Ocular Manifestation with Initial Negative Biopsy of Natural Killer Cell Lymphoma
Tam Ramsey1*, Brandon Menke2,
Shawn Iverson2, Andrew S Eiseman3, Rakesh M Patel2
1University
of South Carolina, School of Medicine, Columbia, South Carolina, USA
2Palmetto
Health - USC Medical Group Ophthalmology, Columbia, South Carolina, USA
3Department
of Ophthalmology, Medical University of South Carolina, Charleston, South
Carolina, USA
*Corresponding Author: Tam Ramsey, University of South Carolina, School of Medicine, Columbia, South Carolina, USA. Tel: +18032163300; Email: tam.ramsey@uscmed.sc.edu
Citation: Ramsey T, Menke B, Iverson S, Eiseman AS, Patel RM (2017)
Ocular Manifestation with Initial Negative Biopsy of Natural Killer Cell
Lymphoma. Ophthalmol Res Rep: ORRT-125. DOI: 10.29011/ORRT-125. 100025
1. Introduction
Natural Killer
(NK)/T-cell lymphoma is a rare primary non-Hodgkin lymphoma. It can be divided
into nasal, non-nasal, and aggressive NK leukemia/lymphoma subtypes [1].
Nasal NK/T cell lymphoma refers to malignancies originating in the
nasopharyngeal area, causing destruction of the nasal cavity, paranasal
sinuses, orbits, and surrounding structures. Common presenting signs are
midline mass with obstruction, nasal bleeding, and perforation of the hard
palate [2]. This subtype is more common in Asia and South America and
relatively rare in Western countries [3]. The average age of affected
patients is 50-60 years old, and it occurs three times more in males than
females [2]. Due to its rare incidence and deceiving presentation, it is
often misdiagnosed as chronic sinusitis, granuloma, or fungal infection; thus,
the final diagnosis and treatments can be delayed.
The majority of
patients with nasal NK lymphoma are positive for Epstein Barr Virus (EBV). In
fact, EBV viral load has been used in disease staging [1]. Microscopically,
nasal NK lymphoma is marked by aggressive angioinvasion in a background of CD3+
and CD56+ atypical lymphocytes and inflammatory cells [2]. The prognosis
is relatively poor with a 5-year cumulative survival rate of approximately
40% [4]. CHOP regimen (cyclophosphamide, doxorubicin, vincristine and
prednisolone) is used concurrently with radiotherapy for stage 1 and 2, while
chemotherapy alone is the mainstay of treatment for stages 3 and 4 [5].
Autologous or allogeneic hematopoietic stem cell transplantation has been
considered in advanced disease with unclear prognostic benefits [5].
This report presents
the first case of an elderly Caucasian female with NK lymphoma initially
presenting as orbital cellulitis. Collection and evaluation of protected
patient health information was HIPAA-compliant.
2. Case Presentation
A 92-year-old
Caucasian female with history of hypothyroidism, glaucoma, migraines,
cataracts, and hypertension was admitted to the hospital with a one-week
history of right eye vision loss that was preceded by ipsilateral swelling and
associated bilateral pain for four weeks.
Examination revealed
an afferent pupillary defect and abduction deficit of right eye, partial ptosis
and proptosis, no pain with ocular movements, and no drainage or significant
swelling or abnormality on slit lamp exam. On dilated fundoscopic exam, optic
nerve cup to disc ratios were 0.3 with sharp nerve margins bilaterally; macula,
vessels, and peripheral retina appeared intact. Uncorrected visual acuities
were hand motion on the right, and 20/30 on the left eye. Intraocular pressures
were19 on the right, and 13 on the left. Lab results showed WBC 6.32, Hb 15.3,
platelets 189, ESR 11, CRP 11.1. MRA revealed multifocal atherosclerosis with
no aneurysm or occlusion. MRI demonstrated a right intra-orbital infiltrate
along the medial wall with extension to the orbital apex causing optic nerve
and medial rectus muscle impingement and complete opacification/consolidation
of the right ethmoid air cells and sphenoid sinuses (Figure 1). Orbital
cellulitis was suspected at this point. The patient was started on aggressive
antibiotics and taken for sinus drainage and medial orbitotomy. Endoscopy
observed semi solid and granular whitish material in ethmoid sinuses, extensive
mucus in the sphenoid sinus, and no bony destruction. Several biopsies were
taken of the sinus demonstrating inflamed stromawith mixed serous and mutinous
glands, dense inflammatory infiltrate of acute and chronic inflammatory cells
with areas of necrosis, rare eosinophils and benign respiratory epithelium.
Cultures and special stains for bacteria and fungi were positive only for Propionibacteriumacne.
The leading differential diagnosis at this point was chronic sinusitis with
necrosis. Patient was discharged on rapid prednisone taper and 4 weeks of
vancomycin/ceftriaxone/metronidazole.
