INTRAVITREAL'METHOTREXATE'IN'THE'THERAPEUTIC'MANAGEMENT'OF'
REFRACTORY'EXTRANODAL'NATURAL'KILLER'(NK)/TICELL'LYMPHOMA,'NASAL'
POSTER'40'
TYPE,'WITH'OCULAR'INVOLVEMENT!
'
Dulcelena!Neves,!Ricardo!Ferreira,!Lenka!Ruzickova,!Marília!Gomes!and!Letícia!Ribeiro!
!
Hematology!Department,!Coimbra!Hospital!and!University!Centre!(CHUC),!Coimbra,!Portugal!
!
Background:!
Extranodal! natural! killer/TJcell! lymphoma,! nasal! type! (ENKL)! is! characterized! by! its!
association!with!Epstein!Barr!virus!and!extranodal!involvement.!About!1J3%!of!ocularJtissue!
(OT)!ENKTL!cases!have!been!reported,!mostly!by!invasion!or!dissemination!of!primary!nasal!
lesions.!Since!blood–ocular!barriers!may!limit!the!penetration!of!chemotherapy!into!the!OT,!
systemic! chemotherapy! alone! is! often! unsuccessful! and! adjunctive! treatment! is! required,!
namely!intravitreal!methotrexate!(MTX),!to!effectively!control!intraocular!disease.!
Case'Presentation:!
A! 55JyearsJold! female,! admitted! in! our! institution! with! a! 6Jmonth! history! of! nasal!
obstruction,!epistaxis!and!right!hemifacial!dysesthesia.!No!B!symptoms!were!reported.!Blood!
counts! and! serum! biochemistry! were! normal.! The! tomography! scan! demonstrated! a! left!
nasal!neoformation!that!was!biopsied.!
Anatomopathological! (AP)! study! revealed! mediumJsized! mononuclear! cells! with! extensive!
areas!of!necrosis,!cytoplasmic!CD3,!CD56,!cytotoxic!molecule!granzyme!and!EBER!positive,!
and!CD2,CD4,CD5,!CD7,!CD8,!CD25,!CD20,!CD10!negative;!KiJ67!index!>90%.!Additionally!to!
nasal!involvement,!the!PET!scan!demonstrated!breast!infiltration!and!bilateral!cervical!and!
axillary!adenopathies.!Plasma!EBV!DNA!was!undetected.!
The!patient,!diagnosed!with!ENKL,!stage!IVJA,!PINKJE!high!score,!was!treated!with!modifiedJ
SMILE(SMILEm).!After!5!cycles,!presented!painful!red!right!eye!and!decreased!visual!acuity.!
The!ophthalmic!examination!demonstrated!endothelial!precipitates,!conjunctival!hyperemia,!
and! multiple! vitreous! opacities.! An! ultrasound! showed! moderate! vitritis,! infiltration! of! the!
ocular!wall!and!partial!retinal!detachment.!The!MRI!highlighted!a!right!orbit!mass!infiltrating!
the!eyeball´s!wall!with!a!diffuse!episcleral!extension.!
A! vitrectomy! was! performed.! The! AP! revealed! multiple! and! small! lymphocytes! and! flow!
cytometry!identified!81%!of!NK!cells,!with!a!strong!expression!of!CD56,!cytotoxic!phenotype!
(granzyme!B!and!perforin),!and!of!CD94.!
Complete!remission!was!achieved!with!PJGEMOX!and!intravitreal!MTX!400!μg!(D1!D7!D21!
D35!D56)!followed!by!allogeneic!hematopoietic!stem!cell!transplantation.!Relapse!occurred!
3! months! later,! with! ethmoidal,! sphenoid,! maxillary! sinus,! posterior! nasopharynx,!
hypophysis,! parapharyngeal! and! bilateral! cervical! adenopathies,! and! cerebrospinal! fluid!
involvement.! Despite! the! third! line! treatment! with! SMILEm! and! intrathecal! chemotherapy!
with!MTX!and!Cytarabine,!she!died!21!months!after!the!diagnosis.!
Discussion:!
Primary/secondary! intraocular! ENKTL! are! extremely! rare! and! mostly! associated! with! poor!
outcome.! Multidisciplinary! efforts! are! needed! to! provide! an! accurate! diagnosis! and!
subsequent! therapeutic! management.! No! standard! treatment! is! defined,! although,! in! our!
approach,!we!incorporated!intravitreal!MTX,!as!adjunctive!to!systemic!chemotherapy,!with!a!
complete!response.!Effective!treatment!strategy!is!still!a!matter!of!debate!and!prospective!
clinical!trials!are!still!lacking.!