Atypical Case of Burkitt’s Lymphoma/Leukemia Presenting with Cranial Nerve Palsy

Abbreviations: BL: Burkitt’s Lymphoma; CBC: Complete Blood Count; HU: Hydroxyurea; EBV: Epstein Barr virus; MI: Myocardial Infarction; CNS: Central Nervous System; CR: Cure EFS: Event-Free Survival; LDH: Lactate Dehydrogenase Enzyme; CD: Cluster Differentiating Factor; ALL: Acute Lymphocytic Leukemia; DLBL: Diffuse Large B Cell Lymphoma; Nasogastric; GI: Gastrointestinal; Highly Antiretroviral


Introduction
Burkitt's lymphoma is one of the most aggressive non-Hodgkin B cell lymphomas. Usual presentation in sporadic Burkitt's lymphoma which is the prevalent form in the USA is abdominal symptoms 30-38% and CNS involvement in 13-17% cases [1,2]. The patient's first presentation with leptomeningeal involvement is rare and carries a poor prognosis if left untreated due to comorbidites [3].

Case Description
A 70-year-old male presented with complaints of headache and blurry vision for 3 days. He was seen and evaluated for toothache at the dentist's office and was given amoxicillin/clavulanic acid one week ago. After the intake of the first dose, he started experiencing blurry vision. Besides that, he noticed petechiae started appearing on his lower extremities. He reported an episode of nosebleed lasting for 12 hrs. a few weeks back. A review of the system was negative for weight loss and positive for fatigue. Vitals signs were stable. Physical exam revealed distended belly with splenomegaly.
CBC was significant for WBC count of 47 k with a peripheral smear showing 70% blasts. Other significant labs included Hgb 9 mg/dl, uric acid 19, platelets 11k. The patient was admitted for workup of leukemia/ lymphoma with blast crisis and tumor lysis syndrome.
He was initially treated with Hydroxyurea (HU). Over the next 2 days, his leukocytosis persisted for which HU dose was doubled. His symptoms of headache, nausea and blurry vision continue to get worse. CT abdomen without contrast showed splenomegaly but no evidence of lymphadenopathy. CT scan head without contrast did not show any acute intracranial abnormality.
Ophthalmological evaluation revealed left VI nerve palsy and suggested left eye patch application. Leukemia/lymphoma with meningeal involvement does present with cranial nerve palsy. Lumbar puncture could not be performed due to low platelets. As part of the leukemia workup, flow cytometry of peripheral smear was done, and bone biopsy performed. Seven hours after the bone biopsy was performed under local anesthesia, the patient's clinical condition got deteriorated rapidly. He was transferred to ICU for tachypnea and altered mental status. The patient was intubated and started on the vasopressor's support. He was started on broad-spectrum antibiotics. Due to low platelets, bleeding was observed from the NG tube and he was started on proton pump inhibitor. The patient was transfused cryotherapy, platelets, packed His flow cytometry and bone biopsy revealed Burkitt's lymphoma.
Given old age, a recent history of MI, ventilator support and unable to tolerate the aggressive chemotherapy, the decision was made regarding comfort care. The patient was terminally extubated on the 7th day of admission.

Discussion
Burkitt's lymphoma is one of the most aggressive tumors with a tumor doubling time of 25 hours. It has 3 subtypes based on epidemiology and clinical presentation. Of note, the histologic pattern of all the 3 subtypes remains the same.

Endemic Variant
Found in the equatorial distribution of African countries, strongly associated with EBV virus infection. High malaria prevalence in these countries leads to increase cell turnover making them more prone to genetic instability. Usually seen in African children 4-7 years old, with a male: female ratio of 2:1. It involves the bones of the jaw and other facial bones, as well as kidneys, gastrointestinal tract, ovaries, breast, and other extranodal sites. The incidence is estimated to be 50 times higher than in the U.S. EBV is found in nearly all cases.

Sporadic
It includes those cases occurring with no specific geographic or climatic association. It accounts for 1% -2% of lymphoma in adults and up to 40% of lymphoma in children in the U.S. and western Europe.

Immunodeficiency Associated BL
Not associated with low CD 4 counts of less than 200/cubic mm. BL accounts for 30-40% of non-Hodgkin's lymphomas in HIV patients. Before HAART, the incidence was 1000 times more com- Immunodeficiency associated BL is seen after prolong transplant interval, approx. 5 yrs. per one case series, most of the pa-tients were solid organ transplant recipients, others were stem cell transplant. EBV was also common in this subset of patients.
In the USA and Europe, the sporadic variant is prevalent with an average incidence of 3 cases per 100 million population, accounts for 1-2% of all lymphoma with male to female ratio of 3:1. and a proliferative fraction> 95% as per WHO classification [6].  shows starry sky pattern with empty spaces surrounding macrophages due to increase phagocytosis of the abnormal leukemia cells. C.
anti-c-my stain heavy staining pattern of the leukemic cells. D.
CD45, CD20,CD10,Pax5 + apies that have not been tested but could be useful include those targeted against the c-myc gene, DNA methyltransferase inhibitors, proteasome inhibitors, and cyclin-dependent kinase inhibitors. Patients presenting with the leukemic disease as in our case, previously classified as ALL, L3 type. traditional therapies used to treat lymphoblastic leukemia worked poorly. Newer chemotherapeutic regimens are associated with a better outcome but that too comes at the expense of serious toxicities. Our case is unique due to the fact that this patient did not have any abdominal presentation. Even imaging such a CT scan abdomen did not reveal any lymphadenopathy. His MRI brain did not suggest any leptomeningeal involvement, but his cranial nerve VI palsy highly supported the brain involvement. Due to advance age, high bulk of disease, several co-morbid conditions e.g. MI, acute renal failure, acute respiratory failure, and ventilator dependency, we did not proceed with the chemotherapy options. Despite the fact that even with CNS involvement there has been successful remission achieved, in this unique case, the risk of chemotoxicity outweighs the benefits of chemotherapy treatment.

Conclusion
Burkitt's lymphoma in old age with CNS involvement is a rare presentation with very poor prognosis and non-promising outcomes without intervention.