Ocular Adnexal Mucosa-associated Lymphoid Tissue Research Articles

Risk Potentiality of Frontline Radiotherapy Associated Cataract in Primary Ocular Adnexal Mucosa-associated Lymphoid Tissue Lymphoma

PurposeTo elucidate risk potentiality of frontline radiotherapy associated cataracts in primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML).MethodsData from eight consecutive patients of 41 total OAML patients who had undergone cataract surgery after frontline radiotherapy were analyzed.ResultsThe median patient age was 46 years (range, 36 to 69 years). The median total radiation dose was 3,780 cGy (range, 3,060 to 4,500 cGy), and the mean duration from radiation irradiation to cataract surgery was 36.60 ± 8.93 months. Preoperative lens opacification was primarily at the posterior lens subcapsule, and best-corrected visual acuity (BCVA) was 0.43 ± 0.21. Patients underwent the phacoemulsification surgical procedure with posterior chamber intraocular lens insertion. The average BCVA improved to 0.90 ± 0.14 after cataract surgery. Two patients underwent posterior continuous curvilinear capsulorhexis, and one had posterior capsule rupture. For posterior capsule opacification (PCO), three patients received Nd:YAG laser posterior capsulotomy after the initial surgery, and one patient is currently under consideration for laser posterior capsulotomy.ConclusionsRadiotherapy increased posterior subcapsule opacification at a relatively young age in primary OAML. Phacoemulsification was a manageable procedure without severe complications, and final visual outcomes were good. However, because after-cataracts progressed earlier than did senile cataracts, close follow-up should be considered for PCO management.

Multigene Methylation Analysis of Ocular Adnexal MALT Lymphoma and Their Relationship toChlamydophila psittaciInfection and Clinical Characteristics in South Korea

We investigated the aberrant promoter methylation status of known or suspected tumor suppressor genes in ocular adnexal lymphoma (OAL) and the possible association with clinical characteristics and Chlamydophila psittaci infection. Thirty-five cases of ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma cases were examined for the methylation status of nine genes using methylation-specific PCR and for the detection of C. psittaci DNA using PCR. The medical records were reviewed retrospectively. Patient demographics, clinical characteristics including the response of the lymphoma to the therapy, and C. psittaci infection status were evaluated for possible association with methylation frequencies. CpG island methylation in nine genes was variously found as follows; DAPK (94.3%), ECAD (77.1%), MT1G (48.6%), THBS1 (37.1%), RAR-β (31.4%), p16 (20%), MGMT (5.7%), p14 (0%), and RASSF1A (0%). Methylation was not observed in any of 13 control cases. C. psittaci DNA was observed in 25 (75.8%) of 33 patients with available tumor tissues, and ECAD hypermethylation was significantly higher in C. psittaci-positive cases (P = 0.041). Promoter hypermethylation status was not correlated with clinical characteristics. Aberrant CpG island methylation of tumor suppressor genes is a frequent event in ocular adnexal MALT lymphoma. In particular, high frequencies of DAPK and ECAD methylation may be strongly correlated with ocular adnexal MALT lymphomagenesis in South Korea. Furthermore, ECAD hypermethylation is closely associated with C. psittaci infection, which may shed light on the mechanisms of bacterium-induced oncogenesis.

A20 inactivation in ocular adnexal MALT lymphoma

Recent studies showed A20 inactivation by deletion, mutation and promoter methylation in ocular adnexal mucosa-associated lymphoid tissue lymphoma. However, the incidences of A20 abnormalities and their clinical impact remain for the most part unknown. It is also unknown whether ABIN-1 and ABIN-2, the components of the A20 NF-κB inhibitor complex, are inactivated by genetic changes in ocular adnexal mucosa-associated lymphoid tissue lymphoma. A total of 105 cases were investigated for A20 mutation/deletion, ABIN-1/2 mutation, MALT1 and IGH involved translocation. Somatic mutation was seen frequently in A20 (28.6%) but rarely in ABIN-1 (1%) and ABIN-2 (1%). A20 mutations were significantly associated with A20 heterozygous deletion, and both were mutually exclusive from the MALT1 or IGH involved translocations. A20 mutation/deletion was also significantly associated with increased expression of the NF-κB target genes CCR2, TLR6 and BCL2. The cases with A20 mutation/deletion required significantly higher radiation dosages to achieve complete remission than those without these abnormalities.

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.

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.

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.

