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CASE REPORT
Year : 2019  |  Volume : 14  |  Issue : 2  |  Page : 86-89
 

Primary central nervous system Burkitt lymphoma in HIV positive pediatric patient: A rare case report


Department of Medical and Pediatric Oncology, Gujarat Cancer Research Institute, Ahmedabad, Gujarat, India

Date of Web Publication20-Aug-2019

Correspondence Address:
Dr. Asha S Anand
Department of Medical and Pediatric Oncology, Gujarat Cancer Research Institute, Ahmedabad, Gujarat.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpn.JPN_81_18

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   Abstract 

Burkitt lymphoma is a high-grade B-cell lymphoma with aggressive course of disease and primarily systemic nodal involvement. Primary Burkitt lymphoma with isolated central nervous system (CNS) involvement and that too in pediatric population has been rarely reported. Here, we present a case of a primary Burkitt lymphoma involving brain in an human immunodeficiency virus–positive pediatric patient who was on antiretroviral therapy. Currently, there are no established protocols or guidelines for management of primary CNS Burkitt lymphoma thus posing challenges in the management of such cases. Our patient was successfully treated by surgical resection followed by chemotherapy and radiotherapy.


Keywords: Burkitt lymphoma, chemotherapy, HIV, intracranial, pediatric, radiotherapy


How to cite this article:
Patel PA, Anand AS, Parikh SK, Patel AD, Kulkarni RS. Primary central nervous system Burkitt lymphoma in HIV positive pediatric patient: A rare case report. J Pediatr Neurosci 2019;14:86-9

How to cite this URL:
Patel PA, Anand AS, Parikh SK, Patel AD, Kulkarni RS. Primary central nervous system Burkitt lymphoma in HIV positive pediatric patient: A rare case report. J Pediatr Neurosci [serial online] 2019 [cited 2019 Sep 19];14:86-9. Available from: http://www.pediatricneurosciences.com/text.asp?2019/14/2/86/264749





   Introduction Top


Burkitt lymphoma is high-grade B-cell lymphoma of germinal center origin, and it has rarely been reported as a primary brain neoplasm. We present a case of a primary Burkitt lymphoma of the brain predominantly involving the temporal lobe in a human immunodeficiency virus (HIV) positive pediatric patient who was on antiretroviral therapy. Patient was primarily treated by surgical resection followed by chemotherapy and radiotherapy.


   Case Report Top


A 7-year-old boy, living with HIV since birth, presented with complaints of dimness of vision in left eye and headache for the last 2 weeks. He was investigated outside and his magnetic resonance imaging (MRI) of the brain revealed a middle cranial fossa mass measuring 79.3mm × 68.0mm × 58.9mm involving left fronto-parieto-temporal region with post-contrast enhancement, mass effect with compression, and buckling of the adjacent brain parenchyma, left basal ganglia, and upper brainstem with midline shift. Hence, the patient was transferred to neurosurgery department at our center for further investigation and management.