The patient was
readmitted 2 weeks later for lower extremity deep vein thrombosis in the
setting of a thrombocytopenia of 65000 and a persistent medial orbital mass. A
new antibiotic regimen of doxycycline/metronidazole resulted in resolution of
the thrombocytopenia. Antibiotics were later discontinued all together due to
lack of ocular improvement. The patient was taken back to the operating room
for a repeat biopsy due to a CT scan showing an enhancing mass involving the
extraconal soft tissue paralleling the posterior ethmoid air cells, concerning
for a possible neoplasm. Intraoperatively, the medial rectus appeared to be
grayish in color concerning for muscle infarction. Final pathology noted a
partial fibro vascular and fibro muscular necrosis containing only a few
crushed lymphocytes and scattered acute inflammatory cells. Cultures continued
to be negative. Flow cytometry was negative for lymphoma. No diagnostic evidence
of malignancy or features of lymph proliferative disorder were indicated on
histology. CT chest/abdomen/pelvis to rule out metastatic malignancy was only
notable for a 1 cm pulmonary nodule in left lower lobe. Idiopathic orbital
inflammatory syndrome labs showed mildly elevated erythrocyte sedimentation
rate and CRP; negative RPR, ANA, c-ANCA and p-ANCA. Given these findings, the
diagnosis of chronic sinusitis with orbital extension was still the leading
diagnosis. The patient was discharged again on a steroid taper (Figure 2).
A month later, the
patient presented for the third time after sustaining a fall with accompanying
fever. On examination, complete ophthalmoplegia and complete ptosis of the
right side with V1-V2 anesthesia consistent with orbital apex syndrome was
identified. CT sinus showed that the orbital apex mass had increased in size
and now involved the maxillary sinus and the contra lateralside (Figure 3). The
patient also endorsed intermittent fever, night sweats, and 6 pounds of weight
loss over the past month. She was transferred to a tertiary care facility for
further workup. There, chest X-ray and CT head were again negative. She
initially did well with medial wall orbital decompression and biopsy and was
started on antifungal and antibiotics regimens, but subsequently developed
altered mental status. Due to her deteriorating condition, the patient and
family declined further interventions and instead opted for home palliative
care. The biopsy results were positive for CD56 consistent with the diagnosis
of NK lymphoma.
3. Discussion
Natural Killer
(NK)/T-cell lymphoma is a rare malignancy accounting for less than 1 percent of
all lymphomas in North America and Europe [6]. The nasal type involves the
nose and sinuses with possible orbital extension. Common presenting signs are
midline mass with obstruction, nasal bleeding, and perforation of the hard
palate [3]. Ocular manifestations are infrequently reported [7].
However, if orbital extension does occur, it may be the first sign of disease
and present as orbital cellulitis that does not improve with adequate
antibiotics [8]. Imaging may demonstrate bony destruction and a soft
tissue mass invading surrounding structures [9]. However, these findings
are nonspecific and can indicate systemic granulomatous disease or local
tumors. Histologically, NKTL shows polymorphic inflammatory infiltration with
angio destruction. However, in early stages, atypical cells are scarce and
obscured by inflammatory cells recruited from tumor secreting cytokines, which
can lead to a misdiagnosis of inflammatory processes and infection [10].
EBV, CD56, and CD3 are strongly associated with NKTL and have been used to
define NKTL in published case series [11].
Our case
demonstrates a rare presentation of NK/T lymphoma mimicking orbital cellulitis
and chronic sinusitis. This 92-year-old Caucasian female patient was not part
of the typical demographic which is a 50-year-old Asian male. There was no
nasal obstruction, ulcer, or epistaxis as frequently described in literature.
The patient’s slight improvement on antibiotics and steroid initially gave
false reassurance of the diagnosis of cellulitis. Furthermore, over the course
of 4 months, multiple tissue biopsies and flow cytometry performed specifically
to rule out malignancy were negative.
Clinicians must
maintain a high index of suspicion and have NKTL in their differential
diagnoses in patients that appear to have persistent orbital cellulitis despite
antibiotics, especially when orbital apex signs are present without significant
pain. Initial negative immunohistochemistry and histology cannot be used to
completely rule out this type of lymphoma due to a lack of sensitivity. Bony
destruction in the context of what appears to be cellulitis or sinusitis should
raise suspicion of malignancy and as in this case, multiple biopsies may be
required to make the diagnosis.
4. Conflict of Interest
and Source Funding
None declared
Figure 1: Abduction
deficit, partial ptosis, and proptosis of the right eye (top: straight gaze,
middle: left gaze, bottom: right gaze).
Figure 2:
Retrobulbarextraconal mass along the medial orbit near the apex impinging on
the right optic nerve, and consolidation in the ethmoid air cells and the
sphenoid sinus.
Figure 3: Persistent pacification
of sphenoid sinuses, right ethmoidal air cells with extension from medial orbit
into the orbital apex (arrow). New involvement of maxillary and possible
frontal sinuses.
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