Comprehensive analysis of orbital lymphoma in a Turkish cohort: clinical characteristics, histological subtypes, treatment modalities, prognostic factors, and implications for management.

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.

Clinical characteristics and treatment outcomes of secondary ocular adnexal lymphoma.

BACKGROUND: To describe the clinical characteristics and treatment outcomes of secondary ocular adnexal lymphoma (OAL), and emphasise the impact of timely biopsy and systemic evaluation on the diagnosis and treatment. METHODS: The data of patients with secondary OAL in our hospital from January 2010 to June 2021 were retrospectively reviewed. RESULTS: A total of 54 patients (30 men and 24 women) were included in the study. The mean age at presentation was 60 years (median 62 years; range 37-83 years). The main symptoms included ocular mass (74%), periorbital swelling (43%), and proptosis (39%). The main histopathological types were mucosa-associated lymphoid tissue lymphoma (30%), diffuse large B-cell lymphoma (28%), and natural killer/T-cell lymphoma (18%). In particular, three patients exhibited different pathological types of ocular lymphoma compared to previously diagnosed systemic lymphoma. The most common site of ocular and systemic involvement was the orbit (85%) and lymph nodes (56%), respectively, and 25 (46%) patients had occult extraocular lesions. Additionally, the 5-year overall survival rate of the entire cohort was 56%, and significant differences were observed between the three main pathological types and stages of the disease (all p < 0.001). CONCLUSIONS: Secondary OAL is a rare disease with a poor prognosis. That the disease is associated with a more aggressive pathological type is well established, indolent lymphoma is not uncommon. Furthermore, OAL and previously diagnosed systemic lymphoma may be pathologically distinct in some patients. Therefore, we recommend a prompt excision biopsy and a thorough systemic evaluation of patients with suspected OAL.

The treatment results in patients with lmphoma disease in the orbit.

INTRODUCTION: Lymphoma is a malignant disease that can affect several structures of the orbit and eye adnexa. In the area of orbit the non-Hodgkins lymphoma (NHL) is typical, which may be indolent or aggressive. Indolent subtypes include MALT (mucosa-associated lymphoid tissue), follicular lymphoma (FL), lymphoplasmocytic lymphoma (LPL). Conversely, subtypes such as diffuse large cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and Burkitt lymphoma (BL) are aggressive. The disease can be presented as primary or secondary malignancy of the orbit. MATERIAL AND METHODS: A group of 35 patients from the Department of Ophthalmology, Faculty of Medicine, Comenius University in Bratislava in the period from January 1 2009 to December 31 2016 with diagnosed non-Hodgkins lymphoma located in the area of the orbit. For all patients, the generally valid diagnostic criteria for the NHL in the eye area were met. We processed the first signs of disease, the proportion of women and men with NHL, the percentage of NHL types in the orbit area. Statistically, we evaluated the age at which NHL occurred in patients and evaluated the incidence of the disease over the reference period. We have statistically processed the forms of the applied therapy, their adverse effects, the recurrence of the disease, the presence of other malignancies in the lymphoma patient. RESULTS: Of the total number of NHL patients in orbit region 13 (37%) were male and 22 (63%) female. The overall mean age at which lymphoma was diagnosed was 60 years. Median for the total age of patients was 61. In women, a slightly higher average age and median was found. On the other hand, lower values of both parameters were present in men. The modus of both sexes was the same, 70 years. We have seen various first symptoms in our group. We found that the most common symptom is red eye, and the rarest is the deterioration of the central visual acuity. The longest lasting symptom was swelling of eyelids (on average, up to 10 years) and the shortest described eye itching. Overall, the average duration of symptoms was 28 months, with a median of 13 months. In our group of patients were 3 % of LPL, 6 % of Burkitts lymphoma, 6 % of FL, 8 % of MCL, 17 % of DLBCL, and 60 % of malignant lymphoma. MALT lymphoma occurred in 62 % in orbital and 38 % in conjunctival localization. In 2 patients with MALT lymphoma of the conjunctiva to start with systemic therapy wasn't neccessary. In 21 patients with MALT lymphoma excisional biopsy or orbitotomy was the first step to diagnose lymphoma disease in 3 cases; in 18 patients the infiltration of the orbit or conjunctiva occured 1 to 3 years after primary diagnose of systemic lymphoma disease. In general, NHL localization was 29 % in conjunctiva and 71 % in the orbital area. In 9 % of the orbital lymphoma, we observed lymphoma ingrowth to the conjunctiva. Systemic therapy was initiated in patients in II. stage and higher stage of the disease according to the Ann Arbor system. Totally 63 % of the group were treated by systemic therapy. Recurrence occurred in 5 patients, representing 14 % of the observed, but only in one patient with MALT lymphoma. Preoperative and postoperative (excisional biopsy, orbitotomy) central visual acuity (CVA) stayed unchanged, postoperative swelling did not affect CVA, and CVA didn't change even during long-term follow-up. CONCLUSION: Careful differential diagnosis determines the therapy of the disease, since the primary symptoms are usually nonspecific for ocular lymphoma. Significant factors for therapy include tumor grading and clinical staging by AJCC 2009 (American Joint Committee on Cancer, Chicago, Illinois). Correct evaluation of the symptoms is an important step to indicate excisional biopsy or orbitotomy: After histopathological results we can start adequate therapy in the cooperation with oncohematologist. Key words: conjunctival tumors, orbit, lymfoma, orbitotomy.

