Ocular Adnexal MALT Lymphoma Research Articles

Assessment of the role of hepatitis C, Helicobacter pylori and autoimmunity in MALT lymphoma of the ocular adnexa in 45 Austrian patients

Introduction. A recent series from Italy has suggested a pathogenic link between hepatitis C virus and MALT lymphoma of the ocular adnexa. The hypothesis of our study was to prove this concept in Austrian patients with MALT lymphoma of the ocular adnexa. Materials and methods. A total of 45 patients presenting with MALT lymphoma of the ocular adnexa were assessed for the presence of infection with hepatitis A, B and C. Furthermore, extensive staging to evaluate the extent of disease along with analysis of Helicobacter pylori-infection, the presence or absence of autoimmune diseases (AD) and assessment of MALT-lymphoma specific genetic changes was performed. Results. Only 2/45 (4%) patients were tested positive for hepatitis C, while 10/45 (22%) had an underlying AD and 15/39 (38%) had HP infection. Chromosomal aberrations were detected in 19 (54%) of 35 patients analyzed. Disseminated disease was a significant risk factor for relapse (p=0.014). Discussion. Our series suggests that infection with hepatitis C is not a significant contributor to the pathogenesis of ocular adnexal MALT lymphoma in the Austrian population, while a substantial proportion of these patients suffer from autoimmune conditions.

High Frequency of Loss of Heterozygosity Due to Uniparental Disomy or Allele Deletion of Ocular Adnexal MALT-Type Lymphoma.

Majority of malignant lymphoma arising from the ocular adnexae are ocular adnexal MALT lymphomas (OAL). Several genetic abnormalities, including t(14;18)(q32;q21), trisomy 18 and trisomy 3 have been reported in OAL. However, none of them are found in more than half of cases with OAL by conventional methods. High density Single Nucleotide Polymorphism (SNP) array analysis with CNAG/AsCNAR algorithm allows high-resolution and genome-wide detection of both loss of heterozygosity (LOH) and copy number abnormality, especially uniparental disomy (UPD), without depending on the availability of paired normal DNA (Yamamoto et al, Am J Hum Genet . 2007; 81:114–26). UPD is acquired by somatic recombination and therefore not detected by conventional cytogenetic analysis or array CGH. In this study we analyzed DNA from OAL for the presence of LOH with or without copy number changes. Tissue samples from patients with OAL at our institute between 1995 and 2003 (N=32) were subject to SNP-array (250K NspI) analysis with CNAG/AsCNAR algorithm. The patients included 21 males and 11 females, and the median age of 56.5 years at the time of diagnosis (range, 15–90 years). Clinical stage was I (29 cases), II (1 case), and IV (2 cases). Trisomy of 3, 18, and 21 were found in 9, 7 and 1 cases, respectively. Overall, LOH due to UPD more than one chromosomal band were found in 16 cases (50%). Recurrent one allele deletion was detected at 6q23-24, 12p13 and 17q21 (N=15, 15 and 21, respectively). In total, 28 (82%) among 32 cases showed one or more of the above changes. Characterization of these recurrent genetic abnormalities might reveal the pathogenesis of OAL.

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.

P067 FMC/FMC-R regiments efficiency in treatment of primary ocular adnexal MALT-lymphomas

P067 FMC/FMC-R regiments efficiency in treatment of primary ocular adnexal MALT-lymphomas

Absence of chlamydial infection in Japanese patients with orbital adnexal MALT lymphoma

