Ocular Adnexal Lymphoma Research Articles

Expression and meaning of MTDH and β-catenin in ocular adnexal lymphoma

Expression and meaning of MTDH and β-catenin in ocular adnexal lymphoma

Long-term course of patients with primary ocular adnexal MALT lymphoma: a large single-institution cohort study

AbstractWhile primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML) is the most common orbital tumor, there are large gaps in knowledge of its natural history. We conducted a retrospective analysis of the largest reported cohort, consisting of 182 patients with POAML, diagnosed or treated at our institution to analyze long-term outcome, response to treatment, and incidence and localization of relapse and transformation. The majority of patients (80%) presented with stage I disease. Overall, 84% of treated patients achieved a complete response after first-line therapy. In patients with stage I disease treated with radiation therapy (RT), doses ≥30.6 Gy were associated with a significantly better complete response rate (P = .04) and progression-free survival (PFS) at 5 and 10 years (P < .0001). Median overall survival and PFS for all patients were 250 months (95% confidence interval [CI], 222 [upper limit not reached]) and 134 months (95% CI, 87-198), respectively. Kaplan-Meier estimates for the PFS at 1, 5, and 10 years were 91.5% (95% CI, 86.1% to 94.9%), 68.5% (95% CI, 60.4% to 75.6%), and 50.9% (95% CI, 40.5% to 61.6%), respectively. In univariate analysis, age >60 years, radiation dose, bilateral ocular involvement at presentation, and advanced stage were significantly correlated with shorter PFS (P = .006, P = .0001, P = .002, and P = .0001, respectively). Multivariate analysis showed that age >60 years (hazard ratio [HR] 2.44) and RT<30.6Gy (HR=4.17) were the only factors correlated with shorter PFS (P = .01 and P = .0003, respectively). We demonstrate that POAMLs harbor a persistent and ongoing risk of relapse, including in the central nervous system, and transformation to aggressive lymphoma (4%), requiring long-term follow-up.

Lymphoproliferative Tumors of the Ocular Adnexa.

The ocular adnexa include the eyelids, conjunctiva, lacrimal apparatus, and orbital soft tissue. One percent of all lymphomas and approximately 8% of all extranodal lymphomas arise in the ocular adnexa and their incidence is increasing. Reactive lymphoid hyperplasia comprises 16% of all lymphoproliferative tumors of the ocular adnexa. The relative frequencies of ocular adnexal lymphoma presentation are in the orbit, 37%; conjunctiva, 29%; lacrimal apparatus, 20%; and eyelid, 14%. The most frequent primary lymphoma types of the ocular adnexa are extranodal marginal zone lymphoma, 62%; follicular lymphoma, 17%; and diffuse large B-cell lymphoma, 10%. The eyelids show the highest proportion of secondary lymphoma involvement, 49% of all eyelid lymphoproliferative lesions, compared with 24% in all ocular adnexa. The specific aspects of the site, histologic, immunohistochemical, cytogenetic, and molecular findings of the most relevant lymphoma types occurring in the various parts of the ocular adnexa will be discussed in relation to clinical parameters and relevance for therapy choice. Furthermore, the implications of the updated version of the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues in relation to ocular adnexal lymphoma are reviewed.

An Atypical Association of Hepatitis C Infection With Extranodal Marginal Zone Lymphoma

Marginal zone lymphomas (MZLs) are an uncommon form of B-cell non-Hodgkin lymphomas (NHLs). They can be further classified into three specific groups depending on the tissue involved: extranodal MZL or mucosa-associated lymphatic tissue (MALT) lymphoma, splenic MZL and nodal MZL. MALT lymphoma is among the most common malignant lymphomas of the ocular adnexa as seen with this case. Infectious agents play a decisive role in the development of these ocular adnexal lymphomas. Chlamydia psittaci , HSV1, HSV2, ADV8 and ADV19 are usually linked with these lymphomas. We present a rare case of extranodal MZL of the ocular adnexa with nodal and bone marrow involvement likely due to hepatitis C infection. Hepatitis C infection has been associated with diffuse large cell lymphoma, small lymphocytic lymphoma, splenic and nodal MZL, but to the best of our knowledge, there are very few documented cases of extranodal MZL of the ocular adnexa with hepatitis C infection. The paucity of evidence of this association makes our case rare and also offers a different therapeutic outcome with treatment of hepatitis C infection in conjunction with the traditional chemotherapy. Clin Infect Immun. 2017;2(2-3):40-42 doi: https://doi.org/10.14740/cii68e

