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Background: Ocular adnexal B cell lymphoma is the most common orbital malignancy in adults. Large chromosomal translocations and alterations in cell-signaling pathways were frequently reported in lymphomas. Among the altered pathways, perturbations of NFκB signaling play a significant role in lymphomagenesis. Specifically, the MYD88 L265P mutation, an activator of NFκB signaling, is extensively studied in intraocular lymphoma but not at other sites. Therefore, this study aims to screen the MYD88 L265P mutation in Ocular adnexal B cell lymphoma tumors and assess its clinical significance. Methods and results: Our study of twenty Ocular adnexal B cell lymphoma tumor samples by Allele-Specific Polymerase Chain Reaction identified two samples positive for the MYD88 L265P mutation. Subsequent Sanger sequencing confirmed the presence of the heterozygous mutation in those two samples tested positive in Allele-Specific Polymerase Chain Reaction. A comprehensive review of MYD88 L265P mutation in Ocular adnexal B cell lymphoma revealed variable frequencies, ranging from 0 to 36%. The clinical, pathological, and prognostic features showed no differences between patients with and without the MYD88 L265P mutation. Conclusion: The present study indicates that the MYD88 L265P mutation is relatively infrequent in our cohort, underscoring the need for further validation in additional cohorts. [ABSTRACT FROM AUTHOR]

We herein report a middle-aged gentleman who initially presented with ocular adnexal mantle cell lymphoma (MCL) on the right eyelid. The lesion was excised and the patient was treated with radiation therapy. During the initial presentation, a PET CT was performed and did not reveal disease involvement beyond the eyelid. The patient presented 3 months later with ocular adnexal MCL of the contralateral eye. Re-evaluation using PET CT revealed a slight increase in the uptake in several lymph nodes and the spleen, which, after biopsy, confirmed systemic MCL. The patient was started on six cycles of chemotherapy. The patient also underwent autologous hematopoietic stem cell transplant. Approximately 80% of primary ocular adnexal lymphomas are B-cell in origin, with MCL being the rarest subtype constituting only 5% of B-cell ocular adnexal lymphomas. Despite its rarity, it is crucial for clinicians to detect the entity early and ensure rapid initiation of appropriate therapy. [ABSTRACT FROM AUTHOR]

We describe the first reported case of granulomatosis polyangiitis (GPA)-associated sclerokeratitis in a patient with treated ocular adnexal lymphoma (OAL). The patient presented with pain and decreased vision in the left eye over several weeks. Past medical history was significant for recent bilateral relapsing OAL that was treated successfully with radiotherapy. Examination of the eyes revealed sectoral scleritis and peripheral ulcerative keratitis. Magnetic resonance imaging (MRI) of the orbits excluded recurrence of OAL and serum antineutrophil cytoplasmic autoantibody (ANCA) titres confirmed the diagnosis of GPA. Disease was poorly responsive to systemic steroids, azathioprine and rituximab. Ultimately, resolution was achieved with successive subconjunctival dexamethasone and subconjunctival triamcinolone injections. This case highlights the need to consider ocular inflammation in patients with a history of malignant hemopathies. [ABSTRACT FROM AUTHOR]

Abstract To investigate the imaging manifestations and pathological features of ocular adnexal lymphoma (OALs) in order to provide relevant information for ophthalmologists. A total of 94 patients with OALs were pathologically confirmed between August 2018 and July 2023, and their demographics, location, subtype, treatment, and prognosis were retrospectively studied. 94 patients with OALs were included in this study, of whom 28 were female (29.79%) and 66 were male (70.21%). The age of the patients ranged from 21 to 80 years, with a predominance of 50–60 years (60/94); monocular onset was common (90/94), and the most site of onset was orbital (74/94), followed by conjunctiva (12/94), eyelids (4/94), vitreous (3/94), and lacrimal gland (1/94). CT and MRI can show the involvement and extent of the lesions, and the pathology of the disease is characterized by mucosa‐associated lymphoid tissue marginal zone B‐cell lymphoma (72/94), diffuse large B‐cell lymphoma (10/94), T‐cell lymphoma (4/94), mantle cell lymphoma (2/94), Burkitt's lymphoma (2/94), small lymphocytic lymphoma (2/94), and follicular lymphoma (1/94). All patients received surgical treatment, 42 patients received local radiation therapy, 35 patients received chemotherapy, 13 patients received radiation therapy and chemotherapy successively, and 3 patients received comprehensive treatment. During the follow‐up, three patients relapsed, four died, one was lost to follow‐up, and the remaining patients had stable conditions. The majority of OALs are mucosa‐associated lymphoid tissue marginal zone B‐cell lymphomas (MALT) with an excellent prognosis. It mostly occurs in people over 50 years of age and most site of the onset is orbital.

To provide insights into targetable oncogenic pathways, this retrospective cohort study investigated the genetic profile of 26 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), and two patients with high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL) presenting in the ocular adnexa. Pathogenic variants and copy number variations in 128 B-cell lymphoma-relevant genes were analyzed by targeted next-generation sequencing. Genetic subtypes were determined with the LymphGen algorithm. Primary ocular adnexal DLBCL-NOS constituted 50% (n = 14) and was generally characterized by non-germinal center B-cell origin (non-GCB) (n = 8, 57%), and LymphGen MCD subtype (n = 5, 36%). Primary ocular adnexal DLBCL-NOS presented pathogenic variants in genes involved in NF-κB activation and genes which are recurrently mutated in other extranodal lymphomas of non-GCB origin, including MYD88 (n = 4, 29%), CD79B (n = 3, 21%), PIM1 (n = 3, 21%), and TBL1XR1 (n = 3, 21%). Relapsed DLBCL-NOS presenting in the ocular adnexa (n = 6) were all of non-GCB origin and frequently of MCD subtype (n = 3, 50%), presenting with a similar genetic profile as primary ocular adnexal DLBCL-NOS. These results provide valuable insights into genetic drivers in ocular adnexal DLBCL-NOS, offering potential applications in future precision medicine. [ABSTRACT FROM AUTHOR]