Change of Serum IgG4 in Patients with Ocular Adnexal Marginal Zone B Cell Lymphoma Associated with IgG4-Related Ophthalmic Disease After Treatment.

PURPOSE: To investigate the change of serum IgG4 concentrations correlated with clinical evolution in patients with ocular adnexal marginal zone B cell lymphoma associated with IgG4-related ophthalmic disease (IgG4-ROD). METHODS: Three consecutive patients with histopathologically confirmed ocular adnexal marginal zone B cell lymphoma associated with IgG4-ROD were evaluated. Two patients received radiotherapy and 1 patient received steroid therapy. Treatment outcome was evaluated by clinical symptoms, radiologic examination, and change of serum IgG4 level in these patients. RESULTS: All patients had elevated serum IgG4 before treatment (462, 338, and 780 mg/dL respectively.) The 2 patients who received radiotherapy achieved complete remission and the serum IgG4 decreased to 345 and 92 mg/dL, respectively. The patient who underwent systemic steroid achieved partial remission and the serum IgG4 decrease to 161 mg/dL. CONCLUSION: Our study showed elevated serum IgG4 in all patients with ocular adnexal marginal zone B cell lymphoma associated with IgG4-ROD. In addition, the elevated serum IgG4 may decrease or keep stable after treatment, accompanied by improvement in clinical symptoms and reduction of lesions.

Orbital/Periorbital Plexiform Neurofibromas in Children with Neurofibromatosis Type 1: Multidisciplinary Recommendations for Care.

TOPIC: Children and adults with neurofibromatosis type 1 (NF1), a common autosomal dominant condition, manifest a variety of ophthalmologic conditions. Plexiform neurofibromas (PNs) involving the eyelid, orbit, periorbital, and facial structures (orbital-periorbital plexiform neurofibroma [OPPN]) can result in significant visual loss in children. Equally important, OPPNs can cause significant alteration in physical appearance secondary to proptosis, ptosis, and facial disfigurement, leading to social embarrassment and decreased self-esteem. CLINICAL RELEVANCE: Although NF1 is a relatively common disease in which routine ophthalmologic examinations are required, no formal recommendations for clinical care of children with OPPNs exist. Although medical and surgical interventions have been reported, there are no agreed-on criteria for when OPPNs require therapy and which treatment produces the best outcome. METHODS: Because a multidisciplinary team of specialists (oculofacial plastics, pediatric ophthalmology, neuro-ophthalmology, medical genetics, and neuro-oncology) direct management decisions, the absence of a uniform outcome measure that represents visual or aesthetic sequelae complicates the design of evidence-based studies and feasible clinical trials. RESULTS: In September 2013, a multidisciplinary task force, composed of pediatric practitioners from tertiary care centers experienced in caring for children with OPPN, was convened to address the lack of clinical care guidelines for children with OPPN. CONCLUSIONS: This consensus statement provides recommendations for ophthalmologic monitoring, outlines treatment indications and forthcoming biologic therapy, and discusses challenges to performing clinical trials in this complicated condition.

Systemic Rituximab Immunotherapy in the Management of Primary Ocular Adnexal Lymphoma: Single Institution Experience.

