Grand Rounds CAVERNOUS SINUS SYNDROME Denis Jusufbegovic M

Grand Rounds CAVERNOUS SINUS SYNDROME Denis Jusufbegovic, M. D. University of Louisville Department of Ophthalmology and Visual Sciences 01/04/13

Subjective CC: “ blurred vision OD x 1 month, double vision x 1 -2 wks” HPI: 34 yo WM was referred to oculoplastics clinic on 09/25/12 for occasional double vision x 1 -2 wks. Pt. also c/o of numbness around his R eye, intermittent headache and episodes of vomiting. Patient’s problems started on 08/28/12 after being splashed with power hose at work sustaining blunt trauma to R eye and face. He sought no medical attention. -

n He started developing ocular pain, photophobia, facial numbness and worsening vision OD few days after his injury. Was seen by local ophthalmologist on 09/07/12: n Exam was significant for: BCVA OD 20/200 OS: 20/20 Slightly dilated min reactive pupil OD, no APD Full EOM OD: Eyelid edema, conj. injection, 4+cells/2+flare, no vitritis, retina flat Diagnosed with traumatic iritis, treated with PF q 1 -2 h

n 3 days follow up by local ophthalmologist on 09/10/12 showed: - improved BCVA OD 20/80 from 20/200 - OD: 2+cells, 2+flare, mutton-fat KPs - no other exam changes Diagnosis: Iritis OD Tx: Prednisone 80 mg PO to be tapered over 2 wks

n He returned to local ophthalmologist on 09/15/12 c/o “eye making popping sounds” n Significant exam findings: BCVA OD 20/70 OS 20/20 No APD, full EOM “sunken eye socket OD” AC was deep and quiet OD Plan: complete PO Prednisone taper and obtain CT orbits

1 st oculoplastics visit HPI: Pt. c/o intermittent binocular diplopia x 1 -2 wks, photophobia OD, daily headaches assoc. with nausea/vomiting, numbness and tingling around R eye POH: unremarkable except recent injury PMH: negative FH: non-contributory All: NKDA MEDS: Pred. Forte OD QID ROS: negative

Objective 20/25 BCVA 20/20 P 4 2 3 2 O RAPD, brisk OU EOM: inconsistent mild -1 adduction deficit OD 12 T 13 Hertel: 10 100 12 External: partial numbness R V 1 and V 2, intact V 3

Objective SLE: OD L/L C/S K AC I/L Vit OS normal OU clear OU 1+ c/f quiet faint pigment clear on ant. capsule no cells OU DFE: unremarkable except inf. temp PVD OD

$Imaging Single coronal CT face image demonstrates questionable small R orbital floor fracture and$

Imaging Single coronal CT face image demonstrates questionable small R orbital floor fracture and extensive pneumatization of sinuses of unknown significance

Impression and Plan n Resolving iritis OD, no obvious orbital fxs n Observation, RTC in 2 -3 weeks. Repeat CT scan if symptoms persist

Follow up on 10/02/12 Pt. returned to clinic in 1 week c/o worsening diplopia, headaches, episodes of vomiting and facial numbness. He reported his R eye was “stuck”. No other complaints such as fever, chills, night sweats. BCVA 20/50 P 5 NR 3 2, brisk No RAPD External: pronounced decreased sensation R V 1 and V 2 and RUL ptosis with decreased LF of 4 mm EOM: -3 limitation in all gaze directions OD; full OS SLE: unchanged 1+ c/f

Impression n Rapidly progressive R cranial nerve III, IV, V and VI palsy consistent with cavernous sinus process n DDx: Inflammatory ( orbital pseudotumor, Talosa-Hunt syndrome, sarcoid, etc) Vascular (c-c fistula, cavernous sinus thrombosis) Neoplastic ( infiltration by hematologic or solid malignancies) Infectious (bacterial, fungal)

