Ocular Adnexal MALT Lymphoma Research Articles

Distinct groups of autoantigens as drivers of ocular adnexal MALT lymphoma pathogenesis.

Chronic B-cell receptor signals incited by cognate antigens are believed to play a crucial role in the pathogenesis of mucosa-associated lymphoid tissue lymphomas. We have explored the immunoglobulin variable regions (IGHV) expressed by 124 ocular adnexal MALT lymphomas (OAML) and tested the in vitro reactivity of recombinant IgM derived from 23 OAMLs. Six of 124 OAMLs (5%) were found to express a high-affinity stereotyped rheumatoid factor. OAMLs have a biased IGHV4-34 usage, which confers intrinsic super auto-antigen reactivity with poly-N-acetyllactosamine (NAL) epitopes, present on cell surface glycoproteins of erythrocytes and B cells. Twenty-one OAMLs (17%) expressed IGHV4-34-encoded B-cell receptors. Five of the 23 recombinant OAML IgMs expressed IGHV4-34, four of which bound to the linear NAL i epitope expressed on B cells but not to the branched NAL I epitope on erythrocytes. One non-IGHV4-34-encoded OAML IgM was also reactive with B cells. Interestingly, three of the 23 OAML IgMs (13%) specifically reacted with proteins of U1-/U-snRNP complexes, which have been implicated as cognate-antigens in various autoimmune diseases such as systemic lupus erythematosus and mixed connective tissue disease. The findings indicate that local autoimmune reactions are instrumental in the pathogenesis of a substantial fraction of OAMLs.

Mucosa-associated lymphoid tissue lymphoma of the lacrimal gland: A case report and literature review.

The most common subtype of primary lymphoma of the ocular adnexa is the mucosa-associated lymphoid tissue (MALT) subtype. MALT lymphoma of the lacrimal gland is relatively rare among the lacrimal gland tumors, and the early clinical symptoms are atypical, which can easily lead to misdiagnosis and missed diagnosis. Here, we report a case of MALT lymphoma of the lacrimal gland and explore its clinical manifestations, pathological characteristics, management, and pathogenesis, with the aim of helping clinicians gain an in-depth understanding of ocular adnexal MALT lymphoma. A 60-year-old man presented to our hospital with proptosis and diplopia. The right eye deviated and shifted toward the lower part of the nose. Orbital enhanced magnetic resonance imaging suggested a mass with a maximum cross-section of 3.2 × 2.1 cm. T1 weighted image was isointense, and the enhancement was more uniform and obvious. The right orbital mass was treated surgically, and the final pathology report was MALT lymphoma. After the pathological report was released, the patient was transferred to the hematology department for further diagnosis and no further treatment was given eventually. Seven months later, the patient did not complain of discomfort. Whole-body positron emission tomography-computed tomography, superficial lymph node examination and orbital magnetic resonance imaging revealed no abnormal changes. The clinical manifestations of MALT lymphoma are heterogeneous. Imaging examination is important for assessing the size of the tumor and its relationship with adjacent tissues. Postoperative pathological examination may provide further evidence for the evaluation of the patient's surgical efficacy and prognosis. Management of MALT lymphoma of the lacrimal gland requires a multidisciplinary approach involving ophthalmologists, hematologists, and radiotherapists.

Guiding function of positron emission tomography-computed tomography examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma.

To explore the role of positron emission tomography-computed tomography (PET-CT) examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma (OAML). The general clinical data, postoperative PET-CT results, treatment regimens, and the prognosis of 21 histopathologically confirmed OAML patients between October 2017 and September 2021 were collected. Among the 21 patients, five patients underwent surgical treatment alone, 13 patients underwent surgical treatment combined with radiotherapy, and three patients underwent surgical treatment combined with chemotherapy. The follow-up period ranged from 8 to 79mo, with four cases of recurrence and no deaths. Through PET-CT examination, two patients exhibited both local ocular metabolic elevation and systemic metastasis, and one of these patients had cervical lymph node metastasis, while the other had submandibular and parotid gland metastasis. Nine patients showed only local ocular metabolic elevation, while 10 patients had no abnormal metabolic activity locally. PET-CT examination plays a crucial role in detecting residual lesions and recurrence following tumor resection, aiding in precise disease staging, and facilitating the development of personalized treatment plans, ultimately improving patient prognosis.

