University of Iowa Health Care

Ophthalmology and Visual Sciences

EyeRounds.org

Orbital Lymphoma:

Two presentations of chronic symptoms

Authors: Nicole C. Morrow, BS; Anthony T. Chung, MD; Audrey C. Ko, MD

Posted June 3, 2019

INITIAL PRESENTATION

Chief Complaint

Chronic dull ache of the left eye

History of Present Illness

A 73-year-old man was referred to the University of Iowa oculoplastics service for evaluation of intermittent, dull aching pain of his left eye (OS) for one year.  He also noticed progressive bulging of both eyes (OU) with associated redness, swelling, intermittent tearing, and mattering that did not improve with artificial tears. Otherwise, he denied changes in vision, pain with eye movements, or diplopia in any gaze position.

Past Ocular History

  • No history of ocular trauma or surgery

Past Medical History

  • Hypertension
  • Hyperlipidemia
  • Atrial fibrillation
  • Thyroid nodules
  • Chronic obstructive pulmonary disease
  • Obstructive sleep apnea

Medications

  • Apixaban
  • Atorvastatin
  • Citalopram
  • Diltiazem
  • Lorazepam
  • Losartan-hydrochlorothiazide

Allergies

  • No known allergies

Family History

  • Non-contributory

Social History

  • Tobacco: 1 pack per day

Review of Systems

  • Negative except for what is detailed in the history of present illness

OCULAR EXAMINATION

Visual Acuity with/without correction (Snellen)

  • Right eye (OD): 20/20
  • Left eye (OS): 20/25 (20/20 via pinhole)

Ocular Motility

  • OD: Full
  • OS: Full

Intraocular Pressure (IOP)

  • OD: Soft to palpation
  • OS: Soft to palpation

Pupils

  • OD: No relative afferent pupillary defect (RAPD)
  • OS: Trace RAPD

External

  • Right: unremarkable; margin to reflex distance 1 (MRD1): 3 mm
  • Left: exophthalmos; MRD1: 0.5 mm

External photograph OU demonstrating left upper eyelid ptosis and mild injection of the left eye

Figure 1: External photograph OU demonstrating left upper eyelid ptosis and mild injection of the left eye

Slit lamp exam, OS

  • Lids/lashes: Left upper eyelid ptosis with fullness inferotemporally
  • Conjunctiva/sclera: Superior salmon-patch lesion with conjunctival hyperemia
  • Cornea: Clear
  • Anterior chamber: Deep and quiet
  • Iris: Normal architecture
  • Lens: Nuclear sclerotic cataract

An external photograph OU demonstrating a unilateral lesion OS with the classic salmon patch appearance of orbital lymphoma OS.

Figure 2: An external photograph OU demonstrating a unilateral lesion OS with the classic salmon patch appearance of orbital lymphoma OS.

An external photograph OS demonstrating the classic salmon-patch appearance of orbital lymphoma and hyperemia of the conjunctiva OS.

Figure 3: An external photograph OS demonstrating the classic salmon-patch appearance of orbital lymphoma and hyperemia of the conjunctiva OS.

Additional testing

Goldmann visual field

  • OD: Superomedial cecocentral defect
  • OS: Full visual field

Differential Diagnosis

  • Orbital lymphoma
  • Benign lymphoproliferative lesion
  • Epithelial tumor
  • Inflammatory/ infectious lesion
  • Metastasis of extraocular tumor
  • Orbital fat prolapse
  • Epibulbar dermoid
  • Orbital Amyloidosis
  • Melanocytic tumor

CLINICAL COURSE

The patient had magnetic resonance imaging (MRI) of the orbits completed; this imaging showed the presence of a left orbital mass encasing the left optic nerve (Figure 4). He underwent left anterior orbitotomy and biopsy of the left orbital lesion. Pathology showed extranodal marginal zone B-cell lymphoma. The patient was referred to hematology-oncology for additional work-up and management of the lymphoma, which included whole body PET/CT and MRI brain and orbits with and without contrast.

 

Figure 4: Axial (left) and coronal (right) cuts of a T1 weighted MRI of the bilateral orbits demonstrating a left-sided orbital mass surrounding the optic nerve.

DIAGNOSIS

Orbital lymphoma, subtype: extranodal marginal zone B-cell lymphoma


Case #2

60-year-old male who was evaluated by internal medicine 1 week earlier for "conjunctivitis" in the left eye

Authors: Andrew Doan, MD, PhD, Thomas Oetting, MD

February 21, 2005

Chief Complaint

60-year-old man who was referred for conjunctivitis.

History of Present Illness

The patient complained of gradual worsening of redness OS over several months. He denied any pain, discharge, discomfort, or itching. He reported fullness of the superior aspect of the left medial canthus as well. The patient also complained of blurry vision of the left eye and binocular diplopia.