On examination, the patient was alert, conscious, and oriented, and all his vital signs were stable. He was found to have papilloedema in left eye. There was no focal neurological deficit. Blood tests including complete blood count with differential count, liver function and renal function, and uric acid were normal. Lactate dehydrogenase was 684 U/L. Serological test results for hepatitis B and hepatitis C were unremarkable. Lymphocyte subset analysis revealed normal absolute CD4 positive T-helper cells 659/µL. Differential cell count did not show any abnormal cells. In view of middle cranial fossa mass with mass effect and midline shift, patient underwent left fronto-temporo-parietal craniotomy and a gross total excision of the lesion was achieved with a curative intent. Frozen section showed malignant round cell tumor and possibility of non-Hodgkin lymphoma. On microscopic examination, a diffuse monotonous infiltrate of medium-sized cells, with a slight molding pattern was observed. The distinct starry-sky pattern caused by interspersed tingible-body macrophages was present. The cells showed round nuclei, with coarse chromatin and basophilic nucleoli, with a notable rim of basophilic cytoplasm [Figure 1]A. Karyorrhectic debris and mitotic figures were frequent. Immunohistochemical staining showed the tumor cells to be positive for CD10, CD20, CD79a, and Bcl-6. Tumor cells were negative for Bcl-2, CD2, CD99, CD 117, MUM1. MIB1 labeling index was 100% thus confirming the diagnosis of Burkitt lymphoma [Figure 1]B–F. Cerebrospinal fluid cytology examination did not reveal any abnormal cell. Computerized tomography scans of neck, chest, abdomen, and bone marrow biopsy did not show any signs of extracranial disease. Hence a final diagnosis of primary central nervous system (CNS) Burkitt lymphoma was made. His postoperative MRI brain revealed presence of 26mm ×17mm × 33mm residual lesion in left temporal lobe [Figure 2]A and [Figure 2]B. Postoperative course was uneventful. He was given five cycles of high-dose methotrexate (HDMTX) (3.5g/m2) in combination with intrathecal methotrexate, procarbazine, dexamethasone, and vincristine followed by whole-brain radiotherapy and two cycles of high-dose cytarabine as consolidation therapy (De Angelis protocol). Because of the lack of consensus for appropriate treatment regimen for pediatric primary CNS Burkitt lymphoma in the literature, we decided to choose this regimen by extrapolating from data available for primary CNS lymphoma (PCNSL) for adults. Interim 10-week MRI of brain showed a very good response to the chemotherapy with significant reduction in size as compared to initial postoperative scans. At the end of treatment and radiotherapy follow-up MRI scan showed postoperative gliotic changes without any evidence of tumor suggestive of complete remission. Patient is on regular follow-up and doing well till today (disease-free survival of 1 year) and serial MRI showed no abnormality.
Figure 1: (A and B) Postoperative T1 weighted post-contrast MRI of brain showing intensely homogenously enhancing well-circumscribed lobulated lesion in left medial temporal lobe suggestive of residual lesion. (C and D) Interval MRI after 10 weeks of multiagent chemotherapy showing significant interval reduction in size suggestive of significant improvement. (E and F) Post-completion of treatment MRI showing complete resolution of previously noted residual lesion

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Figure 2: (A) Hematoxylin and eosin stained ×40 histopathology showing cells with high N:C ratio with noncleaved round nuclei, coarse chromatin, and multiple distinct and scant cytoplasm. (B) BCL 6 positive. (C) CD20 positive. (D) CD10 positive. (E) MiB1 index 100%. (F) BCL 2 negative

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   Discussion Top


The most common cancers in children are leukemia (32%), brain tumors (18%), and lymphomas (11%).[1 PCNSL is a rare extranodal lymphoma confined to brain],[ leptomeninges],[ eyes],[ or spinal cord in the absence of systemic disease. It accounts for 2% of brain tumors.[2],[3] Overall, PCNSL accounts for 0.5%–2% of all primary brain tumors and 0.7%–0.8% of all lymphomas.[4] In PCNSL, most common subtype is diffuse large B-cell lymphoma (DLBCL), and primary CNS Burkitt lymphoma is very rare and only few cases have been reported in literature.[5],[6],[7] The exact incidence of pediatric PCNSL is unknown. The median age of PCNSL in adults is 65 years and 13 years in children with male predominance.[8] PCNSL is more common in immunodeficiency especially AIDS.[2],[9] As the number of CD4 cells drops significantly, the patient develops AIDS, opportunistic infections, and tumors such as cervical cancer, Kaposi’s sarcoma, and certain types of non-Hodgkin’s lymphoma and brain lymphoma.[2] PCNSL most commonly arise in cerebral hemisphere, basal ganglia, thalamus, and corpus callosum.[4] Dubuisson et al.[9] reported a series where the vast majority of PCNSL s were supratentorial; approximately 60% were deeply located; and 25% of patients presented multiple lesions.[9] In a multicenter study of PCNSL in children, the most common subtype was DLBCL (69%), followed by anaplastic large T-cell lymphoma (17%), lymphoblastic lymphoma (7%), and Burkitt lymphoma (7%).[3] Primary CNS Burkitt type lymphoma (PCNSBL) as the first manifestation of AIDS occurs very rarely and has not been reported frequently.

No established, efficacy-proven treatment exists for pediatric PCNSL. The current treatment recommendations place chemotherapy as the first line of treatment.[10] In adult patients, the backbone of the treatment in PCNSL is CNS irradiation and chemotherapy with HDMTX.[10] Systemic Burkitt lymphoma is treated with intensive short-course chemotherapy and intrathecal injection regimen, and for PCNSL including PCNSBL HDMTX-based chemotherapy regimen has been commonly used, which improves median disease-free and overall survival of up to 30–40 months from the survival of 12–18 months usually seen after using cranial radiotherapy (CRT) alone.[11] A pediatric series of PCNSL reported that immunocompetent and immunodeficient children with PCNSL may be cured with chemotherapy alone without cranial radiotherapy.[2] So the role and the timing of CRT are yet to be defined.