824O Treatment and survival in patients with localized primary ocular adnexal MALT lymphoma: A large bicentric cohort study

824O Treatment and survival in patients with localized primary ocular adnexal MALT lymphoma: A large bicentric cohort study

MALT Lymphoma Presenting as Symptomatic Optic Neuritis: A Case Report (P14-13.001)

<h3>Objective:</h3> To report a case of MALT lymphoma presenting as optic neuritis and highlight its inherent diagnostic challenges. <h3>Background:</h3> Optic neuritis (ON) is the inflammation of the optic nerve associated with multiple sclerosis,. ON with atypical clinical features require thorough evaluation. Primary ocular adnexal lymphomas are the most common orbital tumors, and IgG4-related ocular disease also presents with optic neuropathy and consists of morphologically similar immune infiltrates. Their diagnoses are challenging as corticosteroids can incur non-diagnostic biopsies, complicating further workup. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> 51-year-old healthy African American woman presented with one month of progressive left monocular blurry vision, color desaturation and_pain. Exam showed left visual acuity of 20/60, afferent pupillary defect, and 0/13 Ishihara plates identified in left eye. Remainder of exam was intact. MRI demonstrated left optic nerve sheath enhancement and enlargement. Another enhancing lesion was identified in the right inferior orbit. Despite visual impairment, corticosteroids were deferred prioritizing diagnostic tests. Workup was negative for autoimmunity, systemic neoplasm, and infection. CSF showed a bland profile without malignant cells. Serum and CSF IL2 receptor levels returned normal. Oligoclonal bands and IgG were elevated in serum and CSF; IgG4 levels were high at 156, raising concern for IgG4-related ocular disease. Right intra-orbital mass biopsy demonstrated atypical CD20+ lymphoid infiltrates with rare germinal centers, but &lt;10% plasma cells expressed IgG4. Further molecular analysis was positive for monoclonal IgH gene rearrangement, diagnosing mucosa-associated lymphoid tissue (MALT) lymphoma in the right orbit and probable left optic nerve involvement. She was initiated on bendamustine and rituximab with stabilization of her ocular symptoms. <h3>Conclusions:</h3> Atypical presentations of ON warrant thorough workup. IgG4-related ocular disease and ocular adnexal MALT lymphoma share similarities that require histologic and molecular analysis to differentiate. Early identification of MALT lymphoma is crucial to initiate proper therapies, maintain disease control, and preserve visual acuity. <b>Disclosure:</b> Dr. Jia has nothing to disclose. Ms. Wyckoff has nothing to disclose. Dr. Cohen has nothing to disclose. Dr. Bryar has nothing to disclose. Dr. Lukas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck and Company, Inc.. Dr. Lukas has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Merck and Company, Inc.. Dr. Lukas has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novocure. Dr. Lukas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for EBSCO. Dr. Lukas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medlink Neurology. Dr. Lukas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Lukas has received research support from BMS. The institution of Dr. Lukas has received research support from BrainUp. The institution of Dr. Lukas has received research support from National Cancer Institute. The institution of Dr. Lukas has received research support from National Cancer Institute. The institution of Dr. Lukas has received research support from Ziopharm. Dr. Dixit has nothing to disclose.

Clinicopathologic Characteristics Associated with Prognosis in Ocular Extranodal Marginal Zone B Cell Lymphoma.

