Conjunctival Lymphoma Research Articles

Conjunctival Lymphoma in a Child

To report a rare case of large conjunctival B-cell lymphoma in a child. A 13-year-old girl was initially diagnosed with a right lower eyelid chalazion. After 3 weeks during which the mass was growing, she was referred for treatment to our department. Because of the unusual appearance of the mass, an excisional biopsy was performed. Pathological findings were consistent with those of a large B-cell lymphoma. CD20 and Ki67 staining were positive, and polymerase chain reaction analysis showed monoclonality of B cells. Although conjunctival lymphoma is a very rare entity in children, it should be included in the differential diagnosis of an eyelid or conjunctival mass.

Canaloplasty for Pigmentary Glaucoma with Coexisting Conjunctival Lymphoma

This case report presents canaloplasty as a bleb-free surgical option for lowering intraocular pressure in cases with postoperative conjunctival scarring.

CyberKnife Radiosurgery for the Treatment of Intraocular and Periocular Lymphoma

To evaluate efficacy, patient tolerance, and adverse effects of CyberKnife radiosurgery for the treatment of intraocular and periocular lymphoma. Retrospective case series of 13 patients who underwent CyberKnife radiosurgery was conducted. Fourteen eyes of 13 patients were included. The tissue location of the lymphoma was orbit (7 eyes), conjunctiva (3 eyes), choroid (2 eyes), and retina (2 eyes). The lymphoma type was classified as extranodal marginal zone B-cell lymphoma in 7 eyes (50%), diffuse large B-cell lymphoma in 3 eyes (21%), follicular lymphoma in 2 eyes (14%), and benign reactive lymphoid hyperplasia in 2 eyes (14%). The mean treatment dose was 1718 centigrays (cGy) (range, 1350-2250 cGy) given over a mean of 5 days (range, 3-5 days) with a mean dose rate of 320 cGy per fraction. Complete tumor resolution without local recurrence over a mean follow-up of 23 months was documented in all cases. Radiation-associated adverse effects included mild dry eye in 2 patients and cataract in 1 patient with conjunctival lymphoma. There was no radiation retinopathy or papillopathy, and visual acuity was preserved or improved in 13 eyes and decreased in 1 eye due to the presence of cataract. CyberKnife radiosurgery is a well-tolerated technique for the treatment of intraocular and periocular lymphoma, allowing for local resolution of the lesions. An important benefit is that treatment was completed over 5 days.

Intralesional Rituximab: A New Therapeutic Approach for Patients with Conjunctival Lymphomas

The tolerability and activity of the intralesional administration of rituximab, a chimeric monoclonal antibody that targets the CD20 antigen, was assessed in patients with conjunctival B-cell lymphoma. The systemic administration of rituximab has varying response rates with different types of lymphoma, generally with a mild toxicity level. Intralesional administration of this drug has increased local disease control in cases of cutaneous mucosa-associated lymphoid tissue (MALT) lymphoma. This was an interventional pilot study of 3 patients with relapsed CD20+ conjunctival lymphomas treated with intralesional injections of rituximab. Two patients with conjunctival MALT lymphoma refractory to previous systemic treatment with rituximab and 1 patient with relapsed follicular lymphoma of the eyelid were included in the study. Patients received 4 weekly intralesional injections followed by 6 monthly injections of undiluted rituximab together with xylocaine 2%. Side effects and tumor response were assessed before each intralesional injection and at 3-month intervals after treatment conclusion. The 2 conjunctival MALT lymphoma patients achieved complete remission after intraconjunctival rituximab treatment, which shows that this method of administration can overcome the primary resistance to this monoclonal antibody. The patient with the eyelid follicular lymphoma did not achieve tumor regression after the first intralesional injections of rituximab. In this patient, the addition of autologous serum resulted in lymphoma remission at the end of treatment, suggesting that drug inefficacy can be related to the low bioavailability of effectors in the tumor tissue. Although follow-up is still short, these preliminary findings suggest that intralesional rituximab is a well-tolerated strategy in marginal-zone and follicular lymphomas of the conjunctiva. An increased bioavailability of effectors in the tumor tissue, by means of the addition of autologous serum, may improve rituximab activity. This strategy could be used in other extranodal CD20+ indolent lymphomas to improve local control, even in patients who are initially refractory to systemic rituximab treatment.

