Ocular Adnexal Mucosa-associated Lymphoid Tissue Research Articles

The Dilemma for Early-Stage Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma: To Treat or Not to Treat?

Primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (MALToma) is typically treated with radiotherapy. Some studies suggested a "wait and watch" approach due to the adverse effects of radiotherapy. However, the benefits of observation for localized conjunctival MALToma remain unclear. Therefore, we aimed to explore the clinical course of early-stage conjunctival MALToma, distinguish heterogeneity between T1 and T2 patients, and identify prognostic factors. This retrospective study involved patients with stage T1-T2 conjunctival MALToma and lasted >6 months. Clinical characteristics were compared between T1 and T2 subjects. Prognostic factors were examined with Cox regression. The research comprised 32 subjects with early-stage conjunctival MALToma, of whom 25% underwent observation. No individuals expired regardless of choosing observation or radiotherapy. The T1 patients were younger (p = 0.002) and more inclined towards observation only (p = 0.035) than the T2 subjects. Despite more of the T1 patients undergoing watchful waiting than the T2 subjects, the T1 patients seemed to have longer systemic relapse-free survival than the T2 subjects (17 vs. 13 years, p = 0.343). CD43 may imply poor prognosis (p = 0.049). Careful observation may be suggested for early-stage conjunctival MALToma. While more of the T1 individuals were younger and chose observation than the T2 patients, survival seemed longer in the T1 subjects without significance. CD43 may indicate shorter survival in early-stage cases.

Machine Learning Model with Texture Analysis for Automatic Classification of Histopathological Images of Ocular Adnexal Mucosa-associated Lymphoid Tissue Lymphoma of Two Different Origins

Purpose The purpose of this study was to develop artificial intelligence algorithms that can distinguish between orbital and conjunctival mucosa-associated lymphoid tissue (MALT) lymphomas in pathological images. Methods Tissue blocks with residual MALT lymphoma and data from histological and flow cytometric studies and molecular genetic analyses such as gene rearrangement were procured for 129 patients treated between April 2008 and April 2020. We collected pathological hematoxylin and eosin-stained (HE) images of lymphoma from these patients and cropped 10 different image patches at a resolution of 2048 × 2048 from pathological images from each patient. A total of 990 images from 99 patients were used to create and evaluate machine-learning models. Each image patch of three different magnification rates at ×4, ×20, and ×40 underwent texture analysis to extract features, and then seven different machine-learning algorithms were applied to the results to create models. Cross-validation on a patient-by-patient basis was used to create and evaluate models, and then 300 images from the remaining 30 cases were used to evaluate the average accuracy rate. Results Ten-fold cross-validation using the support vector machine with linear kernel algorithm was identified as the best algorithm for discriminating between conjunctival mucosa-associated lymphoid tissue and orbital MALT lymphomas, with an average accuracy rate under cross-validation of 85%. There were ×20 magnification HE images that were more accurate in distinguishing orbital and conjunctival MALT lymphomas among ×4, ×20, and ×40. Conclusion Artificial intelligence algorithms can successfully distinguish HE images between orbital and conjunctival MALT lymphomas.

Watchful waiting is an acceptable treatment option for asymptomatic primary ocular adnexal mucosa-associated lymphoid tissue lymphoma: A retrospective study.

Primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML) is the most common subtype of indolent ocular adnexal lymphomas. Although radiotherapy (RT) is the standard of care for localized POAML, it can occasionally lead to permanent side effects. Other treatment strategies, such as rituximab (R) monotherapy and immunochemotherapy, have been used for POAML treatment, but their long-term benefits and relative merits remain unclear. While watchful waiting (WW) is a potential option for some indolent lymphomas, the benefits of WW for POAML patients are also unclear. We here retrospectively analyzed 75 patients who were diagnosed with POAML between 2008 and 2019 in the institutions of the Kyoto Clinical Hematology Study Group. Commonly involved sites were conjunctiva (42.7%), orbit (36.0%), and lacrimal gland (12.0%), and most patients (92.0%) presented with Ann Arbor stage IE disease. The treatment strategy was selected at the physicians' discretion. More patients without subjective symptoms by tumor mass were subjected to WW (29 patients), while more patients with tumor-derived subjective symptoms were treated by tumor-directed therapy (24 received focal RT, and 19 received R monotherapy). Complete response rates were 79.2% and 42.1% in the RT and R groups, respectively. At 60 months of follow-up, the estimated proportions of POAML patients not requiring new treatment were 69.4%, 85.2%, and 53.8% in the WW, RT, and R groups, respectively. There were no significant differences in the time to start a new treatment between WW and RT groups (median: both not reached [NR], p=0.187) and between WW and R groups (median: NR vs. 69.0 months, p=0.554). No specific predictive factor for the future need of treatment was identified in the WW group. Our results demonstrate WW may be an acceptable treatment option for POAML, especially for asymptomatic patients.