Background and Objectives: Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) type is the most common subtype of the ocular adnexal lymphoma. Despite its excellent prognosis, some patients experience partial remission or progressive disease. We aimed to evaluate clinicopathologic differences in the treatment responder group by comparing complete remission (CR) and non-complete remission (non-CR). Materials and Methods: This study retrospectively reviewed 48 patients who were diagnosed with ocular adnexal MALT lymphoma at Ulsan University Hospital between March 2002 and August 2018. Patients who were followed up for less than 6 months were excluded. Histologic and clinical features were analyzed. The patients were divided into two groups: CR and non-CR. Results: Among the 48 patients, 33 achieved CR and 15 achieved non-CR during the median follow-up period of 40.00 months (range, 7–109 months). In univariable analysis, more patients tend to undergo treatment in the CR group, and post-radiotherapy (post-RT) SUVmax, PET and serum lactate dehydrogenase (LDH) levels were higher in the non-CR group (p = 0.043, p = 0.016, and p = 0.042, respectively). In a multivariable analysis, only application of treatment, including radiotherapy or chemotherapy with immunotherapy, was related to CR (odd ratio 7.301, 95% confidence interval 1.273–41.862, p = 0.026). In subgroup analysis according to the site of involvement, none of the variables were significant except for the post-RT SUVmax of PET and level of serum LDH in the non-conjunctiva group (p = 0.026, and p = 0.037, respectively). Seven (14.6%) patients had a recurrence, and those with a recurring site other than the primary site had a higher Ki-67 labeling index, although it was not statistically significant (9.56% vs. 18.00%, p = 0.095). Conclusions: Although belonging to the early stages, the non-CR rate was high in patients with high serum LDH levels, and recurred patients had higher Ki-67. Thus, considering active treatment is recommended in this group of patients.

Lack of Association between Chlamydophila psittaci and Ocular Adnexal MALT Lymphoma in Korean Patients-Is the Geographic or Genetic Difference Significant?

Clamydophila psittaci (C. psittaci) has been proposed to be an etiologic factor in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the ocular adnexa. However, the pathogenetical significance of the infection has not been fully elucidated. Many previous studies have shown controversial results regarding C. psittaci detection rates in said patients, ranging from 0 to 87%. We investigated the presence of C. psittaci in a single institutional cohort (n = 150) of ocular adnexal MALT lymphoma (OAML) patients in Korea. We tried to exclude the methodological biases derived from the different primer sets in polymerase chain reaction-based studies. For that reason, we applied five sets of primers, including four previously reported and one newly designed primer set. There was no case of C. psittaci-positive OAML in repeated trials validated with appropriate positive and negative controls. All 150 cases showed negative results with five primer sets. These results suggest that the pathogenetic role of C. psittaci in ocular adnexal MALT lymphoma might have been overestimated to date, at least in the Korean population. Therefore, the molecular diagnosis of C. psittaci is considered a very low priority.

Ocular adnexal mucosa-associated lymphoid tissue lymphoma: a narrative review.

Lymphoma is the most common primary tumor of the orbit, accounting for 55% of all orbital malignancies. When divided into histopathological subtypes, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises the largest proportion. Clinical manifestations are unspecific, but in patients with slow-growing painless orbital mass, or red conjunctival lesion suggestive of ‘salmon patch’, ocular adnexa lymphoma (OAL) should be suspected. Although the pathogenetic mechanism of ocular adnexal MALT lymphoma (OAML) is not yet fully understood, the relationship between OAML and Chlamydia psittaci has been hypothesized recently, similar to that between gastric MALT lymphoma and Helicobacter pylori. This suggests a new treatment option for OAML; bacterial eradication therapy with systemic antibiotics. Several other treatment methods for OAML have been introduced, but no treatment guidelines have been established yet. In this article, we summarize the current knowledge on the clinical features, pathogenesis, diagnostic methods, therapeutic strategies, and prognosis of OAML.