A Novel Prognostic Index for Ocular Adnexal Lymphoma

Background: Ocular adnexal lymphoma (OAL) is a rare malignancy with a heterogeneous patient population. We sought to identify prognostic factors for OAL and to incorporate them into a novel prognostic index by using a large national database.Methods: We identified patients diagnosed with histologically confirmed OAL in 1973-2013 using all registries of the Surveillance, Epidemiology, and End Results database. Patients with regional or distant disease at diagnosis were excluded. Indolent histologies were defined as follicular, marginal zone, small lymphocytic not otherwise specified, and lymphoplasmacytic. We determined the association between OAL histology, orbital site, and overall survival (OS) using adjusted proportional hazards analysis and Kaplan-Meier estimates. Relative survival (RS) was calculated relative to a matched cohort of patients categorized by race, gender, and age using the SEER*Stat Program.Results: Among the 3,070 patients included, 941 (30.6%) had conjunctival tumors, 418 (13.7%) had lacrimal gland tumors, and 1711 (55.7%) had orbital-not otherwise specified tumors. Indolent histology was present in 2,073 (67.5%) patients. The 10-year OS and RS were 61% and 86%, respectively. In univariable and multivariable models, conjunctival site location (P<0.001) and indolent histology (P<0.001) were both associated with superior OS. Three primary OAL prognostic groups were identified: Group I (indolent histology, conjunctival location), Group II (indolent histology, non-conjunctival location or aggressive histology, conjunctival location), and Group III (aggressive histology, non-conjunctival location). The adjusted 10-year hazard ratios for OS were 1.4 (95% CI, 1.1-1.7, P<0.001) and 3.1 (95% CI, 2.5-4.0, P<0.001) for groups II and III, respectively, compared to group I. Groups I, II, and III had 10-year OS of 75%, 61%, and 37%, respectively, and 10-year RS of 96%, 89%, and 55%, respectively.Conclusions: Both conjunctival location and aggressive histology were independent predictors of survival. Our proposed prognostic index could have implications on OAL staging and management, though it must first be externally validated. DisclosuresNo relevant conflicts of interest to declare.

R-CVP Chemoimmunotherapy for Limited-Stage Ocular Adnexal MALT Lymphoma with Adverse Factors: A Phase II Study