P1127: WATCHFUL WAITING IS AN ACCEPTABLE TREATMENT OPTION FOR PRIMARY OCULAR ADNEXAL MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA: A RETROSPECTIVE STUDY

Background: Primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML) is the most frequent subtype of ocular adnexal lymphomas. Radiotherapy (RT) is the standard of care for localized POAML, despite several complications, such as cataracts, retinitis, dry eye, and optic neuropathy. Watchful waiting (WW) is expected to be a therapeutic option for POAML, however, its efficacy for POAML remains to be verified. Aims: The aim of the study was to clarify the validity of WW for POAML. Methods: We retrospectively analyzed the background, disease status, treatments, and clinical outcomes of patients histologically diagnosed with POAML between 2008 and 2019 at seven institutes belonging to the Kyoto Clinical Hematology Study Group. The primary ocular adnexal disease sites were defined as involvement of the conjunctiva, orbit, eyelid, or lacrimal gland. Bilateral ocular adnexal lymphoma without other lymphomatous involvement was defined as stage IE disease. Results: One hundred and three patients were diagnosed with POAML, of which 11 were excluded from analysis because of lost follow-up, 11 due to missing data, and 6 due to short follow-up within 1 year. As a result, 75 patients were analyzed in this study. The median age was 68 years, and 41 patients (54.7%) were females. The most common involved site was the conjunctiva (42.7%), followed by the orbit (36.0%), lacrimal gland (12.0%), and eyelid (8.0%). Sixty-nine patients (92.0%) presented with stage IE disease, and 61 patients (81.3%) presented with a unilateral ocular region. According to the International Prognostic Index, most patients (92.0%) were classified as low risk. The tumor was completely resected at diagnosis in 17 patients (22.7%), while a residual tumor existed after biopsy in 58 patients (77.0%). WW was the most frequent first-line modality, selected for 29 patients (38.7%), including 14 patients with complete tumor resection at diagnosis. Twenty-four patients (32.0%) were treated with RT and 19 (25.3%) with rituximab monotherapy (R). In the RT group, most patients had a residual tumor after the biopsy, and the orbit was the most frequent site of lymphoma, which caused treatment-emergent symptoms that potentially impair visual function. Complete response rates were 79.2% and 42.1% in the RT and R groups, respectively. With a median follow-up of 48.8 months, there were no significant differences in the time to start of new treatment between WW and RT groups (median: both not reached [NR], p = 0.187) and between WW and R groups (median: NR vs. 69.0 months, p = 0.554). At 60 months follow-up, the estimated proportions of POAML patients not requiring new treatment were 69.4%, 85.2%, and 53.8% in the WW, RT, and R groups, respectively. All patients enrolled in this study were alive at the time of analysis. In the WW group, 9 patients (31.0%) showed disease progression, seven of whom received treatments with a median time to next treatment of 15.6 months, but the remaining two patients continued WW even after disease progression because of no subjective symptoms. In the RT group, 16 patients (66.7%) developed adverse events, most of which were mild, while grade 3 cataracts occurred in five patients. We compared the clinical characteristics to identify predictive factors for disease progression in the WW group, however, all factors analyzed were not significantly associated with disease progression. Summary/Conclusion: WW may be an acceptable treatment option for POAML, especially in asymptomatic patients.

Long-Term Clinical Outcomes in Treatment-Naïve Patients With Orbital Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma: A Single-Center Study.

Ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (OAML) is the most common type of ocular lymphoma with a higher prevalence in Asia than in Western countries. OAML represents 1%–2% of all non-Hodgkin’s lymphoma, 5%–15% of extranodal lymphomas, and approximately 55% of orbital malignancies. “Watch and wait” after biopsy or surgical resection, radiation therapy, and systemic treatment, including antibiotics administration and chemotherapy with various combinations of regimens can be considered for OAML treatment. Radiotherapy is adapted for limited-stage disease with excellent clinical outcomes of 85–100% complete remission and relatively superior local control efficacy and treatment duration. In contrast, chemotherapy has rarely been tested as frontline therapy. Nonetheless, several studies have reported a favorable response and long duration of progression-free survival using chemotherapy adaptations. When the disease involves both eyes or spreads beyond the conjunctiva, the risk of recurrence increases and limited-stage OAML has a recurrence rate of approximately 25% following radiotherapy only. Therefore, although recent consensus in the literature is that patients with limited-stage OAML recommended treating with radiation, physicians may choose the treatment modality not only by its efficiency but also by its adverse events profile and patients’ well-being. Herein, we present a large single-center study on OAML that included 292 patients who were followed up for up to 237 months. We collected and analyzed real-world data focusing on treatment outcomes and the role of radiotherapy as frontline therapy, and aimed to compare outcomes and complication profiles of chemotherapy, especially in limited-stage OAML, to identify an optimal treatment strategy.

Analysis of Genetic Alterations in Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma With Whole-Exome Sequencing.

Next-generation sequencing studies on ocular adnexal marginal zone lymphoma of mucosa-associated lymphoid tissue (OAML) have to date revealed several targets of genetic aberrations. However, most of our current understanding of the pathogenesis and prognosis of OAML is primarily based on studies conducted in populations from Europe and the US. Furthermore, the majority were based on formalin-fixed paraffin-embedded (FFPE) tissue, which generally has poor integrity and creates many sequencing artifacts. To better investigate the coding genome landscapes of OAML, especially in the Chinese population, we performed whole-exome sequencing of 21 OAML cases with fresh frozen tumor tissue and matched peripheral blood samples. IGLL5, as a novel recurrently mutated gene, was found in 24% (5/21) of patients, with a higher relapse rate (P=0.032). In addition, mutations of MSH6, DIS3, FAT1, and TMEM127 were found in 10% of cases. These novel somatic mutations indicate the existence of additional/alternative lymphomagenesis pathways in OAML. Moreover, the difference between our and previous studies suggests genetic heterogeneity of OAML between Asian and Western individuals.

The role of 18F-FDG PET/CT in diagnosis and treatment evaluation for ocular adnexal mucosa-associated lymphoid tissue lymphoma.

The purpose of this study is to evaluate the value of fluorine-18-fludeoxyglucose positron emission tomography (18F-FDG PET)/CT in the diagnosis and treatment evaluation of ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma. 70 patients with OAML who received radiotherapy were recruited in our study. All the patients had the 18F-FDG PET/CT examination before the treatment. We retrospectively reviewed the medical records, pathological reports, laboratory results, and imaging features of all patients. The associations between 18F-FDG PET/CT parameters and Epstein-Barr virus antibodies, treatment response, MRI data, and Ki-67 expression were investigated. The PET/CT scan indicated that 80% (56/70) of the patients showed orbital FDG avidity. The median level of maximum standardized uptake value (SUVmax) of the lesions was 4.65 ± 3.00 (range:1.2-13.5). 92.0% (46/50) of the mass-forming lesions showed 18F-FDG avidity, while only 50.0% (10/20) of the non-massive lesions had 18F-FDG avidity (χ2 = 13.23, p=0.01). The SUVmax in orbit, conjunctiva, and lacrimal gland lymphoma were 5.6, 2.9, and 3.7, respectively. A significant difference was identified of SUVmax among the three locations' lymphoma using one-way ANOVA analysis (F = 5.039, p = 0.01). After completion of radiotherapy, the complete remission rate was achieved in 30.8% (4/13) of the patients without 18F-FDG avidity, and 70.4% (38/54) in cases with 18F-FDG avidity (χ2 = 5.43, p = 0.02). The correlation between high Ki-67 score and 18F-FDG avidity was confirmed (χ2 = 3.916, p = 0.048); however, no significant correlation was found between the SUVmax and Ki-67 score of the lesions (p = 0.971). Three patients (3/70, 4.3%) were upregulated the stage via PET/CT. 18F-FDG PET/CT had some potential values in the diagnosis and assessment of treatment response in patients with OAML. The value of 18F-FDG PET/CT for patients with OAML.

Radiation Therapy Efficacy and Toxicity for Orbital and Ocular Adnexal Mucosa-Associated Lymphoid Tissue (OAMALT): A Single-Center, Retrospective Study of 32 Cases.