Clinical analysis of ocular adnexal mucosa-associated lymphoid tissue lymphoma with IgG4-related ophthalmic disease

ABSTRACT Purpose To analyse the incidence and characteristics of ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) with immunoglobulin G4 (IgG4)-related ophthalmic disease (IgG4-ROD), and to compare with IgG4-negative OAML. Methods We enrolled 130 patients with pathology-confirmed OAML at a single tertiary medical centre. Patients were divided into IgG4-positive and IgG4-negative groups based on the pathologic criteria for IgG4-ROD. The data were reviewed and compared between the groups. Results IgG4-positive OAML was identified in 5.4% (7/130) of OAML and 13.5% (7/52) of non-conjunctival OAML. IgG4-positive group had a higher incidence of involvement of the lacrimal gland (7/7 vs. 18/123, p = .001), extraocular muscles (3/7 vs. 10/123, p = .022) and infraorbital nerve (2/7 vs. 0/123, p < .001), and had a lower incidence of involvement of the conjunctiva (0/7 vs. 84/123; p < .001) than IgG4-negative group. IgG4-positive group had higher T and N categories of the American Joint Committee on Cancer classification (T1:T2:T3:T4 ratio of 0:6:0:1 vs. 78:32:8:5, p < .001; and ≥N1 ratio of 2/7 vs. 7/123, p = .021). There were no differences in the response rate to initial treatment (5/6 vs. 39/41, p = .343) or the relapse rate (1/6 vs. 5/41, p = 1.000) between the groups. Conclusion IgG4-positive OAML showed clinical features similar to IgG4-ROD, such as predominant disease involvement of the lacrimal gland, extraocular muscles, infraorbital nerve and lymph nodes, but not the conjunctiva. However, treatment outcomes were favourable with or without background IgG4-ROD. Physicians should be aware that IgG4-ROD might undergo a malignant transformation and that thorough treatment and surveillance of IgG4-ROD are important.

Ultra-low-dose radiation treatment for early-stage ocular adnexal MALT lymphoma

To investigate the long-term outcomes of ultra-low-dose (4 Gy) radiation treatment (RT) in patients with early-stage ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma. This retrospective case series includes eight patients with ocular adnexal MALT lymphoma who received ultra-low-dose RT at a single tertiary referral center between March 2016 and February 2018. Response to treatment and the time taken to respond were analyzed. Of the eight patients (three men, five women), seven patients had conjunctival lymphoma (T1N0M0), and one patient had orbital lymphoma (T2N0M0). Six patients with T1 disease showed complete response (CR), and the median time to CR was 4.5 months (range 2-5). Partial response was achieved in the remaining two patients (one each with T1 and T2). During the median follow-up period of 44 months (range 30-54), none of the patients had a relapse or needed additional treatment. RT was well-tolerated in all patients with no ocular complications, including cataracts and dry eye. This case series suggests that ultra-low-dose RT is effective and well-tolerated in patients with early-stage ocular adnexal MALT lymphoma. Further studies with a larger sample size and long-term follow-up are needed to evaluate the local control rate and disease-free survival precisely.

Bacterial Infection and Non-Hodgkin B-Cell Lymphoma: Interactions between Pathogen, Host and the Tumor Environment.

Non-Hodgkin B-cell lymphomas (NHL) are a heterogeneous group of lymphoid neoplasms with complex etiopathology, rich symptomatology, and a variety of clinical courses, therefore requiring different therapeutic approaches. The hypothesis that an infectious agent may initiate chronic inflammation and facilitate B lymphocyte transformation and lymphogenesis has been raised in recent years. Viruses, like EBV, HTLV-1, HIV, HCV and parasites, like Plasmodium falciparum, have been linked to the development of lymphomas. The association of chronic Helicobacter pylori (H. pylori) infection with mucosa-associated lymphoid tissue (MALT) lymphoma, Borrelia burgdorferi with cutaneous MALT lymphoma and Chlamydophila psittaci with ocular adnexal MALT lymphoma is well documented. Recent studies have indicated that other infectious agents may also be relevant in B-cell lymphogenesis such as Coxiella burnettii, Campylobacter jejuni, Achromobacter xylosoxidans, and Escherichia coli. The aim of the present review is to provide a summary of the current literature on infectious bacterial agents associated with B-cell NHL and to discuss its role in lymphogenesis, taking into account the interaction between infectious agents, host factors, and the tumor environment.

