ArticlePDF Available

Orbital lymphoma: Diagnostic approach and treatment outcome

Authors:
Andre M. Eckardt at Hannover Medical School
Andre M. Eckardt
Juliana Lemound at Ruhr University Bochum
Juliana Lemound
Majeed Rana at Heinrich Heine University Düsseldorf
Majeed Rana
Nils-Claudius Gellrich
Nils-Claudius Gellrich
Nils-Claudius Gellrich
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Download full-text PDFDownload full-text PDF
Read full-text
Download citation

Abstract and Figures

Background Lymphomas of the orbit and orbital adnexae are rare tumors, comprising only 1% of all non-Hodgkin’s lymphoma. The majority of non-Hodgkin’s lymphomas of the orbit are extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue type. Because of nonspecific clinical signs and symptoms, some diagnostic delay may occur. The purpose of the study was to evaluate the diagnostic approach in orbital lymphomas and to analyze their treatment outcome. Methods In the period from 2005 to 2012, from a group of 135 patients with tumors of the orbit, we identified 11 patients diagnosed with orbital lymphoma. This patient cohort was reviewed retrospectively. Results The patient group consisted of 11 patients (seven females, male males) with a median age of 57.7 years (range 42 to 88 years). Orbital swelling, pain and motility impairment were the leading clinical symptoms. Diagnosis was confirmed by surgical biopsy. Depending on the anatomic location of the tumor, a surgical biopsy was taken using a blepharoplasty incision, a lateral orbitotomy or a navigation-guided biopsy. The predominant histology was extranodal non-Hodgkin’s lymphoma of mucosa-associated lymphoid tissue type (82%). All patients underwent complete clinical staging. These were clinical stage IEA in seven patients, and stages IIEA (n = 2) and IIIEA (n = 2) in four patients . Patients in stage IEA were treated with radiation therapy alone, with radiation doses between 25 and 40 Gy, and patients with stage IIEA received systemic chemotherapy with bendamustin/rituximab. Those two patients diagnosed with diffuse large B-cell lymphoma and mantle cell lymphoma received systemic chemotherapy according to the R-CHOP protocol. Conclusions Owing to unspecific clinical symptoms, some diagnostic delay may occur in orbital lymphoma. If unspecific orbital symptoms are present, adequate imaging studies followed by early surgical biopsy will contribute to early diagnosis. Once diagnosis is established and staging is complete, radiation therapy is the recommended treatment for stage IEA patients. Systemic chemotherapy is indicated in selected stage IIEA patients and in patients with stage IIIEA disease.
Figures - uploaded by Andre M. Eckardt
Author content
All figure content in this area was uploaded by Andre M. Eckardt
Content may be subject to copyright.
00b49529b53f4e46060000
00.pdf
Content uploaded by Andre M. Eckardt
Author content
All content in this area was uploaded by Andre M. Eckardt
Content may be subject to copyright.
Orbital lymphoma: Diagnostic approach and treatment outco
me.pdf
Available via license: CC BY 2.0
Content may be subject to copyright.
A preview of the PDF is not available
... Although it was seen as a rare case in the 1st years of its definition, its frequency has increased with the development of diagnostic technologies over time. Orbital lymphoma accounts for approximately 10% of all orbital tumors and approximately 2% of all nodal and extra-nodal lymphomas (1)(2)(3)(4)(5). Orbital lymphoma treatment varies depending on the type of underlying disease. ...
... Orbital lymphoma treatment varies depending on the type of underlying disease. Accordingly, treatment options include the "watchful wait strategy," surgery, radiotherapy (RT), chemotherapy, immunotherapy, and chemoimmunotherapy (1,(6)(7)(8). ...
View
... Therefore, orbital surgery is generally not recommended, as it may lead to significant visual complications and is not considered a therapeutic approach. However, in some situations, including but not limited to these malignant tumors, partial tumor resection may be necessary to alleviate patient discomfort and help restore visual function [6,7]. ...
View
... Ocular adnexal lymphoma (OAL) is a type of systemic lymphoma that affects the orbit, lacrimal glands, eyelids, and conjunctiva. Although it accounts for 1% of non-Hodgkin's lymphomas, OAL is the most common malignant orbital tumor in adults [48,49]. OAL is a low-grade that has seen important advances in immunotherapy [49]. ...