PurposeLymphomas of the orbit and ocular adnexa are histologically heterogeneous and their incidence rate has been increasing lately. However, because of their rarity and diversity, few cases have been analyzed. This study evaluated patients with orbital and ocular adnexal mucosa-associated lymphoid tissue (OAMALT), who received radiotherapy, and categorized their clinical characteristics, treatment outcomes, and complications.Patients and MethodsWe collected data on clinical presentation, age, sex, imaging, tumor location, treatment methods, pathological diagnosis, cataract incidence, cataract incidence periods, overall survival (OS), and disease-free survival (DFS) from 32 patients with orbital involvement and pathologically confirmed marginal zone B-cell lymphoma of MALT who were treated between 2009 and 2018. Twenty-two patients received 20 Gy/10 Fr using intensity-modulated radiation therapy (IMRT) plus 14 Gy/7 Fr using a 6–14-MeV electron beam therapy using a lens-sparing approach. Ten patients received 32 Gy/16 Fr or 34 Gy/17 Fr using IMRT without the lens shield technique. Kaplan–Meier analysis was used to estimate DFS and OS.ResultsThe median follow-up time was 83.4 ± 24.5 months. No patient had local recurrence, although three patients developed distant metastases. The 5-year and 10-year OS rates were both 100%. The 5-year and 10-year DFS rates were 96.7% and 74.2%, respectively. Overall, 11 (32.4%) of the 34 lenses developed cataracts. The estimated 5-year, 7-year, and 10-year cumulative cataract rates were 6.9%, 30.9%, and 60.8%, respectively. The median cumulative cataract incidence period was 107.0 months. Age was the only significant parameter associated with cataract formation.ConclusionA radiation dose of 32–34 Gy yields excellent local control, DFS, and OS for OAMALT. Some patients may have systemic relapse, and better identification of these patients is necessary. Reducing the prescription radiation dose or using better radiation techniques to spare the ipsilateral lens could reduce cataract formation.

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.

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.

The preliminary observation of intralesional rituximab administration in primary ocular adnexal mucosa-associated lymphoid tissue lymphoma

Objective: To observe the efficacy of intralesional rituximab administration in primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML). Methods: Retrospective case series study. The clinical and follow-up data of eight patients with POAML in the treatment group from September 2017 to December 2018 at the First Affiliated Hospital of Zhengzhou University were collected and analyzed retrospectively. The patients (3 males and 5 females) were 35 to 83 years old, with a median of 58 years. All patients received surgical treatment (most of the tumor were removed). The diagnosis of mucosa-associated lymphoid tissue lymphoma was confirmed by histopathology and immunohistochemical staining showed CD20+. Examinations such as chest CT, abdominal CT, bone marrow biopsy or positron emission tomography-CT to exclude lymphoma with systemic lesions. Patients with conjunctival POAML were injected through the subconjunctival infiltration. For the lacrimal gland POAML and the orbital POAML, the injection was performed through the periocular space by using a post-bulb syringe needle at multi-points with an interval of 1 cm, before the pressure dressing. All patients were injected 1.5 to 5.0 ml (15 to 50 mg) once every three weeks, 4 to 6 times as a treatment cycle. The injection range included or exceeded the lesion area. Then consider whether to supplement the number of treatments based on the remaining tumor. The patients' treatment doses, drug onset time, tumor regression, local reactions (local pain and swelling), systemic reaction indicators (fever, gastrointestinal reactions, complete blood count and the lymphocyte subsets), and systemic recurrence indicators (serum β2 microglobulin and lactate dehydrogenase detecting) were recorded. Results: Two patients, including one patient with bilateral lesions, had conjunctival POAML, one patient had lacrimal gland POAML, and five patients had orbital POAML. They received 2 to 7 injections, and the total dose was 45 mg to 280 mg. There were tolerable local pain upon injections in all patients, local redness and swelling in one patient, fever in two patients, mild gastrointestinal reactions in one patient, fatigue in one patient, and palpitation and discomfort in one patient. After close observation or corresponding symptomatic treatment, the symptoms subsided. No special treatment was given. The follow-up time was 9 to 30 months, and the median was 20 months. The lymphomas in all patients were controlled without recurrence. The MRI showed that local lesions disappeared completely in five patients, and the conjunctiva and the extraocular muscle became thickened in three patients. There was no abnormity in complete blood count, serum β2 microglobulin and lactate dehydrogenase. Conclusion: The intralesional rituximab administration is a simple, effective therapy for localized POAML with no systemic invasion. (Chin J Ophthalmol, 2020, 56: 839-845).

CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease: multi-institutional case series.

