A 24-year-old man presented with an enlarging growth in his right eye that had been progressively growing larger over 8 months since being kicked in the eye. Examination found a growth in the right eye with full vision and eye movement. Biopsy of the growth found characteristics of mucosa-associated lymphoid tissue (MALT) lymphoma. MALT lymphoma can occur in the conjunctiva and has a generally favorable prognosis when treated locally. Further testing will be done to evaluate if the cancer is localized or has spread systemically.

1. Doheny Eye Institute Grand Rounds Ying Pan, MD

2. History of Present Illness CC: 8 months of progressively enlarging growth in right eye HPI: 24 year old Hispanic man from jail presented with increasing right eye redness since he was kicked in the eye 8 months ago. +Ocular irritation and foreign body sensation, but denied discharge, bleeding, pain or changes in vision. His symptoms did not improve with topical drops and ointments.

3. History POH:none PMH: none PSH: none Meds: none NKDA SH: Jail for 1 year FH: unremarkable ROS: 10 LB weight loss, occasional night sweats

4. Exam VA: 20/25 OU Pupils: Round and reactive to light, no APD Motility: Full OU IOP (Tp): 12 OD , 15 OS CVF: Full OU

5. Exam

6. Exam

10. H & E

11. H & E

12. H & E

13. Immunohistochemical staining CD 3 (T cell) CD 20 (B cell)

14. Immunohistochemical staining CD 21 Ki-67

15. Mucosa-Associated Lymphatic Tissue characteristic arrangement of lymphoid tissues in the mucosa conjunctiva-associated lymphoid tissue -minimal organized lymphatic tissue -small number of lymphocytes -few mast cells & langerhans cells

16. MALT Lymphoma spectrum from benign hyperplasia to malignant lymphoma common site: gastrointestinal tract extraintestinal locations: tonsils, skin, breast, lung, orbit

17. Conjunctival MALT Lymphoma Mainly occurs in the fifth to sixth decades Bilateral involvement: 20% Systemic disease: 30% 117 conjunctival lymphoid tumors (Shields et al. Ophthalmology 2001) unilateral disease: 11 of 64 (17%) bilateral disease: 25 of 53 (47%) Favorable prognosis Minimally aggressive Localize course Favorable response to treatment Recurrence

18. Standard Treatment Localized Excision Cryotherapy Radiotherapy (tumor control: 89-100%) 50 patients with ocular adnexal lymphoma ( Uno et al. Cancer 2003 ) 49 patients: tumor control at 24 months 6 patients: disease reoccurrence from 4-97 months Systemic Chemotherapy (+/- excision)

19. Observation ( Matsuo & Yoshino, Ophthalmology 2004) 13 patients with Conjunctival MALT Lymphoma excisional biopsy leaving small lesion behind Observation (8) Radiation (5) Tumor Tumor Tumor Regression (7) Regrowth (1) Regression (5) at 5 years at 3 years

20. Local Chemotherapy with Interferon  ( Blasti et al. Ophthalmology 2001 ) Interferon: resistance to viral infections, inhibit cell proliferation and modulate immune response. 4 patients with conjunctival MALT Lymphoma Subconjunctival interferon injection (1,500,000IU 3X/wk for 4 wks) Tumor regression (3) Recurrence/systemic disease follow up time: 12-36 months at 11 months

21. Antibiotics ( Ferreri et at. J Natl Cancer Inst 2004 ) Predisposing condition (ie autoimmune, infection)  acquisition of MALT  reactive lymphoid tissue  Lymphoma Link between chlamydia psittaci infection and chronic antigenic stimulation  Lymphoma?

22. Antibiotics ( Ferreri et at. J Natl Cancer Inst 2004 ) Chlamydia psittaci DNA in ocular tissue Ocular adnexal lymphoma: 32 of 40 (80%) Reactive lymphadenopathy: 3 of 26 (12%) Nonneoplastic samples: 0 of 20 (0%) 8 patients with C psittaci positive MALT lymphoma of adnexal- Doxycycline (3 wk regimen) At 12 months follow up: Complete response: 2 > 50% tumor reduction: 2 < 50% tumor reduction: 2 Minimal reduction: 1 Tumor progression: 0

23. Patient Up-Date Systemic Evaluation Blood Bone marrow biopsy CT Scan (head, thorax, abdomen) Chlamydia Psittaci IGM and IGG

24. References Blasti et al. Local Chemotherapy with Interferon  for conjunctival mucosa-associated lymphoid tissue lymphoma. Ophthalmology 2001; 108: 559-562 Ferreri et at. Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 2004; 96: 586-94. Isaacson PG et al. Extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue. In: Jaffe ES, Harris NL. Stein H, et al. editors. WHO classification of tumours. Pathology and genetics of haematopoietic and lymphoid tissues. Lyon: IARC press, 2001: 157-160. Knowles L, Jakobei FA, McNally NS, Burke JS. Lymphoid hyperplasia and malignant lymphoma occurring in the ocular adnexa (orbit, conjunctiva, and eyelids): a prospective multiparametric analysis of 108 cases during 1977 to 1987. Hum Pathol 1990; 21 pp 959-973. Le Qt et al. Primary radiotherapy for localized orbital MALT lymphoma. Int J Radiot Oncol Biol Phys 2002; 53: 657-663. Shields et al. Conjunctival lymphoid tumors: clinical analysis of 117 cases and relationship to systemic lymphoma. Ophthalmology 2001; 108:979-984 Matsuo T, Yoshimo T. Long-term follow up results of observation or radiation for conjunctival malignant lymphoma. Ophthalmology 2004; 111:1233-1237. Uno et al. Radiotherapy for extranodal, marginal zone, B cell lymphoma of mucosa-associated lymphoid tissue originating in the ocular adnexa. Cancer 2003; 93: 865-71. .