Conjunctival lymphocytic infiltrates associated with Epstein-Barr virus

PURPOSE: To describe the clinicopathologic features of two patients with Epstein-Barr virus (EBV) associated conjunctival lymphocytic infiltrates. DESIGN: Two case reports. METHODS: The clinical histories and pathologic findings of two patients with salmon-colored conjunctival infiltrates are described. MAIN OUTCOME MEASUREMENTS: Clinical observation and pathologic examination of conjunctival biopsy specimens with accompanying immunohistochemical staining, flow cytometric immunophenotyping, and polymerase chain reaction analysis when appropriate. RESULTS: One patient had ipsilateral preauricular lymphadenopathy, elevated serum EBV titers, and a unilateral reactive lymphocytic infiltrate resulting in a conjunctival mass. The other patient had bilateral conjunctival lymphocytic infiltrates causing conjunctival masses. There was an expanded clonal population of B lymphocytes in the conjunctival mass in the second patient. Both patients had EBV antigen in their conjunctival lymphocytic infiltrates. CONCLUSIONS: Conjunctival lymphocytic lesions associated with EBV represent a spectrum of reactive infiltrates to monoclonal populations.     

Concomitant Choroidal Melanoma and Non-Hodgkin Lymphoma in Two Adult Patients: Case Report

Objective

To report two cases of concomitant choroidal melanoma and intraocular non-Hodgkin lymphoma in two patients.

Design

Case report.

Participants

Two patients with yellow creamy infiltrates in fundo.

Intervention

Both patients had a complete ophthalmologic evaluation and histology was obtained after enucleation of the affected eye.

Main Outcome Measures

Histology findings of the enucleated eyes.

Results

One patient showed a choroidal melanoma with a primary non-Hodgkin lymphoma located solely in the affected eye. The other patient showed a systemic non-Hodgkin lymphoma with ocular manifestations concomitant with a choroidal melanoma.

Conclusions

In the presence of yellow creamy infiltrates one should include a choroidal lymphoma in the differential diagnosis even if there is another clear pathologic condition. Furthermore in those cases systemic disease should be excluded.Key Words: Non-Hodgkin lymphoma, Uveal melanoma, Choroidal melanoma     

Retinal manifestations of ocular lymphoma (reticulum cell sarcoma).

BACKGROUND: Diagnosis and treatment of ocular large cell lymphoma may lessen visual loss and prolong life. Although reports in the literature have described retinal infiltrates in eyes with large cell lymphoma, they have focused on the more prominent vitreous and subretinal pigment epithelial findings. Eyes with retinal infiltrates and hemorrhagic retinal necrosis are usually believed to harbor a microbial infection. The authors describe 5 patients, aged 57 to 85 years, with ocular lymphoma in whom the most prominent initial findings were in the retina. METHOD: Patients presented with findings suggestive of an infectious retinal necrosis. When the initial therapy failed, investigators performed a vitreous biopsy. Two patients had a concomitant retinal biopsy. Radiation therapy was given to four patients. RESULTS: All five patients had vitreous cells. Three patients had prominent perivascular exudate. Four patients had grayish-white retinal infiltrates, and three patients had associated retinal hemorrhage. Three patients had subretinal small white spots. An edematous thickened retina developed in three patients, and hemorrhagic retinal necrosis developed in three patients. The initial diagnosis was believed to be acute retinal necrosis (ARN) in three patients, toxoplasmosis in one patient, and frosted branch angiitis in one patient. Vitreous biopsy was positive in two patients but negative in three patients. In two of these three patients, the diagnosis was established by retinal biopsy. CONCLUSION: Ocular lymphoma should be considered in the differential diagnosis of retinal vasculitis or necrotizing retinitis in a middle-aged or older patient. Retinal biopsy may be helpful in establishing the diagnosis.     

Benign lymphoid infiltrate of the iris simulating a malignant melanoma

PURPOSE: To report a clinicopathologic correlation of an unusual benign lymphocytic iris mass in a patient who had no systemic lymphoproliferative disease. METHODS: Case report. RESULTS: A 49-year-old man developed a circumscribed, tan lesion in his left iris. The lesion was suspected clinically to be an atypical iris melanoma. Histopathologic studies of the resected mass revealed a solid tumor that was comprised of lymphocytes and histiocytes. Immunohistochemical studies identified that most of the cells were T lymphocytes. The histopathologic diagnosis was atypical lymphoid infiltrate. Workup for systemic lymphoma and Epstein-Barr virus infection was negative. CONCLUSION: Lymphoid infiltrate can manifest as a solitary mass that can simulate an iris melanoma.     

