Choroidal Lymphoma Research Articles

Review of spectral domain enhanced depth imaging optical coherence tomography of tumors of the choroid.

Background:Spectral domain enhanced depth imaging optical coherence tomography (EDI-OCT) can provide anatomic localization of intraocular tumors.Aims:The aim was to identify topographical and intrinsic patterns of choroidal tumors on EDI-OCT.Settings and Design:Retrospective review.Materials and Methods:Analysis of published reports and personal observations using office based EDI-OCT.Results:Using EDI-OCT, choroidal nevus displayed a smooth, dome-shaped topography with overlying retinal pigment epithelium alterations, drusen, and occasional subretinal cleft demonstrating photoreceptor loss. Small choroidal melanoma showed smooth, moderately dome-shaped topography, commonly with overlying shallow subretinal fluid that often depicted “shaggy” photoreceptors. Choroidal metastasis showed a minimally “lumpy, bumpy” surface topography and with overlying subretinal fluid and shaggy photoreceptors. Choroidal hemangioma showed a smooth, dome-shaped topography, with expansion of the affected small, medium, and large choroidal vessels. Choroidal lymphoma showed varying topography with increasing tumor thickness as “flat, rippled, or undulating (seasick)” surface. Choroidal osteoma displayed a smooth undulating surface with visible intralesional horizontal lines suggestive of bone lamellae and occasional horizontal and vertical tubules with intralesional “spongy” flecks. Choroidal melanocytosis appeared as uniformly thickened choroid with increased stromal density surrounding the normal choroidal vascular structures.Conclusions:Enhanced depth imaging-OCT can depict characteristic patterns that are suggestive of various choroidal tumors.

Enhanced depth imaging optical coherence tomography of intraocular tumors: from placid to seasick to rock and rolling topography--the 2013 Francesco Orzalesi Lecture.

To review enhanced depth imaging optical coherence tomography of intraocular tumors. Review of tumor surface topography and internal characteristics based on published reports and personal experience. Using enhanced depth imaging optical coherence tomography, choroidal nevus showed smooth moderate dome-shape and with overlying retinal pigment epithelial alterations, subretinal cleft, and photoreceptor loss. Choroidal melanoma was smooth, moderately dome-shaped, and with overlying "shaggy" photoreceptors. Choroidal metastasis showed "lumpy, bumpy" irregular surface topography, subretinal fluid, and shaggy photoreceptors. Choroidal hemangioma was smooth, acutely dome-shaped and with subretinal fluid and/or cystoid retinal edema. Choroidal lymphoma showed "placid, rippled, or seasick" surface, correlating with increasing tumor thickness. Choroidal osteoma displayed smooth undulating surface with intralesional lamellar lines and tubules, representing bone lamellae or vessels. Choroidal melanocytosis produced flat but uniformly thickened choroid with increased stromal density. Choroidal hemorrhage displayed slightly "scalloped" surface in the outer choroid. All choroidal tumors showed inward compression of the choroidal vasculature, except for hemangioma in which the vessels were expanded. Sclerochoroidal calcification arose within the sclera as a "rocky" or "rolling" topography and solitary idiopathic choroiditis appeared as a domed or "volcanic" focal scleral thickening, each causing intense choroidal compression. Retinal tumors such as small retinoblastoma, astrocytic hamartoma, and hemangioblastoma arose abruptly adjacent to normal retina. Exophytic retinoblastoma and retinal hemangioblastoma depicted a full-thickness disorganized retinal mass with normal retina draped over the margins. Flat astrocytic hamartoma arose within the nerve fiber layer, and thicker tumors involved full-thickness retina with "moth-eaten" or cavitary appearance. Retinal pigment epithelial lesions such as congenital hypertrophy of retinal pigment epithelial showed flat topography with transmission of light through lacunae, occasional subretinal cleft and uniform photoreceptor loss, whereas combined hamartoma of retina/retinal pigment epithelial showed "sawtooth" pattern of vitreoretinal traction leading to mini-peak or maxi-peak retinal folds. Enhanced depth imaging optical coherence tomography shows characteristic topographical and intralesional patterns that appear to be suggestive for selected intraocular tumors.

