Research status and progress of laboratory diagnostic tests for intraocular lymphoma / 中华眼底病杂志

Intraocular lymphoma (IOL) is a rare lymphocytic malignancy. The gold standard for the definite diagnosis remains histopathologic examination of the ocular specimen. But cytologic confirmation of malignant lymphoma cells in vitreous or chorioretinal specimens is challenging and dependending on highly skilled cytopathologist, due to the sparse cellularity and specimen degeneration. Consequently, false-negative rates arecommon, which delays diagnosis and treatment seriously. Because of the limited diagnostic capacity of cytology, other adjunct diagnostic tools have been developed. Additional procedures that may support IOL diagnosis include flow cytometry, immunocytochemistry, cytokines study with identification of interleukin (IL)-10 and IL-6 level, and polymerase chain reaction amplification. And more recently, new techniques of mutational analysis have been validated for the diagnosis of vitreoretinal lymphoma (VRL) and may represent a helpful diagnostic tool for the detection of early cases. Metagenomic deep sequencing technology may provide an important basis for IOL diagnosis and personalized treatment. In the future, it is expected to deepen the understanding of IOL disease phenotypes at the molecular level, discover new target therapies, monitor response to treatment, and detect intraocular recurrences. These may offer insights into how we might create a tailored therapeutic approach for each patient's VRL in the future.

Progress in diagnosis and treatment of ciliary body lymphoma / 中华实验眼科杂志

Intraocular lymphoma with ciliary body involvement is extremely rare, which can be divided into primary and secondary types.The common pathological patterns are mucosa-associated lymphoid tissue B-cell lymphoma and diffuse large B-cell lymphoma, and T-cell lymphoma is relatively rare.The clinical manifestations of ciliary body lymphoma are similar to anterior uveitis.Hypopyon and secondary glaucoma can result from the disease, and the differentiating features include iris patches, iris neovascularization, and hyphema.Diffuse infiltration or space-occupying lesions of ciliary body lymphoma can be found by ultrasound biomicroscopy.Cytological and/or histopathological examination is the gold standard for its diagnosis.Immunohistochemistry, flow cytometry, cytokine analysis, and gene rearrangement are often used in combination to improve the diagnosis rate.Radiotherapy, chemotherapy, or combination therapy can achieve a better prognosis.This paper reviewed classification, pathological types, ocular manifestations, examinations, diagnosis, and treatment of ciliary body lymphoma to provide a reference for clinical practice.

Analysis of the diagnostic value of gene rearrangement detection combined with vitreous fluid IL-10 and IL-6 cytokine detection for primary intraocular lymphoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the diagnostic value of gene rearrangement detection combined with vitreous fluid interleukin-10(IL-10)and interleukin-6(IL-6)cytokine detection for primary intraocular lymphoma(PIOL). <p>METHODS: A total of 27 patients with suspected PIOL who were admitted to the hospital between January 2015 and December 2019 were enrolled in this study according to the inclusion and exclusion criteria. Totally 21 cases of PIOL and 6 cases of uveitis were diagnosed by pathological examination of diagnostic vitrectomy. Results of gene rearrangement and cytokine levels were retrospectively analyzed. Receiver operating characteristic(ROC)curves were used to analyze the diagnostic value of gene rearrangement, cytokines detection and the combination of the two in PIOL. <p>RESULTS: Of the 21 patients with PIOL, 15 had IhH FR2 monoclonal rearrangement, with a positive rate of 71%(15/21), and 4 were detected with TCRG clonal gene rearrangement. ROC curve analysis showed that the area under the curve(AUC)of gene rearrangement for diagnosis of PIOL was 0.857. Its sensitivity and specificity were 71.43% and 100.00%. Patients with PIOL had significantly higher vitreous humor IL-10 and IL-10/IL-6 levels than those with uveitis, but no statistically significant difference was found in the IL-6 level between the two groups(<i>P</i>>0.05). ROC curve analysis showed that the AUC of IL-10 was the highest for diagnosis of PIOL. With 170.90pg/mL as the cut-off value, its sensitivity and specificity of IL-10 in diagnosing PIOL were 66.67% and 100.00%, respectively. With 1.95 as the cut-off value, the sensitivity and specificity of IL-10/IL-6 ratio in diagnosing PIOL were 52.40% and 100.00%. The AUC, sensitivity and specificity of gene rearrangement combined with cytokines detection in diagnosing PIOL were 0.893, 95.24% and 83.33%, respectively. <p>CONCLUSION: The sensitivity of gene rearrangement alone is poor in diagnosing PIOL. Combined use of cytokines detection can improve the diagnostic sensitivity and specificity.

