Ocular Adnexal Lymphoma Research Articles

Reactive lymphoid hyperplasia of the ocular surface: clinicopathologic features and search for infectious agents

Editor, Reactive lymphoid hyperplasia (RLH) is a benign and reversible enlargement of lymphoid tissue composed of dense lymphocytic infiltrates with formation of well-defined reactive lymphoid follicles with germinal centres (Sigelman & Jakobiec 1978; Coupland et al. 1998). There is some evidence that infectious agents, in particular Chlamydia (C.) psittaci for ocular adnexal lymphoma (OAL) (Ferreri et al. 2004) and Epstein–Barr virus (EBV) for RLH (Feinberg et al. 2000), may contribute to the pathogenesis of lymphoid neoplasia. This study provides a detailed analysis of clinical features of RLH on the ocular surface and screening for infectious agents by polymerase chain reaction (PCR) and liquid hybridization. Clinical features of seven histologically proven RLHs of the ocular surface were analysed. DNA from paraffin-embedded formalin-fixed tissue of 6 RLHs and 8 conjunctival non-Hodgkin lymphomas was extracted and screened for Chlamydia species (C. trachomatis, C. pneumoniae, C. psittaci) and EBV. Particular PCR protocols were developed. The PCR product was visualized by agarose gel electrophoresis. To verify the amplification results, each PCR product underwent additional liquid hybridization testing. Specific probes were designed for the detection of each Chlamydia species and EBV. (Please contact the corresponding author for detailed information). In this case series, RLH occurred over a wide spectrum of ages (range: 8–77 years, median: 23 years) with a main incidence within the third decade (Fig. 1). The lesions were predominantly located nasally, except for one tumour occurring in the lower fornix. In two cases, the process was confined to the caruncle, and in one case, to the plica. The remainder developed in the nasal conjunctiva. All tumours were of salmon-coloured appearance. The clinical appearance varied between cyst-like (n = 2), nodular (n = 1) and pemphigoid-like (n = 1) lesions, as well as lesions mimicking the diffuse conjunctival thickening of a lymphoma (n = 3) were observed. In two patients, the tumour followed the manifestation of a conjunctival lymphoma in the fellow eye. Follow-up (1–11 years) was uneventful in all patients with no recurrence or transformation into a true lymphoma. Clinical picture illustrating different manifestations of reactive lymphoid hyperplasia (RLH). (A) Cystoid lesion in the left caruncle of a 22 years old female patient. (B) Plain and salmon-coloured lesion in the left conjunctiva (next to the plica) of an 11 years old male patient. (C) Nodule-like lesion in the left caruncle of a 23 years old male patient. (D) Salmon-coloured lesion in the right lower fornix of a 26 years old female patient. This lesion developed 1 month after the patient was diagnosed with a conjunctival non-Hodgkin lymphoma in the lower fornix of the fellow eye. In none of the investigated specimens either Chlamydia species or EBV were detected. In our cohort, RLH was presented as a mostly unilateral circumscribed lesion with varying clinical morphology and an apparent preference for the nasal conjunctiva/caruncle. Six of seven patients were younger than 31 years, which is different from the average age reported in the literature. RLH has – similar to malignant lymphoma – been reported to affect adults typically in the 5th through 7th decade (Sigelman & Jakobiec 1978; Coupland et al. 1998). The proposed aetiology of RLH as a reaction to antigen hyperstimulation (Sigelman & Jakobiec 1978), however, might account for a more likely occurrence in children and young adults, as well as for the nasal location. Two of our patients with a non-Hodgkin lymphoma and subsequent treatment with radiation therapy of the affected eye developed RLH in the fellow eye. Whether the occurrence of RLH is connected to radiation therapy or lymphoma remains unclear. There is still an ongoing debate on a possible association between OAL and C. psittaci (Ferreri et al. 2004; Decaudin et al. 2008). Differences in the prevalence of C. psittaci infection in various geographical regions and technical differences in the application of the assays have to be considered (Decaudin et al. 2008). However, from our results, we would not recommend a change in treatment strategy unless the association with an infectious agent can be unequivocally proven for single cases. Especially, in young adults and children, RLH should be considered in the differential diagnosis of salmon-coloured lesion of the ocular surface, even if cyst like and located at unusual sites such as the caruncle (Herwig et al. 2008).