Summary: The study analysed the clinical characteristics, treatment approaches, and survival outcomes of 97 consecutive patients with orbital lymphoma (OL) over a 25-year period at. The median age of the patients was 57.6 years, and 59.8% (n = 58) were male. Marginal zone lymphoma constitutes the most prevalent subtype, accounting for 67% of cases, whereas other common subtypes include diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma, and T-cell lymphomas. Unilateral involvement was observed in the majority of cases (72.3%). Common clinical presentations included mass (30.9%), swelling (26.8%), and epiphora (11.3%). Of the patients, 7.2% received rituximab alone, 14.4% received radiotherapy alone, 48.5% received chemotherapy, 27.8% received radiotherapy plus rituximab, 22.7% received radiotherapy plus chemotherapy, and 5.2% underwent surgery as the first-line treatment. During a median follow-up of 4.3 years, 15.5% of patients experienced relapse or disease progression. The 5-year and 10-year progression-free survival rates were 84.1% and 79.1%, respectively. This study contributes to our understanding of OLs and provides a foundation for further investigations in this field. Male gender, presence of B symptoms, advanced stage, secondary orbital lymphoma, aggressive histological subtype, and elevated serum lactate dehydrogenase levels were associated with poorer (either inferior or worse) progression-free survival. [ABSTRACT FROM AUTHOR]

Introduction: Diffuse large B-cell lymphoma (DLBCL) is a prevalent subtype of non-Hodgkin lymphoma (NHL) affecting predominantly elderly individuals. Case description: A 68-year-old man with a history of hypertension, hyperlipidaemia and a small pituitary gland tumour presented with sudden-onset binocular diplopia and right-eye blurry vision. A magnetic resonance imaging (MRI) of the brain revealed enhancing soft tissue in the right superolateral orbit inseparable from the lacrimal gland, extending medially to the right superior rectus muscle and soft tissue. Further scanning showed widespread metastasis to the bilateral retroperitoneal lymph nodes, adrenal gland, spine and lymph nodes in the neck. A biopsy of the lacrimal gland confirmed DLBCL. Conclusion: Primary lacrimal gland DLBCL is a rare and delayed diagnosis that often stems from the resemblance of its clinical manifestations to more benign conditions such as dacryocystitis, dacryostenosis or mucocele. Timely recognition and accurate diagnosis are essential for initiating appropriate treatment and improving patient outcomes.

Helicobacter pylori is a common gram-negative bacterium, which is associated with a variety of gastroenteric diseases, such as gastritis, duodenal ulcer and gastric cancer. Recent studies suggested a potential role of Helicobacter pylori in the pathogenesis of common ocular diseases, such as central serous chorioretinopathy, glaucoma, anterior uveitis and ocular adnexal lymphoma. Helicobacter pylori might affect the pathophysiological process of ocular diseases through oxidative damage, circulatory disorders and immune injury. Some studies also suggested that eradication of Helicobacter pylori had certain effects on some ocular diseases. This review aims to summarize current evidence of the Helicobacter pylori in the pathogenesis of common ocular diseases, so as to encourage innovative approaches in the prevention and treatment of these ocular diseases.

Abstract Objective To investigate the prevalence of histopathological subtypes, the clinical stage at presentation and treatment modalities in Polish patients with orbital lymphoma (OL) and to determine prognostic outcomes. Methods The retrospective study of 107 patients with OL treated in a 14‐year period in Polish hematological centers. The analysis included histopathological subtype, disease clinical advancement, treatment modalities, progression‐free survival (PFS), and overall survival (OS). Results The median patient age was 60 years (range 51–71). Mucosa‐associated lymphoid tissue (MALT) lymphoma accounted for slightly more than half of all cases of orbital lymphoma (51%). The second most common subtype was diffuse large B‐cell lymphoma (DLBCL) (29%). Primary orbital lymphoma was diagnosed in 48% of all patients. According to the Ann Arbor, localized stage IE of orbital lymphoma was diagnosed only in 39% of all patients. Systemic involvement was observed in more than half of all patients (52%). The median follow‐up period was 30 months (range 0–160 months). Patients with non‐MALT lymphoma had a significantly inferior PFS compared to patients with MALT lymphoma, (p = 0.047). Patients with primary orbital lymphoma had a superior PFS compared to patients with secondary orbital lymphoma [median PFS 104.5 months vs. 33.4 months], (p = 0.069). Younger patients with MALT lymphoma were characterized by superior PFS (median PFS not reached) compared to other studied subgroups of patients (older patients with MALT lymphoma, younger and older non‐MALT lymphoma patients) with a median PFS of 30.5, 32.2, 32.6 months respectively (p = 0.039). Patients treated with chemotherapy alone had inferior PFS compared to patients treated with combined therapies (p = 0.034). The median PFS across patients who received chemotherapy alone was 23.7 months, whereas across other patients was 73.9 months. Conclusions Secondary lymphoma accounts for more than half of the orbital lymphoma in Polish population. The advanced clinical stage of the disease (non‐IE according to Ann Arbor) concerns two‐thirds of the overall population of patients with orbital lymphomas and one‐third of MALT lymphoma patients. The high incidence of advanced stages of orbital lymphoma may indicate the need for combined treatment. Combined orbital lymphoma treatment is associated with superior PFS compared to chemotherapy alone in overall population of patients with orbital lymphoma.