Is it Worthwhile to Undergo the Extended Stage Assessment in Orbital and Ocular Adnexal MALT Lymphoma with Symptoms Limited to the Ocular Adnexa?

Compared to ocular adnexal lymphoma of mucosa-associated lymphoid tissue-type (OAML) patients with symptoms related invasion beyond the ocular adnexa, the different approaches to staging assessment may be required in OAML patients with symptoms limited to the ocular adnexa. Seventy-six patients to be diagnosed with OAML and performed bone marrow biopsy and imaging study at Yeungnam University Hospital in 1995-2014 were enrolled. Patients with symptoms limited to the ocular adnexa were included. Computed tomography, magnetic resonance imaging, positron emission tomography (PET), and bone marrow biopsies were performed for diagnosis, NM staging and follow up evaluation. Most patients were treated with external beam irradiation (median dose, 30Gray (Gy)).The relapse-free survival (RFS) was analyzed according to the tumor laterality and TNM stage. The median follow-up period was 72months. The 5-year RFS and overall survival rates were 82.1% and 95.6%respectively.Of all76patients, lymph node and bone marrow involvement was identified in 1 patient, respectively. Among the 3 patients withT4 stage as tumor invasion beyond ocular adnexa, bone marrow involvement was confirmed in a patient with left cheek invasion. Only 11 of the 43 patients who underwent PET showed positive uptakes in orbital lesion. The patients with advanced stage were alive without recurrences. Bone marrow examination is useful in OAML patients with T4 for extended stage assessment. The AJCC TNM staging system was not significantly predictive factor for relapse, but may contribute to clarifying the patient group that needs bone marrow study.

Examining the utility of lower dose radiotherapy for localised primary ocular adnexal MALT lymphoma.

IntroductionMost primary ocular adnexal lymphomas are those involving mucosa‐associated lymphoid tissue (MALT). Radiotherapy (RT) dose regimens in the literature vary from the historically used high doses (up to 56 Gy) to lower dose RT. We aimed to examine our institution’s experience with the use of orbital RT for treating early‐stage primary ocular adnexal MALT lymphoma (POAML).MethodsPatients treated for stage I or II POAML over a 12‐year period (July 2006 to June 2018) were identified through institutional databases. Data were retrospectively collated through review of patient records. Descriptive statistical methods were employed to analyse the data.ResultsEighteen patients (median age of 67; range 44‐87yrs) with localised POAML (3 cases of bilateral disease) were identified, resulting in a total of 21 evaluable orbits. Eight (44%) patients were female, and all were documented to be of good performance status (ECOG 0‐1). The median follow‐up was 34 months (range 8‐75 months). The commonest dose fractionation used was 20 Gy in 10 fractions (n = 13 orbits) and a 3D conformal or volumetric modulated arc therapy (VMAT) technique was used in the majority of cases. None of the patients experienced an in‐field recurrence. One patient had experienced a contralateral orbital recurrence two years post‐unilateral orbital RT for orbital MALT lymphoma. Three patients experienced distant relapse.ConclusionThe use of lower dose orbital RT such as 20 Gy in 10 fractions (or radio biologically equivalent) yields excellent local disease control in the management of ocular adnexal MALT lymphoma. The durability of the response appears to be favourable. Given the indolent nature of the disease and the low levels of toxicity associated with lower dose orbital RT, this regimen remains our favoured approach to the management of localised POAML.