Flecked retina in systemic large-cell non-Hodgkin's lymphoma: case report

We report on a patient with a past medical history of successfully treated systemic large-cell non-Hodgkin's lymphoma (SNHL), who presented with multifocal yellowish retinal infiltrates (flecked retina) involving the post-equatorial retina of one eye. Fluorescein angiography revealed that the retinal infiltrates were hypofluorescent throughout the examination. The correct diagnosis of this ocular picture was important because the retinal lesions indicated central nervous system recurrence of systemic large-cell non-Hodgkin's lymphoma.     

Conjunctival lymphoid tumors: clinical analysis of 117 cases and relationship to systemic lymphoma

OBJECTIVE: To investigate the clinical features of conjunctival lymphoid tumors and factors predictive of systemic lymphoma. DESIGN: Retrospective, observational case series. SETTING: Clinical practice of ocular oncology. PARTICIPANTS: The participants included 117 consecutive patients with lymphoid tumors of the conjunctiva treated at the Oncology Service of Wills Eye Hospital between 1974 and 1999. MAIN OUTCOME MEASURE: The main outcome measure was the development of systemic lymphoma. Cox proportional regression models were used to calculate the risk of eventual systemic lymphoma. Kaplan-Meier survival estimates were used to analyze the development of systemic lymphoma as a function of time. RESULTS: There were 55 males (47%) and 62 females (53%); 110 patients (94%) were white and 7 patients (6%) were African AMERICAN: The mean age at ocular presentation was 61 years, and the conjunctival lymphoid infiltrate was unilateral in 72 patients (62%) and bilateral in 45 patients (38%). In 8 patients (7%), initial unilateral conjunctival disease evolved into bilateral involvement over a mean of 32 months. Additional sites of ocular involvement were found in 27 patients (23%) and included lymphoid tumor in the eyelid in 3 cases, orbit in 18, choroid in 5, and vitreous in 1. Systemic lymphoma was known to exist before ocular diagnosis in 16 patients; (14%; for a mean of 51 months) and was found subsequent to ocular diagnosis in 20 patients (17; at a mean of 21 months). Therefore, of 117 patients with conjunctival lymphoid infiltration, 36 (31%) had or eventually developed systemic lymphoma, and 81 (69%) did not manifest systemic lymphoma during the mean follow-up of 38 months. Of the 64 patients with unilateral conjunctival involvement, 11 (17%) manifested systemic lymphoma, and of the 53 patients with bilateral involvement, 25 (47%) manifested systemic lymphoma. By univariate analysis, the clinical factors at date first seen predictive of the presence or development of systemic lymphoma included location of the tumor at an extralimbal site (fornix or midbulbar conjunctiva; P = 0.02) and increasing number of conjunctival tumors (P = 0.02). Using Kaplan-Meier life table analysis of those 101 patients who had conjunctival lymphoid tumor(s) and no evident systemic lymphoma at presentation, systemic lymphoma was eventually discovered in 7% of patients at 1 year, 12% at 2 years, 15% at 5 years, and 28% at 10 years. Overall, only one patient (<1%) died of systemic lymphoma, at 28 months after the diagnosis of the ocular disease. CONCLUSIONS: Lymphoid tumors of the conjunctiva are associated with systemic lymphoma in 31% of patients. Systemic lymphoma is found more often in those patients with forniceal or midbulbar conjunctival involvement and in those with multiple conjunctival tumors. Long-term systemic follow-up is advised, because related systemic lymphoma can manifest many years later.     