18523 Background: The extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a distinct B-cell lymphoma that develops in extranodal sites and usually has an indolent clinical course as a localized disease. Recent clinicopathological studies suggest a strong relation between MALT lymphoma and inflammatory diseases of the epithelium such as autoimmune diseases and infections (Sjogren’s syndrome, Hashimoto’s thyroiditis, Helicobacter pylori infection, and etc.), because chronic antigen stimulation has been causally linked to the development of B-cells lymphoproliferative diseases. MALT lymphoma grows in extranodal lymphoid tissue and exists in epithelium tissues, and it is often difficult to distinguish malignant lymphoid tissue from benign inflammation. This is one cause since recent positive or negative correlations between ocular adnexal MALT lymphomas and chlamydial infections have been reported from different researchers, indicate several possible explanations. Methods: Twenty-three cases of ocular adnexal MALT lymphoma in southern regions of Japan, whose monoclonality was confirmed by immunoglobulin heavy chain gene rearrangement and/or cell surface antigens, were analyzed for evidence of several causative factors using ELISA analysis to detect antibodies and Southern blot analysis followed by specific PCR gene amplification. Results: Our series of patients did not show any serological relations to Epstein-Barr virus, Hepatitis C virus, and Chlamydophila psittaci. Two cases had positive serum antibodies for autoimmunity, and another two cases had positive antibodies against Chlamydia trachomatis. None of our cases showed the presence of chlamydial 16S rRNA and 16S-23S spacer rRNA genes (C. psittac, C trachomatis, C. pneumoniae, and C. felis) after Southern blot analysis followed by PCR amplification. Conclusions: Inflammatory agents are still unknown in our series of orbital adnexal MALT lymphomas, and some types of chlamydial infections are not associated with orbital adnexal MALT lymphoma in southern regions of Japan. No significant financial relationships to disclose.

Extranodal Marginal Zone B-cell Lymphomas of the Ocular Adnexa

Extranodal marginal zone B-cell lymphomas of MALT type (MALT lymphomas) show site-dependent variations in their morphologic, phenotypic, and/or cytogenetic findings. This report describes a comprehensive analysis of 34 ocular adnexa MALT lymphomas, including interphase fluorescence in situ hybridization for MALT lymphoma-associated cytogenetic abnormalities and polymerase chain reaction for Chlamydia psittaci, which has recently been suggested to be associated with ocular adnexa lymphomas. A typical morphologic pattern was identified in 79% of cases, while overtly monocytoid cytology (12%), predominantly plasmacytic features (9%), and lymphoepithelial lesions (3%) were uncommon. Aberrant CD43 or CD5 expression was also uncommon (12% and 3%, respectively). Plasmacytic differentiation (41%) was associated with stage IV disease (P=0.036) and gains of chromosomes 3 and/or 18q (P=0.021) (79%). +3 was more frequent in the orbit than in lacrimal gland or conjunctiva (P=0.005). Each of 31 cases was negative for MALT1 translocations. IGH translocations were identified in 3 cases (10%), although the translocation partner gene could not be identified. Polymerase chain reaction assays targeting species-specific regions within the C. psittaci omp1 and omp2 genes were negative in each of 30 cases. This study identifies the characteristic morphologic, phenotypic, and cytogenetic findings in ocular adnexa MALT lymphoma, including a subset differing from those arising at other anatomic sites. The frequent presence of +3 and/or +18q suggests that these abnormalities may contribute to lymphomagenesis. The lack of C. psittaci in this series, in contrast to some prior reports, indicates that there may also be geographic heterogeneity in the pathogenesis of ocular adnexa MALT lymphoma.

Primary Ocular Adnexal MALT Lymphoma: A Long-term Follow-up Study of 114 Patients

Although primary ocular adnexal MALT (mucosa-associated lymphoid tissue) lymphoma (POAML) is a recently recognized unique entity, its natural history, prognostic factors, behavior of progression and death, and standard initial management have not been fully elucidated. The data of 114 patients with histologically verified POAML who were treated at our institution between 1970 and 2003 were retrospectively analyzed. With a median follow-up duration of 5.7 years (0.6-34.0), estimated overall survival (OS) rate and progression-free survival (PFS) rate at 10 years was 89% and 57%, respectively. Thirteen (11%) patients died, but only three (3%) of them due to progressive lymphoma. Thirty-one (27%) patients progressed: eight who progressed at contra lateral sites were limited to those who had initially involved in the orbit (P = 0.036) and their OS and PFS were significantly longer (P = 0.035 and 0.039, respectively). Patients who initially received radiation-containing therapy were superior in PFS but not in OS to those initially treated with other modalities (P = 0.016 and 0.091, respectively). When we compared the outcomes of the observation cohort and the immediate therapy cohort, there were no significant differences in OS and PFS (P = 0.499 and 0.073, respectively). The majority of patients with POAML showed the behaviors of localized and indolent diseases. Our preliminary observation that no initial therapy is an acceptable approach for selected patients was confirmed. Considering the possible heterogeneity of POAML among initial sites, further investigations are warranted.

