as individuals infected with human immunodefi-ciency virus (HIV). However, after the introduction of highly active antiretroviral therapy into clinical practice and close monitoring with heightened awareness in these risk groups, the incidence of PCNSL decreased substantially in these patients.2 Recently, frequency of PCNSL is much higher in immunocompetent individuals due to improved investigative modalities (stereotactic brain biop-sies of deep-seated lesions), greater clinical and neuropatological awareness, and widespread avail-ability of immunohistochemistry.5

Patient with PCNSL rarely present with the symptoms associated with other non-Hodgkin’s lymphomas which include night sweats, fever, and weight loss.2,6 The clinical presentation of PCNSL patients includes 70% focal neurological deficits, 43% neuropsychiatric symptoms, 33% increased intracranial pressure, 14% seizures, and 4% ocular symptoms.6 Aki H, et al found the major symptoms were headache (30.7%) and paresthesia or para-plegia (23%). This may be due to the majority of parietal lobe involvement (28.2%).2 In this case the patient had throbbing headache, particularly on the left side, and weakness of right-side body, shuffling

Figure 1 CT scan before operation. (A, B, C) Non contrast scan. (D,  E,  F)  Contrast scan, note the single mass with rim contrast enhancement in left parietal lobe (F)

61Medicina 2018; 49(1): 59-62 | doi: 10.15562/Medicina.v49i2.264

CASE ILLUSTRATION

gait, blurred vision, vomiting episodes, facial asym-metry, and unclear voice. These symptoms resem-bled ischemic stroke however they developed progressively from first onset of attack.

Computed tomography scans of PCNSL are potentially associated with a large spectrum of radiological presentations, such as other neoplasms (meningiomas, malignant gliomas, and brain metastasis) or non-neoplastic disease (multiple sclerosis, stroke, cerebral toxoplasmosis, and pyogenic abscess).7,8 Typical CT scan feature of PCNSL are involvement brain parenchyma,

location in periventricular and superficial brain regions, isodense or hypodense lesions with marked contrast enhancement, and the enhancement pattern of non-HIV patients are 90% homogenous contrast enhancement and 0-13% ring contrast enhancement.7

The PCNSL is one of the most sensitive tumors with large variety of treatments. These include radiotherapy, chemotherapy, and combined-mo-dality therapy.8 The surgery is restricted to diagnostic biopsy. Whole brain radiotherapy is recommended based of the microscopically diffuse nature of PCNSL.2 Radiotherapy provides complete radiographic and clinical response from 60-90%.8,9 Although a high rate of response, radiotherapy alone provides limited survival benefit with median survival time 10-18 months, a 5 year survival rate <5%, and 90% recur within one year.2,8,9

High dose methotrexate (MTX), given at doses above 3-5 g/m2 in intervals 2-3 weeks, is the most active drug for PCNSL.9 Methotrexate is currently the mainstay of the treatment, but complete radio-graphic response with chemotherapy alone range from 30-100%.8 Thiel E, et al found median overall survival was 37.1 months in MTX chemotherapy alone and 32.4 months in MTX chemotherapy and whole brain radiotherapy.9

Combined-modality therapy (chemotherapy and radiotherapy) has achieved high response rates.8 High dose MTX based chemotherapy and radiotherapy results in longer survival time than radiotherapy alone with median survival time 2-4 years and 5 year survival rate 20-40%.2 Standard chemotherapy for systemic lymphoma such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP regimen) and radiotherapy do not result in longer survival than radiotherapy alone.2 The combined-modality therapy induced high response rates and associated with intolera-ble long term neurotoxicity, especially in elderly patient.9 So the combination therapy is more indi-cated in young patients.8

Whole brain radiotherapy, high dose MTX chemotherapy, and combination of treatment can lead to delayed neurotoxicity that occur after 3  months of treatment.2 It is characterized by ataxia, attention deficit, cognitive impairment, incontinence, and dementia.2,8 This complication occurs in up to 30% and often happens in patients aged more than 60-year-old. This can happen after 13.2  months after treatment.8 Thiel E, et  al found neurotoxicity was more common in patients receiv-ing combined therapy (49% by clinical assessment and 71% by neuroradiology) than in those who only received chemotherapy (26% by clinical assessment and 46% by neuroradiology).9

Figure 2 CT scan one month after operation. (A, B) Non contrast scan. (C, D) Contrast scan, residual mass with contrast enhancement

Figure 3 Clinical feature one month after surgery

62 Medicina 2018; 49(1): 59-62 | doi: 10.15562/Medicina.v49i2.264

CASE ILLUSTRATION

SUMMARY

Primary brain non-Hodgkin’s lymphoma is a rare disease in immunocompetent patient and the prognosis has improved with appropriate treat-ment. This can lead to prolonged remission and the patient can recover and continue daily activities. Future treatment should improve the efficacy while minimizing the risk of neurotoxicity. Brain tumor resection and radiotherapy in this case can improve patient’s quality of life and activity of daily living.

REFERENCES1. Pasricha S, Gupta A, Gawande J, Trivedi P, Patel D. Primary

central nervous system lymphoma: A study of clinico-pathological features and trend in western India. Indian Journal of Cancer. 2011;48:199-203.

2. Aki H, Uzunaslan D, Saygin C, Batur S, Tuzuner N, Kafadar  A, et  al. Primary central nervous system lym-phoma in immunocompetent individuals: a single center experience. Int J Clin Exp Pathol. 2013;6:1068-75.

3. Sierra del Rio M, Rousseau A, Soussain C, Ricard D, Hoang-Xuan K. Primary CNS Lymphoma in Immunocompetent Patients. Oncologist. 2009;14:526-39

4. Guinto G, Félix I, Aréchiga N, Arteaga1 V, Kovacs K. Primary central nervous system lymphomas in immuno-competent patients. Histol Histopathol. 2004;19:963-72.

5. Paul TR, Challa S, Tandon A, Panigrahi MK, Purohit AK. Primary central nervous system lymphomas: Indian expe-rience, and review of literature. Indian Journal of Cancer. 2008;45:112-8.

6. Slaviero F, Frighetto L, Casali JJ, Santos MN, Vanzin  JR, AzambujaJr ND. Primary Central Nervous System Lymphoma in an Immunocompetent Host. Arq Neuropsiquiatr. 2008;66:542-4.

7. Haldorsen IS, Espeland A, Larsson EM. Central Nervous System Lymphoma: Characteristic Findings on Traditional and Advanced Imaging. Am J Neuroradiol. 2011;32:984-92.

8. Sierra del Rio M, Rousseau A, Soussin C, Richard D, Hoang-Xuan K. Primary CNS Lymphoma in Immunocompetent Patients. Oncologist. 2009;14:526-39.

9. Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, et al. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): A phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010;11:1036-47.

This work is licensed under a Creative Commons Attribution