Extranodal lymphoma of the head and neck: a pictorial essay / Linfoma extranodal da cabeça e pescoço: ensaio iconográfico

Abstract Primary extranodal lymphoma is defined as a lymphoma at a solitary extranodal site, with or without involvement of the lymph nodes. The clinical and radiological features of extranodal lymphoma have been documented in recent studies. In this pictorial essay, we reviewed imaging findings of extranodal lymphoma in the head and neck region.

Resumo Linfoma extranodal primário é definido como um sítio extranodal solitário de linfoma, com ou sem envolvimento dos gânglios linfáticos. As características clínicas e radiológicas do linfoma extranodal foram documentadas em estudos recentes. Neste ensaio revisamos os achados de imagem do linfoma extranodal da região da cabeça e pescoço.

Ultrasonographic features of intraocular lymphoma / 中华超声影像学杂志

Objective To describe the ultrasonographic features of intraocular lymphoma . Methods It was a retrospective analysis of 19 patients ( 26 eyes ) with intraocular lymphoma at the department of ophthalmology ,Beijing Tongren Hospital from January 2015 to December 2017 . T he diagnosis was established by tissue biopsy in 4 patients with diagnostic vitrectomy and 8 with enucleation ,and other 7 cases were clinically diagnosed followed by pathological examination of central nervous system lymphoma . T he ultrasonographic features of all patients were analyzed . Results Of the 19 patients ( 26 eyes ) with intraocular lymphoma ,12 cases ( 19 eyes) of vitreoretinal lymphoma accounted for 63 .2% ,of which 7 cases were bilateral eyes ,and 7 cases ( 7 eyes ) of uveal lymphoma accounted for 36 .8% ,all of w hich were monocular . Ultrasonography of vitreoretinal lymphoma included vitreous opacity , posterior vitreous detachment ,partial retinal detachment ,irregular hypoechoic lesions under the retina ,and CDFI detected blood flow signals in the lesion . T here were two different types of ultrasound findings in uveal lymphoma . Five cases ( 5 eyes ) showed diffuse thickening of the uveal membrane with low echo , and irregular hypoechoic mass around the optic nerve and the ball wall ,in w hich CDFI detected abundant blood flow signals . Ultrasound biological microscope examination showed that the iris‐ciliary body thickened and the internal echo decreased . T his ultrasound finding accounted for 71 .4% of uveal lymphoma . T wo cases ( 2 eyes) showed a solitary ciliary‐choroid choroidal hypoechoic mass ,combined with retinal detachment and blood flow signals with CDFI ,accounting for 28 .6% of uveal lymphoma . Conclusions T he ultrasonography of intraocular lymphoma is various . T he ultrasound findings of vitreoretinal lymphoma are not specific , w hile the diffuse thickened uvea and retrobulbar hypoechoic lesions encircled optic nerve and eye wall suggest the possibility of uveal lymphoma .

Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma

We describe a case of spontaneous hyphema associated with anterior uveitis presents in a 69-year old female as the prominent sign of the intraocular spread of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic lymphoma, characteristic findings on B-scan ultrasonography and magnetic resonance imaging scan, and identification of atypical lymphoid cells in aqueous sample established the diagnosis of intraocular metastasis of systemic DLBCL. Therefore, this report highlights that life-threatening malignant systemic lymphoma may masquerade as anterior segment ocular inflammation or neovascular glaucoma.

