2010.10.7 Case Conference Orbital Lymphoma R3 김소윤/Pf.양석우

Case 1 M/50 고O석 C.C) Proptosis(OS) onset)1yr ago P.Hx) N-S painful LOM(-), pain(-) P.Ex) VA OD 0.8 OS 0.8 IOP OD 14mmHg OS 19mmHg EOM Straight at 1 position by ACT, no LOM(OU) Exo OD 13mm OS 15.5mm (base 103mm) Lid evaluation MRD1 IPF LFT Bell’s Lago OD 1 5 10 + - OS 1 5 10 + -

r/o Orbital Lymphoma(OS) Imp: r/o TAO(OS) r/o Pseudotumor(OS) r/o Orbital Lymphoma(OS) Plan: routine lab TFT Imaging W.N.L 2.6x1.7x1.6cm mass at retroglobal sup. portion ; r/o lymphoma r/o inflammatory pseudotumor r/o neurogenic tumor

Plan: Ant. Orbitotomy(OS) Op.: SR disinsertion+ant.orbitotomy+retrobulbar excisional Bx. +SR reinsertion(OS) Bx.: Malignant lymphoma, extra-nodal marginal zone lymphoma(MALToma) BM: normocellular bone marrow without lymphoma involvement RTx.(3600cGY)

8mo later Size decreased (1.1x4x1.1cm)

Case 2 F/65 김O순 C.C) Proptosis(OD) onset)8mo ago P.Hx) HBP(+) Diplopia(-), pain(-) P.Ex) IOP OD 19mmHg OS 13mmHg at PM 14:00 EOM Straight at 1 position by ACT LOM - unchecked Exo OD 10mm OS 7mm (base 93mm)

r/o inflammatory pseudotumor(OD) Imp: r/o TAO(OD) r/o inflammatory pseudotumor(OD) r/o Orbital lymphoma(OD) Plan: routine lab TFT Imaging W.N.L r/o lymphoma involving lacrimal gl. and lateral rectus muscle

Plan: Ant. orbitotomy c Ex.&Bx. Bx.: Malignant Marginal zone lymphoma(OD) CTx.(CHOP) & RTx.(3600cGY) *CHOP ; Cyclophosphamide+Adriamycin+vincristine+prednisone

4mo later

Case 3 F/56 김O희 C.C) Upper eyelid swelling(OD) onset)10yrs ago *size 증가(+) P.Hx)HBP(+) 12년전 지방제거술(OD) & Blepharoplasty d/t upper eyelid swelling(OD) at local PS P.Ex) VA OD 0.02(0.63) OS 0.32(0.8) IOP OD 17mmHg OS 15mmHg EOM Straight at 1 position by ACT Lid OD mod swelling, 1cm sized palpable & movable mass(+),skin change(-), Td(-) ,protruding at down gaze OS no swelling Lid evaluation MRD1 IPF LFT Bell’s Lago OD 3 9 8 - - OS 4 9 13 + - Ptosis(OD)

Imp: r/o Upper eyelid mass (OD) r/o TAO(OD) r/o lacrimal gland mass(OD) r/o lymphoma(OD) Plan: routine lab TFT Imaging W.N.L Lymphoma involving right lacrimal gl.

Plan: Ant. Orbitotomy c Ex. & Bx. of lacrimal gland mass(OD) Bx.: Lacrimal gland maltoma(OD) CTx.(CHOP)& RTx.(3600cGY)

6mo later marked regression of lymphoma. but still remained at orbital roof inner layer

Case 4 F/65 김O자 C.C) Proptosis(OD) c headache onset)1yr ago P.Hx) 내원전 1주일가량 steroid p.o medi(10mg) d/t pseudotumor(OD) at local painful LOM(+/-) P.Ex) EOM Straight at 1 position by ACT, no LOM(OU) Exo OD 15mm OS 13mm (base 115mm) Lid no swelling(OU)

Orbit CT: Rt. SR myositis -> r/o Pseudotumor Imp: r/o Pseudotumor(OD) Plan: Steroid pulse therapy 1.Enhancing mass at sup. of right orbit. Combined with bone destruction 2. Enhancing extraaxial mass on plaum sphenoidale : r/o malignant neurogenic tumor

Steroid tapering 중 headache 및 Ocular pain, swelling 발생 -> Consult to NS Bx.:Malignant lymphoma, large B cell type(OD) Nodule at sphenoidal region at Brain MR -> Craniotomy c tumor removal at NS (Meningioma) Whole body multiple mass c chest, shoulder pain -> CTx. At IH (Diffuse large B cell lymphoma)

1yr later

Case 5 M/55 박O진 C.C) Red eye(OS) onset)4~5yrs ago P.Hx) N-S P.Ex) IOP OD 12mmHg OS 14mmHg at PM 14:00 EOM Straight at 1 position by ACT, no LOM(OU) Exo OU no exophthalmos Lid OU no swelling Conj. OD not injected OS mild injected, pinkish elevated bulging mass at upper nasal subconjunctival area