Antibiotic treatment for bacteria-associated extranodal marginal zone lymphoma

: Infectious agents have been frequently linked to lymphoproliferative disorders, and marginal zone lymphomas (MZL) certainly represent the most investigated entity. From the discovery of the role of Helicobacter pylori (Hp) in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphomas, other bacteria have been proposed as agents with lymphomagenesis capability. The associations between Chlamydia psittaci (Cp) infection and ocular adnexal MALT lymphoma, Borrelia strains and cutaneous MALT lymphoma, and Campylobacter jejuni (Cj) and immune-proliferative small intestine disease (IPSID) are those better studied. However, level of supportive evidence of these lymphoma-bacteria associations is variable and, often, their prevalence shows relevant variations among different geographical areas. Some of these micro-organisms have been proposed as targets of anti-lymphoma treatments based on the use of antibiotics, sometimes with encouraging results. In view of their indolent behavior, MZL represent an ideal model for a therapeutic approach less invasive and toxic as antibiotic therapy. The emerging role of macrolides, not only for the anti-infective properties, but also as direct antineoplastic agents has also been investigated. In vitro studies and preclinical models support the anticancer use of antibiotics, and a few clinical experiences have reported encouraging results with the use of macrolides, both as single agents and in combinations with other drugs, in some hematological malignancies, and in particular, multiple myeloma, Waldestrom macroglobulinemia and MZL. Herein, we review biological and clinical aspects as well as therapeutic implications of this bacteria-lymphoma association with the aim to provide diagnostic and therapeutic recommendations and discuss future perspectives in this interesting field of lab and clinical research.

Treatment for Ocular Adnexal Mucosa-Associated Lymphoid Tissue (OA-MALT) Lymphoma

Ocular adnexal mucosa-associated lymphoid tissue (OA-MALT) lymphoma is one of the B lymphoid malignancies that originates in the orbit and shows indolent progression with a predominantly localized stage. Radiotherapy appears to be recognized as the most common treatment for localized OA-MALT lymphoma. Surgical resection, eradication of Chlamydia psittaci (C. psittaci) based on the reports of the existence of C. psittaci DNA, and ‘watchful waiting’ are also selected in some cases. Systemic immunochemotherapies including anti-CD20 antibodies may be another option for advanced stages of OA-MALT lymphoma. However, due to the lower frequency of this disease and the difficulty of conducting large-scale clinical trials, no randomized, controlled trial evaluating these treatments has been reported. Therefore, the optimal treatment strategy for OA-MALT lymphoma has not been established. This review provides an update on treatments and discusses the appropriate treatment for OA-MALT lymphoma.

TBL1XR1 Mutations in Primary Marginal Zone Lymphomas of Ocular Adnexa are Associated with Unique Morphometric Phenotypes

ABSTRACT Purpose Extranodal marginal zone B-cell lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT) that affects the ocular adnexa, also known as ocular adnexal MALT lymphomas (OAML), are low-grade lymphomas that mostly affect elderly individuals. This study was conducted to explore the genetic and microbial drivers of OMAL, and unique morphometric phenotypes associated with these mutations and infections. Materials and Methods In this study, we performed targeted deep sequencing of 8 OAML cases to identify its potential genetic and microbial drivers. We additionally performed computational digital image analysis of cases to determine if morphologic features corresponded to genetic mutations and disease biology. Results We identified TBL1XR1 as recurrently mutated in OAML (4/8), and mutations in several other oncogenes, tumor suppressors, transcription regulators, and chromatin remodeling genes. Morphologically, OAML cases with mutations in TBL1XR1 showed lymphoma cells with significantly lower circularity and solidity by computational digital image analysis (p-value <0.0001). Additionally, cases of OAML with mutations in TBL1XR1 showed equivalent or increased vascular density compared to cases without mutations in TBL1XR1. Finally, we did not find any infectious microbial organisms associated with OAML. Conclusions Our study showed recurrent mutations in TBL1XR1 are associated with unique morphometric phenotypes in OMAL cases. Additionally, mutations in genes associated with the methylation status of histone 3, nuclear factor (NF)-κB pathway, and NOTCH pathway were enriched in OMAL cases. Our findings have biologic and clinical implications as mutations in TBL1XR1 and other genes have the potential to be used as markers for the diagnosis of OAML, and also demonstrate a specific biologic phenotypic manifestation of TBL1XR1 mutations.