CHOROIDAL LYMPHOMA SHOWS CALM, RIPPLED, OR UNDULATING TOPOGRAPHY ON ENHANCED DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY IN 14 EYES

To describe the features of choroidal lymphoma on enhanced depth imaging optical coherence tomography. This retrospective observational case series included 14 eyes of 13 patients, with choroidal lymphoma, studied by enhanced depth imaging optical coherence tomography. The mean age at presentation was 63 years (median, 65 years; range, 32-87 years). Systemic lymphoproliferative disease was present in 2 cases as non-Hodgkin lymphoma (n = 1) or Waldenstrom macroglobulinemia (n = 1). On clinical examination, the choroidal infiltrate was classified as unifocal (n = 3), multifocal (n = 4), or diffuse (n = 7). Enhanced depth imaging optical coherence tomography scans through the tumor epicenter revealed infiltration of the choroid with apparent inward compression of choroidal vascular structures, creating an anterior tumor surface topography that appeared smooth (calm) (n = 7), mini-wavy (rippled) (n = 2), or maxi-wavy (undulating) (n = 5). Greater tumor thickness correlated with increasing tumor surface fluctuation as calm was mean 1.7mm, rippled was 2.8 mm, and undulating surface was 4.1 mm in ultrasonographic thickness. On enhanced depth imaging optical coherence tomography, the mean subfoveolar choroidal thickness, measurable in 9 eyes, was 484 μm (median, 423 μm; range, 156-1,002 μm) (81% greater) versus 267 μm (median, 276 μm; range, 142-501 μm) in the unaffected eye. The mean maximal tumor thickness, measurable in 8 eyes, was 117% greater at 602 μm (median, 538 μm; range, 241-966 μm) compared with the corresponding unaffected choroid in the contralateral eye at 278 μm (median, 245 μm; range, 189-511 μm) (P = 0.046). Inability to measure choroidal thickness was due to dense tumor-induced optical shadowing with inability to visualize the sclerochoroidal junction (P = 0.009). There was no visible infiltration into the overlying retina in any case. Enhanced depth imaging optical coherence tomography of choroidal lymphoma revealed 1 of 3 surface topographical patterns resembling an ocean as calm (n = 7), rippled (n = 2), or undulating (n = 5), correlating with increasing tumor thickness.

Relationship between Suspected Reasons of Intraocular Inflammation and the Results of Diagnostic Vitrectomy: An Observational Study

Background: Intraocular inflammation of the posterior segment may be associated with neoplastic, infectious, and inflammatory diseases. Biopsy of vitreous and additional ocular tissue might be required for a definitive diagnosis. We therefore aimed to investigate the safety and usefulness of diagnostic vitrectomy in intraocular inflammation.Method: We performed an observational retrospective study of patients who underwent vitreous biopsy due to atypical intraocular inflammation, experienced failed resolution to empirical therapy, or for whom there was suspicion of an underlying neoplastic process.Results: Seventy consecutive patients were included due to idiopathic uveitis of the posterior segment unresponsive to systemic corticosteroids (n = 33, 47%), suspected vitreoretinal or choroidal lymphoma (n = 18, 26%), viral retinitis (n = 17, 24%), and suspected endogenous endophthalmitis (n = 2, 3%). Suspected viral retinitis was most often confirmed (13/17, 76%), followed by lymphoma (6/18, 33%). Remarkably, a proportion of suspected idiopathic uveitis was infectious (7/33, 21%). The most prevalent adverse event following diagnostic vitrectomy was cataract surgery in phakic patients (n = 16/41, 39% of phakic patients). Retinal detachments were observed chiefly in infectious or neoplastic disease (n = 5, 7%) after a median time of 105 days.Conclusion: Diagnostic vitrectomy was helpful in substantiating the clinical suspected diagnosis of posterior segment inflammation. Potential secondary adverse events should be kept in mind.

