Orbital Lymphoma Research Articles

The Role of Radiotherapy in Indolent Ocular Adnexal and Orbital Lymphomas.

This study evaluates the oncological outcomes and toxicities of indolent ocular adnexal and orbital lymphomas (OOLs) treated with radiotherapy (RT) ± systemic therapy. A retrospective analysis of 44 patients with indolent OOLs treated with RT was conducted. Most patients (87%) had early-stage disease. Treatment involved RT alone (34%) or RT + systemic therapy (66%). The median RT dose was 30 Gy, with a median follow-up of 45 months. Local and systemic recurrence rates were 4% and 9%, respectively. Five-year overall and disease-free survival (DFS) rates were 96.2% and 83.6%. Early-stage patients showed similar DFS rates regardless of whether they received RT alone or RT plus systemic therapy. No grade 3 RT-related toxicity occurred, but systemic therapy led to grade 3 toxicity in 17% of patients. RT is essential for treating indolent OOLs, and combination with systemic therapies does not enhance outcomes for early-stage patients.

7824 Orbital Lymphoma masquerading as Thyroid Eye Disease

Abstract Disclosure: S. Ganawa: None. S. Joseph: None. C. Anshuman: None. D. Luciane L: None. A. Sajid: None. C. Anne: None. S. Dhage: None. Thyroid eye disease (TED) is the most common extrathyroidal manifestation in Graves’ disease (GD). In this case report, we present a case of a 64 years old lady, who was initially diagnosed with thyroid eye disease about 9 years ago. However, she was clinically and biochemically euthyroid. She was offered an orbital decompression surgery by local ophthalmology team. Patient wasn’t keen on the surgery at this stage.Recently she experienced increased swelling of her eyes, with conjunctival redness, oedema, and diplopia bilaterally, more evident on the left side. She was initiated on intravenous methylprednisolone (IVMP) weekly, by local ophthalmology team and was referred to our specialist thyroid eye clinic for further management.On presentation to us, her clinical activity score (CAS) was 5/7, but she was euthyroid clinically and biochemically. She was continued on weekly IVMP and oral mycophenolate mofetil (MMF) was added on as per the latest EUGOGO guidelines published in 2021. Her treatment was reviewed after the anti thyroperoxidase (TPO) and anti-Thyroid Stimulating Hormone receptor (TSH) antibodies were reported as negative and her eyes worsened despite the treatment with IVMP and MMF.Her repeat MR orbit at this stage showed possible orbital lymphoma. Her immunosuppressive medications were discontinued at this stage. After further discussions at regional thyroid eye MDT and radiology MDT, an orbital biopsy was arranged for, which confirmed Extra nodal Marginal Zone lymphoma, with no high-grade component. She has been referred to the oncology unit for further assessment and management.This case highlights the importance of considering alternative differential diagnosis in certain patients with atypical features or those who are non-responders to the first line immunosuppressive therapies for thyroid eye disease. Details of this case and relevant literature will be reviewed in this report. Presentation: 6/3/2024

Ocular adnexal lymphoma - a retrospective study and review of the literature.

To review the characteristics of all Slovenian patients with ocular adnexal lymphoma (OAL) in the period of 24 years with the aim of evaluating demographic data, lymphoma location and type, disease stage, treatment modality, local control rate and survival rate. All patients with histologically diagnosed OAL in the main tertiary centre of Slovenia, Eye Hospital, University Medical Centre Ljubljana, who were treated at Institute of Oncology Ljubljana were included in the study. Patients' data were collected from October 1995 through April 2019. Seventy-four patients were included in the study having a median age of 68 years at diagnosis. The majority of lymphomas were of B-cell origin (98.6%). The most frequent type was the extranodal marginal zone B-cell lymphoma (MALT) (71.6%). Orbital lymphomas were diagnosed in 56 cases (75.7%) and conjunctival in 18 cases (24.3%). Ocular manifestation was the first sign of the disease in 78.4% of patients and in 67.6% of patients ocular adnexa were the only disease location. Fifty-one patients (68.9%) were treated with radiotherapy, 7 patients (9.4%) with systemic treatment, 5 patients (6.8%) with combined radiotherapy and systemic treatment and in 11 patients, biopsy and active surveillance strategy was applied (14.9%). Local control of the disease was achieved in 96.6% of treated patients. Median overall survival of the whole study group has not been reached yet. Five-year overall survival rate was 80.1% (95% CI 68.1% - 88.5%) and 5-year lymphoma specific survival rate was 87.2% (95% CI 83.2%-91.2%). OALs comprise a group of heterogeneous diseases with variable outcomes depending predominately on the patient's age and lymphoma type, with low grade lymphomas carrying good prognosis even in elderly patients.