Bilateral Severe Vitritis, an intraocular recurrence of B cell lymphoma: a case report / Vitritis severa bilateral, una recurrencia intraocular de linfoma de células B: reporte de caso

Purpose: To report a case of bilateral vitritis originated from Primary Central Nervous System Lymphoma. Diagnosis was made from a careful history taking and confirmed with vitrectomy. Case report: 65-year-old Vietnamese male had one month of progressive blurred vision in both eyes without other eye complaint. History revealed that about one year previously, he was diagnosed with primary diffuse large B cell lymphoma. He was treated with chemotherapy of Methotrexate 3.5 g/m2and cytarabine 2 mg/m2, and a whole brain radiation therapy. There was a complete remission after the therapy. Fundus of both eyes was partly obscured by cells mainly in the posterior vitreous. Sequential bilateral vitrectomies were done on 5/1/17 and 7/17/17 without complication. The vitreous sample from the first eye having vitrectomy was sent for study which demonstrated large B cell lymphoma. Post-operative vision improved to 20/25 both eye without the complaint of hazy vision. Conclusion: Good history taking assisted in the diagnosis of intraocular lymphoma in this case with bilateral vitritis. However, bilateral vitrectomy restored the vision and further confirmed the diagnosis of lymphoma for future follow up care

Objetivo: Reportar un caso de vitritis bilateral originada por un Linfoma del Sistema Nervioso Central Primario. El diagnóstico se realizó a partir de una cuidadosa historia clínica y confirmada con vitrectomía. Reporte de caso: Varón vietnamita de 65 años con un mes de visión borrosa progresiva en ambos ojos sin otra afección ocular. La historia reveló que hace aproximadamente un año, se le diagnosticó un linfoma difuso primario de células B grandes. Fue tratado con quimioterapia con Methotrexate 3.5 g/m2 y citarabina 2 mg/m2 y una radioterapia cerebral completa. Hubo una remisión completa después de la terapia. El fondo de ambos ojos estaba parcialmente oscurecido por las células, principalmente en el vítreo posterior. Las vitrectomías bilaterales secuenciales se realizaron el 5/1/17 y el 17/7/17 sin complicaciones. La muestra vítrea del primer ojo sometida a vitrectomía fue enviada a un estudio que demostró linfoma de células B grandes. La visión postoperatoria mejoró a 20/25 ambos ojos sin la queja de la visión borrosa. Conclusión: una buena historia clínica fue útil en el diagnóstico de linfoma intraocular en este caso con vitritis bilateral. Sin embargo, la vitrectomía bilateral restauró la visión y confirmó aún más el diagnóstico de linfoma para el cuidado de seguimiento futuro.

Diagnosis and treatment of primary intraocular lymphoma / 眼科新进展

Primary intraocular lymphoma (PIOL) is mostly composed by diffuse large B-cell lymphoma with a high degree of malignancy and often masquerades as uveitis.Moreover,it has a poor prognosis,therefore the early diagnosis and treatment are very important.Cytology,cytokine analysis,immunohistochemistry and genetic testing are often used in combination to improve the diagnosis rate of PIOL,however,eye tissue biopsy is the gold standard for diagnosis of PIOL.Currently,since there is no unified treatment program,the main treatment is given priority to local chemotherapy and orbital radiotherapy,and the use of multiple therapies can improve the efficacy of refractory PIOL.Base on these,this article reviews the current diagnosis and treatment for providing certain reference.

Vitreoretinal lymphomas misdiagnosed as uveitis: Lessons learned from a case series.

Purpose: To present challenging cases of vitreoretinal lymphoma (VRL) that was misdiagnosed as uveitis because of the apparent intraocular inflammation. At the light of the new classification of intraocular lymphomas, we detail the characteristics that masqueraded the tumors and the clinical aspects that guided us to the correct diagnosis. Materials and Methods: We retrospectively reviewed the patients referred to our uveitis service between January 2006 and December 2014. Results: Seven patients referred with a presumptive diagnosis of idiopathic uveitis received a final diagnosis of VRL. The median time between the onset of symptoms and definitive diagnosis was 25 months for these complex cases. The median time from presentation at our clinic to final diagnosis was 1 month. The described clinical features including dense vitreous cells and subretinal infiltrates were characteristic and tend to be present in all these chronically ill patients. Vitreous samples were collected, and all demonstrated the pathognomonic tumor cells, the specific immunoglobulin heavy chain gene rearrangements, and an interleukin (IL)‑10 to IL‑6 ratio >1. Conclusion: VRLs are severe diseases with a poor prognosis that may be misdiagnosed as idiopathic inflammatory conditions of the eye. Treatment with steroids may occult the tumors and delay the correct diagnosis. Appropriate evaluation may prompt to a timely vitreous sampling and therefore to a faster diagnosis in these peculiar cases where the correct diagnosis was delayed by several months.