Clinical analysis of ocular adnexal mucosa-associated lymphoid tissue lymphoma

Objective To analyse the features of ocular adnexal mucosa-associated lymphoid tissue(MALT) lymphoma. Methods The clinical and imaging data, histopathological feature of 52 patients with ocular adnexal MALT lymphoma from Jul.2010 to Jul.2015 were retrospectively analyzed. Results There were 24 males and 28 females in the total patients. The age ranged 37-80 years, with a mean of (57.1±11.2) years. The course of disease was 1 month-10 years. Clinical manifestations included eyelid swelling in 35 cases, conjunctival mass in 5 cases, exophthalmos in 15 cases, and epiphora in 1 case. There were 9 cases of diffuse growth and 43 cases of localized growth. There were 10 cases located in the superior-medial quadrant, 7 cases in the inferior-medial quadrant, 23 cases in the upper part of the orbit and 3 cases in the inferior-lateral quadrant. Orbital structures was involved by lymphoma, lacrimal gland in 12 cases, conjunctiva in 5 cases, lacrimal sac in 1 case and extraocular muscle in 1 case. Conclusion The clinical manifestations of ocular adnexal MALT lymphoma are various.Ocular adnexal MALT lymphoma show characteristic imaging manifestations that can improve preoperative diagnosis. Individualized treatment should be adopted based on tumor staging. Key words: Adnexa, ocular; Lymphoma, mucosa-associated lymphoid tissue(MALT); Clinical; Pathology; Imaging

Treatment-associated outcomes of patients with primary ocular adnexal MALT lymphoma after accurate diagnosis.

Differentiation between primary ocular adnexal mucosa-associated lymphoid tissue (POA-MALT) lymphoma and reactive lymphoid hyperplasias sometimes may be difficult. We have examined the treatment-associated mortality of POA-MALT lymphoma after confirmed diagnosis and evaluated their proper treatments. From 1991 through 2016, cases of POA-MALT lymphoma were retrospectively analyzed based on their pathological and molecular/immunological diagnoses. A total of 78 cases with POA-MALT lymphoma with a median age of 66years were analyzed over median/mean observations of 6.4/7.1years. Forty-four patients (56%) were diagnosed with IgH gene clonality and 10 patients (13%) were diagnosed with flow cytometric analysis in addition to the pathological decision. The rest (24 patients, 31%) were diagnosed employing pathological decisions of hemato-pathologists and clinical decisions. All patients, except cases of watchful waiting, achieved complete remission. After initial treatment, 68 patients (87%) presented disease-free during the observation period. As treatment, a radiotherapy-based strategy was followed with 15 patients (19%, group A). Immuno-chemotherapy was administered to 24 patients (31%, B). Surgical extraction only was selected for 36 patients (46%, C). Watchful waiting was selected with three patients (4%). Recurrence after the initial treatment was found in one patient (7%) out of A, in three patients (13%) out of B, and in six patients (17%) out of C, respectively. Progression-free survivals at 5 and 10years were 100 and 100% in A, 95 and 75% in B, and 88 and 81% in C, respectively. The recurrence rates between the patients who were diagnosed with only pathological decision (n = 24) and the patients who were diagnosed with molecular and immunological procedures (n = 54) did not show any statistical differences. Our results indicate that radiotherapy-based treatment strategies for patients with POA-MALT lymphoma show a low rate of recurrence and may improve their prognosis even after the accurate diagnosis. However, contamination of the cases with reactive (polyclonal) lymphoid hyperplasia into those with MALT lymphoma should be carefully removed to avoid unnecessary treatment for malignancies that do not exist.