Ultra–Low-Dose Radiation for Extranodal Marginal Zone Lymphoma of the Lung

Definitive intent radiation therapy (RT) for early-stage mucosa-associated lymphoid tissue (MALT) lymphoma typically includes a dose of 24 to 30 Gy. While modest, these doses may have associated toxicity. For patients with indolent B-cell lymphoma, there is increasing support for the use of ultra–low-dose RT (ULDRT) using 4 Gy in 2 fractions as part of a response-adapted approach, as high rates of complete response have been documented. This paradigm has been prospectively evaluated in the management of orbital and gastric indolent B-cell lymphomas; however, there is limited data guiding the use of ULDRT for lung MALT. We describe the use of ULDRT given in a response-adapted approach for 20 patients with lung MALT at our institution. At a median of 17 months following 4 Gy (IQR, 8-37 months), we observed 100% local control. Nineteen patients (95%) experienced a complete response. No patients with stage IE disease at RT (17/20; 85%) experienced distant progression. Nine patients (45%) were symptomatic prior to RT, with improvement or resolution of symptoms in 7 (7/9; 78%). One patient developed grade 2 pleuritic pain following RT, which resolved with a brief course of steroids. No other toxicities were noted. ULDRT, given in a response-adapted approach, is effective and well tolerated by patients with lung MALT.

ABCL-162 Case Report: A Primary Orbital Lymphoma Successfully Treated by High Dose of Chemotherapy

ABCL-162 Case Report: A Primary Orbital Lymphoma Successfully Treated by High Dose of Chemotherapy

Vision preserving role of radiotherapy in orbital plasmablastic lymphoma

An uncommon but aggressive variant of diffuse large B-cell lymphoma is plasmablastic lymphoma (PBL). Although they primarily involve the gastrointestinal tract, lymph nodes, and oral mucosa of immunocompromised males, orbital presentation is rare. In this article, we report a case of an elderly, immunocompetent gentleman presenting with progressive proptosis, ptosis, and diminished vision of the right eye with a palpable mass in the right upper eyelid. Imaging and biopsy confirmed the rare diagnosis of orbital PBL. After obtaining institutional tumor board concurrence, the patient was delivered 45 Gy external beam radiation therapy followed by six cycles of chemotherapy. Post-therapy, he is in remission with improvement in vision and is currently on maintenance chemotherapy.

Case Report: A Primary Orbital Lymphoma Successfully Treated by High Dose of Chemotherapy

Case Report: A Primary Orbital Lymphoma Successfully Treated by High Dose of Chemotherapy

Analysis of the Clinical Value of High-Frequency Ultrasound in Differentiating Orbital Lymphoma from Inflammatory Pseudotumor

This study aims to investigate the clinical value of high-frequency ultrasound in distinguishing between orbital lymphoma and inflammatory pseudotumor. The research questions include: Can high-frequency ultrasound provide sufficient information to differentiate these two lesions? What is its diagnostic accuracy? What are the advantages and limitations of high-frequency ultrasound compared to existing imaging techniques? By addressing these questions, we hope to offer clinicians a more effective and safer diagnostic tool to improve the diagnosis and treatment of patients with orbital lymphoma and inflammatory pseudotumor.