The Hidden Salmon Patch: Ocular Lymphoma Mistaken as Vogt Koyanagi Disease

Ocular inflammation from various causes may have similar clinical presentation thus careful clinical evaluations are mandatory particularly when the disease appear to be resistant to treatment. This paper reports a case of ocular lymphoma which was initially treated as Vogt Koyanagi Harada disease at a different centre. A 65-year-old Sudanese man complained of gradual worsening left eye vision. Careful ocular and slit lamp examination revealed a conjunctival lesion with choroidal infiltration as well as exudative retinal detachment. Computed tomography scan (CT scan) showed left eye axial proptosis, and a homogenous enhancing mass at the posterior coat of the globe. Tissue biopsy of the conjunctival lesion revealed marginal Zone B cell (MALT type), low grade, non-Hodgkin’s lymphoma. AS the ocular signs and symptoms progressed, chemotherapy was initiated. The proptosis, exudative retinal detachment, disc hyperemia and swelling improved after chemotherapy. The post treatment CT scan showed reduction of the posterior ocular coat mass. The possibility of malignant lymphoma should be considered in patients with resistant uveitis despite administration of corticosteroid. Ocular lymphoma is an indolent tumour with good prognosis. Careful ocular examination, adequate imaging studies followed by early surgical biopsy will contribute to early diagnosis.

Two Cases of Primary Intraocular Lymphoma: Fine Needle Aspiration Diagnosis and Intravitreal Methotrexate Treatment / 华中科技大学学报（医学）（英德文版）

We described clinical process of two cases of intraocular lymphoma in aspects of early diagnosis by fime needle aspiration (FNA) and biopsy and treatment by intravitreal methotrexate (MTX).Two patients were suspected to have primary intraocular lymphoma (PIOL) with geographic yellow-white infiltrates and vitreous opacity.FNA confirmed malignant intraocular lymphoma in one patient and failed in the other patient due to complication of vitreous hemorrhage.Subsequent vitreous biopsy confirmed malignant intraocular lymphoma in the other patient.Both patients were treated by intravitreal methotrexate.In case 1 the tumor had complete remission and follow-up of 12 months had not found any signs of recurrence.In case 2 the patient died of brain metastasis 22 months after the ocular biopsy.Our findings demonstrate that although cytological examination of vitrectomy specimens remains the gold standard in diagnosis of PIOL,examination of FNA and biopsy increases the reliability of early diagnosing or excluding a PIOL.Individualized intravitreal methotrexate can be used to effectively treat PIOL.More effective integrated program treating primary central nervous system lymphoma/PIOL is worthy of looking forward to.

A Case of Primary Intraocular Lymphoma Confirmed by Endoretinal Biopsy

PURPOSE: To report one case of primary intraocular lymphoma confirmed by endoretinal biopsy and clinical experience. CASE SUMMARY: A 65 year-old man complaining of persistent decreased visual acuity was referred to our hospital. Biomicroscopic examination showed bilateral vitreous cells and small round yellowish inflammatory lesions at the level of the retinal pigment epithelial cells. The disc of the left eye was pale in color. Fluorescein angiographic examination of the left eye showed intermingling round hyperfluorescent and hypofluorescent lesions. We performed diagnostic vitrectomy due to unresponsiveness to oral steroid therapy, but the result was negative. We finally performed an endoretinal biopsy, which showed tumor cells with H&E staining and strong immunoreactivities against CD 20 and CD 79a indicating the presence of B cells. We diagnosed this case as primary intraocular lymphoma and performed multiple-cycle chemotherapy with high-dose methotrexate. The ocular signs and symptoms were improved after chemotherapy. CONCLUSIONS: Endoretinal biopsy could be another diagnostic tool for confirming suspected primary intraocular lymphoma in cases showing negative results with diagnostic pars plana vitrectomy and cytology.