Choroidal Lymphoma: Clinical Features and Association with Systemic Lymphoma

To describe the clinical and histopathologic features of choroidal lymphoma (CL) and its association with systemic lymphoma. Observational case series. Fifty-nine patients (73 eyes) with CL. Retrospective chart review. Clinical features, histopathology, and systemic lymphoma. Of 59 patients with CL, systemic lymphoma was absent in 41 (primary CL; 69%) and present in 18 (secondary CL; 31%). Of 18 patients with systemic lymphoma at presentation, 14 (78%) had known systemic lymphoma and 4 (22%) were diagnosed with systemic lymphoma shortly after presentation. The most common types of systemic lymphoma in patients with secondary CL were diffuse large cell lymphoma (n= 5, 28%), chronic lymphocytic leukemia/lymphoma (n= 4, 22%), multiple myeloma (n= 2, 11%), Waldenstrom's macroglobulinemia (n= 2, 11%), extranodal marginal zone lymphoma (n= 2, 11%), plasmablastic lymphoma (n= 1, 6%), and unspecified non-Hodgkin lymphoma (n= 2, 11%). Compared with patients with primary CL, patients with secondary CL had a shorter mean duration of ocular symptoms (5 vs. 17 months), had less often received steroids before referral (11% vs. 46%), and were more likely to have bilateral ocular involvement (33% vs. 20%). Eyes with secondary CL had a higher rate of poor vision (≤20/200) (46% vs. 12%), iris (20% vs. 4%) or ciliary body (30% vs. 8%) lymphoma, episcleral vascular congestion (40% vs. 16%), anterior chamber reaction (30% vs. 14%), hyphema (15% vs. 0%), vitreous cellular infiltration (30% vs. 4%), and severe media haziness (20% vs. 0%). Secondary CL was morphologically more high grade (50% diffuse large cell lymphoma) compared with primary CL (37% low-grade non-Hodgkin lymphoma, 27% extranodal marginal zone lymphoma). None of the 33 patients with primary CL and subsequent follow-up developed systemic lymphoma during a mean follow-up of 50 months (median, 35 months; range, 2-231 months). Secondary CL is morphologically high grade and associated with more severe ocular findings. Patients with CL and no known systemic lymphoma at presentation should undergo systemic evaluation to rule out the possibility of undiagnosed concurrent systemic lymphoma. However, none of the patients with primary CL in our study had late development of systemic lymphoma.

The seasick choroid: a finding on enhanced depth imaging spectral-domain optical coherence tomography of choroidal lymphoma.

To describe previously unreported imaging features of choroidal lymphoma using enhanced depth imaging optical coherence tomography (OCT). Enhanced depth imaging OCT was performed before and after the therapy. A 32-year-old white man with a 4-month history of blurred vision in the right eye was found to have a macular fold. There was no visible intraocular tumor. There were no signs of anterior segment inflammation, vascular abnormalities, or infiltrative disease. Visual acuity was 20/150 in the right eye and 20/20 in the left eye. Enhanced depth imaging OCT demonstrated a macular retinal fold and marked thickening of the choroid with striking choroidal surface undulation and folds imparting an appearance similar to a "sea storm" (seasick appearance). Deep choroidal structures could not be visualized, and the sclerochoroidal interface could not be identified. Overlying subretinal fluid and intraretinal fluid was noted. Ultrasonography demonstrated diffuse, relatively smooth thickening of the choroid (4.0-mm thickness) with minor extraocular hypoechoic area. Based on these findings, choroidal lymphoid proliferation was suspected, and fine-needle aspiration biopsy confirmed B-cell lymphoma. Results of systemic evaluation were unremarkable. After external beam radiotherapy with dose of 40 Gy, visual acuity returned promptly to 20/40 and the lymphoid infiltration resolved with flattening of the macular fold and resolution of subretinal and intraretinal fluids. The enhanced depth imaging OCT returned to a more normal appearance with the resolution of the retinal fold and reduction of the choroidal mass with retinal pigment epithelial-choroidal surface features to a "calm sea" appearance. Enhanced depth imaging OCT is a useful tool for subclinical monitoring of choroidal infiltration from lymphoma before and after therapy.

