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.
-

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:

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 q1-2 h

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

He returned to local ophthalmologist on 09/15/12 c/o
“eye making popping sounds”

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
1st 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: PredForte 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 V1 and
V2, intact V3
Objective
SLE:
OD
L/L
C/S
K
AC
I/L
Vit
OS
normal OU
clear 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 extensive pneumatization of sinuses of unknown significance
Impression and Plan

Resolving iritis OD, no obvious orbital fxs

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 V1 and V2
and RUL ptosis with decreased LF of 4mm
EOM: -3 limitation in all gaze directions OD; full OS
SLE: unchanged 1+ c/f
Impression

Rapidly progressive R cranial nerve III, IV, V and
VI palsy consistent with cavernous sinus process

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

Urgent hospital admission

MRI brain and orbits with gadolinium; MRA/MRV

CXR

Lab work:, CBC, CMP, ESR, CRP, ACE, c-ANCA,
p-ANCA, RPR, quantiFERON-TB
Results

MRA/MRV: no C-C fistula, no aneurysm

CXR: no hilar lymphadenopathy

Lab work: negative
MRI
Coronal T1 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 T1 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

Idiopathic inflammation possible Talosa-Hunt
syndrome

IV corticosteroids

Discharged home on 2nd 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 5mm NR, OS 3mm reactive, no RAPD
slightly improved R V1 and V2 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

Mild improvement of R cavernous sinus
syndrome on high dose corticosteroids

Clinical presentation concerning for R
cavernous sinus carcinomatosis

Corticosteroid taper, neuro-ophth and
neurosurgery consult
Neuro-ophth evaluation

Pt. was seen in neuro-ophthalmology clinic
within one week. He reported no
improvements in his symptoms

Corticosteroids were slowly tapered

Given response to corticosteroids and lesion
location, biopsy was postponed at this time

Over the next four weeks pt. reported slight
improvement in his diplopia.

However, he c/o headache, nausea, occasional
vomiting, loss of appetite, 15 lbs. weight loss x 3
weeks
Turn for the worse

Pt. presented to ER on 11/24/12 with dyspnea at rest,
body aches, dry cough, fevers x 1 week

CBC showed pancytopenia: wbc 1.97, Hgb 8.6, plts 12K

CT chest showed diffuse ground glass opacities and left
pleural effusion

Pt. was admitted and started on broad spectrum abx,
underwent thoracentesis with 1L bloody exudate and bone
marrow biopsy
Hospital Course

Pt. continued to worsen and was transferred to
ICU for acute respiratory distress syndrome
(ARDS) and multi system failure

He expired in early December 2012
Final Diagnosis

Thoracentesis fluid flow cytometry analysis showed
monoclonal CD3-/CD4-/CD8-/CD16-/CD 56+
lymphocytes

Bone marrow biopsy confirmed the same results

These findings are consistent with:
Natural killer T cell lymphoma
Discussion
Lymphoma of the Ocular Adnexa

1%-2% of all lymphomas and 8% of extranodal
lymphomas arise in the ocular adnexa

10%-20% of orbital mass lesions are found to
be lymphoid tumors

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

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

NK/T-cell lymphoma, known as "lethal midline granuloma“, is a
rare disorder in the US

Type of extranodal lymphoma most commonly originating from
nasal passages and paranasal sinuses

More prevalent in Asia and South America where it comprises 5%
of all non-Hodgkin lymphomas. Avg age at presentation is 52 yrs

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
virus. 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

Primary orbital/ocular NK/T lymphoma is a very rare
condition with only 8 cases reported

Orbital/ocular involvement is most commonly an
extension of nasal and paranasal sinus disease

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

Hon et al retrospectively studied records of 35 consecutive patients
with NK/T lymphoma between 1996-2000

24 pts had primary nasal/sinus disease

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

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

Extranodal NK/T cell lymphoma is a very
aggressive disease

Patients with extranasal disease have median
survival of 4 months
Thank you
References
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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