3. Incidental Diagnosis of Four Lid Orbital Lymphoma During a Blepharoplasty

3. Incidental Diagnosis of Four Lid Orbital Lymphoma During a Blepharoplasty

Response-Adapted Ultralow-Dose Radiation Therapy for Orbital Indolent B-Cell Lymphoma

Radiation therapy to doses of 24 to 36 Gy is currently used to treat indolent B-cell lymphoma of the ocular adnexa; however, ocular adverse effects are common. To determine if a response-adapted radiation therapy strategy will result in excellent disease outcomes while reducing orbital morbidity. This single-institution, phase 2 prospective nonrandomized controlled trial of a response-adapted strategy involved 50 evaluable patients with stage I to IV indolent B-cell lymphoma of the ocular adnexa enrolled between July 2015 and January 2021. This treatment approach was also retrospectively evaluated with a separate 55-patient cohort treated between March 2013 and October 2021. All data were analyzed between November 2021 and December 2023. Patients were treated with ultralow-dose radiation therapy to 4 Gy in 2 fractions and assessed for response at 3-month intervals. Patients with persistent orbital lymphoma were offered an additional 20 Gy in 10 fractions to complete the response-adapted treatment. The primary end point was 2-year local orbital control within the irradiated field after response-adapted therapy. Secondary end points included overall survival and complete response rate. The 50 prospective patients were a median (range) of 63 (29-88) years old, and 31 (62%) were female. Among the 50 patients, 32 (64%) had mucosa-associated lymphoid tissue lymphoma, 12 (24%) had follicular lymphoma, and 6 (12%) had unclassifiable low-grade B-cell lymphoma. Thirty-one patients (62%) had stage I disease, and 36 (72%) were newly diagnosed. At a median follow-up of 37.4 (95% CI, 33.7-52.5) months, the 2-year local control rate was 89.4% (95% CI, 81.0%-98.7%), and the 2-year overall survival rate was 98.0% (95% CI, 94.1%-100%); 45 patients (90.0%; 95% CI, 78.2%-96.7%) experienced a complete response to response-adapted radiation, including 44 patients with a complete response to ultralow-dose radiation and 1 patient with a complete response after an additional 20 Gy. No local recurrences were observed among patients with a complete response to response-adapted therapy. No grade 3 or higher toxic effects were observed. In a planned subset analysis of 22 patients with newly diagnosed, untreated stage I mucosa-associated lymphoid tissue lymphoma, the 2-year local control rate was 90.7% (95% CI, 79.2%-100%), and the 2-year freedom from distant relapse rate was 95.2% (95% CI, 86.6%-100%). In this nonrandomized controlled trial, response-adapted ultralow-dose therapy for indolent orbital B-cell lymphoma resulted in reduced radiation exposure, negligible toxic effects, and excellent disease outcomes. ClinicalTrials.gov Identifier: NCT02494700.

Long-Term Survival and Factors Associated with Increased Mortality in Patients with Ocular Adnexal Lymphomas.

Orbital and ocular adnexal lymphoma (OAL) affects the orbit and the surrounding structures and can arise as several subtypes with variable prognoses. We performed an observational study on the relationship between OAL subtype, diagnostic features, and prognosis to offer valuable insights into imaging techniques, such as Positron Emission Tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with Computed Tomography (18F-FDG PET-CT), in predicting outcomes. With this aim, we retrospectively reviewed 99 patients with OALs, recording demographics, cancer subtype, location and treatment, 18FDG avidity, and bone marrow positivity. We divided patients into Group 1 (those presenting with extranodal marginal zone lymphoma-EMZL) and Group 2, including all other subtypes. The primary outcome was long-term cancer-specific survival (CSS) based on key predictors, performed through Kaplan-Meier curves and the log-rank test, with a p < 0.05 significance threshold. The mean patient age was 67 years (57-75.5). The most frequent histopathologic subtypes were EMZL lymphoma in 69 patients (69.7%), small lymphocytic lymphoma (11.1%) and diffuse-large B-cell lymphoma (10.1%). Patients of Group 1 showed a better prognosis (CSS = 80%) compared to those of Group 2 (CSS = 60%) (p = 0.01). In patients with high-grade lymphoma, the occurrence of 18FDG avidity (p = 0.003) and bone marrow positivity (p = 0.005) were related to a worse prognosis. In our group, EMZL was the most prominent subtype of OALs and exhibited the best prognosis, low 18FDG avidity, and bone marrow negativity. By observing specific patterns in radiological findings, it is possible to increase our understanding of disease progression, treatment response, and the overall prognosis in OAL patients.