Immunotherapy in Ophthalmic Oncology: Current Trends and Future Directions
Article
Full-text available
  • Jan 2025
Citation: Masalkhi, M.; Wahoud, N.; Moran, B.; Elhassadi, E. Immunotherapy in Ophthalmic Oncology: Current Trends and Future Directions. J. Clin. Transl. Ophthalmol. 2025, 3, 1. https://doi. Abstract: Background: Immunotherapy represents a revolutionary approach in cancer treatment, where it leverages the body's immune system to target and destroy malignant cells. In ophthalmic oncology, immunotherapeutic agents offer potential for managing traditionally challenging ocular malignancies, such as melanoma and retinoblastoma. In this literature review, we aim to provide a comprehensive and up-to-date review of all current research and trends in this field. Methods: This literature reviews data from recent clinical trials, peer-reviewed articles, and meta-analyses focused on immunotherapeutic interventions for eye-related cancers. Emphasis is placed on the types of immunothera-pies being tested, including checkpoint inhibitors, vaccine therapies, and adoptive cell transfer therapies. Results: Recent advancements indicate a growing and significant improvement in survival rates and tumor reduction with minimal adverse effects. Clinical trials focusing on melanoma show significant promise with targeted therapies, while early-stage investigations into retinoblastoma and conjunctival melanoma explore innovative approaches to harness the immune system without harming visual function. Conclusions: Immunotherapy in ophthalmic oncology is evolving rapidly and has demonstrated a remarkable potential as a primary treatment strategy. Although results from various clinical trials are promising, further research is needed to refine these therapies, minimize side effects, and improve overall patient outcomes. The future directions involve more comprehensive clinical trials that integrate immunotherapy with existing treatment modalities to establish more robust treatment protocols.
View
... Compared to other locations, the symptoms suggest expansive rather than invasive growth due to the absence of symptoms like nerve invasion, trismus, and xerostomia, which can be attributed to the anatomical space in the submandibular region allowing tumour expansion without early compression of structures [31]. Unlike more common conditions, submandibular gland lymphomas can be mistaken for benign conditions or other malignancies, because of their nonspecific clinical presentations and imaging [32]. Additionally, the histopathological diagnosis can be challenging, as salivary glands are not a common site for lymphomas, and the tissue architecture can be distorted by the tumour [33]. ...
Lymphomas of the submandibular gland: a nationwide cohort study
Article
Full-text available
  • Oct 2024
  • Eur Arch Oto Rhino Laryngol
Objective This study explores the epidemiology, incidence, and survival outcomes associated with lymphomas of the submandibular gland (SMG) and examines the influence of autoimmune diseases on these parameters. Methods This retrospective nationwide cohort study analysed data from patients diagnosed with SMG lymphomas in Denmark between 2000 and 2020. Information was extracted from medical records, the National Pathology Register, and the Danish Lymphoma Database. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models, focusing on lymphoma subtypes and autoimmune diseases. Results The cohort consisted of 101 patients with a lymphoma diagnosis and involvement of the SMG. Large B-cell lymphoma (LBCL) was diagnosed in 33 cases (32.7%), follicular lymphoma (FL) in 29 cases (28.7%), extranodal marginal zone lymphoma (EMZL) in 27 cases (26.7%), and 12 cases (11.9%) with other subtypes. EMZL had a significantly longer overall survival (OS) compared to other subtypes, with a median OS of 12.4 years (95% CI 11.2–12.4) vs. 8.4 years (95% CI 6.0-12.2). EMZL and FL showed favourable 5-year OS rates of 95% and 89%, respectively. LBCL had a 5-year OS rate of 65%. Age over 60 significantly negatively impacted OS. Traditional poor prognostic indicators did not significantly affect OS. A notable association between EMZL and autoimmune diseases was observed, particularly with Sjögren’s syndrome, indicated by an increased relative risk of 2.67 (CI 95% 0.45–16.01). Conclusions Lymphomas of the SMG are rare and have ambiguous clinical presentations. This study provides novel epidemiological, clinical, and prognostic information.