PURPOSE: To evaluate the efficacy of systemic rituximab immunotherapy in the management of primary ocular adnexal lymphomas (OAL). MATERIALS AND METHODS: Clinical records of 10 consecutive patients (11 eyes) with biopsy-proven OAL managed with systemic anti-CD20 monoclonal antibody (rituximab; 375 mg/m(2) intravenously once every three weeks for 6-8 cycles) between June 2008-March 2013 were evaluated retrospectively. Orbital magnetic resonance imaging and positron emission tomography were performed to evaluate any orbital and systemic involvement, respectively. Clinical response was classified as complete or partial. RESULTS: The age of patients ranged between 27-85 (median, 55) years. Nine patients (90%) presented with unilateral and one (10%) with bilateral conjunctival involvement. Orbit was affected in 4 patients (40%), one of which had also choroidal involvement (10%). None of the patients had systemic involvement at initial presentation. All patients received an average of 7 cycles (range, 6-8) of systemic immunotherapy. After a median follow-up of 31 months (range, 10-61 months), complete response without recurrence could be achieved in 4 eyes (36%) with rituximab monotherapy. No systemic or ocular side effects were observed in any patient. Additional radiotherapy was required in 6 patients (7 eyes; 64%) with partial response or recurrence. CONCLUSIONS: Complete regression of primary OALs without recurrence was observed in about one-third of eyes after systemic rituximab monotherapy. Adjunctive radiotherapy was required in remaining two-thirds of the cases to achieve complete response. Thus, considering the balance between high rate of local control and potential ocular complications of radiotherapy, systemic rituximab can be considered as a first-line therapeutic option in the management of primary OAL.

Clinical features, treatment and outcome of mucosa-associated lymphoid tissue (MALT) lymphoma of the ocular adnexa: single center experience of 60 patients.

BACKGROUND: Orbital marginal zone B-cell lymphoma (OAML) constitutes for the most frequent diagnosis in orbital lymphoma. Relatively little data, however, have been reported in larger cohorts of patients staged in a uniform way and no therapy standard exists to date. MATERIAL AND METHODS: We have retrospectively analyzed 60 patients diagnosed and treated at our institution 1999-2012. Median age at diagnosis was 64 years (IQR 51-75) and follow-up time 43 months (IQR 16-92). All patients had undergone uniform extensive staging and histological diagnosis was made by a reference pathologist according to the WHO classification. RESULTS: The majority of patients presented with stage IE (n = 40/60, 67%), three had IIE/IIIE and the remaining 17 stage IVE. Seven patients with IVE had bilateral orbital disease whereas the others showed involvement of further organs. Treatment data were available in 58 patients. Local treatment with radiotherapy (14/58, 24%) or surgery (3/58, 5%) resulted in response in 82% of patients. A total of 26 patients (45%) received systemic treatment with a response rate of 85%. Nine patients received antibiotics as initial therapy; response rate was 38%. Watchful-waiting was the initial approach in 6/58 patients. In total 28/58 patients (48%) progressed and were given further therapy. Median time-to-progression in this cohort was 20 months (IQR 9-39). There was no difference in time-to-progression after first-line therapy between the different therapy arms (p = 0.14). Elevated beta-2-microglobulin, plasmacytic differentiation, autoimmune disorder and site of lymphoma were not associated with a higher risk for progress. CONCLUSION: Our data underscore the excellent prognosis of OAML irrespective of initial therapy, as there was no significant difference in time-to-progression and response between local or systemic therapy. In the absence of randomized trials, the least toxic individual approach should be chosen for OAML.

Orbital lymphoma: diagnostic approach and treatment outcome.

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.

[Conjunctival squamous cell carcinoma requiring orbital exenteration: case report]. / Carcinoma espinocelular de conjuntiva com evolução para exenteração: relato de caso.

A case of a squamous cell carcinoma of the conjunctiva is presented. The lesion was removed with recurrence in another conjunctival site. The patient received cycles of 5-Fluorouracil as adjuvant treatment to the surgical removal and presented unfavorable evolution, requiring orbital exenteration. Comments are made on the use of antimitotic drugs in the management of these lesions.

Carcinoma espinocelular de conjuntiva com evolução para exenteração: relato de caso / Conjunctival squamous cell carcinoma requiring orbital exenteration: case report

Portador de carcinoma espinocelular da conjuntiva teve a lesão removida, com recorrência em outra localização. O paciente recebeu ciclos de 5-Fluoruracila como tratamento adjuvante à remoção cirúrgica, apresentando evolução desfavorável que chegou à exenteração orbitária. São feitos comentários quanto ao uso de antimitóticos no tratamento destas lesões.

A case of a squamous cell carcinoma of the conjunctiva is presented. The lesion was removed with recurrence in another conjunctival site. The patient received cycles of 5-Fluorouracil as adjuvant treatment to the surgical removal and presented unfavorable evolution, requiring orbital exenteration. Comments are made on the use of antimitotic drugs in the management of these lesions.

Ocular adnexal MALT lymphoma: an intriguing model for antigen-driven lymphomagenesis and microbial-targeted therapy.