Absence of Chlamydial Infection in Japanese Patients with Ocular Adnexal Lymphoma of Mucosa-Associated Lymphoid Tissue

Ocular adnexal extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (ocular adnexal MALT lymphoma) are predominately low-grade, small B-cell types and may be caused by several putative inflammatory agents. Twenty-three ocular adnexal MALT lymphoma cases, the monoclonality of which was confirmed by examination of immunoglobulin heavy chain gene rearrangement and/or cell surface antigens, were analyzed for evidence of several causative factors. A serologic evaluation of our series of patients showed no evidence of infection by Epstein-Barr virus, hepatitis C virus, or Chlamydophila psittaci. Two patients tested positive for serum antibodies for autoimmunity, and another 2 patients tested positive for antibodies against Chlamydia trachomatis. Polymerase chain reaction analysis did not reveal the presence of the chlamydial 16S ribosomal RNA (rRNA) gene or the 16S-23S spacer rRNA gene. These results indicate that the inflammatory agents in our series of ocular adnexal MALT lymphomas are still unknown and that some types of chlamydial infections are not associated with orbital adnexal MALT lymphoma in southern regions of Japan.

Prognosis for Patients in a Korean Population with Ocular Adnexal Lymphoproliferative Lesions

To analyze the clinical features, treatment outcomes, and prognostic factors associated with lymphoproliferative lesions of the ocular adnexa in a Korean population. Data from 69 patients treated for adnexal lymphoproliferative disease in the 12-year period from 1991 to 2002 were retrospectively evaluated. The 69 patients had a median age of 46 years (range, 15-73 years); 60 of these patients were diagnosed with extranodal marginal zone B cell lymphomas (MALT lymphomas) and had 10 year cause specific survival and relapse free survival rates of 95.6% and 82.6%, respectively. Of 6 patients (8.7%) with concurrent systemic lymphoma, including 4 diagnosed with stage IV disease, 3 died from lymphoma. Only one patient with a primary ocular adnexal MALT lymphoma developed systemic lymphoma, which was treated with surgical resection. Local recurrence either at the primary site or in the fellow eye occurred in 11.6% of patients at a median follow-up time of 102 months (range, 79-132 months), and was controlled using repeat irradiation in all cases. Statistical analysis showed the presence of concurrent systemic lymphoma, bilateral disease, and an advanced stage at diagnosis, were linked to lymphoma-related death (Log-rank test, p < 0.05) and systemic progression (Fisher's exact test, p < 0.05), and that the tumor location was not a prognostic factor for lymphoma-related death or relapse at any site. Ocular adnexal lymphoproliferative disease in Koreans occurred at a relatively young age, and was mostly orbitally located and of the MALT subtype, which is highly localized and rarely associated with extraorbital relapse. Primary or secondary status, stage at presentation, and bilaterality were found to be prognostic factors.

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.

Absence of Chlamydial Infection in Japanese Patients with Ocular Adnexal MALT Lymphoma.

The extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a distinct type of B-cell lymphoma that develops in extranodal sites and usually has an indolent clinical course as a localized disease. Recent clinicopathological studies suggest a strong relationship between MALT lymphoma and inflammatory diseases of the epithelium such as autoimmune diseases and infections (Sjogren's syndrome, Hashimoto's thyroiditis, Helicobacter pylori infection, and etc.), because chronic antigen stimulation has been causally linked to the development of lymphoproliferative diseases in B cells. MALT lymphoma grows in extranodal lymphoid tissue and exists in epithelium tissues, and it is often difficult to distinguish malignant lymphoid tissue from benign inflammation. However, this is only one of the possible causes; recent positive and negative correlations between ocular adnexal MALT lymphomas and chlamydial infections reported by different researchers indicate several different possible explanations. Here, we analyze twenty-three cases of ocular adnexal MALT lymphoma whose monoclonality was confirmed by immunoglobulin heavy chain gene rearrangement and/or the analysis of cell surface antigens for evidence of expected causative factors, using both ELISA analysis to detect antibodies and specific PCR gene amplification followed by Southern blot analysis. Our series of patients did not show any serological relations to the Epstein-Barr virus, the Hepatitis C virus, or to Chlamydophila psittaci. Two cases had positive serum antibodies for autoimmunity, another two cases had positive antibodies against Chlamydia trachomatis. None of our cases showed the presence of chlamydial 16S rRNA or 16S-23S spacer rRNA genes (C. psittac, C trachomatis, C. pneumoniae, and C. felis) after PCR amplification. These results indicate that the inflammatory agents are still unknown in our series of ocular adnexal MALT lymphomas, and that some types of chlamydial infections are not associated with ocular adnexal MALT lymphoma in southern regions of Japan.

Fluorescence in situhybridization (FISH) analysis of primary ocular adnexal MALT lymphoma

BackgroundIt remains unknown whether primary ocular adnexal extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a homogeneous entity, as there are few reports of the results of cytogenetic or molecular analyses of these tumors.MethodsWe performed interphase fluorescence in situ hybridization (FISH) analysis to detect translocations and aneuploidy in 34 cases of primary ocular adnexal MALT lymphoma, and reviewed the histopathological findings. Correlations between the results of FISH analysis, the histopathological features and the clinical data were also analyzed.ResultsAmong the 34 cases, FISH analysis revealed t(14;18)(q32;q21) in one case, trisomy 3 in 21 cases (62%), and trisomy 18 in 16 cases (47%). The cases with trisomy 18 had significantly more prominent lymphoepithelial lesions (LELs) and less nodularity in the tumors. In regard to the clinical correlations, tumors with trisomy 18 were observed predominantly in females and younger patients; also, in the majority of the cases, the tumor was of conjunctival origin. All the cases with recurrence showed trisomy 18 in the tumor.ConclusionPrimary ocular adnexal MALT lymphoma is a significantly heterogeneous entity. Cases with trisomy 18 may have unique clinicopathological features.

Bacteria-Eradicating Therapy With Doxycycline in Ocular Adnexal MALT Lymphoma: A Multicenter Prospective Trial

An association between ocular adnexal MALT lymphoma (OAL) and Chlamydia psittaci (Cp) infection has been proposed, and recent reports suggest that doxycycline treatment causes tumor regression in patients with Cp-related OAL. The effectiveness of doxycycline treatment in Cp-negative OAL has not been tested. In a prospective trial, 27 OAL patients (15 newly diagnosed and 12 having experienced relapse) were given a 3-week course of doxycycline therapy. Objective lymphoma response was assessed by computerized tomography scans or magnetic resonance imaging at 1, 3, and 6 months after the conclusion of therapy and every 6 months during follow-up. Cp infection in patients was determined by touchdown enzyme time-release polymerase chain reaction (TETR-PCR). Statistical tests were two-sided. Eleven patients were Cp DNA-positive and 16 were Cp DNA negative. Doxycycline was well tolerated. At a median follow-up of 14 months, lymphoma regression was complete in six patients, and a partial response (> or = 50% reduction of all measurable lesions) was observed in seven patients (overall response rate [complete and partial responses] = 48%). Lymphoma regression was observed in both Cp DNA-positive patients (seven of 11 experienced regression) and Cp DNA-negative patients (six of 16 experienced regression) (64% versus 38%; P = .25, Fisher's exact test). The three patients with regional lymphadenopathies and three of the five patients with bilateral disease achieved objective response. In relapsed patients, response was observed both in previously irradiated and nonirradiated patients. The 2-year failure-free survival rate among the doxycycline-treated patients was 66% (95% confidence interval = 54 to 78), and 20 of the 27 patients were progression free. Doxycycline is a fast, safe, and active therapy for Cp DNA-positive OAL that was effective even in patients with multiple failures involving previously irradiated areas or regional lymphadenopathies. The responses observed in PCR-negative OAL may suggest a need for development of more sensitive methods for Cp detection and investigation of the potential role of other doxycycline-sensitive bacteria.

