1. Grand Rounds October 20, 2006 Jeffrey D. Colburn, M.D., PGY-2 Vanderbilt Eye Institute

2. The Case… CC: Right eye swelling x 3 weeks HPI: 47 y.o. AA male, recently released from jail –“Pressure” in right temple region –Blurry vision, redness & tearing OD –Denies any injuries –Outside ophthalmologist and ENT treating for sinusitis. Thyroid studies pending.

4. History Past Ocular Hx Negative Past Med/Surg Hx Negative Meds Levaquin, Nasacort HQ, Prednisone Allergies: NKDA Family Hx An aunt with Glaucoma Social Hx –“pretty good amount” EtOH –60 pack yr smoking hx –Smokes crack cocaine –Occasional MJN ROS + SOB, fatigue, weakness, dizziness, HA’s, ~ 20 lbs wt loss, Right ear fullness, lightheadedness, - Fever, chills, night sweats, URI symptoms,

5. Exam VA: 20/60 OD, 20/25 OS IOP: 26 OD, 21 OS CVF: Full Pupils: No anisocoria, no RAPD Motility: OD -3 in upgaze/downgaze, -2 left/right gaze Hertel: 25 OD, 18 OS (123mm) Color: 6/15 OD, 13/15 OS External: Proptosis, ptosis & lid edema OD, –No bruit heard over orbit

7. Exam SLE (OS quiet) LLL: lids edematous Conj: arterialized injection, engorged fornix vein K: arcus OU, otherwise clear A/C: Deep & Quiet, no C/F Iris: Intact Lens: clear Ant Vit: quiet

8. Exam DFE: Disks: sharp margins, good color OU C/D: 0.6 OD, 0.4 OS Macula: CWS temporally OD Periphery: few chorio-retinal scars OS Vitreous: clear OU Vascular: mild tortuosity OU

9. Differential Diagnosis

10. Vascular –C-C fistula (Low flow) –Arteriovenous malformation –Cavernous sinus thrombosis Neoplastic –Lymphoma/Leukemia –Cavernous sinus tumors –Orbital tumors –Metastatic tumors –Mucocele Infectious –Orbital cellulitis –Mucormycosis –Tuberculosis Trauma –Retrobulbar hemorrhage –Intraorbital foreign body Inflammatory/Infiltrative –Thyroid eye disease –Orbital inflammatory pseudotumor –Orbital vasculitis Wegener’s granulomatosis Polyarteritis nodosa –Intracranial sarcoidosis –Tolosa-Hunt syndrome Neurologic –Cranial nerve palsy

11. MRI

13. Admitted for  WBC’s, hyperkalemia, alkalosis Labs unrevealing –(RPR, HIV, ANA, thyroid panel, blood cx) CXR: vertebral osteoblastic lesions, +lymphadenopathy, reticulonodular opacities CT – Diffuse pathologic lymphadenopathy Biopsies – poorly differentiated carcinoma GI Work-up / Tumor markers – Negative

16. Diagnosis: Metastatic Carcinoma of Unknown Primary

17. Difficult Course Progression clinically – High IOP despite lateral cantholysis, MMT Partial response to IV steroids Responded to XRT to right orbit Died 5 weeks after presentation – Had completed 1 round of chemotherapy

18. Metastatic carcinoma to the orbit Commonly develop symptoms abruptly Features: – Pronounced restriction – Eyelid swelling, ptosis, mass – Vision loss – Proptosis (less prominent than primary) – > 90% unilateral Often aggressive and poorly differentiated Systemic prognosis is poor

19. Shields, et al. (2001) – 100 malignant neoplasms: 91 carcinomas Breast – 53 Prostate – 12 Lung – 8 Unknown primary – 7 – Thirteen presented first with orbital mets

20. A number of published reports of metastasis to the extraocular muscles Including: – Loes, Wesley, & Lavin (1996) – Lekse, Zhang, & Mawn (2003) Report of such diffuse involvement?

21. Carcinoma of Unknown Primary 2 - 4% of cancer diagnoses Median survival: 4 - 5 mos Treatment options have been poor –Toxicity –Efficacy New chemotherapy regimens hold promise –Greco, et al. (2000) – combination of paclitaxel, carboplatin, etoposide with median survival of 11 mos

22. References Greco, FA, et al. Carcinoma of Unknown Primary Site: Long term follow-up after treatment with paclitaxel, carboplatin, and etoposide. Cancer 2000;89:2655-60. Henderson, JW Orbital Tumors. W.B. Saunders Company, Philadephia, 1973. pp 474-494. Kanski, JJ. Clinical Ophthalmology: A systematic Approach. 5th ed. Butterworth Heinemann, New York, 2003. Lekse, JM, et al. Metastatic gastroesophageal junction adenocarcinoma to the extraocular muscles. Opthalmology 2003;110:318-321 Shields, JA, Shields, CL, et al. Cancer Metastatic to the Orbit: The 2000 Robert M. Curts Lecture. Ophthal Plast Reconstr Surg 2001;17:346-354.