Ocular manifestations of leukemia: leukemic infiltration versus infectious process

OBJECTIVE: To determine whether specific guidelines can be developed to distinguish whether retinal infiltration in leukemia patients represents infection or neoplasia. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Six patients recently seen at University of California San Francisco with retinal infiltrates in a setting of leukemia, for which adequate written and photographic information of disease course was available. INTERVENTION: Observation consisted of retrospective review of clinic charts, hospital medical records, and fundus photographs. MAIN OUTCOME MEASURES: Determination of whether retinal infiltrates represented neoplasia or infection was made by review of medical records. RESULTS: In this series, neoplastic retinal infiltrates were found in patients who had newly diagnosed leukemia and those who were in blast crisis. In contrast, the two patients who were in complete remission, but had undergone bone marrow transplantation, had retinal infiltrates attributable to infection. CONCLUSIONS: Every patient with retinal infiltrates in the setting of newly or previously diagnosed leukemia requires a systemic and central nervous system workup before the initiation of ophthalmologic treatment. The systemic status of the patient is highly informative in determining whether infection or neoplasia is responsible for the infiltration.     

Visual outcomes of sterile corneal infiltrates after photorefractive keratectomy

Purpose:Sterile infiltrates following laser refractive surgery is an uncommon complication. This study was undertaken to analyze the visual outcomes of sterile infiltrates following photorefractive keratectomy (PRK).Methods:This retrospective study included 14 eyes that developed sterile infiltrates following PRK out of a total of 6280 eyes that underwent PRK between 2014 and 2017. Medical records of these patients, including patient demographics, characteristics of the infiltrate, presenting visual acuity, and treatment outcomes were recorded and analyzed.Results:The incidence of sterile corneal infiltrates post-PRK in our study was 0.22% (14/6280). The mean age of the patients was 27.42 ± 4.87 years. The uncorrected visual acuity (UCVA) at presentation was 0.49 ± 0.13 log MAR units. The mean size of the infiltrate was 3.22 ± 2.85 mm². All cases were successfully managed medically with topical steroids. The mean UCVA and best-corrected visual acuity (BCVA) at the last follow-up visit were 0.08 ± 0.08 and 0.05 ± 0.07 log MAR units, respectively. The mean time taken for resolution of the infiltrate was 8.91 ± 4.57 days.Conclusion:Sterile infiltrates following PRK can be effectively treated with aggressive topical steroids. The outcome is generally favorable and does not require surgical intervention if treatment is instituted early.     

Clinicopathologic and immunogenetic analysis of mucosa-associated lymphoid tissue lymphomas arising in conjunctiva.

PURPOSE: To identify mucosa-associated lymphoid tissue (MALT) type lymphoma in conjunctival infiltrates. METHODS: Clinical, histopathologic, immunophenotypic, and immunogenotypic studies were performed on 14 patients with conjunctival lymphoid infiltrates. Surgical biopsy specimens were subjected to histopathologic, immunohistochemical, and gene rearrangement analysis. RESULTS: Thirteen of the 14 patients (92.9%) met the diagnostic criteria for MALT lymphoma, and the remaining patient showed morphologic features of diffuse, small lymphocytic lymphoma. Genotypic analysis confirmed immunoglobulin heavy chain gene rearrangement in all of the 12 patients on whom the analysis was performed. Two patients with bilateral lesions exhibited identical immunoglobulin rearrangement patterns in each pair of lesions. All patients were alive at the last follow-up (mean: 39.9 months). Nine of the 14 patients were alive without disease, 4 had localized recurrences, and 1 had a residual tumor. CONCLUSIONS: These findings indicate that conjunctival lymphoid infiltrates usually have the features of MALT lymphoma with genotypic B lymphocytic monoclonality and a favorable prognosis.     

Multifocal nodular episcleritis and scleritis with undiagnosed Hodgkin's lymphoma

PURPOSE: To report the case of a patient with undiagnosed Hodgkin's lymphoma who presented with coexistent unilateral nodular episcleritis and scleritis. DESIGN: Interventional case report and literature review METHODS: Review of clinical history, laboratory findings, histology of episcleral and cervical lymph node biopsies, and follow-up. RESULTS: A 20-year-old female presented with a 5-month history of redness and pain in her left eye, with associated symptoms of dyspnea, malaise, and fever. The patient was found to have multifocal nodular episcleritis and scleritis that was not responsive to topical steroids or systemic nonsteroidal anti-inflammatory treatment. Laboratory tests subsequently revealed evidence of systemic inflammation, and radiologic studies showed extensive mediastinal and cervical adenopathy. A cervical lymph node biopsy showed Reed-Sternberg cells and a chronic lymphocytic infiltrate consistent with nodular sclerosing Hodgkin's lymphoma. Histopathologic analysis of an episcleral nodule revealed a necrotizing granuloma with vasculitis. Systemic chemotherapy was instituted for the Hodgkin's disease; this therapy abolished the nodular scleritis. CONCLUSIONS: This case raises the possibility of concurrent undiagnosed systemic vasculitis with only an ocular manifestation with Hodgkin's lymphoma, either as a coincidence or as a paraneoplastic syndrome. Moreover, it emphasizes the important role of tissue biopsy in establishing diagnosis and directing treatment.     