Clinical Manifestations of Intraocular Lymphoma

PURPOSE: To investigate the clinical features and prognosis of primary intraocular lymphoma (PIOL). METHODS: A retrospective review of medical records was performed in 9 patients who were diagnosed and treated as PIOL in the Department of Ophthalmology, Seoul National University Hospital. RESULTS: Among patients who were enrolled in the study, 14 eyes were examined. Thirteen eyes (92.9%) showed yellowish subretinal or choroidal infiltrates which is a characteristic finding of PIOL in fundus examination and fluorescein angiography. Three patients presented with ocular symptoms initially, and 5 patients later presented with central nerve system (CNS) involvement. Only 1 patient showed PIOL without CNS involvement. Among 6 patients (9 eyes) that received systemic chemotherapy or ocular irradiation, 5 patients (7 eyes, 77.8%) responded. Among those patients, 3 patients (4 eyes) showed relapse of PIOL. Five patients died during the mean follow-up period of 43.3 months, and the median survival time was 47 months. CONCLUSIONS: The most common characteristic fundus finding of PIOL is subretinal or choroidal infiltration. Ocular irradiation combined with systemic chemotherapy is the first method of treatment, although long-term prognosis is poor.

A Case of Primary Intraocular Lymphoma Treated by Intravitreal Methotrexate

A 40-year-old female visited our clinic for visual disturbance of the right eye, in which a few creamy-yellow retinal lesions and visual field constrictions were noted. She had been treated for primary CNS lymphoma and was in complete remission. After failure to follow-up for three months, she lost vision in the right eye, at which time active panuveitis was seen. Decreased vision and field constriction was observed in the left eye. Her left eye showed a granular pattern and dye leakage from the vessels and disc on fluorescein angiography and small RPE humps were seen in optical coherence tomography (OCT). Diffuse large malignant B-cells with strong immunoreactivities with CD20 immunostaining were seen in the epiretinal membrane biopsy specimen. Intravitreal injections of methotrexate (MTX) (800 microgram/0.1 ml in the right eye, 400 microgram/0.05 ml in the left eye) were performed twice weekly for one month, once weekly for the following month, once every two weeks for the next month, followed by nine monthly injections. Both eyes were free from malignant cells on vitreous biopsy six months later. There was no leakage seen by angiography, but the granular pattern persisted. Visual field constriction was slightly improved, and the small RPE humpsdetachments seen in OCT disappeared. EOG Arden ratio was decreased in both eyes, and b wave amplitude of scotopic ERG was decreased in the left eye. She was free from recurrence until six months later. No ocular complications except minimal opacity of the crystalline lenses were noted in both eyes.

A Case of Primary Central Nervous System Lymphoma with Ocular Involvement

PURPOSE: To report one case of primary central nervous system lymphoma with ocular involvement confirmed by pars plana vitrectomy. METHODS: A 52-year-old healthy man visited our hospital complaining of progressive dysarthria, memory impairment, and chronic headache. Brain CT scans and MRI scans revealed a brain tumor in the left basal ganglia and the frontal lobe. Stereotactic biopsy of the tumor showed a large diffuse B-cell type malignant lymphoma. Three months later, he presented with decreased vision and sensation of floaters in the right eye. Funduscopic examination of the right eye revealed a vitreous opacity peripherally. He underwent pars plana vitrectomy and vitreous biopsy to rule out ocular involvement of lymphoma. Smears from the cytospin of the specimen prepared from vitrectomy in the right eye showed a greater number of large, pleomorphic lymphoid cells. Flow cytometric immunophenotyping showed a clonal population of CD 20 which was conclusive for infiltration with B-cell lymphoma. RESULTS: The patient underwent treatment with radiotherapy to the brain and the right eye in combination with systemic and intrathecal chemotherapy. After five cycles of chemotherapy and radiotherapy, the brain mass disappeared, the neurological symptoms were improved, and the visual acuity of the right eye increased.