Past Ocular History

  • No history of ocular trauma or surgery

Past Medical History

  • Non-Hodgkin's lymphoma (in remission for numerous years)

Medications

  • Non-contributory

Allergies

  • No known allergies

Family History

  • Non-contributory

Social History

  • Non-smoker

Review of Systems

Negative except for what is detailed in the history of present illness

OCULAR EXAMINATION

Best Corrected Visual Acuity (Snellen)

  • OD: 20/20
  • OS: 20/20

Ocular Motility

  • OD: Full
  • OS: Hypotropia with supraduction deficit

Intraocular Pressure (IOP)

  • OD: 18 mm Hg
  • OS: 19 mm Hg

Pupils

  • OU: 4.5 mm in dark; 3.5 mm in light; no RAPD OU

External

  • Hertel exophthalmometry: (base 113 mm)
    • Right: 13 mm
    • Left: 17 mm

Slit lamp exam, OS

  • Lids/lashes: Left upper eyelid ptosis with fullness superotemporally
  • Conjunctiva/sclera: Superior conjunctival hyperemia
  • Cornea: Clear
  • Anterior chamber: Deep and quiet
  • Iris: Normal architecture
  • Lens: Nuclear sclerotic cataract

EOM

Figure 1: EOM- Note the left hypotropia in primary gaze and elevation deficit OS with upgaze.

OS

Figure 2: Left eye with superior conjunctival injection.

Ptosis

Figure 3: Left medial canthus with fullness. Note the asymmetric ptosis OS (more ptosis medially).

Coronal CT without contrast.

Axial CT without contrast.

Note: large medial mass indenting globe Note: large medial mass displacing medial rectus but is not eroding into bone or surrounding soft tissue.
CT CT

Figure 4: CT Scan

Anterior Orbitotomy

Figure 5: Anterior orbitotomy. Note the fleshy mass in the superior-nasal quadrant.

Differential Diagnosis

  • Orbital lymphoma
  • Benign reactive lymphoid hyperplasia or atypical lymphoid hyperplasia
  • Cavernous hemangioma 
  • Optic nerve meningioma 
  • Orbital metastasis 
  • Neurofibroma 
  • Neurilemoma (i.e., benign schwannoma) 
  • Fibrous histiocytoma 
  • hemangiopericytoma 
  • Lymphangioma
  • Mucocele
  • Thyroid disease (most common cause of unilateral proptosis in adults)

CLINICAL COURSE

The patient presented with acute awareness of a long-standing problem: fullness of the upper lid, binocular diplopia, and injection of the left eye. However, he did not have other signs of infection, such as pain, itching, tearing, or discharge. On exam, his left-sided upper eyelid ptosis, unilateral supraduction deficit, proptosis, and a firm palpable mass in the superonasal quadrant raised the suspicion of an orbital mass.  Due to his history of non-Hodgkin's lymphoma, orbital imaging was obtained.  Computed tomography of the orbits showed a large orbital mass that molded to surrounding structures without direct invasion.

An anterior orbitotomy was notable for a large, pink mass. Pathology confirmed the mass to be a CD20 and BCL-2 positive lymphoma.  Extensive imaging studies of the head and body did not reveal any additional tumor.  The patient was treated by radiation oncology with local radiation.

DISCUSSION

Orbital Lymphoma

The cases above describe two presentations of orbital lymphoma with chronic symptoms.  The epidemiology and etiology of various subtypes, the most common presenting signs and symptoms, and initial work-up and management of orbital lymphoma are detailed below.

Etiology/Epidemiology

Ocular adnexal lymphomas can arise in the eyelids, conjunctiva, lacrimal glands, and, most commonly, the orbit [1]. They are the most common primary ocular malignancy in adults and account for roughly 10% of all neoplasms [1, 2]. The vast majority of orbital lymphomas present later in life with 73% of patients over the age of 50 [1]. There is no gender predilection for orbital lymphomas of B-cell origin. However, extra-marginal zone and follicular lymphoma more commonly presents in women, whereas mantle cell lymphoma more commonly presents in men [1].

Orbital lymphoma usually presents unilaterally with bilateral involvement in 10-20% of cases [1, 3]. The extraconal space is the most common location for orbital lymphoma (73% for B-cell origins and 58% for T-cell origins). Approximately half of B-cell lymphomas and one quarter of T-cell lymphomas involve the lacrimal gland. T-cell lymphomas are more likely to have extraocular muscle extension, which is reported in 26% of cases. Conversely, only 9% of B-cell lymphomas involve the extraocular muscles [1].

Signs/Symptoms

The most common presenting symptom of orbital lymphoma is unilateral proptosis. Other symptoms include ocular/orbital pain, decreased vision, double vision, and chronic red eye. Systemic B-symptoms, including fevers, chills, and night sweats, are reported in roughly 8% of patients [1].