Systemic non-Hodgkin's lymphoma simulating primary intraocular lymphoma

PURPOSE: To describe a case of an unusual presentation of systemic non-Hodgkin's lymphoma with clinical and histopathologic findings closely resembling that of primary intraocular lymphoma. DESIGN: Observational case report. METHODS: A 58-year-old woman with a history of treated systemic non-Hodgkin's lymphoma presented 2 years later with a subretinal lesion and intraocular inflammation in her left eye. RESULTS: Diagnostic enucleation and histopathologic studies revealed findings consistent with primary intraocular lymphoma including intraretinal, subretinal, and subretinal pigment epithelial tumor cells without involvement of the choroid. CONCLUSIONS: We conclude that systemic non-Hodgkin's lymphoma can present remotely with findings resembling primary intraocular lymphoma and should be included in the differential diagnosis of intraocular inflammation and subretinal infiltrates.     

Confluent choroidal infiltrates with sarcoidosis

PURPOSE: To report the occurrence of confluent plaquelike choroidal infiltrates in four patients with sarcoidosis. METHODS: The medical records of patients with choroidal plaquelike infiltrates and presumed systemic sarcoidosis seen in the Mayo Clinic were reviewed. RESULTS: The cohort included four patients with confluent plaquelike choroidal infiltrates and systemic sarcoidosis. The most common ophthalmic symptom experienced by the patients was mild blurring of vision. The salient ophthalmic findings were choroidal infiltrates generally unaccompanied by other features frequently seen with sarcoidosis such as periphlebitis, multiple small yellowish choroidal infiltrations, vitreous cellular reaction, and granulomatous anterior uveitis. The choroidal lesions were confluent, yellowish, irregularly thickened infiltrates that frequently radiated peripherally from a peripapillary location in an ameboidlike pattern. Fluorescein angiography demonstrated early hypofluorescence and progressive patchy hyperfluorescence with late staining of the active lesions. Treatment with either systemic or subconjunctival steroids was associated with improvement in vision and partial resolution of the choroidal lesions. In two patients some of the lesions resolved spontaneously and became replaced by areas of chorioretinal atrophy. CONCLUSION: Plaquelike yellowish choroidal infiltrates associated with systemic sarcoidosis may occur in eyes remarkably free of other signs of inflammation. The infiltrates tend to radiate from the region of the optic nerve in a confluent ameboidlike pattern. They generally respond to corticosteroids and may be the first recognized manifestation of systemic sarcoidosis.     

Subepithelial infiltrates in Acanthamoeba keratitis

Six patients had Acanthamoeba keratitis that manifested an unusual type of subepithelial corneal infiltrate late in the course of the disease. These infiltrates occurred in the anterior corneal stroma, often in a location removed from the site of infection. In four of these patients the infiltrates occurred with no other clinical signs of inflammation. Two patients had mild foreign-body sensation that resolved despite the persistence of the subepithelial infiltrates. The infiltrates resolved with topical corticosteroid therapy in three patients; however, in two of these three patients the infiltrates recurred when corticosteroid therapy was tapered or discontinued. The subepithelial infiltrates appeared and behaved similarly to those associated with viral and chlamydial corneal infections. An immunologic mechanism may be responsible for these unusual delayed-in-onset infiltrates.     

Uveal lymphoid infiltrates: immunohistochemical evidence for a lymphoid neoplasia.