Ocular adnexal lymphomas (OALs) are extranodal lymphomas primarilyinvolving the ocular adnexa, which includes the conjunctiva. OALs are considered primary if the involvement of lymphoma is confined to the ocular adnexa alone and secondary if there is lymphoma of the identical type present at another site. Conjunctival lymphomas are uncommon in children, with very few reported cases in published literature, none of which were small lymphocytic lymphomas (SLLs). We report a case of SLL confined to the conjunctiva, in a 15-year-old child, with full pediatric oncology examination, including full body positron emission tomography (PET) scan, revealing no other site involvement. To our knowledge, this is the first case to be reported of a child with primary unilateral conjunctival SLL.

To provide insights into targetable oncogenic pathways, this retrospective cohort study investigated the genetic profile of 26 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), and two patients with high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL) presenting in the ocular adnexa. Pathogenic variants and copy number variations in 128 B-cell lymphoma-relevant genes were analyzed by targeted next-generation sequencing. Genetic subtypes were determined with the LymphGen algorithm. Primary ocular adnexal DLBCL-NOS constituted 50% (n = 14) and was generally characterized by non-germinal center B-cell origin (non-GCB) (n = 8, 57%), and LymphGen MCD subtype (n = 5, 36%). Primary ocular adnexal DLBCL-NOS presented pathogenic variants in genes involved in NF-κB activation and genes which are recurrently mutated in other extranodal lymphomas of non-GCB origin, including MYD88 (n = 4, 29%), CD79B (n = 3, 21%), PIM1 (n = 3, 21%), and TBL1XR1 (n = 3, 21%). Relapsed DLBCL-NOS presenting in the ocular adnexa (n = 6) were all of non-GCB origin and frequently of MCD subtype (n = 3, 50%), presenting with a similar genetic profile as primary ocular adnexal DLBCL-NOS. These results provide valuable insights into genetic drivers in ocular adnexal DLBCL-NOS, offering potential applications in future precision medicine.

We herein report a 76-year-old male who presented to the ophthalmology clinic after complaining from excessive lacrimation for ~6 months prior to presentation. He reports previously undergoing a nasolacrimal recanalization procedure in attempts to resolve his symptoms, but reported no improvement. On examination, a mass on the nasal conjunctiva around the medial canthus of the right eye was noted and subsequently excised. The findings support the diagnosis of low-grade follicular lymphoma. The patient was referred to radiation oncology for radiation therapy and received a total dose of 2400 cGy. Most ocular adnexal lymphomas are B-cell in origin, with follicular lymphomas being one of the rarest forms of such lymphomas. The most common translocation reported in over 85% of follicular lymphomas of the ocular adnexa is t(14; 18) (q32; q21). Traditional treatment options typically include a mix of chemical, surgical, and radio-oncological interventions. [ABSTRACT FROM AUTHOR]

Ocular adnexal lymphomas (OALs) are extranodal lymphomas primarily involving the ocular adnexa, which includes the conjunctiva. OALs are considered primary if the involvement of lymphoma is confined to the ocular adnexa alone and secondary if there is lymphoma of the identical type present at another site. Conjunctival lymphomas are uncommon in children, with very few reported cases in published literature, none of which were small lymphocytic lymphomas (SLLs). We report a case of SLL confined to the conjunctiva, in a 15-year-old child, with full pediatric oncology examination, including full body positron emission tomography (PET) scan, revealing no other site involvement. To our knowledge, this is the first case to be reported of a child with primary unilateral conjunctival SLL. [ABSTRACT FROM AUTHOR]

Background: Ocular adnexal lymphoma (OAL) and idiopathic orbital inflammation (IOI) are malignant and benign lesions for which radiotherapy and corticosteroids are indicated, but similar clinical manifestations make their differentiation difficult. Purpose: To develop and validate an MRI‐based radiomics nomogram for individual diagnosis of OAL vs. IOI. Study Type: Retrospective. Population: A total of 103 patients (46.6% female) with mean age of 56.4 ± 16.3 years having OAL (n = 58) or IOI (n = 45) were divided into an independent training (n = 82) and a testing dataset (n = 21). Field Strength/Sequence: A 3‐T, precontrast T1‐weighted imaging (T1WI), T2‐weighted imaging (T2WI), and postcontrast T1WI (T1 + C). Assessment: Radiomics features were extracted and selected from segmented tumors and peritumoral regions in MRI before‐and‐after filtering. These features, alone or combined with clinical characteristics, were used to construct a radiomics or joint signature to differentiate OAL from IOI, respectively. A joint nomogram was built to show the impact of the radiomics signature and clinical characteristics on individual risk of developing OAL. Statistical Tests: Area under the curve (AUC) and accuracy (ACC) were used for performance evaluation. Mann–Whitney U and Chi‐square tests were used to analyze continuous and categorical variables. Decision curve analysis, kappa statistics, DeLong and Hosmer–Lemeshow tests were also conducted. P < 0.05 was considered statistically significant. Results: The joint signature achieved an AUC of 0.833 (95% confidence interval [CI]: 0.806–0.870), slightly better than the radiomics signature with an AUC of 0.806 (95% CI: 0.767–0.838) (P = 0.778). The joint and radiomics signatures were comparable to experienced radiologists referencing to clinical characteristics (ACC = 0.810 vs. 0.796–0.806, P > 0.05) or not (AUC = 0.806 vs. 0.753–0.791, P > 0.05), respectively. The joint nomogram gained more net benefits than the radiomics nomogram, despite both showing good calibration and discriminatory efficiency (P > 0.05). Data Conclusion: The developed radiomics‐based analysis might help to improve the diagnostic performance and reveal the association between radiomics features and individual risk of developing OAL. Evidence Level: 3 Technical Efficacy: 3 [ABSTRACT FROM AUTHOR]