Survival outcomes in primary orbital diffuse large B-cell lymphoma.

e19075 Background: Orbital diffuse large B-cell lymphoma is a rare entity accounts for less than 1% of all non-Hodgkin lymphoma cases. Large-scale studies describing and evaluating the effect of different type of treatments on survival outcome are lacking. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with primary orbital DLBCL between 2004 and 2020. All patients aged ≥ 18 years diagnosed with primary orbital DLBLC were included. We excluded patients with unknown chemotherapy and radiation therapy status or lost to follow-up (unknown vital status of last contact). Kaplan-Meier and multivariate Cox regression were used in the analyses. Results: The total cohort consisted of 404 patients with primary orbital DLBCL. Out of whom 233 (58%) were females, 326 (81%) were White non-Hispanic, 29 (7%) were White Hispanic and 16 (4%) were African Americans. 113 (28%) received chemotherapy only, 76 (19%) received radiation only, 113 (28%) received chemoradiation, 79 (20%) did not receive any treatment and 23 (6%) had unknown treatment status. The median age at diagnosis was 71 years (range 28-90). The median follow-up time was 132 months (95%CI 117-147), the median overall survival (mOS) for the whole cohort was 110 months (95%CI 82-138). Among patients with known treatment status and vital status of last contact (N=381), patient who received chemoradiation had significantly better mOS compared to patients who received radiation only (169 vs 67 months, P=0.002), but there was no statistically significant difference in mOS between chemoradiation and chemotherapy only (169 vs 124 months, P=0.068) or between chemotherapy only and radiation only (124 vs 67 months, P=0.213). On multivariate analysis, older age and Charlson-Deyo score of 2 were associated with worse OS (HR 1.072 95%CI 1.055-1.089; P&lt;0.001, HR 2.292 95%CI 1.099-4.778; P=0.027, respectively). Compared to no treatment, only chemoradiation was associated with better OS (HR 0.509 95%CI 0.332-0.778; P=0.002), whereas chemotherapy only and radiation only did not add a survival benefit (HR 0.909 95%CI 0.598-1.381; P=656 and HR 0.766 95%CI 0.496-1.185; P=0.231). Conclusions: This large real-world analysis shows a survival benefit with combined treatment of chemoradiation in primary orbital DLBCL compared to single treatment modality.

Incidental Diagnosis of Four Lid Orbital Lymphoma during a Blepharoplasty

Incidental Diagnosis of Four Lid Orbital Lymphoma during a Blepharoplasty

Artificial intelligence-based differential diagnosis of orbital MALT lymphoma and IgG4 related ophthalmic disease using hematoxylin-eosin images.

To investigate the possibility of distinguishing between IgG4-related ophthalmic disease (IgG4-ROD) and orbital MALT lymphoma using artificial intelligence (AI) and hematoxylin-eosin (HE) images. After identifying a total of 127 patients from whom we were able to procure tissue blocks with IgG4-ROD and orbital MALT lymphoma, we performed histological and molecular genetic analyses, such as gene rearrangement. Subsequently, pathological HE images were collected from these patients followed by the cutting out of 10 different image patches from the HE image of each patient. A total of 970 image patches from the 97 patients were used to construct nine different models of deep learning, and the 300 image patches from the remaining 30 patients were used to evaluate the diagnostic performance of the models. Area under the curve (AUC) and accuracy (ACC) were used for the performance evaluation of the deep learning models. In addition, four ophthalmologists performed the binary classification between IgG4-ROD and orbital MALT lymphoma. EVA, which is a vision-centric foundation model to explore the limits of visual representation, was the best deep learning model among the nine models. The results of EVA were ACC = 73.3% and AUC = 0.807. The ACC of the four ophthalmologists ranged from 40 to 60%. It was possible to construct an AI software based on deep learning that was able to distinguish between IgG4-ROD and orbital MALT. This AI model may be useful as an initial screening tool to direct further ancillary investigations.

