Non-Hodgkin\u27s lymphoma of the brainstem is a rare entity. Central Neurogenic Hyperventilation (CNH), an associated manifestation of this disease, is an even rarer event. We report a case of an immunocompetent individual who presented to us with tachypnea and facial nerve palsy. Neuroimaging showed a Cerebellopontine angle tumour which on histopathology showed feature consistent with a Non-Hodgkin\u27s B-Cell Lymphoma. The patient went on to develop severe respiratory alkalosis with findings consistent with CNH. Chemotherapy with Methotrexate was started and high dose Dexamethasone was added to the regimen a month later. Radiologically, the tumour size decreased by 50% but the patient\u27s clinical condition deteriorated. He eventually expired due to cardiopulmonary arrest. Some common clinical presentations of this disease and various diagnostic modalities and treatment options available to such patients are discussed

Ali, Rushna

Enam, S. Ather

eCommons@AKU

eCommons@AKUSection of Neurosurgery Department of SurgerySeptember 2011B-cell lymphoma of the brainstem with centralneurogenic hyperventilationS. Ather EnamAga Khan University, ather.enam@aku.eduRushna AliAga Khan UniversityFollow this and additional works at: http://ecommons.aku.edu/pakistan_fhs_mc_surg_neurosurgPart of the Surgery CommonsRecommended CitationEnam, S., Ali, R. (2011). B-cell lymphoma of the brainstem with central neurogenic hyperventilation. Journal of the Pakistan MedicalAssociation, 61(9), 925-7.Available at: http://ecommons.aku.edu/pakistan_fhs_mc_surg_neurosurg/6925 J Pak Med AssocCase ReportB-Cell Lymphoma of the Brainstem with Central Neurogenic HyperventilationSyed Ather Enam,1 Rushna Ali2Section of Neurosurgery,1 Medical Student,2 Aga Khan University Hospital, Karachi.AbstractNon-Hodgkin's lymphoma of the brainstem is a rareentity. Central Neurogenic Hyperventilation (CNH), anassociated manifestation of this disease, is an even rarerevent. We report a case of an immunocompetent individualwho presented to us with tachypnea and facial nerve palsy.Neuroimaging showed a Cerebellopontine angle tumourwhich on histopathology showed feature consistent with aNon-Hodgkin's B-Cell Lymphoma. The patient went on todevelop severe respiratory alkalosis with findings consistentwith CNH. Chemotherapy with Methotrexate was started andhigh dose Dexamethasone was added to the regimen a monthlater. Radiologically, the tumour size decreased by 50% butthe patient's clinical condition deteriorated. He eventuallyexpired due to cardiopulmonary arrest. Some commonclinical presentations of this disease and various diagnosticmodalities and treatment options available to such patientsare discussed.Keywords: Brainstem, Central NeurogenicHyperventilation, Lymphoma.IntroductionPrimary CNS lymphoma (PCNSL) is a rare form ofextra-nodal non-Hodgkin's lymphoma, accounting for 4% ofall primary brain tumours. It affects the brain, leptomeninges,spinal cord and the eyes. It remains confined to CNS inmajority of the cases.1 Localization primarily in the brainstemoccurs in 3% of PCNSL and most are T-Cell in origin.2 Theonly established risk factor is congenital or acquiredimmunodeficiency. Only 1.9-6% of patients afflicted withAIDS develop PCNSL.2 In the past few years, there has been athreefold increase in the incidence of PCNSL inimmunocompetent individuals. Tumour induced CNH in anawake patient is a rare manifestation of this disease.3 To date,only a few cases have been reported. We report a case ofPrimary Brainstem B-cell Lymphoma in an immunocompetentindividual who eventually developed CNH.Case ReportA 47 year old man, known case of ChronicObstructive Pulmonary Disease and Hypertension waspresented to the ER, with a history of shortness of breath,fever and headache for 3 days. He also developed recurrentleft-sided facial weakness which had started 2 months earlier.There was no other significant past history be it medical,surgical, drug or family. On general physical examination hewas tachypnoeic with a respiratory rate of 47 breaths/minute.He was otherwise vitally stable. Cardiovascular,genitourinary, gastrointestinal and immunologic reviewswere all negative. On chest examination diffuse bilateralcrackles were present. On facial nerve examination there wasleft sided facial drooping with flattening of naso-labial fold,weak gag and inability to close the left eye. Motorexamination showed left-sided motor paresis grade 4/5 inboth upper and lower limbs. Rest of the neurologicalexamination was unremarkable. His Karnofsky performancescore was 50.A CT scan brain was done one month prior toadmission which showed a hypodense irregular lesion in leftcerebellum measuring 2.5x1.8cm. It was suspected to be anintrinsic cerebellar or cerebello-pontine (CP) angle tumour.Further treatment and investigations were deferred by thepatient and his family. The patient was admitted with theprovisional diagnosis of pneumonia with left sided CPtumour and empirically started on Anti-Tuberculous therapy,antibiotics and hydrocortisone.Initial Complete Blood Count (CBC) and SerumElectrolytes results revealed no abnormality. TSH, Creatinineand Liver function tests were normal. HIV, Hepatitis