Intraocular lymphoma: a clinical perspective

Primary vitreoretinal lymphoma (PVRL) is a rare malignancy that is speculated to arise extraocularly, and preferentially invade and flourish in the ocular and CNS microenvironments. The eye is involved in about 20% of primary central nervous system lymphomas, but the brain is eventually involved in about 80% of PVRL. Most are B-cell lymphomas with small numbers of T-cell lymphomas metastatic to the vitreous and retina. Metastatic systemic B-cell lymphoma usually involves choroid. Primary choroidal lymphoma is rare. Intraocular lymphoma can usually be distinguished from uveitis clinically, although there are overlaps, which may be pronounced in eyes with a large component of reactive inflammation related to tumor surveillance and control. There are controversies in diagnosis and treatment. Diagnosis through examination of ocular fluid is technically difficult and can utilize cytology, immunohistochemistry, flow cytometry, molecular detection of gene rearrangements, and cytokine profiling. Treatment of intraocular lymphoma without detectable CNS disease could consist of a full course of systemic chemotherapy with ocular adjunctive treatment, or ocular treatment alone depending on the preference of the clinical center. In ocular only cases where the vitreous has been debulked to improve vision and there is no sight-threatening involvement of the RPE, orbital irradiation or intravitreal chemotherapy stabilizes the intraocular process but does not seem to modify the CNS component, which can present symptomatically in an advanced state. This is a highly malignant disease with a poor prognosis. Close collaboration with a pathologist and oncologist, and good communication with patients is essential.

Diagnosis of choroidal lymphoma, difficulties and possibilities

AbstractPurpose To describe a case of choroidal lymphomaMethods A 66 y old man presented with left vitritis; 3y before presentation a testicular large B‐cel lymphoma was detected and treated by 8x R‐CHOP and 4x intrathecal chemo. General and hematologic examination failed to indicate a recurrence; because of the negative vitreous biopsy, the hematologists decided to give no systemic treatment. The left eye lost slowly vision and had the aspect of diffuse uveal melanocytic proliferation (BDUMP). After 6 methotrexaat vitreal injections, the choroid remain flat with the image of BDUMP, then very fast, a tumour was growing in the choroid and an enucleation was unavoidableResults The first vitreous biopsy showed multiple cells with a majority of macrophages (CD68+, 75%), small mature T‐Lymphocytes (CD3+, 20%) and very few larger B‐lymfocytes (CD20+, 5%). A second vitreous biopsy after 2 years showed a very cellular sample with a majority of macrophages, and small T‐lymphocytes, there were no B‐lymphocytes. 3 months later a spectacular tumour growth in all parts of the uvea necessitated an enucleation. This confirmed the diagnosis of uveal large B‐cell lymphoma, with a Ki‐67 positivity of nearly 100%Conclusion Lymphoma in the eye is a difficult diagnostic problem

Secondary choroidal lymphoma in a child treated for Burkitt lymphoma

A 9-year-old girl presented with a choroidal tumor 6 years after remission of Burkitt lymphoma with no evidence of systemic recurrence. The tumor regressed after plaque radiotherapy. The second tumor could have been related to previous chemotherapy, caused by Epstein-Barr virus infection, or the result of independent lymphoma cell growth.

Unravelling the mysteries of ocular lymphomas

Abstract Purpose There has been a bewildering evolution in the nomenclature of lymphomas, including ocular lymphomas. Confusing as this may seem, this is a reflection of impressive advances in our understanding of lymphoma pathogenesis, mainly as a result of immunohistology and molecular biological research. This overview will summarise the main successes of ocular lymphoma research and its translation into clinical practice. Methods The WHO lymphoma classification is based on the morphology, immunophenotype and genotype of tumour cells and their relationship to a putative cell of origin. Most ocular adnexal lymphomas (OAL) are low‐grade B‐cell lymphomas (EMZL), thought to arise from marginal zones of lymphoid follicles. Their development is associated with chromosomal abnormalities, autoimmune disease & microorganisms. Traditionally, OAL have clinically been staged using the Ann Arbor system, which has many shortcomings. The novel TNM‐based staging system defines disease extent more precisely and allows for analysis of site‐specific factors. Results Retinal lymphoma has been vaguely subsumed under the term "primary intraocular lymphoma": it is a high‐grade B‐cell malignancy, associated with a poor prognosis as a result of CNS disease. Immunophenotyping and genetic analysis suggest that retinal lymphomas arise from early post‐germinal centre cells. Other less common intraocular lymphomas include primary choroidal lymphomas (a low‐grade EMZL), primary iridal and ciliary body lymphomas, and secondary uveal lymphomas. Conclusion Ocular lymphomas are heterogenous tumours with differing subtypes and varying clinical courses. Precise nomenclature together with exact subtyping and clinical staging is essential, to understand ocular lymphoma histiogenesis and to facilitate studies improving prognostication and therapy.