Non-Hodgkin's lymphomas constitute one half of malignancies arising in the orbit and the ocular adnexae. Mucosa-associated lymphoid tissue (MALT)-type lymphoma is the most common histological category in this anatomic region. The incidence of ocular adnexal lymphoma of mucosa-associated lymphoid tissue-type (OAML) is increasing and recent studies offered new relevant insights in molecular, pathogenetic and therapeutic issues on these neoplasms. A pathogenetic model of antigen-driven lymphoproliferation similar to that reported for Helicobacter pylori-related gastric MALT lymphomas has been hypothesized for OAML. This notion is supported by the association between OAML and Chlamydophila psittaci infection, an association that is of likely pathogenetic relevance and may influence both the biological behavior and the therapeutic management of these neoplasms. However, this association displays evident geographical variability indicating that other etiopathogenic agents could be involved. These recent acquisitions coupled with the occurrence of chromosomal translocations and other genetic alterations, as well as additional risk factors like autoimmune disorders have contributed to render OAML an exciting challenge for a broad group of physicians and scientists. OAML is an indolent and rarely lethal malignancy that, in selected patients, can be managed with observation alone. Lymphomatous lesions are frequently responsible for symptoms affecting patient's quality of life, requiring, therefore, immediate treatment. Several therapeutic strategies are available, often associated with relevant side-effects. However, the therapeutic choice in OAML is not supported by consolidated evidence due to the lack of prospective trials. In this review, we analyze the most relevant biological, molecular, pathological and clinical features of OAML and propose some therapeutic guidelines for patients affected by this malignancy.

Resection of an orbital lymphangioma with the aid of an intralesional liquid polymer.

A 28-year-old man with long-standing right proptosis presented with an extensive multilobulated partially cystic orbital mass thought to be a lymphangioma. Because of concern that excision or debulking of the lesion was likely to be complicated by excessive bleeding, the lesion was injected with a mixture of ethiodized oil (Ethiodol) and cyanoacrylate glue under direct observation. The mixture caused the injected lobules to assume a firm, rubbery texture, allowing them to be excised without bleeding.

Retro-orbital tumour--an uncommon cause of headache in pregnancy.

Retro-orbital tumour was the cause of headache and neuropathic facial pain in a 31-year-old pregnant woman. The diagnosis had been overlooked as a result of a long history of migraine. There was exacerbation of the pain throughout the pregnancy, particularly in the third trimester. Pharmacological agents commonly used to manage neuropathic pain states were relatively contraindicated due to potential adverse effects on the fetus. Cognisant of such limitations imposed by pregnancy, we used multimodal therapy in an attempt to control the pain. This included morphine, paracetamol, amitriptyline, ketamine and psychological support. The management challenges are described.

MR-guided laser-induced thermotherapy of the infratemporal fossa and orbit in malignant chondrosarcoma via a modified technique.

A 76-year-old patient presented with a recurrent mass of a malignant chondrosarcoma in the right infratemporal fossa and in the left maxillary sinus with orbital invasion. The patient was treated with a palliative intention with MR-guided laser-induced thermotherapy using a modified applicator technique. Following treatment clinical symptoms improved and MRI revealed complete laser-induced tumor necrosis.

[Local microwave hyperthermia in the combined treatment of malignant tumors of the eyelids and orbit]. / Lokal'naia sverkhvysokochastotnaia gipertermiia v kompleksnom lechenii zlokachestvennykh opukholei vek i orbity.

The paper is concerned with the results of experimental investigation of the effect of different microwave radiation ranges on some segments of the rabbit's eye and its clinical application to the treatment of malignant tumors of the lid and orbit. It has been shown that the effect of definite microwave radiation ranges on the rabbit's eye, while ensuring necessary conditions for local hyperthermia (43-45 degrees C), does not cause clinically visible changes in the refractive media and fundus of the eye during 3 months after irradiation. The results of effective combined therapy of advanced malignant tumors of the lid and orbit in 5 patients are presented. Our experience in using definite ranges of local microwave radiation for therapy of malignant eye tumors has shown the feasibility, prospects and relative safety of the method in cancer ophthalmology.

Treatment of orbital pseudotumors and lymphoma.

Thirty-seven patients were identified in a retrospective review at Hahnemann University and Wills Eye Hospital; they had been treated for pseudotumor or lymphoma of the orbit and had adequate follow-up (x = 61.5 months). Overall, 31 of 37 patients (83.8%) were cleared of their orbital disease. Of the nine patients treated for lymphoma, all were cleared of disease in the orbit. Twenty-two of 28 patients (78.6%) with benign disease were likewise cleared of orbital disease. Ten of 10 patients who received radiation as their initial therapy were cleared. Overall, 17 of 20 (85%) of patients who received radiation as part of their therapy were cleared of orbital disease, with mean dosages of 2,166 cGy (1 cGy = 1 rad) for benign disease and 3,547 cGy for lymphoma. Brief representative case studies and a review of the literature are presented. Two patients with benign disease were cured of disease in the orbit but went on to develop systemic lymphoma. Radiation therapy plays an essential role in the management of patients with orbital lymphomatous diseases.