Spectral-domain optical coherence tomography of conjunctival mucosa-associated lymphoid tissue lymphoma with presumed choroidal involvement

BackgroundConjunctival mucosa-associated lymphoid tissue (MALT) lymphoma has been well-described, but rarely do these lesions demonstrate intraocular involvement. We report a case of conjunctival MALT lymphoma with intraocular involvement and novel spectral-domain ocular coherence tomography (SD-OCT) findings.Patient and methodsA 75-year-old woman with biopsy-proven MALT lymphoma of the conjunctiva presented with ipsilateral yellowish diffuse choroidal infiltrates on fundoscopic examination. Choroidal involvement was documented clinically, on ultrasonography, on fluorescein angiography, and by SD-OCT. Treatment consisted of 3 weeks of oral doxycycline and six cycles of systemic chemotherapy with cyclophosphamide, vincristine, prednisone, and rituximab.ResultsThere was no evidence of progression or recurrence of MALT lymphoma after 9 months of follow-up. Despite complete resolution of clinical findings, ultrasound, and fluorescein angiography, the choroidal lesions remained unchanged on SD-OCT.DiscussionChoroidal involvement of conjunctival MALT is rare, and can be successfully treated. Persistence of irregularities on SD-OCT did not influence management in the presence of clinical improvement and resolution on ultrasonography and fluorescein angiography.

SU‐GG‐T‐559: Novel Treatment Technique for Conjunctival Lymphoma of the Eye

Purpose: This study was designed to develop a new technique to better treat conjunctival lymphoma while limiting dose to the lens. Previous texts have suggested using a “hanging block” approach, for example a lead filled straw suspended in the center of the treatment field. The possibility of using a baby nipple has several advantages, including ease and reproducibility of set‐up, safety for the patient (the baby nipple moves with the patient), and an ideal dose distribution due to the shaping and slight attenuation of the radiation beam through the plastic. Materials/Methods: A typical baby bottle nipple (Philips, 3–6 months) was placed in a 4 cm diameter circle Cerrobend cut‐out and placed in the 6×6 electron cone. A lead rod, a Cerrobend rod, and spherical tungsten fishing weights were each placed in the tip of the bottle nipple and measurements were made with radiochromic film in the sagittal and coronal planes for 6 and 9 MeV beams. Dose distributions were evaluated to determine the best block and ideal energy for the patient's disease. Results: The Cerrobend rod did the best job of blocking the radiation in the center of the field while still treating the area corresponding to the white of the eye. It was determined that energy of 6 MeV generated adequate disease coverage. The patient seen at the Brown Cancer Center was prescribed 26 Gy to the 90% isodose line in 13 fractions at 6 MeV for each eye. The bottle nipple was used to block the lens each day and yielded a successful treatment. Conclusions: This technique is a excellent option for certain diseases of the eye. It provides a safe yet simple way to effectively treat the patient while shielding the lens from radiation that even at relatively low doses could form cataracts in the eye.

Marginal zone B-cell lymphoma of the conjunctiva

Lymphomas are the most common orbital malignancies, marginal zone B-cell lymphoma being the most common histotype. One quarter of these lymphomas exhibit conjunctival involvement, which is almost exclusively observed in indolent lymphomas (96% of conjunctival lymphomas). Primary conjunctival marginal zone B-cell lymphoma exhibits interesting and peculiar features, with some molecular, biological, clinical and prognostic differences from the rest of the ocular adnexal lymphomas. Recent studies demonstrate that chromosomal abnormalities, autoimmune disorders and infectious agents are variably associated with the development and behavior of this lymphoma. Conjunctival lymphomas are rarely lethal tumors and, in selected cases, may be managed without anti-tumor treatment. In other cases, conjunctival lymphomas cause symptoms that require immediate treatment. To date, no guidelines for the management of patients with conjunctival lymphoma exist. Surgical resection, radiotherapy and chemotherapy are the most common approaches to these malignancies, but the use of systemic immunotherapy, bacteria-eradicating antibiotic therapy and local treatments, such as intralesional injections of interferon or rituximab and eyedrops of cytostatics, is progressively growing.

