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
a
r
t
i
c
l
e
i
n
f
o
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.2–4Multiplenerveinvolvementismorecommon
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
159
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.1,6Ahighindexofsuspicionis
requiredduetothevarietyofsymptomsandalargenumber ofdifferentialdiagnosesthatmustbeconsidered.NLisoften misdiagnosedorundiagnosedduetoitsrarityandcomplex clinicalmanifestations.1,5
Diffuseinfiltrationofcranialnervesistheleastcommon metastaticclinicalpresentationofNL.2–4 Tenpercentofall
metastaticnervoussystemlymphomasmanifestasNL.3In
thisarticle,wedescribeararecaseofsecondaryDLBCLwith leptomeningealandmultiplecranialnerveinvolvementinan immunocompromisedpatient.
Magneticresonanceimaging(MRI)ofNLincludes abnor-malenhancementofthe leptomeninges,cranialnerves, or theperiventricularregion.7TheradiographicMRIappearance
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.4,5InMRIdiffusion-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.9Whencranialnervesareaffected,MRItypically
showsenhancementofaffectednerves,soitisthemostused methodtocorroboratethediagnosisofNL.4
In cases withan appropriate clinical context,MRI with gadoliniumis,byitself,adequatetoestablishthediagnosisof leptomeningealmetastasis.3Nervebiopsyremainsthegold
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.2TreatmentofNLisunsatisfactoryandpatients
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.2Early clinical
recognitionandtreatmentofNL,permitspalliationand poten-tiallyretardsneurologicaldiseaseprogression.3
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3. ChamberlainMC,FinkJ.Neurolymphomatosis:arare metastaticcomplicationofdiffuselargeB-celllymphoma.J Neurooncol.2009;95(2):285–8.
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