Ocular Adnexal Lymphoma of the Extraocular Muscles: Case Series From the University of Iowa and Review of the Literature

To review and statistically analyze the data of patients with discrete involvement of the extraocular muscles with ocular adnexal lymphoma from the tumor registry at the University of Iowa and to compile with current cases in the literature. The records of patients with biopsy-proven orbital lymphoma at the University of Iowa Hospitals and Clinics Department of Ophthalmology and the Tumor Registry of the University of Iowa were reviewed. A review of the literature and meta-analysis were conducted. Eleven patients were identified with biopsy-proven ocular adnexal lymphoma with discrete involvement of the extraocular muscles at the University of Iowa. Additionally, 46 patients were identified in the literature with clinical and radiographic involvement of the extraocular muscles, 31 (67%) with biopsy-proven involvement. In the combined group of 57 patients, 16 (35%) of 45 patients with histopathologic documentation had lymphomas classified as extranodal marginal zone lymphomas. Twenty-five (67%) of the 37 patients with tumor-staging documentation had no extraorbital involvement. Ocular adnexal lymphoma with discrete extraocular muscle involvement is rare. Most lymphomas found in this area of the orbit are subtypes of B-cell lymphoma. This disease should be included in the differential diagnosis of enlarged extraocular muscles.

Primary, Unilateral Ocular Adnexal Lymphoma: Disease Progression and Long-Term Survival

This investigation aimed to improve our understanding of the disease characteristics and clinical course for primary unilateral ocular adnexal lymphoma (OAL). In this retrospective case series, all consecutive biopsy confirmed cases of lymphoma confined to a single ocular adnexa (unilateral stage 1E) during a 30-year period were included. All histologic classification conformed to the current World Health Organization classification. Descriptive statistics and standard survival analyses were performed. 122 patients were included in this study. The most common primary unilateral OAL were indolent B-cell lymphomas (mucosa-associated lymphoid tissue (MALT)-type marginal zone, follicular and small lymphocytic lymphoma) representing 80% of cases. Typically aggressive lymphomas were found in only 7% of patients (diffuse large B-cell lymphoma, immunoblastic lymphoma, diffuse large cell lymphoma, and mantle cell lymphoma). Overall, 24.4% of patients experienced progression of their disease after initial therapy, the majority occurring within 5 years. For the 80% of OAL of indolent B-cell type, progression free and disease specific survivals were 71 and 98% at 5 years and 61 and 90% at 10 years, respectively. Diffuse large B-cell lymphoma was more likely to progress overall (p < 0.01) and progress earlier (log rank, p < 0.01). Additionally, these patients were also more likely to succumb to disease (p < 0.01) in a shorter interval (log rank, p < 0.01). Most primary unilateral OALs are indolent lymphomas with good prognosis for survival and freedom from progression. However, a minority present with more aggressive lymphomas (diffuse large B-cell lymphoma, mantle cell lymphoma, immunoblastic lymphoma, and diffuse large cell lymphoma), carrying a more guarded prognosis.

Long-term Outcome and Patterns of Failure in Primary Ocular Adnexal MALT Lymphoma Treated with Radiotherapy

Long-term Outcome and Patterns of Failure in Primary Ocular Adnexal MALT Lymphoma Treated with Radiotherapy

Clinical significance of tumor‐infiltrating FOXP3+ T cells in patients with ocular adnexal mucosa‐associated lymphoid tissue lymphoma