Background: Ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) has an indolent disease course and a generally good response to radiotherapy; hence, limited-stage disease is commonly treated with radiotherapy. However, after localized radiotherapy for limited-stage OAML, a relapse rate of up to 16% was reported and the main relapse sites observed in previous series were in nonirradiated areas. The relapse rate was higher if the disease involved bilateral conjunctivae or tissue beyond the conjunctiva. We designed a phase II study in which patients with newly diagnosed and limited-stage OAML with bilateral or beyond-conjunctival involvement were treated with a regimen of rituximab in combination with cyclophosphamide, vincristine, and prednisolone (R-CVP), which has been widely used for advanced-stage indolent CD20+ B cell lymphoma and in a previous trial has demonstrated efficacy in advanced-stage MALT lymphoma.Patients and methods: Thirty-three patients with Ann Arbor stage I OAML with the adverse factors were enrolled. Patients received six cycles of R-CVP followed by two cycles of rituximab therapy. The enrolment criteria for disease status were Ann Arbor stage IE OAML with bilateral or beyond-conjunctival involvement; bT1 or T>1 based on the tumor-node-metastasis (TNM) staging system for ocular adnexal lymphoma proposed by the American Joint Committee on Cancer. Patients were required to be ©ø18 years old, with Eastern Cooperative Oncology Group (ECOG) performance scores of 0-2, with no prior chemotherapy or radiation therapy. Exclusions were made for disease confined to unilateral conjunctiva (T1N0M0) or Ann Arbor stage III-IV disease. The primary end point of the study was response rate, defined as the CR and partial response (PR) rates, based on the revised response criteria for malignant lymphoma. The secondary end point was PFS and overall survival.Results: The median age of the patients was 49 years (range, 19-74 years). The anatomic location of disease was the conjunctiva in 12 patients (36.4%), the orbit in 13 (39.4%), the eyelid in five (15.2%), and the lacrimal duct or gland in three (9.1%). Fourteen patients (42.4%) had bilateral disease at presentation. All study patients (100%) responded to the treatment. After the treatment, 28 patients (84.8%) were in CR and five patients (15.2%) in PR. With the median follow up of 26.9 months (range, 7.4-41.0 months), the estimated cumulative CR rate was 93.9% at 3 years (Figure 1). The cumulative CR rate was significantly lower in the patients with beyond-conjunctival disease (T>1) than in the patients with bilateral conjunctiva-confined disease (bT1) (91.3% vs. 100%; P = 0.022). The cumulative CR rate was lower for patients aged ©ø49 than in patients younger than 49 years (90.4% vs. 100%; P = 0.034). Multivariate analysis indicated that in our study patients beyond-conjunctival involvement (T>1) was an independent predictor of cumulative CR rate (hazard ratio [HR] 0.424, P = 0.044). Among the study patients, one patient, who had bT1N0M0 disease, relapsed at the same location in the eye at 21.7 months after initiation of treatment. The estimated PFS at 3 years was 95.5 ¡¾ 4.4%. No death was observed and OS was 100%. No patients experienced ophthalmic complications (Figure2).Conclusions: The R-CVP regimen was efficient for disease control up to 3 years because all study patients responded, cumulative CR rate was 93.9% and the PFS was 95.9% at 3 years. The common relapse sites in patients who received radiotherapy were in nonirradiated areas, suggesting that the systemic antitumor coverage of this chemoimmunotherapy may contribute to lowering the risk of distant relapse in our patients. We conclude that the R-CVP regimen can be effective alternative treatment which avoids radiation hazards and efficiently achieves CR in patients with limited-stage OAML, even those with adverse factors of radiotherapy. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Favourable response to rituximab by an ocular adnexal primary lymphoma

Abstract Case report A 70-year-old woman who presented with an extranodal marginal zone B-cell lymphoma in lacrimal gland and conjunctiva. Initial treatment with rituximab yielded an immediate good response. Five months later she showed lymphoid proliferation in her contralateral conjunctiva. Although no additional treatment was performed, the patient has been free of systemic symptoms and recurrences. Discussion Rituximab is a quite good therapeutic agent in low grade adnexal lymphomas.

Linfoma palpebral en paciente con implante de pesa de oro

Case reportA male patient with an exposure keratopathy caused by lagophthalmos. A gold weight was implanted in the right upper eyelid. Eight months later, he presented with erythema and swelling of right upper eyelid. An incisional biopsy was performed, reporting extranodal marginal zone B cell lymphoma. Discussionwhen a tumour at the site of a gold weight implant is refractory to treatment, it is essential to perform an incisional biopsy to establish the histopathological diagnosis. Ocular adnexal lymphomas are relatively common. The presence of foreign material can cause chronic inflammation that could be the stimulus for the development of a lymphoproliferative disorder.

Rates of Positive Findings on Positron Emission Tomography and Bone Marrow Biopsy in Patients With Ocular Adnexal Lymphoma.