Comparison of Selection and Long-term Clinical Outcomes Between Chemotherapy and Radiotherapy as Primary Therapeutic Modality for Ocular Adnexal MALT Lymphoma

BackgroundThe choice of a primary treatment for ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) depends on the extent of tumor spread. However, radiotherapy is commonly used as a first-line therapy despite ophthalmic complications, because most OAMLs are in a limited stage of progression. However, the initial therapeutic modality, including chemotherapy and treatment of the advanced stage, has not been fully established for OAML. Therefore, we evaluated the optimal therapeutic options and survival outcome-related parameters for patients with primary OAML. MethodsWe evaluated 208 consecutive patients with primary OAML who were diagnosed at the Catholic University Lymphoma Group between January 2004 and April 2015. FindingsDuring a median follow-up of 70.0 months (range, 3.2–182.0 months) in 208 patients with primary OAML, most patients were female and the median age was 46 years old. Overall survival (OS) and progression-free survival (PFS) at 13 years were excellent (92.7% and 69.7%, respectively). Of the 117 patients who received the first-line radiotherapy, 92% achieved complete remission (CR), usually by being treated with less than 30 Gy. Radiation-related ophthalmic complications including dry eye syndrome (59%) and cataract (22%) caused a decline in the quality of life (QoL). Chemotherapy alone was used to treat 86 OAML patients, with 84.9% achieving CR and 12.8% achieving partial remission with tolerable toxicities. There were no differences in survival outcomes between patients treated with radiotherapy versus those treated with rituximab-containing chemotherapy, although the latter group had more advanced stages of OAML (OS, p = 0.057; PFS, p = 0.075). InterpretationOAML patients were predominantly female and relatively young, and radiotherapy as a primary therapeutic option was more likely to lead to radiation-related complications, resulting in lower QoL. On the other hand, frontline chemotherapy showed consistent therapeutic outcomes with tolerable toxicities compared to radiotherapy, and there were no long-term or delayed adverse events. Therefore, when considering therapeutic efficacy and therapy-related QoL, chemotherapy is recommended for younger patients, and radiotherapy is recommended for older and chemotherapy-ineligible patients. FundingA National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. NRF-2016R1A2B4007282).

Immunoglobulin G4 (IgG4)-Positive Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma and Idiopathic Orbital Inflammation.

To report clinical and pathological characteristics of idiopathic orbital inflammation and ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma with immunoglobulin G4 (IgG4)-positive plasma cells. A retrospective histopathological review and clinical case series. A total of 51 biopsy samples from January 2005 to December 2015 were used in this study, including 21 cases of biopsy-confirmed idiopathic orbital inflammation and 30 cases of biopsy-confirmed ocular adnexal MALT lymphoma. Most cases of ocular adnexal lymphoma were conjunctival tissue. Retrospective immunohistochemical studies were performed to estimate the IgG4 and IgG4/IgG ratios. Histopathologic features, demographic and clinical data, radiologic findings, treatment, and follow-up information for each patient were analyzed. Among idiopathic orbital inflammation, 6 (28.6%) of the 21 patients were diagnosed as "probable" ocular adnexal IgG4-related diseases and 13 (43.3%) of the 30 patients were diagnosed as MALT lymphoma with IgG4-positive plasma cells. Six cases of 13 IgG4-positive MALT lymphoma group had contralateral chronic inflammatory lesions infiltrated by IgG4-positive plasma cells, which was significantly (p = 0.007) higher than that in the IgG4-negative group. Conjunctival involvement was 69% of the IgG4-positive MALT lymphoma cases. Bilateral involvement of the ocular adnexa was significantly (p = 0.02) more frequent among IgG4-positive MALT lymphoma patients than that in IgG4-positive idiopathic orbital inflammation patients. Recurrence rate in the IgG4-positive group was higher (p = 0.05) than that in the IgG4-negative group but not significantly. This study presented an unusual framework of ocular adnexal IgG4-related inflammation, in conjunctiva. It is important to understand contralateral chronic inflammatory lesions and their relationship with IgG4-positive MALT lymphoma. Tissue biopsy and IgG4 immunostaining are required for all cases because IgG4-positive MALT lymphoma can arise from a pre-existing IgG4-positive chronic inflammatory lesions. This is the first study that performs IgG4 immunostaining for tissue from a relatively large number of conjunctival MALT lymphomas in a single center. Therefore, it will help to diagnose conjunctival lymphoproliferative disease.