Taches suspectes de la conjonctive

The main conjunctival tumors are represented by (i) conjunctival melanoma, ocular surface squamous neoplasia, and conjunctival lymphoma, which are malignant tumors, and (ii) conjunctival nevus, papilloma, and choristoma, which are benign. In usual practice, ophthalmologists need to know how to differentiate conjunctival melanomas and carcinomas from the other conjunctival tumors by clinical examination. Indeed, the therapeutic approach to these two malignant diseases presents a number of particularities such as the need for surgery under general anesthesia, if possible, to minimize the risk of local dissemination and further local recurrence, and detailed information on the tumor location and measurements before surgery (Figures, diagram, sizes) to precisely define the irradiation field during complementary radiotherapy. The clinical signs and main therapeutic principles of conjunctival tumors are reviewed in this article.

Conjunctival lymphoma following treatment with cyclophosphamide

Conjunctival lymphoma following treatment with cyclophosphamide

Comparison between PENELOPE and electron Monte Carlo simulations of electron fields used in the treatment of conjunctival lymphoma

For the treatment of conjunctival lymphoma in the early stages, external beam radiotherapy offers a curative approach. Such treatment requires the use of highly conformed small radiation beams. The beam size is so small that even advanced treatment planning systems have difficulties in calculating dose distributions. One possible approach for optimizing the treatment technique and later performing treatment planning is by means of full Monte Carlo (MC) simulations. In this paper, we compare experimental absorbed dose profiles obtained with a collimator used at the University Hospital Essen, with MC simulations done with the general-purpose radiation transport code PENELOPE. The collimator is also simulated with the hybrid MC code electron Monte Carlo (eMC) implemented in the commercial treatment planning system Eclipse (Varian). The results obtained with PENELOPE have a maximum difference with experimental data of 2.3%, whereas the eMC code differs systematically from the experimental data about 7% in the penumbra tails. We also show that PENELOPE simulations are able to obtain absorbed dose maps with an equivalent statistical uncertainty to the one found with eMC in similar CPU times.

Infectious agents and lymphoma development: molecular and clinical aspects

This review is focused on the role of infectious agents in the development of some lymphoma entities. Associations involving bacterial infections mostly regard marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT)-type. Some paradigmatic examples of these associations include the Helicobacter pylori-related gastric MALT lymphoma and the more recently reported links between Chlamydophila psittaci and ocular adnexal MALT lymphomas and Borrelia burgdorferi and cutaneous MALT lymphomas. The well-documented association between Epstein-Barr virus infection and related lymphoproliferative disorders are analysed as an example of lymphotropic virus with tumourigenic activity. Molecular, biological and clinical features as well as therapeutic implications of these associations are analysed and future perspectives in this field are discussed.

A Six-Month Regimen of Oral Clarithromycin Is a Feasible and Active Therapy for Patients with Relapsed/Refractory Marginal Zone B-Cell Lymphoma of MALT-Type

Background: The antibiotic clarithromycin displays immunomodulatory properties, partially mediated by the suppression of IL-6 and other inflammatory cytokines. This macrolide can directly induce TNF-mediated apoptosis in mouse lymphoma cells, with a DNA fragmentation degree similar to that seen in cells treated with chemotherapeutic agents. In recent trials on multiple myeloma and Waldenstrom's macroglobulinemia, the combination of clarithromycin with other immunomodulatory agents exhibited high tumour regression rates, and some case reports suggested an antineoplastic effect of clarithromycin in marginal zone B-cell lymphoma of MALT-type (EMZL) of the colon and the lung.Method: This is a phase II trial aimed to assess tolerability and activity of a 6-month regimen of oral clarithromycin in patients (pts) with relapsed/refractory EMZL. Clarithromycin (500 mg) was given orally twice daily for 6 months to 14 HIV-negative pts (age 318 ys; ECOG-PS ≤3) with relapsed/refractory EMZL and at least one measurable/parametrable lesion. Pre-registration assessments included physical examination, hemogram and biochemical profile, HIV, HBV and HCV serology, gastroscopy, gastric Helicobacter pylori (Hp) infection assessment (3 methods: histology, breath test, serology, and/or cagA in faeces), Chlamydia psittaci (Cp) infection assessment (PCR on tissue and PBMC, only in pts with ocular adnexal MALT lymphoma), total body CT scan, and bone marrow biopsy. Tolerability (physical examination and blood exams) was assessed every 8 weeks and objective response was assessed every 3 months.Results: Median age of eligible pts was 59 ys. (range 36–81; 7 females). Clarithromycin was the salvage therapy at first relapse in 8 pts, and the 3rd–6th line of treatment in the others. All pts had local disease at the time of treatment, two pts had also systemic dissemination. Extranodal sites were stomach (n=2), conjunctiva (n=4), orbit (n=7), and breast (n=1). No pt had increased LDH serum levels; only one pt had B symptoms. Chronic infections were caused by HCV in 2 pts, Hp in 2 and Cp in 5. Hp and Cp infections were successfully eradicated with specific antibiotics as part of upfront treatment, that is with a median time from bacterial eradication to clarithomycin treatment of 14 (7–40) months. This excludes that a potential clarithomycin antitumor activity could be due to antimicrobial effect.The treatment was completed in 13 pts and is ongoing in the remaining one. Two pts achieved a complete remission (22+, 24+) and 2 pts achieved a partial response (11+, 14), with an ORR of 31%; 1 pt had a minimal response (11+), 5 pts had stable disease (15+, 15+, 16+, 22, 24), 3 pts experienced disease progression (10, 10, 16). The median time to the best response was 10 months. Three of the major responses were observed among the 4 pts with conjunctival lymphoma, treatment is ongoing in the remaining one. The number of previous lines of treatment did not influence response. Tolerability was excellent-good in all pts but two (episodic nausea). No biochemical abnormalities were detected after 6 months of treatment. After a median follow-up of 15 months, 6 pts experienced disease progression, with a median time to progression of 11+ months. The pt with B symptoms experienced a high-grade transformation and was not responsive to clarithromycin. All pts but one (HCV-related cirrhosis) are alive with a median OS of 42 months.Conclusions: This 6-month regimen of oral clarithromycin seems to be safe and active in EMZL, mostly in pts with conjunctival MALT lymphoma. Response to clarithromycin does not seem to be mediated by eradication of common MALT-related bacterial infections. Clarithromycin deserves to be further investigated in EMZL.