The aim of this study was to determine rates of positive findings on positron emission tomography (PET) and bone marrow biopsy performed during staging workup for ocular adnexal lymphoma (OAL). A retrospective review of OAL patients was conducted. Demographics, primary versus secondary OAL, histologic subtype, and findings on PET and bone marrow biopsy performed as part of the initial staging workup for OAL were recorded. The study included 119 patients with OAL. There were 85 primary and 34 secondary OALs. The main histologic subtypes of lymphoma were mucosa-associated lymphoid tissue (n = 61), follicular (n = 26), diffuse large B-cell (n = 17), and mantle cell (n = 10). Positive PET findings were seen in 42 of 68 patients (62%) with primary OAL and 19 of 24 (79%) with secondary OAL. Positive PET findings were seen in 24 of 47 patients (51%) with mucosa-associated lymphoid tissue, 13 of 17 (76%) with follicular, 14 of 15 (93%) with diffuse large B-cell, and 9 of 10 (90%) with mantle cell lymphoma. Positive findings on bone marrow biopsy were seen in 7 of 59 patients (12%) with mucosa-associated lymphoid tissue, 4 of 23 (17%) with follicular, 1 of 17 (6%) with diffuse large B-cell, and 2 of 9 (22%) with mantle cell lymphoma. Our findings suggest that a significant proportion of patients with primary and secondary OAL have positive findings on PET and bone marrow biopsy at initial diagnosis, suggesting a reasonable yield for these tests as part of the initial staging workup in patients with a new diagnosis of OAL.

An analysis of IgG4‐related ocular disease among idiopathic orbital inflammations and mucosa‐ associated lymphoid tissue lymphoma

PurposeTo determine the proportion of idiopathic orbital inflammation (IOI) and mucosa‐associated lymphoid tissue (MALT) lymphoma accounted for by immunoglobulin (Ig) G4‐related orbital disease (ROD) using domprehensive criteria and To report the clinicopathological characteristics of patients with ocular MALT lymphoma with IgG4‐positive ells.MethodsA retrospective histopathological review and clinical case series. 49 patients from January 2005 through August 2015 were included. 20 cases of biopsy‐confirmed IOI, 29 cases of biopsy‐confirmed MALT lymphoma. Immunohistochemistry with IgG and IgG4 immunostaing. MALT lymphoma with IgG4 positive plasma cells were included when the IgG4/IgG ratio was 40% and IgG4 count was over 10/HPF. Histopathologic features, demographic and clinical data, radiologic findings, treatment and follow‐up information for each patient were analysed.ResultsPossible IgG4‐ROD accounted for 50.0% of cases originally diagnosed as IOI and 41.38% of cases originally diagnosed as MALT lymphoma. IgG4 positive MALT lymphoma group has contralateral IgG4 positive chronic inflammation lesion (p = 0.007). Relapse rate is higher than IgG4‐ unrelated group (p = 0.05) but not significantly.ConclusionsOf the MALT lymphoma cases, 12 cases were diagnosed as having possible IgG4‐ROD. Our result have demonstrated that ocular IgG4‐ROD can predispose to the development of ocular adnexal MALT lymphoma. However, further longitudinal observations during the course of disease are needed to confirm whether B‐cell lymphoma originate from IgG4‐ROD.

Recurrent mutations in NF-κB pathway components, KMT2D, and NOTCH1/2 in ocular adnexal MALT-type marginal zone lymphomas.

The pathogenesis of ocular adnexal marginal zone lymphomas of mucosa-associated lymphatic tissue-type (OAML) is still poorly understood. We analyzed 63 cases of such lymphomas for non-synonymous mutations in 24 candidate genes by amplicon sequencing. We validated frequent mutations in the NF-κB regulators MYD88, TNFAIP3 and TNIP1 in OAML, but also identified recurrent mutations in several additional components of the NF-κB pathway, including BCL10 and NFKBIA. Overall, 60% of cases had mutations in at least one component of NF-κB signaling, pointing to a central role of its genetic deregulation in OAML pathogenesis. Mutations in NOTCH1 and NOTCH2 were each found in 8% of cases, indicating a pathogenetic function of these factors in OAML. KMT2D was identified as the first epigenetic regulator with mutations in OAML, being mutated in 22% of cases. Mutations in MYD88 were associated with an inferior disease-free survival. Overall, we identified here highly recurrent genetic lesions in components of the NF-κB pathway, of NOTCH1 and NOTCH2 as well as KMT2D in OAML and thereby provide major novel insights into the pathogenesis of this B cell malignancy.