To date, very few cases of PCNSBL in children are reported in literature. Review of literature showed combination chemotherapy with backbone of HDMTX as mainstay of treatment for PCNSBL.[5],[6],[7] However, the best regimen is still under investigation.

A study by Ferreri et al. reported that in PCNSL patients aged 75 years and younger, the addition of high-dose cytarabine to HDMTX improves outcome with acceptable toxicity when compared with HDMTX alone.[12] Our patient was treated with De Angelis regimen, which includes HDMTX, procarbazine, dexamethasone, and vincristine along with intrathecal chemotherapy followed by cranial radiation and high-dose cytarabine and showed complete response to treatment.


   Conclusion Top


Pediatric primary CNS Burkitt lymphoma is very rare but should be included in the list of differential diagnosis of primary intracranial-space-occupying lesions especially in immunodeficient children so as to avoid inadvertent surgical resection. PCNSBL in pediatric patients can be treated successfully with protocols designed for adult PCNSL. However, the treatment of pediatric PCNSL Burkitt type with immunodeficiency or other severe underlying diseases remains challenging. As brain tumors are the most common solid malignancies in children, it can be easily misdiagnosed and so early suspicion and multidisciplinary care is the key for best outcomes. In view of rarity, multinational cooperative trials are warranted to establish standardized protocols in children.

Ethical approval

This article does not contain any studies with animals performed by any of the authors. Informed consent was obtained from the patient for publication of article.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Kaatsch P, Sikora E, Pawelec G”Epidemiology of childhood cancer”.Cancer treatment reviews. 2010;36:277-85.  Back to cited text no. 1
    
2.
Abla O, Sandlund JT, Sung L, et al. A case series of pediatric primary central nervous system lymphoma-favourable outcome without cranial irradiation. Pediatr Blood Cancer. 2006;47:880-5.  Back to cited text no. 2
    
3.
Abla O, Weitzman S, Blay JY, O’Neill BP, Abrey LE, Neuwelt E, et al. Primary CNS lymphoma in children and adolescents: a descriptive analysis from the International Primary CNS Lymphoma Collaborative Group (IPCG). Clin Cancer Res. 2011;17:346-52.  Back to cited text no. 3
    
4.
Jiang M, Zhu J, Guan Y, Zou L Primary central nervous system Burkitt lymphoma with non-immunoglobulin heavy chain translocation in right ventricle: Case Report. Pediatric Hematology and Oncology. 2011;28:454-8.  Back to cited text no. 4
    
5.
Silfen ME, Garvin JH, Jr, Hays AP, et al. Primary central nervous system lymphoma in childhood presenting as progressive panhypopituitarism. J Pediatr Hematol Oncol. 2001;23:130-3.  Back to cited text no. 5
    
6.
Kobayashi H, Sano T, Ii K, et al. Primary Burkitt-type lymphoma of the central nervous system. ActaNeuropathol (Berl). 1984;64:12-4.  Back to cited text no. 6
    
7.
Spath-Schwalbe E, Genvresse I, Stein H, et al. Primary cerebral highly-malignant B-cell lymphoma of the Burkitt type. Dtsch Med Wochenschr. 1999;124:451-5.  Back to cited text no. 7
    
8.
Abla O, Weitzman S Primary central nervous system lymphoma in children. Neurosurg Focus 2006;21:e8.  Back to cited text no. 8
    
9.
Dubuisson A, Kaschten B, Lénelle J, et al. Primary central nervous system lymphoma: report of 32 cases and review of the literature. Clin Neurol Neurosurg 2004;107:55-63.  Back to cited text no. 9
    
10.
De Angelis LM Primary central nervous system lymphoma.Neurol 1999;12:687-91  Back to cited text no. 10
    
11.
Abrey LE, Yahalom J, DeAngelis LM , et al. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000;18:3144-150.  Back to cited text no. 11
    
12.
Ferreri AJ, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, et al. High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomized phase 2 trial. Lancet 2009;374:1512-20.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2]



 

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    Abstract
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