B andHepatitis C serology were all nonreactive. Initial CSFanalysis did not reveal any abnormalities.A contrast enhanced Magnetic Resonance Imaging(MRI) scan of the brain showed a mass lesion measuring3.2x2.5x2.5cm in left cerebellar peduncle extending into themedulla and midbrain. It showed homogenous enhancementwith gadolinium and diffuse meningeal enhancement. Therewere no signs of hydrocephalus, areas of recent infarction orintracranial haemorrhage.A sub-occipital craniotomy was performed to obtain asample for biopsy. Histopathology showed a neoplastic lesionwith cells predominantly arranged around blood vesselsexhibiting cellular atypia, nuclear pleomorphism,hyperchromasia and increased mitotic activity. The GFAP,LCA, PAN-B and Ki-67 tumour markers were positive.These findings were suggestive of a High Grade Non-Hodgkin's B-cell lymphoma of large cell type. Smears forFungi and Acid Fast Bacilli were negative. Bone MarrowAspirate and Trephine showed no evidence of lymphomatousinfiltration of the bone marrow. CT Chest, Abdomen andPelvis were performed to check for organ metastasis andlymphadenopathy, all of which revealed no disease.The ATT was discontinued and combinationchemotherapy was begun. The patient received ATT only fora period of 10 days, which is too short a time to assess itsefficacy. The patient however showed no clinicalimprovement with it. Chemotherapy with Methotrexate2.5g/m2 alternating with Vincristine was begun. A month laterhigh dose Dexamethasone was added to the regimen. Duringhis hospital stay the patient had multiple progressivelyworsening episodes of hyperventilation which persistedduring sleep. He developed respiratory alkalosis with ABGsshowing pH, 7.54; pCO2 30.2mmHg and pO2 147.6mmHg.No metabolic cause for his tachypnoea could be discernedand his Chest Radiography, ECG and Echocardiography werenormal. His tachypnoea persisted with repeat ABGs showingpH of 7.51, pCO2, 25.6mmHg and pO2 92mmHg. Thefindings suggested the diagnosis of Central NeurogenicHyperventilation (CNH) due to brainstem infiltration.Midazolam resulted in immediate reduction of respiratoryrate but it's effect was transient and repeated administrationwas necessary. He subsequently developed generalized tonic-clonic seizures and septic shock despite being on multipleantibiotics and antiepileptic medication. He had to be shiftedto the intensive care unit where he was mechanicallyventilated. A repeat MRI showed a 50% reduction in size oflymphoma after receiving 4 cycles of chemotherapy.However, the patient's clinical condition progressivelydeteriorated. Despite intensive investigations we could notdiscern a plausible cause for this disparity between a goodradiological response but worsening clinical condition. Hisstatus was discussed with his family and he was declared DoNot Resuscitate (DNR). The decision not to institute anyform of radiotherapy was based on the patients weakenedstate and his personal as well as his family's wishes. Nobenefit of an alternative therapy could be foreseen since thetumour had significantly decreased in size and seemed to bevigorously chemo-sensitive. He went into cardiopulmonaryarrest after 2 months of receiving intensive in-patient care andexpired.DiscussionIn immunocompetent patients PCNSL typicallyoccurs during the 6th and the 7th decade of life and presentswith focal findings. The data of 378 PCNSL patients wascollected by The International Extranodal Lymphoma studygroup. It revealed that the frontal lobe was involved in 44%,parietal lobe in 13%, temporal lobe in 14%, occipital lobe in6%, basal ganglia in 28%, brainstem in 6%, cerebellum in6%.4 Approximately 90% of PCNSLs are Diffuse large B-Cell Lymphomas; the remaining 10% are poorlycharacterized by low-grade lymphomas, Burkitt's lymphomasand T-Cell lymphomas.5 However, the brainstem shows apenchant for T-Cell lymphomas.3 The median age atdiagnosis is 53-57 years with a male-to-female ratio of 1.2 to1.7:1.5In a study that focused on the clinical presentations of248 immunocompetent patients with PCNSL. The authorsreported that 70% had focal neurological deficits, 43% hadneuropsychiatric symptoms, 33% had raised intracranialpressure, 14% had seizures and 4% had ocular symptoms.6Our patient had the most common clinical presentation offocal neurological deficit in the form of facial nerve palsy.Lumbar puncture with CSF sampling should beperformed at the time of initial assessment in patients withsuspected PCNSL. In a study of 96 patients with newlydiagnosed PCNSL, the initial CSF cytological studies werepositive in only 15%.7 However, in another study two-thirdsof PCNSL patients who developed positive CSF cytologicalfindings had negative results on an initial examination,suggesting that the serial CSF samples would result inincreased diagnostic sensitivity.7 CSF sampling in our patientwas deferred due to prior radiological evidence of a space-occupying lesion in the posterior fossa.Contrast enhanced MRI is the optimal imagingmodality for assessing these patients. The lesions areisointense or slightly hypointense in T1-weighted images andslightly hyperintense in T2-weighted images. About 75% ofimmunocompetent patients show an intense homogeneousenhancement after contrast administration. On CT scanPCNSL are isodense or slightly hyperdense with a mild masseffect, showing homogeneous enhancement after contrastadministration.8 Consistent findings were present in ourpatient.Five year survival approaches 4% of patients withprimary malignant lymphomas.2 If untreated, the mediansurvival is only 4.6 months.9 A unique feature of PCNSLcompared with other brain tumours is its unique sensitivity tosteroids. The steroids have a direct cytotoxic effect but purelysteroid-induced remission is short-lived in most patients.However 40% of the patient's tumour shrinks or disappearswith an administered combination of steroids and whole brainradiation therapy (WBRT).9 Radiation and steroid treatmentlead to a median survival of 12-18 months. In the last decadeVol. 61, No. 9, September 2011 926several phase II studies have shown that the 5-year actuarialprobability of survival with certain chemotherapy regimensfollowed by WBRT is approximately 28%-40%. This issuperior to the reported 2-year survival of 28% with WBRTalone. The primary Chemo therapy (CHT) regimen inPCNSL should include Intravenous High Dose methotrexate,the most effective drug against these malignancies in lieu ofits ability to cross the Blood Brain Barrier.1 In a recent study,addition of cytarabine produced a statistically significantimprovement in survival.10 Stereotactic radiosurgery as atreatment option for PCNSL has only been recently exploredand reported in the literature.9Our patient had the unique feature of CentralNeurogenic Hyperventilation (CNH) associated with histumour. Diagnostic criteria for CNH are hyperventilation thatpersists during sleep, low arterial PaCO2, high arterial PaO2and high arterial pH in the absence of drugs or metaboliccauses.3 CNH results from the uninhibited stimulation of bothinspiratory and expiratory centers in the medulla by thelateral pontine reticular formation and by laterally locateddescending neural pathways. Of the 21 cases of CNHreported in the literature, all were associated with either aninfiltrative brainstem lesion or diffuse cerebral involvement.Out of the 18 reported cases that specified tumourhistopathologic features, there were 9 with lymphoma, 6 withslow-growing astrocytoma, 1 with metastatic tumour, 1 withmedulloblastoma and 1 with aggressive astrocytoma.3Despite the highly responsive nature of PCNSL toinitial treatments, local control remains the largest obstacle inthe treatment of this disease. Recurrence occurs in more than90% of patients, most commonly in the brain.7 In conclusion,PCNSL is a rare malignancy; however, the extraordinaryfrequency of primary cerebral lymphoma among the fewpatients with tumour induced CNH suggests that lymphomamust be high in differential diagnosis and should guidetherapy.3 If there is a suspicion of a lymphoma, steroidtherapy should be avoided as it can cause radiological andclinical improvement in the patient, but making thehistopathological confirmation undesirable. Thus delayingdiagnosis. The variable clinical presentation and poorprognosis associated with PCNSL warrant a prompt andcritical evaluation of these patients followed by aggressiveand multidisciplinary treatment approach.References1. Ferreri AJ, Abrey LE, Blay JY. Summary of statement on primary centralnervous system lymphomas from the Eighth International Conference onMalignant Lymphoma, June 12 - 15, 2002. J Clin Oncol 2003; 12: 2407-11.2. Murray K, Kun L, Cox J. Primary malignant lymphoma of the central nervoussystem: results of treatment of 11 cases and review of the literature. J Neurosurg1986; 65: 600-7.3. Andrew WT, Lim C, Bui JD. Central Neurogenic Hyperventilation. Arch Neurol2005; 62: 1632-4.4. Ferreri JM, Blay JY, Reni M. Prognostic Scoring system for primary CNSlymphomas: The International Extranodal Lymphoma Study Group Experience.J Clin Oncol 2003; 21: 266-72.5. Batchelor T, Loeffler JS. Primary CNS Lymphoma. J Clin Oncol 2006; 24:1281-8.6. Bataille B, Delwail V, Menet E. Primary intracerebral malignant lymphoma: Areport of 248 cases. J Neurosurg 2000; 92: 261-6.7. Balmaceda C, Gaynor JJ, Sun M. Leptomeuingeal tumour in primary centralnervous system lymphoma: Recognition, significance and implications. AnnNeurol 1995; 38: 202-9.8. Fitzsimmons AL, Upchurch KU, Batchelor TT. Clinical features and diagnosisof primary central nervous system lymphoma. Hematol Oncol Clin North Am2005; 19: 689-703.9. Roman-Goldstein SM, Goldman DL, Howieson J. MR in primary CNSlymphoma in immunologically normal patients. Am J Neuroradiol 1992; 13:1207-13.10. Campbell PG, Jawahar A, Fowler MR. Primary central nervous systemlymphoma of the brainstem responding favorably to radiosurgery: A case reportand literature review. Surg Neurol 2005; 64: 400-4.11. Ferreri AJ, Reni M, Pasini F. A multicenter study of treatment of primary CNSlymphoma. Neurology 2002; 58: 1513-20.927 J Pak Med Assoc

B-cell lymphoma of the brainstem with central neurogenic hyperventilation

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B-cell lymphoma of the brainstem with central neurogenic hyperventilation

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