Plan: Ex. & Bx.(OS) Imaging Imp: r/o Conjunctival mass(OS) r/o Lymphoma(OS) Plan: Ex. & Bx.(OS) Imaging Bx.: MALT lymphoma(OS) Focal thickening mass at inferomedial and lateral portion in right eye ; r/o lymphoma

Dx.: Oribital MALTOMA(OU) CTx.(Vincristine)+RTx.(3600cGY)

6mo later

Case 6 F/39 신O원 C.C) Red eye(OU) –intermittently onset)several mo. ago P.Hx) 2년전 LASEK(OU) at local P.Ex) VA OD 1.0 OS 1.0 IOP OD 9mmHg OS 8mmHg at AM 8:30 EOM Straight at 1 position by ACT, no LOM(OU) Exo OU no exophthalmos Lid OU no swelling Conj. OU redundant conj. tissue c salmon-patch app. at upper & lower forniceal area

Plan: Lower forniceal Bx(OU) Imaging Imp: r/o MALToma(OU) Plan: Lower forniceal Bx(OU) Imaging unremarkable findings

Bx.: OD Malignant Lymphoma, extra-nodal marginal zone lymphoma OS Malignant Lymphoma, most possible MALT lymphoma RTx.(3600cGY)

2mo later

Case 7 M/32 장O석 C.C) 1.Tearing(OS) onset)1yr ago 2.Swelling of lower punctal area(OS) onset)2mo ago P.Hx) 1년전 syringing x1(OS) at local P.Ex) IOP OD 15mmHg OS 18mmHg EOM Straight at 1 position by ACT, no LOM(OU) Exo OD 17mm OS 17.5mm (base: 112mm) Lid OD no swelling OS severe swelling at lacrimal ductal area Conj. OD not injected OS conj. fold(-) Shirmer OD 10mm OS 20mm BUT OD 3sec OS 4sec DDT OD + OS +++ Syringing (OD) hard stop, well passed

Imp: r/o Acute dacryocystitis(OS) r/o orbital lymphoma(OS) Plan: Imaging r/o minor salivary gl. tumor arising from nasolacrimal duct r/o lymphoma

Plan: Ant. Orbitotomy c mass Ex. & Bx.(OS) Bx.: Malignant lymphoma, diffuse large B cell lymphoma , ethmoidal sinus+lacrimal sac (OS) CTx.(CHOP)

3mo later

Case 8 M/48 정O복 C.C) Eyelid swelling(OD) onset) 1yr ago P.Hx)N-S P.Ex)Diplopia(-) VA OD 0.5(0.8) OS 0.8 IOP OD 16mmHg OS 15mmHg EOM Straight at 1 position by ACT Exo OU no exophthalmos Lid OD palpable huge mass like lesion at upper orbital rim area OS no swelling -3

Imp.: r/o pleomorphic adenoma(OD) r/o inflammatory pseudotumor(OD) r/o Lymphoma(OD) Plan: routine lab Imaging W.N.L r/o adenoid cystic carcinoma r/o lymphoma r/o inflammatory pseudotumor

Plan: Ex.& Bx.(OD) Bx. : Malignant lymphoma, extranodal marginal zone MALToma(OD) Additional Dx.: Thyroid papillary carcinoma, Lt. UPJ MALToma CTx.(Vincristine)

1yr later

Case 9 M/75 조O창 C.C) Lower lid mass(OD) onset) 8mo ago P.Hx)Gastric Ca. Hx.(+) ; s/p gastrectomy , 현재 p.o CTx. 8개월전 촬영한 PET CT 에서 우안 uptake 소견 발견함. ->특별한 치료없이 지냄 Lid OU no swelling Mass symptom 은 호소하지 않음

Imp.: r/o inflammatory pseudotumor(OD) r/o TAO(OD) r/o orbital lymphoma(OD) Plan: routine lab Imaging W.N.L Plan: RLL mass Ex. & Bx.(OD)

Bx.: Mantle cell lymphoma(OD) RTx.(3600cGY) 1yr later

REVIEW

Orbital mass 1.주요질환 Proptosis : TAO, inflammtory pseudotumor, lymphoma, vasculitis Eyelid swelling : Chalazion, dacryocystitis, allergy, orbital cellulitis, Tumor Palpable mass : Dermoid cyst, prolapsed lacrimal gland, Tumor, pseudotumor 2.진단 1) Orbital examination(inspection, palpation, pulsation) 2) Diagnostic imaging (US, plain films, CT, MRI, Venography, Angiography) 3) 전신 및 임상병리 검사 4) 생검 5) 사진

Lymphoproliferative lesion - (Benign) reactive hyperplasia - Atypical lymphoid lyperplasia - Malignant lymphoma 1.안와종양의 20%이상을 차지 2.안와의 가장 흔한 lymphoproliferative lesion : Non-Hodgkin Lymphoma

Identification and Classification Norma architecture & cell composition Reactive hyperplasia Non-Hodgkin lymphoma Atypical Malignant lymphoma Hodgkin’s lymphoma conserved disrupted Majority cell minority cell