View
Clinical characteristics and outcomes of primary orbital lymphoma
Article
  • Apr 2025
Purpose To describe the clinical characteristics, histopathologic subtype distribution, treatment, and outcomes of patients with primary orbital lymphoma. Major Findings There were 126 biopsy-confirmed cases of primary orbital lymphoma, with 81 (64.3%) female and 110 (87.3%) white. The average age at diagnosis was 62.7 ± 13.9 years. There were 26 (20.6%) cases with bilateral involvement. The most frequent lymphoma subtype was MALT lymphoma (N = 76, 60.3%), followed by diffuse large B-cell lymphoma (N = 18, 14.3%) and follicular lymphoma (N = 12, 9.5%). Prognosis was generally favorable, as local recurrence occurred in only 14 (11.1%) patients and final best corrected visual acuity (BCVA) loss of >1 line was seen in 30 (28.0%) patients. Bilateral lymphoma and advanced stage (Ann Arbor Stage III or IV) at presentation were associated with increased risk of local recurrence ( p = 0.0025, p = 0.049). Improved disease-specific survival was associated with diagnosis at Stage I or II ( p = 0.013), MALT subtype ( p = 0.034), or lack of chemotherapy requirement as primary treatment ( p = 0.0073). Conclusions In this single center academic cohort, MALT lymphoma subtype was most common. Overall orbital recurrence frequency was low, and bilateral lymphoma and advanced stage were associated with increased risk of local recurrence. MALT lymphoma subtype was associated with improved disease-specific survival. Long-term follow-up showed that most patients retained good visual acuity in the affected eye(s).
View
Principles and Complications of Chemotherapy
Chapter
  • Mar 2025
One of the most essential methods of treating cancer is systemic chemotherapy. Several primary and secondary ophthalmologic cancers exist that benefit from treatment with chemotherapy. Most chemotherapy drugs have non-selective mechanisms of action against DNA, RNA, proteins, or metabolic pathways in tumor cells, but because of the non-selective properties of chemotherapy, normal cells are also affected. Chemotherapy is often given in combination with other agents to enhance cytotoxic effects, combat multi-drug resistance, and reduce the risk of relapse. Systemic chemotherapy is given intravenously in repetitive cycles at maximum tolerated doses in order to allow for a constant fraction of tumor cell kill and to allow for recovery of affected normal cells. Antineoplastic drugs have the narrowest therapeutic window of any class of drugs, so the treating physician must balance the risk of toxicities against the risk of relapse in choosing chemotherapy regimens for patients with ophthalmologic cancers. This chapter will discuss the basic principles of systemic chemotherapy, review some of the commonly used treatment regimens for ophthalmologic cancers, and review common toxicities of chemotherapy.
View
Burkitt's Lymphoma Presenting as Acute Dacryocystitis in a 14-Year-Old Male with Ataxia Telangiectasia: A Case Report and Review of the Literature
Article
  • Feb 2025
Purpose This report describes an atypical presentation of a case of Burkitt lymphoma in a pediatric patient with ataxia telangiectasia. Main observations A 14-year-old boy with a history of AT was referred to our hospital with lower eyelid swelling and medial canthus abscess. On physical examination, movement of the left eye was limited in downgaze and adduction. Two mm proptosis was observed on the left side. Snellen's Visual acuity in the left eye was 8/20. The rest of the examination was normal. Magnetic resonance imaging (MRI) was performed and showed an infiltrative mass in the inferior of the left orbit, left ethmoidal sinus, and maxillary sinus. The patient subsequently underwent an incisional biopsy. The biopsy specimen was sent for histopathologic evaluation. Histopathology was significant for atypical monotonous cell infiltrations in the fibroconnective tissue and the presence of pleomorphic, irregularly shaped nuclei with multiple mitoses. Immunohistochemistry (IHC) findings were consistent with Burkitt's lymphoma, and the patient was referred to the oncology department for chemotherapy and appropriate treatment. Conclusion and Significance Orbital and lacrimal duct involvement is a rare presentation of Burkitt lymphoma especially in the pediatric population. In the new-onset nasolacrimal duct obstruction (NLDO) in a child or teenager, the differential diagnosis should include malignancies, especially leukemia/lymphoma infiltrations.