Declining incidence and improving survival of ocular and orbital lymphomas in the US between 1995 and 2018

This epidemiological study examined ocular and orbital lymphomas in the United States from 1995 to 2018, using data from the North American Association of Central Cancer Registries database of 87,543 patients with ocular and adnexal malignancies. We identified 17,878 patients (20.4%) with ocular and orbital lymphomas, with an age-standardized incidence rate (ASIR) of 2.6 persons per million (ppm). The incidence was the highest in the orbit (ASIR = 1.24), followed by the conjunctiva (ASIR = 0.57). Non-Hodgkin B-cell lymphoma was the most prevalent subtype (85.4%), particularly marginal-zone lymphoma (45.7%). Racial disparities were noted, with Asia–Pacific Islanders showing the highest incidence (orbit, 1.3 ppm). The incidence increased significantly from 1995 to 2003 (Average Percent Change, APC = 2.1%) but declined thereafter until 2018 (APC = − 0.7%). 5-year relative survival (RS) rates varied, with the highest rate for conjunctival lymphoma (100%) and the lowest for intraocular lymphoma (70.6%). Survival rates have generally improved, with an annual increase in the 5-year RS of 0.45%. This study highlights the changing epidemiological landscape, pointing to initial increases and subsequent decreases in incidence until 2003, with survival improvements likely due to advancements in treatment. These findings underscore the need for further research to investigate the root causes of these shifts and the declining incidence of ocular lymphoma.

Histopathological features of nine cases of primary orbital and ocular adnexal lymphoma

Histopathological features of nine cases of primary orbital and ocular adnexal lymphoma

Orbital pseudolymphoma: a benign condition mimicking malignancy

Orbital lymphomas are not a rare condition that causes systemic and ocular morbidity, in which vision loss often occurs due to compressive optic neuropathy, and whose treatment is complex, involving chemotherapy and radiotherapy. We report a 54-year-old male with protrusion of the right eye associated with mild diminution of vision for one year, limitation of extraocular movements, and a relative afferent pupillary defect with optic disc edema. Imaging revealed a well-defined soft tissue lesion filling the retro-orbital intraconal space, suggestive of orbital lymphoma. Incisional biopsy and fine needle aspiration cytology revealed the lesion to be a reactive lymphoid hyperplasia. Following the administration of oral steroids, the patient showed significant improvement. To our knowledge, a benign lesion with an aggressive presentation is rare, and histopathology plays an important role in diagnosis and management.

Stromal area differences with epithelial-mesenchymal transition gene changes in conjunctival and orbital mucosa-associated lymphoid tissue lymphoma.

To examine the molecular biological differences between conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma and orbital MALT lymphoma in ocular adnexa lymphoma. Observational case series. A total of 129 consecutive, randomized cases of ocular adnexa MALT lymphoma diagnosed histopathologically between 2008 and 2020.Total RNA was extracted from formalin-fixed paraffin-embedded tissue from ocular adnexa MALT lymphoma, and RNA-sequencing was performed. Orbital MALT lymphoma gene expression was compared with that of conjunctival MALT lymphoma. Gene set (GS) analysis detecting for gene set cluster was performed in RNA-sequence. Related proteins were further examined by immunohistochemical staining. In addition, artificial segmentation image used to count stromal area in HE images. GS analysis showed differences in expression in 29 GS types in primary orbital MALT lymphoma (N=5,5, FDR q-value <0.25). The GS with the greatest difference in expression was the GS of epithelial-mesenchymal transition (EMT). Based on this GS change, immunohistochemical staining was added using E-cadherin as an epithelial marker and vimentin as a mesenchymal marker for EMT. There was significant staining of vimentin in orbital lymphoma (P<0.01, N=129) and of E-cadherin in conjunctival lesions (P=0.023, N=129). Vimentin staining correlated with Ann Arbor staging (1 versus >1) independent of age and sex on multivariate analysis (P=0.004). Stroma area in tumor were significant difference(P<0.01). GS changes including EMT and stromal area in tumor were used to demonstrate the molecular biological differences between conjunctival MALT lymphoma and orbital MALT lymphoma in ocular adnexa lymphomas.