We evaluated the association between tumor-infiltrating FOXP3+ T cells and clinical outcomes in patients with ocular adnexal lymphoma of mucosa-associated lymphoid tissue type (OAML). Pretreatment formalin-fixed paraffin-embedded tissues from 42 patients with OAML were stained with 236A/E7 anti-FOXP3 murine monoclonal antibody as well as CD3, CD4 and CD8 antibodies. The amount of FOXP3+ T cells was numerically quantified using an image analysis program. Front-line treatments were as follows: combination chemotherapy (n = 25); radiotherapy (n = 9); doxycycline (n = 6); and wait and see (n = 2). Complete response (CR) was observed in 20 (50%) of 40 evaluable patients. Median progression-free survival (PFS) was 50 months. A high number of FOXP3+ T cells (n = 21, ≥ 180/0.58 mm(2)) showed a higher CR rate (33%vs 71%, P = 0.013) and tendency towards prolonged PFS (48 vs 67 months, P = 0.110). In the combination chemotherapy group, a high number of FOXP3+ T cells was significantly associated with a higher CR rate (29%vs 82%, P = 0.008) and prolonged PFS (17 vs 79 months, P = 0.003). A high number of tumor-infiltrating FOXP3+ T cells correlates with a favorable clinical outcome in OAML patients.

Treatment for orbital diffuse large B-cell lymphoma in an elderly patient by autologous cytokine-induced killer cells

Dear Editor, Ocular adnexal lymphomas (OALs) are largely represented by extranodal marginal zone lymphomas, about 10% are diffuse large B-cell lymphomas (DLBCLs) [1, 2]. The prognosis of DLBCL worsens with age. Therefore, the treatment must be tailored to the condition of the individual elderly patient. Autologous cytokine-induced killer (CIK) cells have been shown to be effective in the treatment of cancer and minimal residual diseases. Here, we report on CIK cells treatment in an elderly orbital DLBCL patient. In May 2009, an 89-year-old patient was admitted to the department of ophthalmology because of a mass in his right eye for 2 months without any other symptoms. After the mass was partly exsected, histopathological diagnosis was DLBCL of the right orbit and immunohistochemical analyses showed CD20+++/MUM-1+/bcl-6+/CD10-/ CD5-/CD3-/Cyclin D1-. In July 2009, the patient was referred to our department for further therapy. A detailed examination showed a possible involvement of the upper pole of the left kidney, extensive enlargement of the lymph nodes, and splenomegaly. He was determined to be stage IV. Because of his age, severe pulmonary and cardiac comorbidities, rituximab was used as the principal therapy. Rituximab was given at a dose of 600 mg once a week for 2 weeks from July 31, 2009, after he signed the informed consent. Twenty days later, the regimen of R-COP (rituximab 0.6 g d1, CTX 0.6 g d3, VDS 2 mg d3, Dex 10 mg d3, Dex 7.5 mg d4-7) was given; the orbital mass, possible involvement of left kidney, and lymph nodes all became smaller, and a partial remission was obtained. But the patient refused to use rituximab and chemotherapy because of some cardiac adverse effects. After this, he received 5 cycles of CIK cells infusion. The first cycle of CIK cell infusion was on October 29, 2009. It had been 2 months from the end of R-COP chemotherapy to the beginning of CIK treatment. His orbital lymphoma and possible involvement of the kidney disappeared after the second cycle of CIK infusion (see Fig. 1). PET showed complete remission on January 25, 2010. The last one was on July 23, 2010. At the end of treatment, enlarged lymph nodes of CT became normal. The side effects of CIK cells treatment were minor. Presently, 20 months after diagnosis, the patient lives well and continues in complete remission. Ocular DLBCL is an uncommon disorder of OALs, rituximab with CHOP has shown good efficacy in treating DLBCL. However, the tolerance is poor for many elderly patients. CIK cells are T lymphocytes that are enriched with CD3CD56 cells, which can be easily and rapidly expanded in vitro from human peripheral blood. It is a promising new treatment that has the potential to kill a wide spectrum of tumor cells, especially malignant hematological diseases [3–6]. The peripheral blood mononuclear cells were isolated and primed with anti-CD3 monoclonal antibody, interferon-γ, interleukin (IL)-2, and IL-1. After 14 days of culture, the immunophenotype and survival rate of the CIK cells were determined with a flow cytometer, then CIK cells were transfused. One course of the therapy was defined as follows: about 2–3×10 of CIK cells (survival rate >95%) were transfused twice, then rhIL-2 S.-X. Li :H.-L. Zhu (*) :B. Guo :X.-C. Lu : B. Yang :Y. Liu : S.-Q. Yao Department of Geriatric Hematology, Chinese People’s Liberation Army General Hospital, Beijing 100853, China e-mail: bjzhuhl301@vip.sina.com