View
Radiology and Oculoplasty
Chapter
Full-text available
  • Jan 2024
Radiological imaging is an essential diagnostic tool in the oculoplastic specialty, particularly in orbital and lacrimal lesions as the pathology cannot be visualized from outside. Moreover, it can be used in the management plan and follow up of the patients.
View
Looking Beyond and Behind a Retinal Detachment
Article
  • Nov 2024
A 63-year-old woman with a history of type 1 diabetes presents with gradually progressive vision loss in the right eye for the past year. What would you do next?
View
Disorders with Ophthalmic and Thoracic Involvement
Article
  • Jul 2024
  • RADIOGRAPHICS
A variety of systemic conditions involve the thorax and the eyes. While subtle or nonspecific eye symptoms can be the initial clinical manifestation of some disorders, there can be additional manifestations in the thorax that lead to a specific diagnosis and affect patient outcomes. For instance, the initial clinical manifestation of Sjögren syndrome is dry eye or xerophthalmia; however, the presence of Sjögren lung disease represents a fourfold increase in mortality. Likewise, patients with acute sarcoidosis can initially present with pain and redness of the eye from uveitis in addition to fever and parotitis. Nearly 90% of patients with sarcoidosis have thoracic involvement, and the ophthalmologic symptoms can precede the thoracic symptoms by several years in some cases. Furthermore, a diagnosis made in one system can result in the screening of other organs as well as prompt genetic evaluation and examination of family members, such as in the setting of Marfan syndrome or Ehlers-Danlos syndrome. Multimodality imaging, particularly CT and MRI, plays a vital role in identification and characterization of these conditions. While it is helpful for ophthalmologists to be knowledgeable about these conditions and their associations so that they can order the pertinent radiologic studies, it is also important for radiologists to use the clues from ophthalmologic examination in addition to imaging findings to suggest a specific diagnosis. Systemic conditions with thoracic and ophthalmologic manifestations can be categorized as infectious, inflammatory, autoimmune, neoplastic, or hereditary in origin. The authors describe a spectrum of these conditions based on their underlying cause. ©RSNA, 2024.
View
Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma
Article
As illustrated in the two cases described in this paper close morphologic and immunohistochemical similarities exist between Mediterranean lymphoma (MTL) and primary gastrointestinal lymphoma of follicle center cell (FCC) origin as it occurs in Western countries. Similarities between the two conditions include a dense noninvasive monotypic lamina propria plasma cell infiltrate, present in all cases of MTL and in some cases of Western gastrointestinal FCC lymphoma, and an invasive infiltrate of FCCs morphologically distinct from the plasma cells. A distinctive lesion produced by individual gland invasion characterizes both types of lymphoma. A clonal relationship between the lamina propria plasma cells and the invasive FCCs, long suspected but never proved in MTL, can be demonstrated in Western cases. Many of the histologic and clinical features common to these lymphomas can be explained in the context of the normal maturation sequences of gut associated lymphoid tissue. It is suggested that MTL and Western cases of primary FCC gastrointestinal lymphoma share a common histogenesis from mucosa associated lymphoid tissue.
View
View
Histological features of ocular adnexal lymphoma (REAL classification) and their association with patient morbidity and survival
Article
  • Aug 2000
BACKGROUND—The histological characteristics of ocular adnexal lymphomas have previously provided only a limited guide to clinical outcome for affected patients. This clinicopathological relation was re-examined using the Revised European American Lymphoma (REAL) system to classify the tumours in a large cohort of patients. METHODS—The biopsies and clinical follow up data for 192 patients with ocular adnexal lymphoma were reviewed, the biopsies being regraded in accordance with the REAL classification. For each of five histological groups, logistic regression analysis was used to determine the odds ratios (OR) for the presence of systemic disease at the time of orbital diagnosis and Cox regression analysis was used to assess the hazard ratios (HR) for disseminated disease and lymphoma related death. For 108 patients in whom extraorbital spread occurred, the histological category of lymphoma was compared with the sites of dissemination. RESULTS—At presentation, the frequency of previous or concurrent extraorbital disease increased from marginal zone lymphoma (OR 1.0), diffuse lymphoplasmacytic/lymphoplasmacytoid lymphoma (OR 2.3), follicle centre lymphoma (OR 3.8), diffuse large B cell lymphoma (OR 4.0) to other histological lymphoma variants (OR 26.8). For all histological types, the estimated risk of extraorbital disease and lymphoma related death continued for many years and the proportion of patients with at least one extraorbital recurrence after 5 years was 47% for MZL, 48% for LPL, 64% for FCL, 81% for DLCL, and 95% for other lymphoma variants. The corresponding estimated rates for 5 year lymphoma related mortality were 12%, 19%, 22%, 48%, and 53% respectively. CONCLUSIONS—Patients with ocular adnexal lymphoma can be classified by REAL into five distinct groups, which show a progressive increase in the risks of extraorbital disease at diagnosis, of disease dissemination with time, and of tumour related death.