Malt lymphoma

Abstract Purpose To review the histomorphology, immunophenotype and genotypic features of conjunctival "MALT" lymphomas. Methods The conjunctival lymphomas represent the malignant end of the spectrum of lymphoproliferative lesions occurring in this site. The new W.H.O. Lymphoma Classification is the most suitable system for subdividing the conjunctival lymphomas, whereby the extranodal marginal zone B‐cell lymphoma of MALT type (or “MALT lymphoma”) represents the most common lymphoma subtype. Results MALT lymphomas are characterized by mainly small B‐cells in the marginal zone. Their immunophenotype is: CD20+, CD43 (+/‐), BCL‐2, IgM+, and a low Ki‐67 growth fraction. A number of chromosomal changes have been described in conjunctival MALT lymphomas, and include trisomy 3, t(14;18), t(3;14), t(11;18), t(1;14) and loss of 6q23.3‐24. Through differing pathways, these chromosomal alterations result in the dysregulation of NF‐KB, and hence the uncontrolled proliferation of lymphocytes. In some geographical regions, there may be an association between these neoplasms and microorganisms, such as Chlamydia, Helicobacter as well as HCV. Management of patients with MALT lymphomas includes a thorough systemic medical examination to establish the clinical stage of the disease. The majority of patients with conjunctival lymphoma have Stage IE disease (Ann Arbor); however, systemic spread is not uncommon. Reported prognostic criteria for MALT lymphomas are few but include stage of disease at presentation; serum lactate dehydrogenase level; and tumour cell growth rate. A new more refined clinical staging system has been proposed by the TNM/AJCC committee and is to be published in its 7th Edition. Conclusion Although the most common lymphoid neoplasm of the conjunctiva, there is still much to learn about MALT lymphomas.

Lymphoma of the conjunctiva

Abstract Purpose Description of the treatment and follow‐up of conjunctival lymphomas Methods Retrospective reportage of 16 patients with a conjunctival lymphoma seen at the department of Ophthalmology of Leiden University. Results In the last 20 years, 15 patients with a local conjunctival lymphoma and one patient with generalized lymphoma of the skin with a conjunctival lymphoma were treated. Histologically all 16 patients showed to have an extranodal marginal zone B‐cell lymphoma (MALT‐lymphoma). Mean age of the patients at presentation was 64.8 years (37.2‐84.5 years). In two patients there was a bilateral lymphoma. Thirteen patients were treated with external irradiation (30 Gray in 15 sessions), one patient with cryotherapy and one patient with CHOP chemotherapy. After a mean follow‐up time of 6 years, all patients are still alive, without recurrence. Conclusion The new international classification of conjunctival lymphoma shows the great differences in survival of conjunctival lymphoma patients. Here we illustrate that patients with the favorable marginal zone B‐cell lymphoma have a very good prognosis. When treated with external irradiation, there is an extremely low rate of recurrence