Ocular adnexal marginal zone lymphoma arising in a patient with IgG4-related ophthalmic disease

A 41-year-old man was diagnosed with immunoglobulin G4-related disease (IgG4-RD) in both eyelids 4 years ago and exhibited good response to steroid therapy. However, rapid swelling of the right eyelid lesion was recently observed. As IgG4-RD progression was suspected, biopsy was performed. Although the histology was consistent with IgG4-RD, the infiltrating large atypical lymphoid cells showed immunoglobulin light-chain restriction and IgH gene rearrangement. Consequently, he was diagnosed with extranodal marginal zone lymphoma with abundant IgG4-positive cells.

Prediction of the response of ocular adnexal lymphoma to chemotherapy using combined pretreatment dynamic contrast-enhanced and diffusion-weighted MRI.

Background There are no established biomarkers predictive of the efficacy of treatment for ocular adnexal lymphoma (OAL). Purpose To evaluate the effectiveness of pretreatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) in predicting the response of OAL to chemotherapy. Material and Methods Twenty-one patients, who were pathologically diagnosed with OAL, were retrospectively analyzed. According to the National Comprehensive Cancer Network (NCCN) response evaluation criteria for non-Hodgkin's lymphoma, patients were divided into responders (n = 14) and non-responders (n = 7). The volume transfer constant (Ktrans), rate constant (Kep), extracellular extravascular volume fraction (Ve), and apparent diffusion coefficient (ADC) were computed. Two independent-sample tests were applied for statistical analysis. For significantly different parameters, receiver-operator characteristics curve analysis was performed. Results The Ktrans value (min-1), Kep value (min-1), and ADC value (10-3 mm2/s) were 0.76 ± 0.36 vs. 0.47 ± 0.18 (mean ± SD), 4.43 ± 1.29 vs. 3.14 ± 1.37, and 0.51 ± 0.12 vs. 0.66 ± 0.15, respectively, in the responders and non-responders groups. Significant differences were found between the two groups regarding these parameters ( P < 0.05). However, no significant difference was observed in Ve (min-1) between the groups ( P > 0.05). Ktrans, Kep, and ADC had a moderately predictive sensitivity or specificity. When Ktrans and ADC or the three parameters were combined, a considerably higher sensitivity (85.7%) and specificity (85.7%) with a significant discriminative accuracy (area under the curve = 0.929; P = 0.002) was found. Conclusion Ktrans, Kep, and ADC could potentially predict OAL response to chemotherapy. A combination of these DWI and DCE-MRI quantitative parameters might increase sensitivity and specificity.

Chlamydia and ocular adnexal lymphomas: An Indian experience

Chlamydia and ocular adnexal lymphomas: an Indian experienceOcular adnexal lymphomas (OALs) are a heterogeneous group of malignancies, majority being extranodal mucosa-associated lymphoid tissue (MALT) type. Different geographical regions have reported association of Chlamydia with OALs (MALT type). In India, role of Chlamydia in OALs remains unexplored. The aim of this study was to detect Chlamydia and to correlate with clinicopathological features of OALs in India. The clinicopathological features of 41 OAL cases were studied prospectively. Chlamydia DNA was detected by genus specific PCR amplifying major outer membrane protein (MOMP) gene followed by DNA sequencing. Chlamydia immunoexpression was evaluated by immunofluorescence and immunohistochemistry. The results were correlated with clinicopathological features including follow-up and survival. Chlamydia genome was detected in 3/41 (7.3%) OAL cases by PCR. Direct sequencing revealed C. trachomatis in 3 positive cases. Immunofluorescence and immunohistochemistry showed Chlamydia antigen in 5/41 and 1/41 cases respectively. Immunofluorescence demonstrated higher sensitivity than immunohistochemistry. A significant association was observed between Chlamydia positivity and orbital location (P=0.05). Follow-up revealed relapse in 2 Chlamydia positive cases (P=0.056). Our results demonstrate for the first time presence of C. trachomatis genome in 7.3% OAL cases in India. As no other reports are documented, more detailed studies from different regions within India are needed to explore status of Chlamydia in OALs.