A 67-year-old man presented with a diffuse choroidal and ciliary body infiltrate, suggesting clinically and ultrasonographically a diffuse uveal melanoma. After enucleation both morphological and immunohistochemical data were highly suggestive of a diffuse, low-grade B cell lymphoma or lymphoplasmacytic immunocytoma. The difficulties of clinical and histopathological differential diagnosis of uveal lymphoid infiltrates are emphasised. In view of the excellent life prognosis of these tumours, treatment of the patient should be directed towards the preservation of ocular function.     

Peripheral keratitis following laser in situ keratomileusis

PURPOSE: To report two different cases of sterile, peripheral keratitis following laser in situ keratomileusis (LASIK). METHODS: A report of two cases (two eyes of two patients). RESULTS: In two patients, peripheral infiltrates appeared 1 day after LASIK. One patient had a history of rheumatoid arthritis and both had peripheral corneal changes that may have represented prior inflammatory events. The presentations were quite different, with one occurring in association with an epithelial defect at the edge of the flap and the other occurring without an epithelial defect peripheral to the microkeratome cut. In the second case a similar infiltrate showed up in the unoperated fellow eye. Both patients were treated with aggressive antibiotic and corticosteroid therapy. Both patients recovered well with no loss of best spectacle-corrected visual acuity. CONCLUSION: Peripheral keratitis can occur in patients following LASIK; preoperative evidence of previous inflammation may be a marker for patients at higher risk. Rheumatoid arthritis patients may be at increased risk for this complication. With careful and aggressive management excellent visual outcomes are still possible.     

Ocular adnexal lymphoid proliferations: clinical,histologic, flow cytometric,and molecular analysis of forty-three cases

PURPOSE: To describe the clinical features, histologic findings, flow cytometric immunophenotypes, and molecular profiles of ocular adnexal lymphoid proliferations. STUDY DESIGN: Prospective noncomparative case series. PARTICIPANTS: Forty-three patients suspected of having ocular adnexal lymphoid proliferations were biopsied and prospectively evaluated. METHODS: Provisional diagnoses were made on the basis of routine histology and immunohistochemistry for B and T cells. Results of flow cytometric immunophenotyping (FCI) and molecular assessment using polymerase chain reaction for immunoglobulin heavy chain (IgH) and TCR gamma chain gene rearrangement and bcl-2/IgH translocation were then incorporated into a final diagnosis. Demographic and clinical outcome data were collected. MAIN OUTCOME MEASURES: Final diagnosis based on histology, flow cytometry, and polymerase chain reaction. RESULTS: Forty-three cases were studied. Final diagnoses included 17 lymphomas, 18 chronic inflammations, 4 reactive lymphoid hyperplasias, and 4 atypical lymphoid infiltrates. Preliminary evaluation accurately categorized all 43 cases as either lymphoma or nonlymphoma. FCI permitted more precise subclassification of the lymphomas according to the Revised European American Lymphoma (REAL) system of nomenclature as follows: eight marginal zone B cell (mucosa-associated lymphoid tissue type), three mantle cell, two follicular, three large cell, and one lymphoplasmacytoid lymphoma. FCI showed a clonal B cell proliferation in 94% (16 of 17) of the lymphomas; FCI identified a clonal B cell population in 4% (1 of 25) of cases of nonlymphomas. Molecular evidence of clonality was identified in 88% (15 of 17) of lymphomas, 39% (7 of 18) of chronic inflammations, and 50% (4 of 8) of reactive lymphoid hyperplasias and atypical lymphoid infiltrates. CONCLUSIONS: The histologic diagnosis of ocular adnexal lymphoid lesions is highly accurate when determined by an experienced pathologist. FCI refines the histologic diagnosis and classification. Results of molecular studies should be interpreted in conjunction with clinical, histologic, and immunophenotyping findings.     

Contact lens-induced peripheral ulcers with extended wear of disposable hydrogel lenses: histopathologic observations on the nature and type of corneal infiltrate.