Recent Developments in Nongastric Mucosa-Associated Lymphoid Tissue Lymphoma

Guidelines and algorithms for the management of gastric mucosa-associated lymphoid tissue (MALT) lymphoma have been developed in the recent past, but the situation regarding nongastric MALT lymphomas is much more complicated. Owing to the heterogeneity of MALT lymphomas arising in various organs, different approaches to treatment have been applied, mostly in an uncontrolled fashion. In the recent past, for example, attempts to use antibiotic therapy in managing ocular adnexal MALT lymphomas have been reported, with response rates varying between 0% and 60% with the use of doxycycline or, more rarely, clarithromycin. Currently, antibiotic therapy remains experimental, with conflicting data and apparent geographic variations. In addition, there is no clear consensus whether radiation or systemic therapy is more effective in MALT lymphomas at different locations, including the lung and the ocular adnexa. This review highlights and briefly discusses some recent developments in the management of nongastric MALT lymphomas.

Evaluation of intraorbital injection of rituximab for treatment of primary ocular adnexal lymphoma: A pilot study

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.

Long-Term Outcome and Patterns of Failure in Primary Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiotherapy

To evaluate the long-term treatment outcome and disease behavior of primary ocular adnexal MALT (mucosa-associated lymphoid tissue) lymphoma (POAML) after treatment with radiotherapy. Seventy-eight patients (42 male, 36 female) diagnosed with stage I POAML between 1991 and 2010 at Kobe University Hospital were included. The median age was 60 years (range, 22-85 years). The median radiation dose administered was 30.6 Gy. Rituximab-based targeted therapy and/or chemotherapy was performed in 20 patients (25.6%). Local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method. The median follow-up duration was 66 months. Major tumor sites were conjunctiva in 37 patients (47.4%), orbita in 29 (37.2%), and lacrimal glands in 12 (15.4%). The 5- and 10-year OS rates were 98.1% and 95.3%, respectively. The 5- and 10-year LC rates were both 100%, and the 5- and 10-year RFS rates were 88.5% and 75.9%, respectively. Patients treated with a combination of radiotherapy and targeted therapy and/or chemotherapy had a trend for a better RFS compared with those treated with radiotherapy alone (p= 0.114). None developed greater than Grade 2 acute morbidity. There were 14 patients who experienced Grade 2 morbidities (cataract: 14; retinal disorders: 7; dry eye: 3), 23 patients who had Grade 3 morbidities (cataract: 23; dry eye: 1), and 1 patient who had Grade 4 glaucoma. Radiotherapy for POAML was shown to be highly effective and safe for LC and OS on the basis of long-term observation. The absence of systemic relapse in patients with combined-modality treatment suggests that lower doses of radiation combined with targeted therapy may be worth further study.

Intralesional administration of rituximab for treatment of CD20 positive orbital lymphoma: Safety and efficacy evaluation

B-cell lymphomas constitute the most frequent malignant neoplasm of the ocular adnexal, often presenting with localized disease. Five patients with primary localized CD20 positive B cell non Hodgkin ocular adnexal lymphomas received intralesional rituximab at the dose of 5 mg once a week for one month, followed by 10 mg weekly in case of incomplete response. Four of five patients obtained regression of symptoms and 2 of them showed complete response. No patients experienced side effects besides pain on the site of the injection. Local treatment with Rituximab for OAL is a safe and useful first-line therapeutic option.