Comprehensive genomic profiling of orbital and ocular adnexal lymphomas identifies frequent alterations in MYD88 and chromatin modifiers: new routes to targeted therapies

Non-Hodgkin lymphoma of the orbit and ocular adnexa is the most common primary orbital malignancy. Treatments for low- (extra-nodal marginal zone and follicular lymphomas) and high-grade (diffuse large B-cell lymphoma) are associated with local and vision-threatening toxicities. High-grade lymphomas relapse frequently and exhibit poor survival rates. Despite advances in genomic profiling and precision medicine, orbital and ocular adnexal lymphomas remain poorly characterized molecularly. We performed targeted next-generation sequencing (NGS) profiling of 38 formalin-fixed, paraffin-embedded orbital and ocular adnexal lymphomas obtained from a single-center using a panel targeting near-term, clinically relevant genes. Potentially actionable mutations and copy number alterations were prioritized based on gain- and loss-of-function analyses, and catalogued, approved, and investigational therapies. Of 36 informative samples, including marginal zone lymphomas (n=20), follicular lymphomas (n=9), and diffuse large B-cell lymphomas (n=7), 53% harbored a prioritized alteration (median=1, range 0–5/sample). MYD88 was the most frequently altered gene in our cohort, with potentially clinically relevant hotspot gain-of-function mutations identified in 71% of diffuse large B-cell lymphomas and 25% of marginal zone lymphomas. Prioritized alterations in epigenetic modulators were common and included gain-of-function EZH2 and loss-of-function ARID1A mutations (14% of diffuse large B-cell lymphomas and 22% of follicular lymphomas contained alterations in each of these two genes). Single prioritized alterations were also identified in the histone methyltransferases KMT2B (follicular lymphoma) and KMT3B (diffuse large B-cell lymphoma). Loss-of-function mutations and copy number alterations in the tumor suppressors TP53 (diffuse large B-cell and follicular lymphoma), CDKN2A (diffuse large B-cell and marginal zone lymphoma), PTEN (diffuse large B-cell lymphoma), ATM (diffuse large B-cell lymphoma), and NF1 (diffuse large B-cell lymphoma), and gain-of-function mutations in the oncogenes HRAS (follicular lymphoma) and NRAS (diffuse large B-cell lymphoma) were also observed. Together, our study demonstrates that NGS can be used to profile routine formalin-fixed, paraffin-embedded orbital and ocular adnexal lymphomas for identification of somatic-driving alterations and nomination of potential therapeutic strategies.

Ocular Adnexal Lymphoma: Clinical Presentation, Diagnosis, Treatment and Prognosis

Ocular adnexal lymphoma (OAL) is a rare tumor with an incidence of 0.2 per 1,00,000 individuals. However, it constitutes the most common orbital tumor especially in older population with an incidence ranging from 11% to 24%. OAL can involve conjunctiva, orbital soft tissues, eyelid, or adnexal structures such as lacrimal gland and lacrimal drainage system. The most common primary OAL is low-grade malignant extranodal marginal zone B-cell lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT) type. Though various classification and staging systems have been proposed for OAL, currently, American joint committee on cancer (AJCC) TNM (tumor node metastasis) staging is most commonly used. Most commonly, conjunctival lymphoma typically presents as ‘salmon-colored patch’ and orbital lymphoma presents as proptosis, which on imaging shows characteristic appearance of molding around the globe without any globe indentation or bone erosion. Orbital radiotherapy and systemic chemotherapy forms the mainstay of treatment. Newer treatment modalities include immunotherapy with interferon and anti-CD20 antibody rituximab that have been shown to be useful either when used alone or in combination with chemotherapy or as radio-immunotherapy.

