50-year-old female had been experiencing blurry vision in both her eyes for three to four months
No other significant past ocular history
Exam Findings
BCVA OD 20/25, OS 20/20, IOP normal in both eyes, no pupil abnormalities
Anterior segment slit lamp exam was normal
Figure 1: Dilated fundus exam was notable for vitreous cells and condensation. The vitreous cells were noted in a sheet-like appearance more in the right compared to the left eye.Figure 2: OCT showed preservation of the retinal layering, but marked vitreous debris obscuring the signal.Figure 3: Fluorescein angiography showed questionable mild vascular leakage.Figure 4: Ocular ultrasonography revealed vitreous opacities and mobile membranes. There were areas of hyperechogenicity and mild irregularity of the choroidal wall without any obvious elevations.
Differential Diagnosis
Intermediate Uveitis
Sarcoidosis
Lyme disease
Multiple sclerosis
Intraocular lymphoma
Pars planitis
Chorioretinitis with vitritis
Behcet disease
Toxoplasmosis
Toxocariasis
CMV retinitis
Tuberculosis
White dot syndromes
Additional Investigations
Previous lab work was carried out to reveal:
HLA-B27, HLA-B51, HLA-A29-Negative
RPR/FTA-ABS-Negative
Quantiferon Gold-Negative
ACE-Negative
ANA-Negative
CMV/VZZ/HSV Serologies-WNL
Toxoplasmosis-Negative
Past medical history revealed that five years prior patient had underwent biopsy for a friable mass of her uterus due to abnormal vaginal bleeding
Prior Prior biopsy revealed: Diffuse infiltrates of large atypical lymphoid cells that expressed markers CD45, CD20, CD79a, PAX-5, MUM-1, BCL-6. These were consistent with diffuse large B-cell lymphoma
Patient underwent hysterectomy and systemic chemotherapy over a four month span five years ago
Patient had a PET-CT scan a few months prior to presentation demonstrating no suspicious uptake
Given that the laboratory work up was negative for any infectious or inflammatory markers, a diagnostic pars plana vitrectomy was carried out and showed the following:
Figure 5: Vitreous biopsy revealed large lymphocytes with hyperchromic chromatin, nuclei that vary in size, and scant cytoplasm (left panel). These cells were CD20 positive (middle panel) and CD3 negative (right panel).Figure 6: Stains (left to right) for IRF4/MUM1, PAX5, BCL6, and BCL2 were all positive.
Repeat full body PET-CT revealed hypermetabolic subcentimeter bilateral cervical and hypermetabolic and enlarged bilateral axillary lymph nodes concerning for malignancy
Diagnosis
The vitreous biopsy showed abnormal lymphocytes staining positive for markers CD20, PAX-5, MUM-1, BCL-6, BCL-2, (CD3 negative) consistent with intraocular diffuse B-cell lymphoma with PET-CT demonstrating metastatic disease
Pathophysiology
Diffuse large B-cell lymphoma is the most common form of adult non-Hodgkins lymphoma and is the most frequent lymphoma subtype arising in the eye
The incidence of intraocular lymphoma represents less than 2% of ocular malignant tumors with overall incidence of 0.47 cases per 100,000 people per year
Treatment depends on level of systemic involvement
Prognosis and Future Directions
Prognosis depends on whether CNS is involved, histopathologic type (worse for T cell types), treatment opportunity, and whether it represents metastatic disease or primary disease
The delay between positive diagnosis and onset of ocular or neurological symptoms can be four to 40 months in primary intraocular lymphoma cases
Vitrectomy samples can be negative due to scarcity of cells-then chorioretinal biopsies may be required
Gene expression profiling has provided prognosis and treatment regimens:
Co-expression of BCL6 and IRF4/MUM1 by CD20 positive cells in a vitreous biopsy is suggestive that B-cells are malignant
Staining of Ki-67 usually indicates high tumor cell growth
This patient’s disease is due to metastasis from previously treated lymphoma, likely finding safe harbor in the ciliary body for several years due to the unique vascularity of the tissue and relative immune privilege
References
Akpek et al., Elevated vitreous interleukin-10 level is not diagnostic of intraocular-central nervous system lymphoma. Ophthalmology 106: 2291-2295, 1999.
Coupland SE. Molecular pathology of lymphoma. Eye 27: 180-189, 2013.
Hoang-Xuan K et al., Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology. Lancet Oncol, 16: e322-e332, 2016.
Kim et al., Survival outcomes of primary intraocular lymphoma: a single-institution experience. Am J Clin Oncol., 39: 109-113, 2016.
Korfel A and Schlegel U. Diagnosis and treatment of primary CNS lymphoma. Nat Rev Neurol 9: 317-327, 2013.
Sen HN, et al., Primary intraocular lymphoma: diagnosis and differential diagnosis. Ocul Immunol Inflamm, 17: 133-141, 2009.
Tang L-J, Gu C-L, Zhang P. Intraocular lymphoma. Int J Ophthalmol., 10: 1301-1307, 2017.
Contact
Damien Rodger, MD, PhD, Assistant Professor of Clinical Ophthalmology and Research Assistant Professor of Biomedical Engineering, damien.rodger@med.usc.edu
Due to ongoing developments with COVID-19, we are only able to see patients with urgent eye problems at this time. If you have any questions or concerns, please call us at 323-442-6335.