PURPOSE: Contact lens-induced peripheral ulcer (CLPU), a sudden-onset adverse event observed with extended wear of hydrogel lenses, is characterized by a single, small, circular, focal anterior stromal infiltrate in the corneal periphery or midperiphery. The condition is always associated with a significant overlying epithelial loss and resolves in a scar. The aim was to determine, by using histopathologic techniques, the nature and type of the corneal infiltrate of these events. METHODS: Three CLPUs observed in three patients using disposable hydrogel lenses on an extended-wear schedule were examined. The eye was topically anesthetized, and a corneal section including all of the infiltrate was taken. A small triangular piece of conjunctiva immediately adjacent to the infiltrate was sectioned. The tissue was immediately fixed, processed, stained using hematoxylin and eosin and periodic acid-Schiff stains, and examined by using light microscopy. RESULTS: The diameter of these three corneal infiltrates varied from 0.3 to 0.6 mm. Histopathology of the corneal sections revealed a focal epithelial loss corresponding to the infiltrated stroma in all three patients. The adjacent epithelium was thinned. Bowman's layer was intact in two patients and had a localized area of loss in the remaining patient. The anterior stroma was densely infiltrated with polymorphonuclear leukocytes and had focal areas of necrosis. The infiltration was most dense in the region immediately underlying Bowman's layer. No other infiltrative cell type was seen in any of the sections. Histopathology of the conjunctiva revealed features consistent with normal conjunctival tissue. CONCLUSIONS: On histopathology of CLPU, distinctive features (i.e., focal corneal epithelial loss, an intact Bowman's membrane, and a localized infiltration of the anterior stroma with polymorphonuclear leukocytes) were seen. These features suggest that the event is an acute inflammatory process and probably noninfective in nature.     

Pathogenesis and treatment of "sterile" midperipheral corneal infiltrates associated with soft contact lens use

PURPOSE: To demonstrate the sterile nature of presumed sterile midperipheral corneal infiltrates associated with soft contact lens (SCL) use and to show that withholding antibiotics or the occasional use of a topical corticosteroid alone may, with strict guidelines, have a role in the treatment of this entity. METHODS: Nine consecutive patients presenting with typical midperipheral corneal infiltrates after SCL wear were seen in the office (O.H.D.) during a 2-year period, 1996-1998. All patients were initially placed on topical fluorometholone as the only treatment. RESULTS: Eight of the nine patients experienced a rapid relief of symptoms and the infiltrates were noted to be smaller and less dense in 34 days. Therapy was discontinued after 7 days, by which time the lesions had cleared. The ninth patient developed a microbial keratitis from which Pseudomonas aeruginosa was cultured. With appropriate therapy, visual acuity returned to 20/25. Two different algorithms are offered for the treatment of a putative sterile infiltrate associated with SCL use. CONCLUSION: The use of a topical corticosteroid alone may have a role in the treatment of presumed sterile midperipheral corneal infiltrates associated with SCLs when strict guidelines are followed. Such therapy suggests that the infiltrates are not the result of infection.     

MALT-type B-cell lymphoma masquerading as scleritis or posterior uveitis

PURPOSE: Diagnostic and therapeutic management of masquerade syndromes associated with MALT-type lymphoma. PATIENTS AND METHOD: We report the cases of three patients referred for acute or chronic severe loss of visual acuity. All of them suffered from uveitis or scleritis resistant to corticoid treatment. Each one had posterior uveitis associated with retinochoroidal infiltration, anterior scleritis associated with uveal effusion syndrome, or bilateral pan-uveitis associated with serous retinal detachment. Two patients had medical records of systemic malignancies. They underwent an extensive work-up. Search for an infectious, immune or malignant disease was negative but orbital imaging showed a posterior scleral thickening in all cases. RESULTS: Diagnosis of mucosa-associated lymphoid tissue (MALT) ocular lymphoma was assessed in all cases after scleral biopsy. Immunohistochemical analysis showed CD20(+) and CD5(-) scleral lymphocyte infiltrates. The three patients underwent chemotherapy associated with radiotherapy. Lesions were stabilized in the first case, whereas six lines of visual acuity improvement was noted in the second one, and full recovery was achieved after treatment in the third case. DISCUSSION: Clinical manifestations of this ocular lesion seem to be multiple, masquerading as different types of posterior uveitis or scleritis. In the three cases, we did found other systemic locations of MALT-type lymphoma. Diagnosis was mainly based on pathological analysis. Fast visual recovery in two cases demonstrated the importance of an early diagnosis and a specific treatment. All cases of chronic and corticoid-resistant posterior uveitis require a specialized radiological evaluation followed, if necessary, by multiple orbital biopsies.