Chemotherapy Alone Is Effective to Treat Localized and Disseminated Ocular Adnexa Lymphomas

Background:The treatment strategies for ocular adnexa lymphomas (OALs), including conjunctiva, orbital, and lacrimal gland lymphomas, remain controversial. In this study, we assessed the efficacies and outcomes of different modality treatment, including chemotherapy, radiotherapy, and surgery for OALs.Methods and Materials:Between Jan. 1990 to Dec. 2013, patients receiving first-line chemotherapy (oral alkylating agents, rituximab-based treatment, or CHOP [cyclophosphamide, doxorubicin, vincristine, and steroid]-like regimens), radiotherapy (30 to 50 Gy, in 1.8- to 2.0- Gy per daily fractions), and surgery for newly diagnosed OAL were included in this study. The clinicopathologic features, including patients' characteristics, primary lymphoma locations, pathology subtypes, treatment modality, event-free survival (EFS) following first-line therapy, and OS (OS) were analyzed.Results:There were 56 men and 37 women with median age of 58 years were included. Of them, 79 patients (85%) were diagnosed with low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, 5 (5%) with high-grade transformed MALT lymphoma, and 9 (10%) with diffuse large B cell lymphoma. Orbit was the most common involved location (45 patients, 48%), followed by conjunctiva (35 patients, 38%), and lacrimal gland (13 patients, 14%). Of 79 patients with stage I-IIE1 disease, 22 received chemotherapy, 34 with radiotherapy, and 23 patients with other modality treatments (18 with surgery, 4 with combined radiotherapy and chemotherapy, and 1 with intra-lesional injection of rituximab). The 5-year EFS for chemotherapy, radiotherapy, and other modality treatment was 89.2%, 89.7%, and 83.1%, respectively, whereas the 5-year OS for chemotherapy, radiotherapy, and other modality treatment was 100%, 90.4%, and 87.5%, respectively. Of 14 patients with stage IIE2 to IV disease, the 5-year EFS for chemotherapy alone (n=9) and combined radiotherapy and chemotherapy (n=5) were 68.6%, 80%, respectively, whereas the 5-year OS for both group was 80.0%. Among 42 patients receiving radiotherapy, 7 (16.7%) patients developed cataract, 4 (9.5%) patients with keratitis, and 2 (4.8%) patients with maculopathy. In multivariate analysis, high-grade transformation (P=0.049) was the significant factor for shorter EFS of 1st -line treatment. Old age (> 60 years) (p = 0.014), advanced stage (stages III and IV) (p = 0.03), and high-grade transformation (p = 0.018) were the prognostic factors of poor OS.Conclusions:In addition to radiotherapy, our data indicate that chemotherapy as first-line therapy provides good disease control and less radiotherapy-associated side effects for patients with stage I to IIE1 OALs. Old age, advanced stage, and high-grade histology subtype remain poor prognostic factors for OALs, and new treatment strategies for these patients are warranted. DisclosuresNo relevant conflicts of interest to declare.

Clinical Manifestations and Treatment Results in Accordance with Frontline Treatment Modalities for Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma (OAML)