Abstract Background Approximately 50% of limited‐stage ocular adnexal mucosa‐associated lymphoid tissue lymphoma (OAML) patients with adverse prognostic factors relapse after radiotherapy. Chemoimmunotherapy has been proposed as an alternative frontline therapy. However, only a few studies have reported its long‐term treatment outcome. Methods In 2011, we commenced a phase 2 trial to investigate the efficacy of rituximab, cyclophosphamide, doxorubicin, and prednisolone (R‐CVP) in bilateral and non‐conjunctival limited‐stage OAML patients. Results of the clinical trial showed a response rate of 100% and a 4‐year progression‐free survival of 90.3% without significant toxicity. We extended the study period to December 2020 to determine the long‐term efficacy of R‐CVP chemoimmunotherapy. Results At a median observation period of 66.0 months, eight of 33 study patients had relapsed. The cumulative incidence of relapse was 18.9% at 5 years and 44.7% at 8 years. The majority of relapses developed more than 4 years after treatment. Local relapse was more prevalent than distant relapse. The relapse risk of orbital and lacrimal diseases was likely to be higher than that of conjunctival and eyelid diseases (HR: 2.5, 95% CI: 0.498–12.500, p = 0.25). Conclusion Although the response rate was remarkable for chemoimmunotherapy, the risk of late relapse was considerable. Based on our findings, clinical trials for limited‐stage OAML patients should have a long‐term observation period. To minimize radiation toxicity and reduce the risk of delayed relapse (local relapse and distant relapse), a future study with sequential or combination treatment of local low‐dose radiation and systemic chemoimmunotherapy can be considered.

Abstract Background Ocular adnexal B-cell lymphoma (OABL) is a rare subtype of non-Hodgkin lymphoma. The molecular characteristics of OABL remain poorly understood. We performed an integrated study to investigate the proteotranscriptome landscape and identify novel molecular characteristics and biomarkers of OABL. Methods Integrated quantitative proteome and transcriptome were performed on 40 OABL 12 idiopathic orbital inflammation, 6 reactive lymphoid hyperplasia, and 13 aesthetic orbital plastic surgery specimens. Complete clinicopathologic and prognostic data of the patients were recorded. Results We identified high global protein-mRNA concordance as a novel characteristic of OABL. High concordance was related to OABL recurrence. By integrated expression profile, motif enrichment and trend analysis, we found that alternative splicing is inflammation-independently dysregulated in OABL. After portraying the aberrant alternative splicing event landscape, we demonstrated the oncogenic role of ADAR, a core splicing regulator that regulates the splicing of Rho GTPase and cell cycle members. We found that ADAR regulates cell proliferation and Rho GTPase inhibitor sensitivity of lymphoma. We identified DNAJC9 as a potential biomarker for OABL in proteomic analyses. Immunohistochemistry and immunofluorescent staining showed the nuclear staining of DNAJC9 was significantly higher in extranodal marginal zone lymphomas compared with inflammation specimens. Conclusions These results provide an integrated gene expression profiling and demonstrate that high global protein-mRNA concordance is a prognosis-related molecular characteristic of OABL. We portray the alternative splicing events landscape of OABL, and reveal the oncogenic role of ADAR. We identified strong nuclear staining of DNAJC9 as a promising pathology diagnostic biomarker for extranodal marginal zone lymphomas.

Objective: To investigate the prevalence of histopathological subtypes, the clinical stage at presentation and treatment modalities in Polish patients with orbital lymphoma (OL) and to determine prognostic outcomes. Methods: The retrospective study of 107 patients with OL treated in a 14‐year period in Polish hematological centers. The analysis included histopathological subtype, disease clinical advancement, treatment modalities, progression‐free survival (PFS), and overall survival (OS). Results: The median patient age was 60 years (range 51–71). Mucosa‐associated lymphoid tissue (MALT) lymphoma accounted for slightly more than half of all cases of orbital lymphoma (51%). The second most common subtype was diffuse large B‐cell lymphoma (DLBCL) (29%). Primary orbital lymphoma was diagnosed in 48% of all patients. According to the Ann Arbor, localized stage IE of orbital lymphoma was diagnosed only in 39% of all patients. Systemic involvement was observed in more than half of all patients (52%). The median follow‐up period was 30 months (range 0–160 months). Patients with non‐MALT lymphoma had a significantly inferior PFS compared to patients with MALT lymphoma, (p = 0.047). Patients with primary orbital lymphoma had a superior PFS compared to patients with secondary orbital lymphoma [median PFS 104.5 months vs. 33.4 months], (p = 0.069). Younger patients with MALT lymphoma were characterized by superior PFS (median PFS not reached) compared to other studied subgroups of patients (older patients with MALT lymphoma, younger and older non‐MALT lymphoma patients) with a median PFS of 30.5, 32.2, 32.6 months respectively (p = 0.039). Patients treated with chemotherapy alone had inferior PFS compared to patients treated with combined therapies (p = 0.034). The median PFS across patients who received chemotherapy alone was 23.7 months, whereas across other patients was 73.9 months. Conclusions: Secondary lymphoma accounts for more than half of the orbital lymphoma in Polish population. The advanced clinical stage of the disease (non‐IE according to Ann Arbor) concerns two‐thirds of the overall population of patients with orbital lymphomas and one‐third of MALT lymphoma patients. The high incidence of advanced stages of orbital lymphoma may indicate the need for combined treatment. Combined orbital lymphoma treatment is associated with superior PFS compared to chemotherapy alone in overall population of patients with orbital lymphoma. [ABSTRACT FROM AUTHOR]