On exam, orbital lymphoma may have a classic "salmon-patch" appearance (Figures 2 and 3), restriction in extraocular motility, periorbital edema, ptosis, hyperemic conjunctiva, and/or a firm palpable mass [4]. The time to presentation varies greatly between the subtypes of lymphoma. Higher grade subtypes, such as Burkitt lymphoma, usually present within a few days, whereas lower grade subtypes, such as small lymphocytic lymphoma, may not present until 18 months after initial onset of symptoms [1]. This delay for some subtypes may partly be due to an indolent nature and/or misdiagnosis secondary to atypical appearance on imaging studies [5].

Testing/Laboratory work-up/Imaging

Work-up initially includes CT or MRI of the orbit followed by chest and abdominal imaging to identify additional spread of the disease. A bone marrow biopsy may be indicated to determine bone marrow involvement.  Diagnosis is confirmed via anterior orbitotomy with histopathologic and immunohistochemical examination [1].

Treatment/Management/Guidelines

Treatment is managed by a multi-disciplinary team of ophthalmologists, radiation-oncologists, and hematology-oncologists.  Management is tailored based on the subtype of lymphoma and clinical stage of the disease. Chemotherapy regimens and radiation therapy are the mainstay of lymphoma management [1]. The most frequently reported complications are due to the effects of orbital radiation therapy, which include cataracts (12.1%), dry eye (8.5%), conjunctivitis (6.8%), and keratitis (4.9%) [3]. Additional side effects, such as radiation retinopathy, corneal ulceration, and macular degeneration, are less commonly reported but are associated with higher radiation doses [1, 3].

Prognosis is highly dependent upon subtype. Extra-marginal zone lymphoma has the best prognosis with a mortality of 12% at five years versus 53% at five years for mantle cell lymphoma, small lymphocytic lymphoma, Burkitt lymphoma, and T-cell lymphoblastic lymphoma [1].

DIAGNOSIS

Orbital Lymphoma

EPIDEMIOLOGY

  • Incidence: in Florida, 2 cases per million
  • Age: all ages
  • Among the most common orbital tumors seen in the adults: cavernous hemangioma, lymphoid tumors, and meningiomas

SIGNS

  • Salmon patch lesion on globe
  • CT scan will show a lesion that pushes and molds surrounding structures and bone. There is no erosion into surrounding tissue.
  • Non-tender, firm mass

SYMPTOMS

  • Gradual onset
  • Painless
  • Slow progression
  • Binocular diplopia
  • Extraocular motility problems
  • Proptosis
  • Mechanical ptosis from tumor pushing down lid

TREATMENT

  • Depends on type of tumor and extension.
  • Chest and abdominal CT are used to identify abnormal nodes and spread.
  • Bone marrow aspiration to rule out marrow involvment.
  • If there is no systemic involvement, orbital lymphomas are typically sensitive to local radiation.
  • Chemotherapy is an option for patients with systemic involvment.
  • Incisional biopsy is needed for pathologic diagnosis.

References

  1. Olsen TG, Heegaard S. Orbital lymphoma. Surv Ophthalmol 2019;64(1):45-66.  https://PubMed.gov/30144455. DOI: 10.1016/j.survophthal.2018.08.002
  2. Watkins LM, Carter KD, Nerad JA. Ocular adnexal lymphoma of the extraocular muscles: case series from the University of Iowa and review of the literature. Ophthalmic Plast Reconstr Surg 2011;27(6):471-476.  https://PubMed.gov/22072211. DOI: 10.1097/IOP.0b013e31822e5c1b
  3. Yen MT, Bilyk JR, Wladis EJ, Bradley EA, Mawn LA. Treatments for Ocular Adnexal Lymphoma: A Report by the American Academy of Ophthalmology. Ophthalmology 2018;125(1):127-136.  https://PubMed.gov/28712656. DOI: 10.1016/j.ophtha.2017.05.037
  4. Maheshwari A, Finger PT. Cancers of the eye. Cancer Metastasis Rev 2018;37(4):677-690.  https://PubMed.gov/30203109. DOI: 10.1007/s10555-018-9762-9
  5. Briscoe D, Safieh C, Ton Y, Shapiro H, Assia EI, Kidron D. Characteristics of orbital lymphoma: a clinicopathological study of 26 cases. Int Ophthalmol 2018;38(1):271-277.  https://PubMed.gov/28364339. DOI: 10.1007/s10792-017-0457-y

Suggested citation format

Doan A, Oetting TA: Verticillata: Orbital Lymphoma: 60-year-old male who was evaluated 1 wk ago for "conjunctivitis" OS by internal medicine. February 21, 2005; Available from: http://www.EyeRounds.org/cases/case9.htm.

last updated: 02/01/2005; Revised 6/3/2019
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