Feasibility of the TNM‐based staging system of ocular adnexal extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma)

The American Joint Committee on Cancer has proposed the tumor, node, metastasis (TNM) staging system to overcome the limitations of the Ann Arbor staging system for ocular adnexal lymphoma. We performed this study to evaluate the feasibility of the TNM staging system for ocular adnexal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (OAML). The data form 66 total eyes from 54 patients with biopsy-confirmed OAML according to World Health Organization classification were retrospectively analyzed. Using the TNM staging system, we reclassified all patients into two categories: (1) T1N0M0 stage group (n = 26), for patients with lymphoma involving only the conjunctiva; and (2) above T1N0M0 or bT1N0M0 stage group (n = 28), for patients with lymphoma extending to the orbit, eyelid, or adjacent structures, and/or bilateral OAML. After a 24-month median follow-up period for all patients, the T1N0M0 group revealed higher progression-free survival (PFS) than the above T1N0M0 or the bT1N0M0 group (P = 0.041). In a separate analysis of only 50 patients categorized as Ann Arbor stage IE, the T1N0M0 group demonstrated higher PFS (100%) than the above T1N0M0 or the bT1N0M0 group (84.7%; P = 0.067). Our data show that the poor prognostic group classified as Ann Arbor stage IE can be further distinguished by using the TNM staging system. Thus, further studies to develop treatment strategies for reducing relapse after treatment for OAML should use the TNM staging system.

Recurrent Extranodal Marginal Zone B-Cell Lymphoma Presenting as a Huge Cheek Mass after Radiotherapy on Ocular Adnexal Lymphoma

Extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT), also known as MALT lymphoma, is a distinctive group of B-cell lymphomas specified in the World Health Organization classification. The most common anatomic site of origin of MALT lymphoma is the stomach. Other common sites include the skin, salivary glands, ocular adnexa, intestines, and lung. However, it is known that virtually any extranodal anatomic site in the body can be involved by MALT lymphoma. Because patient with MALT lymphoma exhibits an indolent natural history and a favorable prognosis, treatments like excision or radiotherapy or antibiotics should be chosen carefully. Results from radiotheraphy series have demonstrated relatively good local controls with a prolonged clinical course in patients with ocular adnexal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (ocular MALT lymphoma). We report a case of recurrent extranodal marginal zone Bcell lymphoma that presented in the unusual location of the cheek after initial treatment with radiotherapy in ocular MALT lymphoma. To our knowledge, this presentation has not previously been reported in the literature.

Chlamydia psittaci Infection in Nongastrointestinal Extranodal MALT Lymphomas and Their Precursor Lesions

Extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) are associated with various infectious pathogens. We analyzed the presence of Chlamydia psittaci, Chlamydia pneumoniae, and Chlamydia trachomatis DNA in 47 nongastrointestinal and 14 gastrointestinal MALT lymphomas, 37 nonmalignant control samples, and 27 autoimmune precursor lesions by polymerase chain reaction amplification and direct sequencing. In 47 nongastrointestinal MALT lymphomas, 13 (28%) were positive for C psittaci DNA compared with 4 (11%) of 37 nonmalignant control samples (P = .09). C psittaci was detected at variable frequencies in MALT lymphomas of different sites: lung, 100% (5/5; P < .01); thyroid gland, 30% (3/10; P > .05); salivary gland, 13% (2/15; P > .05); ocular adnexa, 15% (2/13); and skin, 25% (1/4). Of 27 autoimmune precursor lesions (11 Hashimoto thyroiditis and 16 Sjögren syndrome), 11 (41%) contained C psittaci DNA. Only 1 (7%) of 14 gastrointestinal MALT lymphomas was positive for C psittaci. All specimens were negative for C trachomatis and C pneumoniae. Besides ocular adnexal lymphomas, C psittaci infection is associated with nongastrointestinal MALT lymphomas and autoimmune precursor lesions, suggesting possible involvement of C psittaci-induced antigenic-driven MALT lymphomagenesis.