Relationship between primary ocular adnexal mucosa-associated lymphoid tissue lymphoma and eye infection

To study the role of pathogenic microorganisms commonly associated with chronic eye disease, including Chlamydia psittaci, Chlamydia trachomatis, Chlamydia pneumoniae, herpes simplex virus (HSV) type 1 and type 2, and adenovirus type 8 and type 19, in the development of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma in Chinese patients. Sixty-eight archival cases of primary ocular adnexal lymphoproliferative lesions, including 38 cases of MALT lymphoma, 3 cases of non-MALT lymphoma and 27 cases of chronic inflammation, were enrolled into the study. DNA was extracted from the paraffin-embedded tissue samples. The presence of DNA of C. psittaci, C. trachomatis, C. pneumoniae, HSV type 1, HSV type 2, adenovirus type 8 and adenovirus type 19 were analyzed by multiplex touchdown enzyme time-release polymerase chain reaction (TETR-PCR). All of the specimens yielded PCR products of over 100 base pairs and were thus suitable for TETR-PCR screening of infectious agents. The prevalence of DNA of C. psittaci, C. trachomatis and adenovirus type 19 were 0 in MALT lymphoma, non-MALT lymphoma and chronic inflammation. There were 2 cases positive for C. pneumoniae DNA, amongst the 38 cases of MALT lymphoma studied (5.3%, 2/38). HSV type 1, HSV type 2 and adenovirus type 8 DNA was found in each of the 3 patients with chronic inflammation. The study indicates that C. psittaci, C. trachomatis, C. pneumoniae, HSV type 1, HSV type 2, adenovirus type 8 and adenovirus type 19 probably play little role in the pathogenesis of ocular adnexal MALT lymphoma in Chinese patients.

Abnormal BCL10 nuclear expression and chromosomal translocation in ocular adnexal mucosa-associated lymphoid tissue lymphomas

To detect the BCL10 expression and several types of chromosomal translocations [including t (11;18)/API2-MALT1; t (1;14)/IgH- BCL10 and t (14;18)/MALT1-IgH] in ocular adnexal mucosa-associated lymphoid tissue lymphomas (OA-MALT lymphomas). Sixty OA-MALT lymphomas were collected from Cancer Hospital of Fudan University. BCL10 was detected by immunohistochemical studies, and API2-MALT1 fusion gene, BCL10, MALT1 and IgH chromosomal abnormalities were detected by fluorescent in situ hybridization (FISH). Fisher's exact test was used to analyze the relation between nuclear BCL10 expression and chromosomal translocation. BCL10 expressed in 85.0% (51/60) OA-MALT lymphomas. Among these positive cases, 25 cases (41.7%) were expressed in the cytoplasm, and 26 cases (43.3%) were expressed in the nucleus. FISH results showed that no chromosomal abnormalities related with BCL10 and IgH genes, except 2 cases with API2-MALT1 fusion gene. Under statistic of Fisher exact test, nuclear BCL10 expression and API2-MALT1 fusion gene were two independent factors (P > 0.05). BCL10 nuclear expression is common in OA-MALT lymphomas and may be used as a potential marker for the diagnosis of MALT lymphomas arising from ocular adnexa. Aberrant chromosomal translocations reported in the other sites MALT lymphomas are rare in OA-MALT lymphomas.

Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma with Polyclonal Hypergammaglobulinemia

To determine the characteristics of patients with primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma associated with polyclonal hypergammaglobulinemia. Case series study. Among 81 Japanese patients with primary ocular adnexal MALT lymphoma, seven patients (9%) were diagnosed with polyclonal hypergammaglobulinemia. Patient clinical data included a history of autoimmune disease and dissemination. Peripheral blood collected from all patients was analyzed for serum levels of rheumatoid factor, soluble interleukin-2 receptor (sIL-2R), and immunoglobulins at the time of diagnosis and after each treatment. Seven patients with polyclonal hypergammaglobulinemia had elevated serum levels of rheumatoid factor, sIL-2R, immunoglobulin G (IgG), and immunoglobulin E (IgE) at the time of diagnosis. One patient had Sjogren syndrome. Six patients (86%) had a dissemination of the MALT lymphoma or lymphadenopathy at the time of diagnosis. Histopathologic examination of the patients with lymphadenopathy revealed not only MALT lymphoma but also secondary follicles. None of the seven patients showed improvement in serum levels of IgG, rheumatoid factor, or sIL-2R in spite of complete regression of the ocular lesions after radiotherapy. After administration of cyclophosphamide/doxorubicin/vincristine/prednisone and/or rituximab to three patients, all three showed improved serum levels of IgG, rheumatoid factor, and sIL-2R. Patients with ocular adnexal MALT lymphoma and polyclonal hypergammaglobulinemia have elevated serum levels of rheumatoid factor, sIL-2R, and IgE, and high dissemination or lymphadenopathy. These unique characteristics may correlate with the systemic immunologic imbalances.

Significance of detection of Bcl-10 novel mutation in ocular adnexal mucosa-associated lymphoid tissue lymphoma