To report CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease (IgG4-MALT lymphoma), a rare but clinically important complication of ocular adnexal IgG4-related disease. We retrospectively reviewed all cases of histologically confirmed ocular adnexal IgG4-related disease at three tertiary and one secondary referral centers, between February 2003 and December 2016. Seven cases of histopathologically diagnosed IgG4-MALT lymphoma were identified. CT and MR images were analyzed by consensus of two experienced head and neck radiologists. Lacrimal glands were the main site of involvement in all seven patients. The lesions typically showed well-demarcated margins, iso- to hyperattenuation on precontrast CT, T2 hypo- to isointensity, T1 isointensity, and homogenous internal architecture with homogenous enhancement pattern. Lesions were mostly hyperdense and isointense to normal extraocular muscles on postcontrast CT and MR images, respectively. Unlike in typical ocular adnexal IgG4-related disease, T2 isointensity and hyperattenuation on precontrast CT images were noted in some IgG4-MALT lymphoma cases. Although the findings may be nonspecific, the possibility of accompanying MALT lymphoma may need to be considered, when ocular adnexal lesions in patients clinically suspected of having IgG4-related disease are refractory to glucocorticoids and show T2 isointensity and hyperattenuation on precontrast CT for the optimal management of the patients. However, this is a case series of a very rare complication of ocular adnexal IgG4-related disease, and thus caution is warranted to generalize the conclusion.

Radiotherapy alone for stage IE ocular adnexal mucosa-associated lymphoid tissue lymphomas: long-term results

BackgroundTo evaluate the long-term efficacy and toxicity of radiation therapy in patients with Stage IE primary ocular adnexal mucosa-associated lymphoid tissue lymphoma.MethodsWe designed a retrospective analysis to evaluate 81 patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma treated with radiation therapy between 2006 and 2016. The median radiation dose was 30 Gy (range, 30–36 Gy in 15–18 fractions). Local control, progression-free survival, overall survival, and cumulative incidence of Grade 3 cataract were calculated by using the Kaplan–Meier method.ResultThe median follow-up time was 74 months (range, 4–157 months). The 5-year local control was 100%. Although local relapse was suspected in 3 patients after radiation therapy, 2 patients were pathologically diagnosed as IgG4-related inflammation and in 1 patient as intense inflammatory cell infiltration. The 5-year progression-free survival was 94.4%. Five patients had relapse at distant sites. The 5-year overall survival was 98.8%. Twenty patients had Grade 3 cataract. The 5-year cumulative incidences of Grade ≥ 3 and Grade ≥ 2 cataract for 58 patients treated without a lens shield were 38 and 40%, respectively. The incidence of Grade ≥ 3 cataract was 42% for 50 patients treated with 6-MV X-rays (estimated lens dose: 29 Gy) and 17% for 8 patients treated with 9-MeV electrons (estimated lens dose: 24 Gy).ConclusionsRadiation therapy alone yielded excellent local control and long-term survival in Stage IE ocular adnexal mucosa-associated lymphoid tissue lymphoma. Long-term observation with careful attention to relapse at distant sites is necessary. In the case of suspected local relapse, IgG4-related disease should be carefully ruled out.

Effects of radiation therapy on the meibomian glands and dry eye in patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma

BackgroundRadiation therapy (RT) is the treatment of choice in patients with low-grade ocular adenexal mucosa-associated lymphoid tissue lymphoma (OAML) and many of them experience post-RT dry eye with varying severity. The purpose of the present study was to investigate ocular effects of RT on meibomian glands and dry eye by directly visualizing structural changes. Secondly, we focused on the comparison of two groups of patients according to tumor location and radiation technique.MethodsSixty-four eyes with OAML of conjunctiva, orbit, lacrimal gland, or lacrimal sac were grouped into conjunctival lymphoma and “orbital-type” lymphoma (i.e., orbit, lacrimal gland, and lacrimal sac). Subjects were investigated for morphological changes in meibomian glands by meiboscore grading system. Radiation technique was examined and Ocular Surface Disease Index (OSDI) questionnaire, Schirmer’s test, tear film break-up time (TBUT), slit lamp examination of corneal surface and lid margin abnormality were conducted before and after RT.ResultsThe increase in meiboscore was statistically significant over time after RT in both groups (P < 0.001). The extent of increase in meiboscore was significantly greater in the “orbital-type” lymphoma group than in the conjunctival lymphoma group (P < 0.001). The changes in OSDI, TBUT, corneal fluorescein staining score and lid margin abnormality score after RT were significantly different across two groups (P = 0.042, 0.001, 0.035 and 0.001, respectively). Schirmer’s value decreased after RT in both groups. Dry eye symptoms were most severe right after RT in both groups, but a gradual resolution was noted in most patients with conjunctival lymphoma, whereas symptoms persisted in “orbital-type” lymphoma patients. The OSDI score and corneal fluorescein staining score were positively correlated with meiboscore in “orbital-type” patients at post-RT 6 months (r = 0.43, P = 0.04; r = 0.39, P = 0.03, respectively).ConclusionsPatients with OAML had different degrees of morphological changes in meibomian glands according to tumor location and radiation technique. “Orbital-type” lymphoma patients are more likely to experience severe injury to meibomian glands, which eventually leads to persistent dry eye. Patients with “orbital-type” lymphoma should be well informed of post-RT damage on meibomian glands and persistent dry eye.