Radiologic Features of Well-circumscribed Orbital Tumors With Histopathologic Correlation: A Multi-center Study.

To delineate specific imaging characteristics of solitary fibrous tumors, schwannomas, cavernous venous malformations, and well-circumscribed orbital lymphoma. Patients undergoing excisional biopsy of solitary fibrous tumor, schwannomas, cavernous venous malformations, or well-circumscribed orbital lymphoma with preoperative MRIs available for review were identified at 3 academic centers in the United States and Australia. An exploratory statistical analysis was performed to identify important radiologic features, which were subsequently included in a random forest model. Histopathologic correlates were evaluated in representative cases. A total of 91 cases were included with a mean age of 52.9 ± 17.2 years. Nearly all solitary fibrous tumors were located in the anterior or mid orbit (87.5%) and they more commonly demonstrated intralesional heterogeneity on T2-weighted imaging (45.5%) ( p < 0.01). Compared with the other tumors, schwannomas tended to be intraconal (66.7%) and were often in the mid or posterior orbit (83.4%) ( p < 0.01). Cavernous venous malformations characteristically demonstrated progressive contrast enhancement (93.9%; p < 0.01). Most lesions in all 4 groups were hypointense on T1-weighted imaging (80%-100%; p = 0.14) and only well-circumscribed orbital lymphoma tended to also be hypointense on T2 (81.8%) ( p < 0.01). Finally, cases of lymphoma had significantly lower apparent diffusion coefficient ratios (0.9 ± 0.2) ( p < 0.001), while the other 3 groups were not significantly different from one another (cavernous venous malformations: 1.8 ± 0.4; schwannomas: 1.8 ± 0.5; and solitary fibrous tumor: 1.6 ± 0.6) ( p = 0.739). Key features that aid in the differentiation of these 4 tumors from one another include T2 intensity and homogeneity, early contrast-enhancement pattern, and ADC ratio.

Epidemiology and Clinical Features Analysis of Orbital and Adnexal Lymphoma in the Western Area of Gyeongsangnam-do

Purpose: We compared the epidemiology and clinical features of patients with orbital and adnexal lymphoma in western Gyeongsangnam-do with those reported previously, domestically and internationally.Methods: Of the 25 patients diagnosed with lymphoproliferative disorder, a retrospective analysis was conducted on 21 patients with orbital and adnexal lymphoma between January 2010 and December 2021.Results: In total, 21 patients were diagnosed with orbital and adnexal lymphoma, with an average annual incidence rate of 0.18 per 100,000 people, exceeding the national average in Korea. The median age of the patients was 57 years and the ratio of 1.1 to 1. The most common presenting symptoms included proptosis, conjunctival mass, conjunctival injection, eyelid swelling and epiphora. Primary and metastatic lesions accounted for 85.7% and 14.3% of cases, respectively. Histologically, the most common subtype was extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (90.4%). Furthermore, diffuse large B-cell lymphoma and NK/T-cell lymphoma of T-cell origin each accounted for 4.8% of cases.Conclusions: The reported incidence rate in the present study exceeded the national average in Korea. However, no significant differences were observed in clinical symptoms, primary and metastatic lesions, histological classification, or post-treatment effects compared to findings from domestic and international studies.