Background: localized ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) was effectively treated with frontline radiotherapy. however it is sometimes associated with radiation-related complications of ocular structures, as well as distant relapse or delayed relapse. Although there are no definitive optimal treatment approaches for these patients, we investigated the results in accordance with frontline treatment modalities for OAML.Patients and methods: 159 patients with biopsy-confirmed primary OAML between 2007 and 2015 were analyzed retrospectively. All the patients were sorted by risk-stratification with Ann-Arbor staging and the tumor, node, metastasis (TNM) staging system, and treatment modalities according to anatomic location, prognosis factors, which were supported by ophthalmologist.Results: first-line radiotherapy had overall survival(OS) of 100%, event-free survival(EFS) of 90%. However frontline-radiotherapy group has 100% of survival with 55% of moderate to severe dry eye syndrome, 37.4% of cataract incidence, 11% of cataract-related operations, and 1% (n=1) of radiation-related blindness. Although 5-year EFS is good in radiotherapy group (90% vs 64% in radiotherapy group vs chemotherapy, p<0.001), most of aggressive factors (young age at diagnosis, conjunctival lesions, Ann Arbor stage I, early T1N0M0 stage, and no distant extranodal metastasis including of bone marrow involvement) showed in radiotherapy group in comparison with chemotherapy group. In subgroup analysis of first-line chemotherapy, rituximab-containing group has more good response of event-free survival (p= 0.041) with tolerable hematologic toxicities compared to frontline radiotherapy group.Conclusion: OAML with localized to conjunctiva alone was treated with frontline-radiotherapy and non-conjuctival lesions treated with chemotherapy. Radiotherapy as first-line is good local control-therapeutic option in patients with localized to conjunctiva alone, but management of radiation-associated complication is concerned troubles. In advanced OAML including of extra-conjunctival lesions, systemic chemotherapy is best options. rituximab-based regimen could be feasible to obtain good disease-free survival and response rate.Table 1Patient's characteristics between frontline-chemotherapy and radiation group (n= 159)FactorsPrimary Chemotherapy group(n = 68)Primary Radiation group(n = 91)P-valueGender (male)37 (54%)28 (30.8%)0.003Age at diagnosis (median, year)50430.003involvement of both eyes at diagnosis22 (32.4%)23 (25.3%)0.75Conjuctival lesion at diagnosis22 (32.4%)76 (83.5%)<0.001Ki-67 on pathologic stain (median, %)540.545Ann-Arbor stage I23 (66.2%)3 (96.7%)<0.001LDH at diagnosis (mg/L)3553440.216Patients no. with T1N0M021 (30.9%)78 (85.7%)<0.001Bone marrow involvement7 (10.3%)0 (0%)<0.001Patients no. with N1~N3 staging10 (14.7%)0 (0%)<0.001Patients no. with T0N0M1~27 (10.3%)0 (0%)<0.001Patients treated with frontline chemotherapy were classified in more aggressive or advanced stage which compare to patients treated with primary radiotherapy statistically.Table 2Patient's characteristics between Rituximab containing group and non-rituximab in frontline chemotherapy subgroup (n=68)FactorsRitixumab-containing(n = 26)No Rituximab(n = 42)P-valueGender (male)0.942Age at diagnosis (median, year)52490.411involvement of both eyes at diagnosis0.057Conjuctival lesion at diagnosis0.087Ki-67 on pathologic stain (median, %)430.540Ann-Arbor stage I0.532LDH at diagnosis (mg/L)3533560.782Patients no. with T1N0M00.585Patients no. with N1~N3 staging0.659Patients no. with T0N0M1~20.695There are statistically no differences between patients treated with Rituximab-containing regimen and non-rixuximab in frontline chemotherapy subgroup. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinicopathologic characteristics and treatment of marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).

Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) accounts for 7% to 8% of newly diagnosed lymphomas. Because of its association with infectious causes, such as Helicobacter pylori (HP) or Chlamydophila psittaci (CP), and autoimmune diseases, it has become the paradigm of an antigen-driven malignancy. MALT lymphoma usually displays an indolent course, and watch-and-wait strategies are justified initially in a certain percentage of patients. In patients with gastric MALT lymphoma or ocular adnexal MALT lymphoma, antibiotic therapy against HP or CP, respectively, is the first-line management of choice, resulting in lymphoma response rates from 75% to 80% after HP eradication and from 33% to 65% after antibiotic therapy for CP. In patients who have localized disease that is refractory to antibiotics, radiation is widely applied in various centers with excellent local control, whereas systemic therapies are increasingly being applied, at least in Europe, because of the potentially systemic nature of the disease. Therefore, the objective of this review is to briefly summarize the clinicopathologic characteristics of this distinct type of lymphoma along with current data on management strategies.

An update on ocular adnexal lymphoma.

Ocular adnexal lymphoma (OAL) is a relatively common lesion in the practice of ophthalmic oncology. Although OALs are usually primary tumors, secondary involvement of the ocular adnexae by systemic lymphoma is also possible. The clinical and radiological features of OAL are non-specific. Thorough morphological evaluation, aided by immunostaining, cytogenetic studies and molecular testing, are necessary for accurate diagnosis.