Local Recurrence as Immunoglobulin G4 (IgG4)-Related Disease 10 Years after Radiotherapy to Ocular Adnexal Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

In 2000, a 48-year-old woman developed a left orbital mass with lacrimal gland involvement and then, in 2003, a right orbital mass with lacrimal gland involvement, both of which were diagnosed as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). She underwent 30 Gy external beam radiation to bilateral orbital lesions. The lymphoma cells in both lesions did not share the same clonality, as shown by amplification by polymerase chain reaction of the immunoglobulin heavy chain gene. Immunoglobulin light chain analysis by immunohistochemistry and messenger RNA in situ hybridization showed λ chain monotype in the left orbital lesion but κ chain monotype in the right orbital lesion. She developed recurrent left orbital mass with high uptake on fluorodeoxyglucose positron emission tomography fused with computed tomography in 2010, and excisional biopsy disclosed the formation of follicles and infiltration with immunoglobulin G4 (IgG4)-positive plasma cells mainly in interfollicular areas. The immunoglobulin light chain analysis showed the λ chain and κ chain bitype. With the immunohistopathological diagnosis of IgG4-related disease, the serum IgG4 level was found to show elevation at 376 mg/dL, and the patient chose observation. This is the first reported case of development of IgG4-related disease after bilataral orbital MALT lymphoma with external beam radiotherapy.

Extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type of the ocular adnexa: Retrospective single institution review of 95 patients

Context:There are few reports on the management of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT), which are based on the experience of a single institution, as opposed to large multicenter randomized trials.Aim:The aim of this study was to report on the clinical experience of a single institution.Materials and Methods:A retrospective review was undertaken of records of 95 patients with MALT lymphoma of the ocular adnexa. Histologic diagnosis of MALT lymphoma was made according to established criteria, and clinical staging was carried out to determine treatment modalities. All patients were treated by external beam irradiation (30.6–45.0 Gy) after biopsy. Additional chemotherapy was performed in accordance with the clinical stage of the disease. All the patients were treated by the same hemato-oncologist and radio-oncologist.Results:Almost all patients showed complete response, except for four patients who showed partial response. In two of 95 patients, contralateral eye showed recurrence, and they were salvaged by additional radiotherapy. The 3-year overall survival and event-free survival rates were 100 and 97%, respectively, by Kaplan–Meier survival analysis. Moreover, there were no serious radiation-associated complications.Conclusions:Radiotherapy alone can be an important treatment modality for the local control and survival in patients with localized MALT lymphoma of ocular adnexa. Systemic chemotherapy should be considered in patients with advanced stage disease.

Primary ocular adnexal mucosa‐associated lymphoid tissue lymphoma (MALT): single institution experience in a large cohort of patients

Extranodal marginal zone B-cell lymphoma is the most common orbital tumour. We conducted a retrospective analysis to examine: (i) the impact of initial presentation and staging on outcome and (ii) response to various treatment modalities and the effect of the latter on recurrence. Ninety patients with primary ocular adnexal marginal zone lymphoma (POAML) diagnosed at our institution between 1984 and 2009 were studied. POAML was associated with monoclonal gammopathy (13%) at presentation. Most POAML patients (86%) presented with Ann-Arbor stage I disease. Radiotherapy led to excellent local control, but relapses occurred in 18% of Ann-Arbor stage I patients during a median follow-up of 5 years. Local relapses, including secondary central nervous system (CNS) involvement, were observed in patients receiving radiation doses <30·6 Gy. No differences in relapse rate and survival were observed between patients who did or did not undergo staging bone marrow biopsy. Ann-Arbor stage II-IV disease and high lactate dehydrogenase levels were associated with shorter freedom from progression. In conclusion, POAML is an indolent lymphoma with continuous risk for relapse. Radiation doses of at least 30·6 Gy should be given in Ann-Arbor stage I disease, since lower doses may be more frequently associated with relapses, including CNS relapses.