To examine the expression of Bc1-10 gene in mucosa-associated lymphoid tissue (MALT) lymphomas, atypical lymphatic hyperplasia and reactive lymphatic hyperplasia; as well as to discover novel mutations and their role in clinical diagnosis and pathogenesis of ocular adnexal lymphatic disorders. Thirty-one specimens of ocular adnexal lymphoma were obtained from the department of ophthalmology of Shanghai Changzheng hospital, second military medical university during surgery and were preserved in liquid nitrogen immediately after harvesting. The expression of Bc1-10 gene in ocular adnexal specimens was examined by molecular biological methods. The DNA sequences were analyzed by Sanger method and the results were compared with those of the Gene Bank blast to identify novel mutations. The protein expression of mutant Bc1-10 and NF-kappaB in these specimens were detected by immunohistological method and immunofluorescence. Confocal microscope was used to observe the colocalization of Bc1-10 and NF-kappaB expressions. Of the 31 specimens, 14 were positive for Bc1-10, of which 10 showed novel mutations of Bc1-10. One of the four atypical lymphatic hyperplasia specimens was positive for Bc1-10, this mutation was reported by others previously. One of the four reactive lymphatic hyperplasia specimens was positive for Bc1-10. Fourteen (60.8%) of the 23 MALT lymphoma specimens were positive for aberration of Bc1-10, including 6 cases with nuclear expression at moderate intensity and 8 cases with expression in the cytoplasm at weak to moderate intensities. Mutations of Bcl-10 were also expressed in the cytoplasm at moderate intensity in two cases with atypical lymphatic hyperplasia and expressed at moderate intensity in one case with reactive lymphatic hyperplasia. I kappa alpha was expressed diffusely in the cytoplasm in 20 cases, among which co-expression of I kappa alpha and Bcl-10 was present in 14 cases. Novel mutation of Bc1-10 gene in ocular adnexal MALT lymphoma is detected in Chinese patients. Detection of genetic mutation is consistent with and more sensitive than the pathological diagnosis. It can be used to identify the stage and the quality of the disease even no morphological changes are present for discrimination. It can be used as a sensitive index for early diagnosis.

Gastric relapse of stage I ocular adnexal mucosa-associated lymphoid tissue lymphoma

A 57-year-old male with right ocular adnexal mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) was successfully treated with local radiation therapy. The gastroendoscopic examination revealed a slight inflammatory change of the gastric mucosa, and the urease test was positive. Eradication therapy against Helicobacter pylori was successfully done, however, the patient developed gastric MALT lymphoma two years after the initial treatment. Southern blot analysis of the immunoglobulin heavy chain gene rearrangement revealed that the lymphoma cells from the ocular adnexal and gastric MALT lymphomas were identical, indicating that the gastric MALT lymphoma was not the primary but the metastatic region from the ocular adnexal MALT lymphoma. Further, immunohistochemical staining demonstrated the expression of integrin alpha4beta 7 on ocular adnexal MALT lymphoma cells, which is essential for the adhesion of lymphocytes to gastrointestinal mucosa. These results indicate that ocular adnexal MALT lymphoma cells can metastasize to the stomach, depending on the adhesional function of integrin alpha4 beta7.

Progress of the molecular genetics of ocular adnexal mucosa-associated lymphoid tissue lymphoma

黏膜相关淋巴组织(MALT)淋巴瘤是非霍奇金淋巴瘤中结外边缘带淋巴瘤(MZL)的一种特殊类型.眼附属器MALT淋巴瘤是眼眶恶性肿瘤中较常见的一种,可发生在结膜、泪腺、眼睑和眼眶.近年来,国外许多学者在MALT淋巴瘤的临床特点、病理形态学、免疫表型、分子遗传学及分子生物学方面对它的发生机制在基因水平有了新的认识.就国外对眼附属器MALT淋巴瘤的分子遗传学异常在肿瘤细胞内部信号转导通路中作用的研究做一综述。

Conjunctival Marginal Zone B-cell Lymphoma (MALT Lymphoma) with Amyloid and Relapse in the Stomach

The authors report a localized (primary) conjunctival marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue (MALT)-type), with amyloid deposition with relapse in the stomach, 14 months after the initial diagnosis. Ocular adnexal marginal zone B-cell MALT lymphoma is often localized at diagnosis; some relapse in typical MALT sites. There are few reports of localized conjunctival lymphoma with a relapse in the stomach. The authors suggest that all patients with localized ocular adnexal lymphoma be followed for an extended period.

Lymphomas involving the eye and the ocular adnexa

To describe recent advances in the understanding of the pathogenesis of the most common malignant lymphomas that occur as primary and secondary tumors in ocular tissues. Advances have been made in the understanding of the genetic alterations in mucosa-associated lymphoid tissue lymphomas, including various chromosomal translocations, such as the most recently described t(3;14)(p14.1;q32) involving the FOXP1 gene. Further, the development of ocular adnexal mucosa-associated lymphoid tissue lymphomas has been associated with Chlamydia psittaci in some geographic areas. Subdivision of diffuse large B-cell lymphoma into clinically prognostic groups had been achieved on the basis of gene expression profiles using complementary DNA microarrays. Tumor-infiltrating cells, such as macrophages, have been demonstrated to be of prognostic significance in follicular lymphoma. Understanding of the ocular adnexal and intraocular lymphomas has advanced with progress in lymphoma classification systems, namely the World Health Organization lymphoma classification. This knowledge is being fine tuned with advances in technology, such as complementary DNA microarrays. The clinical significance of this scientific progress has yet to be determined.

Ocular adnexal mucosa-associated lymphoid tissue lymphoma treated with radiotherapy

Forty-two patients with stage IE ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma were retrospectively analyzed. Five-year local control and progression-free survival rates were 100 and 77%, respectively. The most common relapsed site was the contralateral orbit. Thirty Gy of local irradiation seemed to be quite effective and safe.