Targeted monoclonal antibody therapy and radioimmunotherapy for lymphoproliferative disorders of the ocular adnexa

The goal of this review is to update ophthalmologists and orbital and adnexal specialists with the emerging role of targeted monoclonal antibody therapy and radioimmunotherapy for orbital and adnexal non-Hodgkin's lymphoma and other lymphoproliferative disorders of the orbit. Rituximab as monotherapy for indolent lymphoma of the orbit and conjunctiva may be associated with good initial response, but the risk of distant relapse is about 50%. Rituximab may be used in combination with conventional chemotherapy, and such combination therapy may be associated with a higher durable response rate and improved progression-free survival compared with chemotherapy alone. Radioimmunotherapy using targeted monoclonal antibodies with radioactive conjugates is also associated with a more durable response rate than monotherapy with rituximab alone and may be an alternative for treatment of ocular adnexal lymphoma. Radioimmunoconjugates are associated with transient pancytopenia during the first 3 months after treatment. Rituximab monotherapy may be considered as an alternative to systemic steroids for treatment of orbital benign lymphoid hyperplasia. Targeted monoclonal antibody therapy is an intriguing new modality for treatment of orbital, eyelid, or conjunctival lymphoma and can be used in combination with radioimmunotherapy or standard chemotherapy for a more durable response.

CD5-undetected by immunohistochemistry, t(11;14)(q13;q32)-positive conjunctival mantle cell lymphoma: A case report

Most primary ocular adnexal lymphomas are extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT). A few cases of ocular adnexal mantle cell lymphomas have been reported in the literature. We present a case of mantle cell lymphoma presenting as conjunctival mass. A 58-year-old man presented with a palpable mass in the left lower tarsal conjunctiva incidentally detected one month previously. Histopathologic examination showed proliferation of monomorphous small-to-medium sized lymphoid cells. On immunohistochemistry, tumor cells were positive for CD20, bcl-2, and cyclin D1, and negative for CD5. PCR analysis for immunoglobulin heavy chain gene rearrangement showed monoclonal B-cell proliferation. t(11;14)(q13;q32), involving the CCND1 and IGH genes, was detected in interphase fluorescent in situ hybridization using formalin-fixed, paraffin-embedded tissue; however, MALT1 gene translocation was not observed. The final diagnosis was mantle cell lymphoma. There was no lymphadenopathy; however, bone marrow involvement of the lymphoma was suspected. The patient has been receiving systemic chemotherapy. This case emphasizes the differential diagnosis of conjunctival mantle cell lymphoma from extranodal marginal zone B-cell lymphomas of MALT regarding the clinical and pathological aspects.

The association between conjunctival MALT lymphoma and Helicobacter pylori

Background/aims:Helicobacter pylori is well known to be responsible for gastric mucosa-associated lymphoid tissue (MALT) lymphoma. This study evaluates whether H pylori is also responsible for conjunctival MALT lymphoma and which...

In vivo confocal microscopy in a patient with conjunctival lymphoma

A case of primary conjunctival mucosa-associated lymphoid tissue lymphoma studied by in vivo corneal confocal microscopy (IVCM) is described for the first time. Examination of the lower mediobulbar and forniceal conjunctiva of the left eye of a 37-year-old female patient showed a typical salmon-pink patch. IVCM examination of the conjunctival lesion showed irregular, polygonal, conjunctival bulbar epithelial cells with blurred edges and without visible nucleus. Many small, roundish, hyper-reflective cells were also seen. These cells were arranged diffusely or in nests in cyst-like hypo-reflective spaces. A few highly reflective cells were also visible among deep stromal collagen fibres. The IVCM picture recalled the histological profile of low-grade mucosa-associated lymphoid tissue lymphoma, characterized by sheets of neoplastic cells around reactive follicles. IVCM enabled non-invasive evaluation of the eye surface at high magnification and with good contrast, and could be useful for early differential diagnosis of conjunctival lesions.

Role of Helicobacter pylori in Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma

Role of Helicobacter pylori in Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma

Role of Helicobacter pylori in Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma

Role of Helicobacter pylori in Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma