Rev. Bras. Hematol. Hemoter. vol.38 número2

rev bras hematol hemoter. 2016;38(2):158–160

w w w . r b h h . o r g

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Case

Report

Involvement

of

cranial

nerves

in

a

patient

with

secondary

central

nervous

system

lymphoma

Roberta

Dantas

Azevedo,

Fabiano

Reis

_,

_Marcia

_Torresan

_Delamain,

Cármino

Antônio

de

Souza

UniversidadeEstadualdeCampinas(UNICAMP),Campinas,SP,Brazil

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Articlehistory:

Received20November2015 Accepted11February2016 Availableonline8March2016

Introduction

Neurolymphomatosis(NL)isararediseasethatcanbecaused byT cell,Bcell or naturalkiller cell (NK) lymphomas, but mostcommonlybyBcelllymphomas.1 _{NLischaracterized}

by direct infiltration of the central nervous system (CNS), nerveroots/plexusor peripheralnervesbyahematological malignancy.2–4_{Multiplenerveinvolvementismorecommon}

than single nerve involvement.1 _{Secondary NL occurs as}

relapseortheprogressionoflymphomas.5

Case

report

A67-year-old male with ahistory of hepatic transplant in 2002and undertreatmentwithimmunosuppressiveagents (entecavirand everolimus),received the diagnosis ofa dif-fuselargeB-celllymphoma(DLBCL)inMay2014(lymphnode conglomerate intheright armpit).Thepatientwas treated withfivecyclesofrituximabpluscyclophosphamide, doxo-rubicin,vincristineandprednisone(R-CHOP).InSeptember,

∗ _{Correspondingauthorat:RuaVitalBrasil,251,CidadeUniversitáriaZeferinoVaz,13076008Campinas,SP,Brazil.}

E-mailaddress:fabianoreis2@gmail.com(F.Reis).

at the end of the treatment, the patient was admitted to an urgent carefacility withleft frontotemporal headaches related to eye and facial pain (V1 and V2 territory), as wellasdiplopia.Magneticresonanceimaging(MRI)showed parenchymalandpachymeningealinvolvementinright tem-poralregion,leptomeningealthickeningandenhancementof theoculomotor,trigeminal,facial,andvestibulocochlear cra-nialnerves(Figure1).Cerebrospinalfluid(CSF)cytologywas negative.ThepatientandthefamilyrefusedtheoptionofCNS biopsy,butoptedforpalliativeradiotherapyinordertocontrol theheadache.ThepatientdiedinNovember2014.

Discussion

Primary NL is defined by neurological involvement as the initial manifestation of a hematological malignancy. Secondary NL occurs as relapse or progression of previ-ously diagnosedlymphomaor leukemia.5 _SymptomsofNL

include sensorimotor deficits, muscular atrophy, hypoto-nia,hyporeflexia, spontaneouspain, headachesand cranial nerve dysfunction.2–4 _{The differential diagnoses include}

http://dx.doi.org/10.1016/j.bjhh.2016.02.001

revbrashematolhemoter.2016;38(2):158–160

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Figure1–(A)CoronalT1-weightedmagneticresonanceimagingaftergadoliniumadministrationshowingrighttemporal leptomeningeal,parenchymal(arrow)andpachymeningealenhancement;(B)diffusionweightedimagewithhyperintensity and(C)apparentdiffusioncoefficientmapwithhypointensity(arrow),confirmingrestricteddiffusion;(D)axialT1-weighted magneticresonanceimagingaftergadoliniumadministration,showingabnormalenhancementintheleftfacialnerve (arrow).

nerve damage from herpes zoster, chemotherapy, inflam-matory neuropathy, drug-induced neuropathy, nerve root compression,radiotherapy,lymphoma-associatedvasculitis, andparaneoplasticsyndromes.1,6_{Ahighindexofsuspicionis}

requiredduetothevarietyofsymptomsandalargenumber ofdifferentialdiagnosesthatmustbeconsidered.NLisoften misdiagnosedorundiagnosedduetoitsrarityandcomplex clinicalmanifestations.1,5

Diffuseinfiltrationofcranialnervesistheleastcommon metastaticclinicalpresentationofNL.2–4 _{Tenpercentofall}

metastaticnervoussystemlymphomasmanifestasNL.3_In

thisarticle,wedescribeararecaseofsecondaryDLBCLwith leptomeningealandmultiplecranialnerveinvolvementinan immunocompromisedpatient.

Magneticresonanceimaging(MRI)ofNLincludes abnor-malenhancementofthe leptomeninges,cranialnerves, or theperiventricularregion.7_{TheradiographicMRIappearance}

ofNL includescontrast enhancement ofperipheralnerves oftenwithenlargementandnodularity.Involvednervesare isointense on T1-weighted MRI and hyperintense due to increasedsignalonshortinversiontimeinversionrecovery (STIR) and T2-weighted MRI.3 _{Leptomeningeal,}

subependy-mal, dural, or cranial nerve enhancement are findings suggestive of leptomeningeal metastases in neuroimaging tests.8 _{MRI contrast is the imagingtechnique of choice to}

detectleptomeningealmetastasis.Computerizedtomography (CT) is less sensitive.8 _{Parenchymal metastases}

originat-ingfromnon-Hodgkin lymphomaoftenappearassingleor multipleenhancedlesionsandmaybeaccompaniedby lep-tomeningealmetastases.8

Tumors are frequently more cellular than the tissue from whichtheyoriginatetherefore, theyexhibitrelatively highsignalintensityandrestricteddiffusioniscommonfor CNSlymphomalesions.4,5_{InMRIdiffusion-weightedimages,}

CNS lymphomas usually present a low apparent diffusion coefficient (ADC), featuring diffusion restriction.9

Involve-ment of cranial nerves can be seen, but this is relatively infrequent.9_{Whencranialnervesareaffected,MRItypically}

showsenhancementofaffectednerves,soitisthemostused methodtocorroboratethediagnosisofNL.4

In cases withan appropriate clinical context,MRI with gadoliniumis,byitself,adequatetoestablishthediagnosisof leptomeningealmetastasis.3_{Nervebiopsyremainsthegold}

standard in the diagnosis ofNL, but it isnot usually per-formedifnoninvasivetechniquesaresufficientfordiagnosis2_.

Positron emissiontomography-computed tomography (PET-CT)isbetterthanMRIandcanoftenelucidatethediagnosis ofNLwhenotherdiagnosticmodalitiesareindeterminate.1,6

Cerebrospinalfluidexaminationsarenothighlysensitiveto diagnoseNL.Inaseriesof96patientswithCNSlymphoma, 12 had MRIfindings suggestive ofleptomeningeal involve-ment,butonlysevenofthesepatients(58.3%)hadpositiveCSF cytology.4 _{Thediagnosis ofsecondaryneurolymphomatosis}

wasreachedbasedonclinicaldataandMRIfindings. Theprognosis ofNLvaries greatlyamongpatients. The overall prognosis of patients with DLBCL has improved significantly with the addition of rituximab to the CHOP (cyclophosphamide,doxorubicin,vincristineandprednisone) regimen.10 _{Patientswithlymphomaand NLhaveanoverall}

mediansurvivalof21monthsand15monthsaftertheonsetof NLsymptoms.2_{TreatmentofNLisunsatisfactoryandpatients}

havepooroutcome.Thepatientdiedtwomonthsafterthe beginningofNLsymptoms.Currently,intravenous methotrex-ateisthefirstlinetherapytotreatNLduetoitspenetration oftheblood–brainbarrier.Additionaltreatmentsmaybe com-bineddependingonthedistributionandextentofdisease.2

NL is an increasingly recognized complication of non-Hodgkin lymphoma and leukemia in patients undergoing therapyanditsincidenceisincreasingworldwide,mainlydue toincreasedawarenessofthisconditionandearlydetection bymoresophisticateddiagnostictechniques.2_{Early clinical}

recognitionandtreatmentofNL,permitspalliationand poten-tiallyretardsneurologicaldiseaseprogression.3

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2. Kamiya-MatsuokaC,ShroffS,GildersleeveK,HormozdiB, ManningJT,WoodmanKH.Neurolymphomatosis:acase seriesofclinicalmanifestations,treatments,andoutcomes.J NeurolSci.2014;343(1–2):144–8.

3. ChamberlainMC,FinkJ.Neurolymphomatosis:arare metastaticcomplicationofdiffuselargeB-celllymphoma.J Neurooncol.2009;95(2):285–8.

4. ScottBJ,DouglasVC,TihanT,RubensteinJL,JosephsonSA.A systematicapproachtothediagnosisofsuspectedcentral nervoussystemlymphoma.JAMANeurol.2013;70(3): 311–9.

5. TanakaH,YoshinoK,SakaidaE,HashomotoS,TakedaY, KawajiriC,etal.Secondaryneurolymphomatosisdetected bywhole-bodydiffusion-weightedmagneticresonance imaging:acasereport.JClinExpHematop.2013;53(3): 221–6.

6.GanHK,AzadA,CherL,MitchellPL.Neurolymphomatosis: diagnosis,management,andoutcomesinpatientstreated withrituximab.Neuro-Oncology.2010;12(2):212–5.

7.JordanJT,PlotkinS,DietrichJ.Magneticresonanceimaging observationsinprimarycentralnervoussystemlymphoma. JAMANeurol.2014;71(7):918–9.

8.HaldorsenIS,EspelandA,LarssonEM.Centralnervous systemlymphoma:characteristicfindingsontraditionaland advancedimaging.AmJNeuroradiol.2011;32(6):984–92.

9.ReisF,SchwingelR,NascimentoFB.Centralnervoussystem lymphoma:iconographicessay.RadiolBras.2013;46(2):110–6.

10.DengL,SongY,ZhuJ,ZhengW,WangX,XieY,etal. Secondarycentralnervoussysteminvolvementin599 patientswithdiffuselargeB-celllymphoma:arethereany changesintherituximabera?IntJHematol.