Molecular pathology of intraocular lymphomas

This article describes recent advances in the understanding of the molecular genetics of intraocular lymphomas. These comprise vitreoretinal lymphoma, primary choroidal lymphoma, primary iris lymphoma and secondary choroidal lymphomas. Following WHO principles, their classification is now based on morphological, immunophenotypical and genotypical features. Retinal lymphoma is a high-grade lymphoma, usually of B-cell type, and is associated with a poor prognosis because of CNS involvement. Immunophenotyping and somatic mutation analysis suggest derivation from early postgerminal center B cells. Chromosomal translocation data suggest that some arise from germinal center B cells, which may have a better prognosis. Primary choroidal lymphoma is a low-grade B-cell lymphoma similar to nonocular, extranodal marginal zone B-cell lymphomas (EMZL). The putative cell of origin is a postgerminal center (memory) B cell. Primary iridal lymphomas are rare, with an equal distribution of B- and T-cell types and with a variable clinical course, most patients succumbing to systemic dissemination. Only one case of primary ciliary body lymphoma has been reported. Secondary choroidal lymphomas/leukemias tend to represent advanced systemic disease. Progress has been made in understanding the histiogenesis of intraocular lymphoma. Further investigations, such as gene expression profiling, are required to identify oncogenic pathways, to enhance prognostication and improve therapy.

Understanding intraocular lymphomas

The purpose of this review is to describe the clinical features, pathology and molecular biology of intraocular lymphomas, which represent a heterogenous group of malignant neoplasms; to propose an anatomical classification of these tumours according to whether they occur in the retina or uvea; and to overview laboratory investigations and highlight factors required for successful biopsy. Recent findings show that retinal lymphomas are high-grade (i.e. aggressive), B-cell malignancies and are associated with a poor prognosis, with most patients dying of central nervous system disease. Immunophenotyping and somatic mutation analyses indicate that these lymphomas are probably derived from early post-germinal centre cells. Primary choroidal lymphomas are typically low-grade (i.e. indolent), B-cell tumours with morphological, immunophenotypical and genotypic features similar to extranodal marginal zone B-cell lymphomas (EMZL) elsewhere in the body. The putative cell of origin is the post-germinal centre (memory) B cell. Primary iridal lymphomas are very rare, with an equal distribution of B- and T-cell types and with a variable clinical course, most patients succumbing to their disease as a result of systemic dissemination. Primary lymphomas limited to the ciliary body are exceptionally rare. Secondary uveal lymphomas/leukaemias occur in patients with advanced systemic lymphoma or leukaemia, respectively. In summary, the term 'primary intraocular lymphoma (PIOL)' is imprecise. It would be preferable to refer to the various forms of intraocular lymphoma according to whether they are retinal, choroidal, ciliary or iridal and whether they are primary or secondary in these locations.

Ocular pathology in acquired immunodeficiency syndrome

The gross and microscopic ocular findings were prospectively studied in 38 human immunodeficiency virus (HIV)-seropositive subjects undergoing postmortem examination. Pathologic lesions were detected in 27 patients (71%), including cytomegalovirus retinitis in 7, cytoid bodies in 6, cryptococcosis in 6, and choroidal histoplasmosis, mycobacteriosis, choroidal lymphoma, optic nerve demyelination, and microglial nodule formation in the optic nerve in 1 patient each. Of the abnormal ocular findings, 67% were detected only microscopically.