View
View
View
View
Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma
Article
As illustrated in the two cases described in this paper close morphologic and immunohistochemical similarities exist between Mediterranean lymphoma (MTL) and primary gastrointestinal lymphoma of follicle center cell (FCC) origin as it occurs in Western countries. Similarities between the two conditions include a dense noninvasive monotypic lamina propria plasma cell infiltrate, present in all cases of MTL and in some cases of Western gastrointestinal FCC lymphoma, and an invasive infiltrate of FCCs morphologically distinct from the plasma cells. A distinctive lesion produced by individual gland invasion characterizes both types of lymphoma. A clonal relationship between the lamina propria plasma cells and the invasive FCCs, long suspected but never proved in MTL, can be demonstrated in Western cases. Many of the histologic and clinical features common to these lymphomas can be explained in the context of the normal maturation sequences of gut associated lymphoid tissue. It is suggested that MTL and Western cases of primary FCC gastrointestinal lymphoma share a common histogenesis from mucosa associated lymphoid tissue.
View
Clinical features of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue
Article
We newly diagnosed 131 patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue lymphoma between 1998 and 2010. We retrospectively studied 124 patients for whom complete clinical data were available at presentation and who had minimally undergone tumour staging by physical examination, computed tomography (CT), bone marrow aspiration, and biopsy. A slight female predominance (men, 58; women, 66) was observed in the study population; the median age was 67 years. The primary locations at presentation were the stomach (38%), orbita (20%), lung (12%), intestinal tract (8%), thyroid gland (6%), others (14%), and unknown (2%). Seventy per cent of patients had localized disease. Of the 124 patients, 14 (11%) had lymph node involvement, and 5 (4%) had bone marrow involvement. Five (4%) patients had both lung and gastric involvement. The 5-year overall survival rate for the 124 patients was 96.1%. The overall vital prognosis was excellent. Moreover, gastro-intestinal fiberscopic examination is essential, especially in cases with lung involvement at presentation. Copyright © 2012 John Wiley & Sons, Ltd.
View
Localized Orbital Mucosa-Associated Lymphoma Tissue Lymphoma Managed With Primary Radiation Therapy: Efficacy and Toxicity
Article
  • Jun 2011
To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients. The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade ≥2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). POML responds favorably to moderate doses of RT but results in significant late morbidity. The majority of late effects were successfully managed. Lens shielding reduced the risk of cataracts and other late sequelae.
View
Evaluation of intraorbital injection of rituximab for treatment of primary ocular adnexal lymphoma: A pilot study
Article
An interventional pilot study to assess the tolerability and activity of the intralesional injection of rituximab, a chimeric mAb that targets the CD20 antigen, in patients with orbital B-cell lymphoma. Five patients received four intralesional injections (one injection a week) of rituximab together with ropivicaine 2%. Side-effects and tumor response were assessed after each injection and during the follow-up (20 months). Two patients obtained complete remission of the intraorbital lesion. Two patients showed incomplete response after induction therapy and received planned escalating rituximab doses, obtaining regression of subjective symptoms. One patient did not achieve tumor regression after the first injection and underwent systemic treatment. This small exploratory study suggests that intralesional rituximab is a well-tolerated treatment for patients with primary ocular adnexal lymphoma. These preliminary findings suggest that intralesional rituximab is a well-tolerated strategy in anterior intraorbital lesion localization of lymphoma.
View