Plan n Urgent hospital admission n MRI brain and orbits with gadolinium; MRA/MRV n CXR n Lab work: , CBC, CMP, ESR, CRP, ACE, c-ANCA, p-ANCA, RPR, quanti. FERON-TB

Results n MRA/MRV: no C-C fistula, no aneurysm n CXR: no hilar lymphadenopathy n Lab work: negative

MRI Coronal T 1 MRI orbital/brain post contrast images show enhancement of R orbital soft tissue extending toward orbital apex, extensive pneumatization of sinuses and bilateral maxillary sinus disease

MRI Axial T 1 MRI orbital/brain post contrast images demonstrate R orbital soft tissue enhancement extending through orbital apex/superior orbital fissure to cavernous sinus. Soft tissue fullness R cavernous sinus, streaky enhancement of retrobulbar fat of both orbits R>L

Impression/Plan n Idiopathic inflammation possible Talosa-Hunt syndrome n IV corticosteroids n Discharged home on 2 nd hospital day on Prednisone PO 80 mg daily

Follow up on 10/09/12 Pt. continues to c/o binocular horizontal/vertical diplopia and headaches. BCVA Pupils: External: EOM: SLE: OD 20/100 OS 20/20 OD 5 mm NR, OS 3 mm reactive, no RAPD slightly improved R V 1 and V 2 sensation, improved ptosis OD slightly improved motility +0. 5 cells/flare OD

Image montage of five gaze positions demonstrates mild RUL ptosis and -2 limitation of extraocular motility in all gaze directions

Impression/Plan n Mild improvement of R cavernous sinus syndrome on high dose corticosteroids n Clinical presentation concerning for R cavernous sinus carcinomatosis n Corticosteroid taper, neuro-ophth and neurosurgery consult

Neuro-ophth evaluation n Pt. was seen in neuro-ophthalmology clinic within one week. He reported no improvements in his symptoms n Corticosteroids were slowly tapered n Given response to corticosteroids and lesion location, biopsy was postponed at this time

n Over the next four weeks pt. reported slight improvement in his diplopia. n However, he c/o headache, nausea, occasional vomiting, loss of appetite, 15 lbs. weight loss x 3 weeks

Turn for the worse n Pt. presented to ER on 11/24/12 with dyspnea at rest, body aches, dry cough, fevers x 1 week n CBC showed pancytopenia: wbc 1. 97, Hgb 8. 6, plts 12 K n CT chest showed diffuse ground glass opacities and left pleural effusion n Pt. was admitted and started on broad spectrum abx, underwent thoracentesis with 1 L bloody exudate and bone marrow biopsy

Hospital Course n Pt. continued to worsen and was transferred to ICU for acute respiratory distress syndrome (ARDS) and multi system failure n He expired in early December 2012

Final Diagnosis n Thoracentesis fluid flow cytometry analysis showed monoclonal CD 3 -/CD 4 -/CD 8 -/CD 16 -/CD 56+ lymphocytes n Bone marrow biopsy confirmed the same results n These findings are consistent with: Natural killer T cell lymphoma

Discussion Lymphoma of the Ocular Adnexa n 1%-2% of all lymphomas and 8% of extranodal lymphomas arise in the ocular adnexa n 10%-20% of orbital mass lesions are found to be lymphoid tumors n Lymphomas are the most common orbital malignancy Ferry JA, Fung CY, et al. Lymphoma of the ocular adnexa: A study of 353 cases. Am J Surg Pathol. 2007 Feb; 31(2): 170 -84.