High-grade B-cell lymphoma (HGBL) with c-MYC and BCL2 and/or BCL6 rearrangements, also known as a double-hit and triple-hit lymphoma, is an aggressive non-Hodgkin lymphoma affecting older adults. After formal recognition of this entity in the 2017 revision of the World Health Organization Classification of lymphoid neoplasms, only two well-documented cases of triple-hit lymphoma of the orbit appear in the literature. Herein, we describe a 70-year-old man with progressive diplopia, ophthalmoplegia, and rapidly enlarging temporal mass. Biopsy revealed a tumor morphologically consistent with HGBL, coexpressing CD20, CD10, BCL6, BCL2, and c-MYC on immunohistochemical analysis. Fluorescence in-situ hybridization showed rearrangements in c-MYC and BCL-2 genes, confirming double-hit HGBL. Systemic workup revealed Ann Arbor stage IV disease. This report reviews the existing literature on ocular adnexal double-hit and triple-hit lymphoma and provides an update on the diagnostic ancillary studies, prognostic implications, and latest management for this aggressive hematolymphoid malignancy. [ABSTRACT FROM AUTHOR]

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.

Purpose: To report a 65-year-old male patient with primary lateral rectus large B cell lymphoma. Observations: The patient had been referred because of progressive proptosis and limitation of ductions, especially abduction (ortho position at primary gaze) and conjunctival injection. Computerized tomography of the orbit and paranasal sinuses depicted a massive lateral rectus muscle enlargement without any other orbital involvement. Lateral orbitotomy and lateral rectus belly incisional biopsy was done, and histopathologic and immunohistochemical staining and systemic evaluations revealed the diagnosis of primary orbital large B-cell lymphoma. Conclusions and importance: This case indicated that, though rare, extraocular muscle enlargement could be the main finding of primary orbital lymphoma. Large B-cell lymphoma could involve only the orbital tissues, although it is more prevalent with systemic involvement.

Background: Ocular adnexal B-cell lymphoma (OABL) is a rare subtype of non-Hodgkin lymphoma. The molecular characteristics of OABL remain poorly understood. We performed an integrated study to investigate the proteotranscriptome landscape and identify novel molecular characteristics and biomarkers of OABL. Methods: Integrated quantitative proteome and transcriptome were performed on 40 OABL 12 idiopathic orbital inflammation, 6 reactive lymphoid hyperplasia, and 13 aesthetic orbital plastic surgery specimens. Complete clinicopathologic and prognostic data of the patients were recorded. Results: We identified high global protein-mRNA concordance as a novel characteristic of OABL. High concordance was related to OABL recurrence. By integrated expression profile, motif enrichment and trend analysis, we found that alternative splicing is inflammation-independently dysregulated in OABL. After portraying the aberrant alternative splicing event landscape, we demonstrated the oncogenic role of ADAR, a core splicing regulator that regulates the splicing of Rho GTPase and cell cycle members. We found that ADAR regulates cell proliferation and Rho GTPase inhibitor sensitivity of lymphoma. We identified DNAJC9 as a potential biomarker for OABL in proteomic analyses. Immunohistochemistry and immunofluorescent staining showed the nuclear staining of DNAJC9 was significantly higher in extranodal marginal zone lymphomas compared with inflammation specimens. Conclusions: These results provide an integrated gene expression profiling and demonstrate that high global protein-mRNA concordance is a prognosis-related molecular characteristic of OABL. We portray the alternative splicing events landscape of OABL, and reveal the oncogenic role of ADAR. We identified strong nuclear staining of DNAJC9 as a promising pathology diagnostic biomarker for extranodal marginal zone lymphomas. [ABSTRACT FROM AUTHOR]

Background: Approximately 50% of limited‐stage ocular adnexal mucosa‐associated lymphoid tissue lymphoma (OAML) patients with adverse prognostic factors relapse after radiotherapy. Chemoimmunotherapy has been proposed as an alternative frontline therapy. However, only a few studies have reported its long‐term treatment outcome. Methods: In 2011, we commenced a phase 2 trial to investigate the efficacy of rituximab, cyclophosphamide, doxorubicin, and prednisolone (R‐CVP) in bilateral and non‐conjunctival limited‐stage OAML patients. Results of the clinical trial showed a response rate of 100% and a 4‐year progression‐free survival of 90.3% without significant toxicity. We extended the study period to December 2020 to determine the long‐term efficacy of R‐CVP chemoimmunotherapy. Results: At a median observation period of 66.0 months, eight of 33 study patients had relapsed. The cumulative incidence of relapse was 18.9% at 5 years and 44.7% at 8 years. The majority of relapses developed more than 4 years after treatment. Local relapse was more prevalent than distant relapse. The relapse risk of orbital and lacrimal diseases was likely to be higher than that of conjunctival and eyelid diseases (HR: 2.5, 95% CI: 0.498–12.500, p = 0.25). Conclusion: Although the response rate was remarkable for chemoimmunotherapy, the risk of late relapse was considerable. Based on our findings, clinical trials for limited‐stage OAML patients should have a long‐term observation period. To minimize radiation toxicity and reduce the risk of delayed relapse (local relapse and distant relapse), a future study with sequential or combination treatment of local low‐dose radiation and systemic chemoimmunotherapy can be considered. [ABSTRACT FROM AUTHOR]