Hodgkin and Non-Hodgkin Lymphomas (Excludes ocular adnexal lymphoma) Ann Arbor classification

Limitations Disproportionate staging distribution Anatomic location Extent of primary tumor infiltration Multiple tumors Lymph node involvement Multicentricity and bilaterality of OAL Noncontiguous involvement of tissues external to the ocular adnexa

TNM staging

Orbital Lymphoma lymphoid tissue (MALT) type 대부분 B-cell 에서 유래하며, T-cell lymphoma 는 드물며 치명적 B-cell lymphoma 1) Hodgkin tumor 2) Non-Hodgkin tumor (orbital lymphoproliferative disease 의 90%이상) m/c orbital lymphoma 1) Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type 2) Chronic lymphocytic lymphoma(CLL) 3) Follicular center lymphoma 4) High-grade lymphoma ; diffuse large cell lymphoma, lymphoblastic lymphoma, Burkitt lymphoma

MALT lymphoma 호발연령 : 60~80대 호발성별 : 여자 호발빈도 : Orbit ( 약 40%) >conjunctiva (35~40%) > lacrimal gland (10~20%)> eyelid (약 10%) 한국인과 일본인에서 더 높은 비중으로 나타나며(80~90%), 서양에 비하여 젊은 연령층에서 호발함 10년동안 50%이상의 환자가 전신증상을 나타냄 5~15% 환자가 spontaneously resolution 진행하며 high-grade lesion 으로 바뀌는데 보통 large cell type (15~20%)

Clinical characteristics 대개 점진적으로 증가하는 무통성의 결절 (salmon patch appearance를 띄며 보통 안와 앞이나 결막밑에 위치) 양성과 악성 모두 안와조직을 직접 침범하기보다 그 주위를 둘러쌈 -> extraocular motility 나 visual function 이 불량한 경우는 드묾 Reactive lymphoid hyperplasia 나 low grade lymphoma는 수개월에서 수 년에 걸쳐 서서히 증가->puttylike tumor molding Bone erosion, infiltration 은 high grade malignant lymphoma 를 제외하 고는 드묾 90%의 orbital lymphoproliferation 이 monoclonal 이며 10%가량이 polyclonal 함 -> 대부분이 malignant

Clinical characteristics 반수이상의 periocular lymphoma 에서 양성과 악성 모두 systemic spread 가능 - 20~30% : 발병과 같이 systemic disease 동반 - 30% : 5년이후에 systemic disease 동반 systemic disease의 가능성이 높은경우 : bilateral involvement(7~24%) original lesion 이 진단된 후 10년이상 조직학적으로 양성의 orbital lymphoid infiltration이 있는 환자는 결국 extraorbital lymphoma 가 발생 악성 lymphoma의 경우 전신적 침습없이 국소적인 치료에 반응을 잘하는 경 우가 많음 Origin의 해부학적 위치는 systemic한 NHL의 예측에 도움 ; 위험성 – conjunctiva <orbital lesion(esp. lacrimal fossa) <eyelid

Diagnosis Staging 형태학적, 면역학적, 분자생물학적, 세포유전학적인 특성에 따라 진단 Choice of Diagnosis : Open Biopsy ** Clinical Stage 는 histologic type 에 의해 크게 좌우됨 (85~90%의 orbital lymphoma가 stage IE 로 분류) Ophthalmologic & clinical examination Routine laboratory studies Imaging : CT, PET, MRI, etc. Serum protein eletrophoresis ß2-microglobulin Serum JDH Bone Marrow Biopsy

Management 임상적으로 다양한 lymphoproliferative lesion 이 overlapping 할 수 있 으므로 hypercellular lymphoid lesion 을 보이는 모든 환자는 내과의 협 진이 필요함 안와에 국한된 lymphoma가 systemic하게 퍼질 수 있으므로 주기적인 검 사가 필요함 Systemic steroid therapy: idiopathic orbital inflammation에 도움이 되나, lymphoproliferative lesion에는 도움이 되지 않음

Ferreri AJ et al. J Natl Cancer Inst 2004 RTx.: 1) local ocular adnexal lymphoproliferative lesion ->local control, prevention for systemic spread 2) S/E: ocular toxicity, distant recurrence(6~50%) CTx : 1) DLBCL 2) stage II 이상의 ocular adnexal lymphoma 이미 전신에 퍼진 low-grade lymphoid lesion: poor response to RTx. & CTx.치료하지 않아도 long-term survival이 가능 Aggressive Lymphoma: RTx.+CTx. (병변의 1/3 이 치료되기까지) Surgical Tx.: 1)lymhoma 의 infiltrative nature로 효과적이지 않음 2)localized and/or encapsulated lesions of the conjunctiva or lacrimal gland Immunotherapy, radioimmunotherapy, antibiotic therapy.. Chlamydia psittaci The DNA of C. psittaci, an obligate intracellular pathogen, had been detected in 80% of OAML patients Ferreri AJ et al. J Natl Cancer Inst 2004

감사합니다.