Lymphoma of the Ocular Adnexa n Most lymphomas arising in the ocular adnexa are low-grade B-cell lymphomas SYSTEMIC OCULAR ADNEXAL LYMPHOMA (OAL), n=353 Diffuse large B-cell 30. 6% MALT 52% Follicular 22. 1% Follicular 23% MALT 7. 6% Diffuse large B-cell 8% CLL 6. 7% Mantle Cell 5% Mantle Cell 6. 0% CLL 4% Ferry JA, et al. Lymphoma of the ocular adnexa: A study of 353 cases. Am J Surg Pathol. 2007 Feb; 31(2): 170 -84. Harris NL, et al. The World Health Organization classification of neoplasms of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting--Airlie House, Virginia, November, 1997. Hematol J. 2000; 1(1): 53 -66

Natural Killer T (NK/T)-cell lymphoma n NK/T-cell lymphoma, known as "lethal midline granuloma“, is a rare disorder in the US n Type of extranodal lymphoma most commonly originating from nasal passages and paranasal sinuses n More prevalent in Asia and South America where it comprises 5% of all non-Hodgkin lymphomas. Avg age at presentation is 52 yrs n Virtually all cases contain monoclonal episomal EBV DNA Kanavaros P, et al. Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr vi Blood. 1993; 81(10): 2688. Jaffe ES, et al. . Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology. Am J Surg Pathol. 1996; 20(1): 103.

Ocular complications of NK/Tcell lymphoma n Primary orbital/ocular NK/T lymphoma is a very rare condition with only 8 cases reported n Orbital/ocular involvement is most commonly an extension of nasal and paranasal sinus disease n Vision-threatening complications stem from orbital inflammation or uveitis/vitritis Ely A, et al. Orbital involvement in extranodal natural killer T cell lymphoma: an atypical case presentation and review of the literature. Orbit. 2012 Aug; 31(4): 267 -9.

Ocular complications n Hon et al retrospectively studied records of 35 consecutive patients with NK/T lymphoma between 1996 -2000 n 24 pts had primary nasal/sinus disease n 6 out of 24 pts (25%) developed ocular complications: 3 pts had orbital infiltration only 1 pts with orbital infiltration and uveitis/vitritis 2 pt with uveitis/vitritis only n Intraocular involvement such as uveitis and vitritis is an important feature predicting high probability of leptomeningeal or CNS involvement Hon et al. Vision-threatening Complications of Nasal T/NK Lymphoma. American Journal of Ophthalmology 2002; 134 (3): 407 -410.

Prognosis n Extranodal NK/T cell lymphoma is a very aggressive disease n Patients with extranasal disease have median survival of 4 months

Thank you

References 1. 2. 3. 4. 5. 6. 7. 8. Ely A, Evans J, Sundstrom JM, Malysz J, Specht CS, Wilkinson M. Orbital involvement in extranodal natural killer T cell lymphoma: an atypical case presentation and review of the literature. Orbit. 2012 Aug; 31(4): 267 -9. Ferry JA, Fung CY, Zukerberg L, Lucarelli MJ, Hasserjian RP, Preffer FI, Harris NL. Lymphoma of the ocular adnexa: A study of 353 cases. Am J Surg Pathol. 2007 Feb; 31(2): 170 -84. Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD. The World Health Organization classification of neoplasms of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting--Airlie House, Virginia, November, 1997. Hematol J. 2000; 1(1): 53 -66 Hon et al. Vision-threatening Complications of Nasal T/NK Lymphoma. American Journal of Ophthalmology 2002; 134 (3): 407 -410. Jaffe ES, Chan JK, Su IJ, Frizzera G, Mori S, Feller AC, Ho FC. Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology. Am J Surg Pathol. 1996; 20(1): 103. Jakobiec FA. Ocular adnexal lymphoid tumors: progress in need of clarification. Am J Ophthalmol. 2008 Jun; 145(6): 941 -50. Kanavaros P, Lescs MC, Brière J, Divine M, Galateau F, Joab I, Bosq J, Farcet JP, Reyes F, Gaulard P. Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus. Blood. 1993; 81(10): 2688. Woog JJ, Kim YD, Yeatts RP, Kim S, Esmaeli B, Kikkawa D, Lee HB, Korn BS, Punja K, Habermann TM, Colgan JP, Salomao D, Cameron JD. Natural killer/T-cell lymphoma with ocular and adnexal involvement. Ophthalmology. 2006 Jan; 113(1): 140 -7