The aim of the study is to emphasize the frequency, clinical presentation, histopathologic features and TNM staging for each type of ocular adnexal lymphoma (OAL), and investigating treatment results and prognosis in our region. A retrospective review of 54 patients treated for primary and secondary OAL between Jan 2012 and Jan 2019 was made. Epidemiologic data, clinical characteristics of the tumor and recurrence free survival rates were evaluated. Patients with ocular adnexal lymphoma included 27 (50%) women and 27 (50%) men, with a mean age of 60.38±15.36 (range: 18-93) years at the time of presentation. Mean follow-up time was 40.88±20.75 (range 1-84) months. Histopathological diagnosis was extranodal marginal zone lymphoma in 75.9%, diffuse large B-cell lymphoma in 14.8%, chronic lymphocytic leukemia/small lymphocytic lymphoma in 5.6%, mantle cell lymphoma in 1.9% and follicular cell lymphoma in 1.9% of patients. Among 54 patients with OAL 66.7% had orbital, 22.2% had conjunctival, 5.6% had orbital plus conjunctival, 3.7% had orbital plus conjunctival and choroidal, 1.9% had conjunctival plus choroidal involvement. No recurrences were observed in 87.1% of patients during their follow-up. Our data indicates patient epidemiologic data, TNM staging, most common clinical presentation and location of primary and secondary OALs from a single center. [ABSTRACT FROM AUTHOR]

Background: N-isopropyl- (123I) p-iodoamphetamine (123I-IMP) is specifically accumulated in primary central nervous system lymphoma (PCNSL) during single-photon emission tomography (SPECT) and contributes to its diagnostic imaging. However, whether 123I-IMP is accumulated in ocular adnexal lymphoma (OAL), one of the malignant intraorbital tumors, remains unclear. This study aimed to evaluate the diagnostic value of 123I-IMP SPECT in OAL. Methods: Between August 2005 and June 2020, 26 patients with intraorbital tumors underwent neurosurgery at the tertiary care center. Of these, 15 patients who underwent 123I-IMPSPECT before surgery were retrospectively examined. The region of interest was set in the cerebellum ipsilateral to the intraorbital tumor on 123I-IMP SPECT, and the tumor-to-cerebellum ratio (T/C ratio) was calculated using the following formula: T/C ratio = [accumulation of tumor (count/pixel)]/[accumulation of ipsilateral normal cerebellar hemisphere (count/pixel)]. Results: Six patients were included in the OAL group, who were pathologically diagnosed with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), diffuse large B-cell lymphoma (DLBCL), and plasmacytoma. The T/C ratio in the OAL group was statistically higher than that in the non-OAL group (p < 0.01). The optimal cutoff values for both groups were between 0.76 and < 0.93. The sensitivity and specificity were 1.00, respectively. Conclusions: 123I-IMP SPECT is useful as one of the examinations in the differential diagnoses of OAL, because it showed a significantly higher accumulation in OAL group than in non-OAL group. [ABSTRACT FROM AUTHOR]

Annemarie Klingenstein,1 Aylin Garip-Kuebler,1 Siegfried Priglinger,1 Christoph Hintschich,1 Ullrich G Mueller-Lisse2 1Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany; 2Department of Radiology, Ludwig-Maximilians-University, Munich, GermanyCorrespondence: Annemarie KlingensteinLudwig-Maximilians-University, Department of Ophthalmology, Klinikum der Universität München, Campus Innenstadt, Mathildenstraße 8, Munich, D-80336, GermanyTel +49 89 44005 3811Fax +49 89 44005 5160Email Annemarie.Klingenstein@med.uni-muenchen.deAim: To detect radiological features that, in addition to clinical findings, may aid in correct differentiation between IgG4-related ophthalmic disease (IgG4-ROD) and ocular adnexal lymphoma (OAL).Methods: In this retrospective, single-center, comparative analysis, we compared cross-sectional imaging findings of 13 consecutive patients with histologically proven IgG4-ROD and a control group of 29 consecutive OAL-patients diagnosed between 10/2014 and 09/2019. Statistical significance was accepted at a p< 0.05 significance level.Results: IgG4-ROD-patients had longer time-to-diagnosis, higher orbital recurrence rates, but smaller lesions compared to OAL-patients (p=0.002; p=0.006 and p=0.006; Mann–Whitney U-test). Frequent cross-sectional imaging findings in both IgG4-ROD-patients and OAL-patients included extraocular muscle enlargement (92% and 93%, respectively; most often in the lateral rectus muscles and the levator-complex), and lacrimal-gland enlargement (85% and 83%, respectively). Other imaging findings comprised infraorbital nerve-involvement (IgG4-ROD, 23%, OAL, 17%) and orbital fat inflammation (IgG4-ROD, 23%, OAL, 28%). Bony infiltration and remodeling, heterogenous contrast-media distribution, and infiltration of the lacrimal system were seen slightly more often in IgG4-ROD (23%, 38%, 15% and 15% versus 17%, 14%, 3% and 7%). However, cross-sectional imaging features did not differ significantly between patient subgroups. Clinical symptoms predominantly occurred unilaterally (IgG4-ROD, 9/13, 69%, OAL, 24/29, 83%), while imaging findings were most often bilateral (IgG4-ROD, 11/13, 85%, OAL, 23/29, 79%, p< 0.001, McNemar test).Conclusion: No morphological cross-sectional imaging sign could reliably distinguish between IgG4-ROD and OAL, leaving histopathology indispensable for definite diagnosis. Yet, importantly, for both IgG4-ROD and OAL, cross-sectional imaging frequently detected bilateral orbital disease when only one eye was clinically affected.Keywords: IgG4, idiopathic orbital inflammation, CT, ocular adnexal lymphoma