Hepatitis C Virus Infection in Ocular Adnexal Lymphomas

To assess the influence of hepatitis C virus (HCV) infection on disease appearance and outcome of ocular adnexal non-Hodgkin lymphoma (ONHL). Retrospective comparative study (from January 1, 1992, through December 31, 2006). The medical records of 129 patients with ONHL were retrospectively reviewed. All the patients were tested serologically for the presence of HCV infection. Patients were divided into 2 groups according to the presence or absence of HCV infection. Prevalence of HCV infection, staging to evaluate the extent of disease at the onset, and clinical outcome data on overall and disease-free survival. The prevalence of HCV infection among the patients with ONHL was 17.8%. Seropositivity for HCV infection was significantly associated with extraorbital lymphoma at the onset (P=.006). High prevalence of mucosa-associated lymphoid tissue disease (79.8%) was registered. Protocol therapy included radiotherapy and chemotherapy, depending on the stage of the disease. Complete remission was achieved in 99 patients (76.7%). A total of 23.6% of patients with HCV-seronegative status and 21.7% of those with HCV-seropositive status experienced relapse of the lymphomatous disease. No significant differences in the 5-year overall survival and disease-free survival between the 2 groups were observed. Prevalence of HCV infection in patients with ONHL is a relevant issue, accounting for 17.8% of the examined patients. Infection with HCV may influence the initial appearance of ONHL because it is associated with more widespread disease at the onset. However, the overall and disease-free survival of the infected patients are not statistically different than that of patients who are not infected.

Hypermethylation of tumour suppressor genes in ocular adnexal lymphoma

Abstract Purpose Promoter hypermethylation occurs in various tumours, including ocular adnexal lymphomas (OAL), and is a mechanism by which tumour suppressor genes can be inactivated during tumourigenesis. This study aimed to investigate the levels of hypermethylation and specific genes that are hypermethylated in different subtypes of OAL using methylation‐specific multiplex ligation‐dependent probe amplification (MS‐MLPA) and pryrosequencing. Methods DNA was extracted from formalin‐fixed, paraffin‐embedded tissues from 33 extra‐marginal zone B‐cell lymphomas (EMZL) and 37 non‐EMZL. Using two MS‐MLPA assays (MRC‐Holland) the methylation status and copy number of 36 genes was detected. MS‐MLPA results were validated using pyrosequencing. Results MLPA and pyrosequencing results were comparable with 75‐100% concordancy. Ten common genes were hypermethylated in the EMZL and non‐EMZL, diffuse large B‐cell lymphomas (DLBCL) and mantle cell lymphomas (CDH13, DAPK1, ESR1, GATA5, IGSF4, PAX6, RARβ, THBS1, TIMP3, and WT1). In non‐EMZLs, a greater number of genes showed hypermethylation when diagnosed in the orbit and patients had a poorer prognosis. Deletion of the 9p21 region was seen in 7/13 DLBCLs including the p14ARF, p15 and p16 genes. Conclusion Hypermethylation is a feature of OALs suggesting a role for epigenetic deregulation in OAL development. In non‐EMZLs greater epigenetic deregulation may be indicative of poorer patient prognosis. We hypothesise that EMZL, DLBCL and mantle cell lymphomas share a similar epigenetic aetiology and that genes in the 9p21 region may be important to DLBCL development. Correlation of hypermethylation and copy number data with clinical presentation and follow‐up could reveal biomarkers of diagnostic and prognostic value in OALs.

Ocular adnexal mucosa-associated lymphoid tissue lymphoma in Northern China: high frequency of numerical chromosomal changes and no evidence of an association with Chlamydia psittaci

Studies from different countries showed variations of genetic changes and association with Chlamydia psittaci in ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma. A total of 38 ocular adnexal MALT lymphoma cases from Northern China were studied. Genetic abnormalities were investigated in 28 cases by interphase FISH. C. psittaci and other infectious agents that are commonly-associated with chronic eye disease were screened in 38 cases by PCR. Genetic abnormalities were detected in 60.7% of cases. Among them, only one showed a break-apart of the IgH gene and all others showed numerical abnormalities, including trisomy 18 in 7 cases (25%), 3 copies of BCL6 gene in 12 cases (43%), and 3 copies of C-MYC gene in 2 cases (7%). C. pneumoniae was positive in two cases (5.3%), and C. psittaci, C. trachomatis, HSV1, HSV2, ADV8, and ADV19 were not detected in any cases. In conclusion, numerical abnormalities are frequent and the chromosomal translocations commonly associated with MALT lymphomas are rare in ocular adnexal MALT lymphoma of Northern China. C. psittaci and other infectious agents are not associated with ocular adnexal MALT lymphoma in these patients.

A possible new role for Helicobacter pylori in the development of ocular adnexal lymphoma

A possible new role for <i>Helicobacter pylori</i> in the development of ocular adnexal lymphoma