Role of F-18 FDG PET/CT in non-conjunctival origin ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphomas

BackgroundDespite the widespread use of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in the diagnosis and response assessment of patients with lymphoma, few studies have assessed its value in ocular adnexal lymphomas. The purpose of this study was to evaluate the role of FDG PET/CT in staging of non-conjunctival origin ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphomas (OAML). In addition, the diagnostic sensitivity of FDG PET/CT was compared with magnetic resonance imaging (MRI). FDG PET/CT of 123 consecutive patients with pathologically proven OAML between January 2009 and February 2016 were retrospectively reviewed. The patients with MALT lymphoma originating from conjunctiva were excluded. A total 50 patients with non-conjunctival origin OAML were assessed. Maximum standardized uptake value (SUVmax) and additional PET parameters were measured for all lesions. Sensitivity for primary tumor detection was compared with MRI.ResultsTen patients had bilateral OAML and total 60 OAML lesions were analyzed. MRI was missing in one patient. The tumor locations were as follows: eyelid, 9; lacrimal gland, 18; orbit, 33. Fifty lesions (83.3%) were FDG-avid tumors with mean ± SD SUVmax 4.8 ± 2.4 (range 2.0~11.1). The mean SUVmax according to tumor location were as follows: eyelid, 3.7 ± 1.1 (2.8~5.3); lacrimal gland, 3.6 ± 1.4 (2.1~6.4); orbit, 5.7 ± 2.6 (2.0~11.1). Mean SUVmax among the 3 locations were statistically different (P = 0.010). The sensitivity was calculated as 83.1% (49/59) for FDG PET/CT and 89.8% (53/59) for MRI, which were statistically comparable (P = 0.219 by McNemar’s test). Seven of 50 patients (14%) were upstaged by detection of extraocular lesions by FDG PET/CT (1 kidney and lung, 1 tonsil, 4 cervical LNs, 1 sacral foramen).Conclusion83.3% of the non-conjunctival origin OAML were FDG-avid tumors, with FDG PET/CT showing comparable sensitivity to that of MRI. FDG PET/CT detected unsuspected extraocular lymphoma involvement in 14% of the patients. FDG PET/CT performed for staging of non-conjunctival origin OAML may thus guide therapeutic management.

Clinical features and treatment outcomes of primary ocular adnexal mucosa-associated lymphoid tissue lymphoma: a single center retrospective analysis of 64 patients in China.

To investigate the clinical features, treatment and prognosis of primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML). A retrospective analysis was performed on 64 patients with POAML who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2006 to December 2018. With a median follow-up of 61mo (range, 2-156mo), estimated overall survival (OS) rate and progression-free survival (PFS) rate at 10y reached 94.5% and 61.5%, respectively. Median OS time and PFS time were not reached. During this period, only 3 patients died, but none of them died directly due to disease progression. One patient (1.6%) developed transformation to diffuse large B-cell lymphoma (DLBCL). Of the 56 patients achieved complete remission after first-line treatment, 5 (8.9%) developed local and/or systemic relapse eventually. Patients ≥60y had significantly shorter PFS than younger patients (P=0.01). For patients with early stages (Ann Arbor stage I and stage II), univariate analysis confirmed that radiotherapy dose lower than 32 Gy were independently associated with shorter PFS (P=0.04). Other factors including gender, bone marrow involvement, the initial location of the disease, and the laterality were not associated with PFS. The data from our center indicate that POAML has a slow clinical progression and has an excellent clinical outcome. Patients with POAML harbor a continual risk of relaps and transformation to aggressive subtype of lymphoma.

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.