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. [ABSTRACT FROM AUTHOR]

To compare characteristics of initial ocular adnexal (OA) mantle cell lymphoma (MCL) and initial systemic MCL. Retrospective, comparative case series. Patients treated for MCL at Mayo Clinic from 1/1/1990 to 11/30/2020. MCL was classified as initial OA if first site was OA or initial systemic if first site was elsewhere with progression or recurrence to the OA region. Features, treatment, and survival. There were 50 patients with MCL, 23 initial OA and 27 initial systemic. Patients with initial OA MCL had more conjunctival (52% vs. 19%, p =.017) involvement and less frequently received chemotherapy plus autologous stem cell transplant (ASCT) (9% vs. 33%, p =.046) as initial treatment. Complete remission was achieved in 41 (91% vs. 74%, p =.152) patients. Five-year disease-specific survival was similar in initial OA and initial systemic MCL (92% vs. 83%, p =.187). Subanalysis of patients with initial OA MCL revealed 9 (39%) patients developed tumor recurrence, with mean time to recurrence of 28 months. Comparison (no recurrence vs. recurrence) of initial OA MCL patients revealed those with no recurrence had shorter mean final follow-up (3.3 vs. 9.8 years, p =.005) and more frequent initial treatment with rituximab-based chemotherapy plus ASCT (43% vs. 0%, p =.048). Recurrence had no effect on the 5-year age-adjusted risk of death from lymphoma (HR 2.17, 95% CI 0.55–9.09, p =.266). Initial OA and initial systemic MCL patients differ in presentation and management but have similar survival. [ABSTRACT FROM AUTHOR]

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.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is a prevalent subtype of non-Hodgkin lymphoma (NHL) affecting predominantly elderly individuals., Case Description: A 68-year-old man with a history of hypertension, hyperlipidaemia and a small pituitary gland tumour presented with sudden-onset binocular diplopia and right-eye blurry vision. A magnetic resonance imaging (MRI) of the brain revealed enhancing soft tissue in the right superolateral orbit inseparable from the lacrimal gland, extending medially to the right superior rectus muscle and soft tissue. Further scanning showed widespread metastasis to the bilateral retroperitoneal lymph nodes, adrenal gland, spine and lymph nodes in the neck. A biopsy of the lacrimal gland confirmed DLBCL., Conclusion: Primary lacrimal gland DLBCL is a rare and delayed diagnosis that often stems from the resemblance of its clinical manifestations to more benign conditions such as dacryocystitis, dacryostenosis or mucocele. Timely recognition and accurate diagnosis are essential for initiating appropriate treatment and improving patient outcomes., Learning Points: Lacrimal sac lymphomas represent diagnostic challenges due to their rarity, non-specific symptoms and frequent misdiagnoses as benign pathologies, hence it is crucial to include this in the differential diagnosis.Timely recognition and accurate diagnosis are important in improving outcomes for lacrimal sac lymphomas., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

PURPOSE: To characterize demographic, clinical, and histopathologic features of ocular adnexal lymphoma (OAL) at a single institution. METHODS: Retrospective review of all patients with pathologic diagnosis of OAL between 2015 and 2020. RESULTS: There were 133 patients with OAL, with a median age of 65 years (range 23-97) and a slight female predominance (male: female = 1:1.46), (n = 79, 59%). The majority of tumors were non-Hodgkin B-cell lymphomas (n = 131, 99%), most frequently Extranodal Marginal Zone B-Cell Lymphoma (EMZL, n = 93, 70%), followed by follicular lymphoma (n = 21, 16%), chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 7, 5%), diffuse large B-cell lymphoma (n = 5, 4%), and mantle cell lymphoma (n = 5, 4%). The most frequently involved sites included the orbit (n = 85, 64%) and conjunctiva (n = 43, 32%). Information was available on oncologic staging in 78 (59%), treatment in 82 (62%), and follow-up in 75 (56%) patients. By the Ann-Arbor classification system, patients were classified as IE (54/78, 69%), IIE (9/78, 12%), IIIE (6/78, 8%), and IVE (9/78, 12%). The most common treatments included external beam radiotherapy (standard and ultra-low-dose) (48/82, 59%), biologics (22/82, 27%), and surgical excision with cryotherapy (14/82, 17%) (some patients had >1 therapy). Median follow-up time was 24 months (range 0-221 months). Recurrence was observed in 13% (10/75) with a median time to recurrence of 60 months (95% confidence interval 47-73 months). Excision with cryotherapy as a sole treatment modality was associated with earlier recurrence (P = 0.003). CONCLUSION: In this largest single-center study of OAL, we found that most OAL were Ann-Arbor Stage IE EMZL, occurring in older patients with a female predominance. Early recurrence was noted in tumors treated with excision and cryotherapy alone. [ABSTRACT FROM AUTHOR]

4 ‡ Parotid gland (from stage IE to IVE), stomach (from stage IE to IVE, confirmed on EGD), thigh muscle (from stage IE to IVE), iliac/inguinal lymph nodes (stage IIE to IVE). 5 § The bone marrow involvement of mucosa-associated lymphoid tissue (MALT) lymphoma was not detectable by PET or CT scans. Keywords: ocular adnexal lymphoma; extranodal marginal zone lymphoma; MALToma; positron emission tomography; bone marrow biopsy; esophagogastroduodenoscopy EN ocular adnexal lymphoma extranodal marginal zone lymphoma MALToma positron emission tomography bone marrow biopsy esophagogastroduodenoscopy 848 851 4 05/17/21 20210515 NES 210515 Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) accounts for 30-90% of ocular adnexal lymphoma, and a majority of ocular adnexal MALT lymphoma (OAML) is stage 1 disease.1 The role of extensive staging procedures, including positron emission tomography-computed tomography (PET-CT), esophagogastroduodenoscopy (EGD), and bone marrow biopsy, has not been thoroughly investigated for OAML due to its rarity. Half of stage IIE patients ( I n i = 4/8) and two-thirds of stage IV patients ( I n i = 6/9) received rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP). [Extracted from the article]

A 10-year-old girl was brought to the clinic with the complaint of a salmon-colored conjunctival lesion for 1 month. With the aid of histopathological evaluation and other tests, extranodal ocular adnexal marginal zone lymphoma was diagnosed. The patient was graded as T1bN0M0 according to AJCC and Stage 1 according to Ann Arbor classification. She was treated with external radiotherapy at 1.8 Gy/day for 17 days for a total dose of 36 Gy. She is in remission for 26 months and still being followed up.

AIM: To study the incidence, clinical features and pathological types of ocular adnexal lymphoma(OAL), in order to improve the level of clinical diagnosis and treatment.METHODS: There were 147 cases of OAL in West China Hospital from August 2005 to July 2013. We collected clinical data such as general conditions, clinical manifestations, clinical examination(imaging, pathology)results, treatment and prognosis for retrospective study.RESULTS: This study consist of 147 patients with OAL, including 91 males(61.9%)and 56 females(38.1%); aged from 3.5 to 87 years old; the course of disease range from 20d to 10a; the most common location of disease is orbit(106/147).The most common clinical manifestations including ocular mass, eyelid swelling and exophthalmos. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue were most common(112/147), it also had the best prognosis while diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma,nasal type showed the worst prognosis.CONCLUSION: The pathological types of OAL were complex, which also had diverse location of disease and clinical manifestations. Immunohistochemically staining is an important basis for the differential diagnosis of OAL, and the prognosis of which is closely related to pathological type.

This review focuses on the biology of ocular adnexal marginal zone B-cell lymphomas of the mucosa-associated lymphatic tissue (MALT) (OAMZL) subtype. The ocular adnexa includes all structures and tissues within the orbit except for the eye bulb. In the region of the ocular adnexa, MALT lymphomas represent the most common subtype of lymphoma, accounting for around 8% of all non-Hodgkin lymphomas. These lymphomas are often preceded by inflammatory precursor lesions. Either autoantigens or infectious antigens may lead to disease development by functioning as continuous antigenic triggers. This triggering leads to a constitutive activation of the NF-κB signaling pathway. The role of antigenic stimulation in the pathogenesis of OAMZL is supported by the detection of somatic mutations (partially with further intraclonal diversity) in their rearranged immunoglobulin V genes; hence, their derivation from germinal-center-experienced B cells, by a restricted IGHV gene usage, and the validation of autoreactivity of the antibodies in selected cases. In the established lymphomas, NF-κB activity is further enforced by mutations in various genes regulating NF-κB activity (e.g., TNFAIP3, MYD88), as well as recurrent chromosomal translocations affecting NF-κB pathway components in a subset of cases. Further pathogenetic mechanisms include mutations in genes of the NOTCH pathway, and of epigenetic regulators. While gene expression and sequencing studies are available, the role of differential methylation of lymphoma cells, the role of micro-RNAs, and the contribution of the microenvironment remain largely unexplored.

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Background: To evaluate biodata, symptoms/signs, lymphoma type, localization, stage level, treatment choice and outcome of ocular adnexal lymphoma (OAL). Patients and Methods: A single-center retrospective analysis of 56 patients with OAL was performed from 1998 to 2018. Results: OAL involved the orbit in 44.6%, the conjunctiva in 32.1%, the lacrimal apparatus in 14.3% and the eyelid in 8.93%. Extranodal marginal zone B-cell lymphoma (EMZL) was found in 60.7%, follicular lymphoma (FL) in 21.4%, diffuse large Bcell lymphoma in 7.14%, mantle cell lymphoma in 5.36% and chronic lymphatic leukaemia in 5.36% patients. No relapse was seen in 76%. EMZL and FL had a significantly better overall survival compared to other lymphoma types (p=0.002). Patients with Ann Arbor stage IE had a significantly better prognosis than those with stages higher than IE (p=0.048). Conclusion: Our data suggest that clinicopathological features such as Ann Arbor stage influence survival. [ABSTRACT FROM AUTHOR]

Objectives: To assess the prevalence of Chlamydia psittaci, Chlamydia pneumoniae, and Chlamydia trachomatis in ocular adnexa lymphoma (OAL) determined by molecular testing in different countries and the potential association of Chlamydia infection with mucosa-associated lymphoid tissue (MALT) histotype by performing a systematic review and meta-analysis.Methods: Electronic databases were searched for studies assessing the presence of Chlamydia in OAL. Pooled prevalence of the three Chlamydia species was calculated in each country. An odds ratio was calculated for the association between Chlamydia and MALT histotype, with a significant P < .05.Results: Thirty-seven studies with 1,188 OALs were included. Pooled prevalence of C psittaci, C pneumoniae, and C trachomatis by country was done. Chlamydia infection was significantly associated with MALT histotype (odds ratio, 2.183; P = .027).Conclusions: The involvement of C psittaci in OAL is highly variable, with the highest prevalence in Italy and Korea. Chlamydia is associated with MALT histotype. [ABSTRACT FROM AUTHOR]