Chlamydia or Not Chlamydia , That Is the Question: Which Is the Microorganism Associated With MALT Lymphomas of the Ocular Adnexa?

In the mid-1990s, the demonstration that Helicobacter pylori infection is a risk factor for gastric marginal-zone B-cell lymphoma of MALT type (MALT lymphoma) and the fi nding that eradication of these bacteria can result in histological lymphoma regression in most patients made this tumor a popular model of antigen-driven lymphomagenesis ( 1 ) . The association of H. pylori with gastric MALT lymphoma led to the hypothesis that the microorganism provides an antigenic stimulus that sustains the growth of the lymphoma in the stomach, and today it is generally accepted that administration of antibiotics to eradicate H. pylori should be the sole initial treatment of gastric MALT lymphoma that is confi ned to the gastric wall. This approach has been validated in more than 20 reported studies ( 2 ) . These advances in the understanding and treatment of gastric MALT lymphoma pro mpted a search for microorganisms responsible for the growth of MALT lymphomas outside the stomach. Although Borrelia burgdorferi and Campylobacter jejuni have been associated with marginal-zone lymphomas arising in the skin and small intestine, respectively ( 3 , 4 ) , results implicating particular infectious microorganisms in nongastric lymphomas have often been elusive. In 2004, Ferreri et al. ( 5 ) reported in this journal that Chlamydia psittaci DNA was detected in 87% of lymphomas arising in the ocular adnexa (orbital soft tissue, lachrymal glands, and conjunctiva), and therefore, it has been proposed that C. psittaci infection may be a cause of these lymphomas. Furthermore, a very recent epidemiologic paper has shown a possible real increase in the incidence of ocular adnexal lymphomas, suggesting C. psittaci or another microorganism as possible causative agents ( 6 ) . However, subsequent to the report of Ferreri et al., other groups analyzed the prevalence of C. psittaci in these lymphomas, and overall, the reported data did not confi rm a strong link between C. psittaci infection and ocular adnexal MALT lymphomas ( Table 1 ). Thus, our understanding of the role of C. psittaci is far from complete. In this issue of the Journal, Ferreri et al. ( 7 ) report the results of a prospective trial in which patients affected by marginal-zone B-cell lymphoma of the ocular adnexa were treated for 3 weeks with the oral antibiotic doxycycline, with the intent of eradicating C. psittaci. The endpoints of the study were the rate of objective lymphoma response to antibiotic treatment and the presence or absence of C. psittaci DNA in peripheral blood mononuclear cells, the latter endpoint serving as a measure of C. psittaci eradication. Twenty-seven patients were enrolled and evaluated for response to treatment, 15 of them were newly diagnosed with ocular adnexal lymphoma and 12 had relapsed after previous therapies. Three patients had lymphoma involving regional lymph nodes and fi ve had bilateral MALT lymphomas. Preliminary results in the fi rst nine cases of the study have previously been published ( 8 ). C. psittaci was detected, using, as in the previous studies, a touchdown enzyme time release polymerase chain reaction ( 5 , 7 – 8 ) in 11 of 27 or 41% of lymphoma biopsies, a percentage lower than in the fi rst report from the same investigators

The tale and molecular trail of a disseminated ocular adnexal malt lymphoma

To report a case of a MALT lymphoma of the eyelid, which recurred in several sites over a time period of 14 years, and where the identical B-cell clone could be demonstrated in most samples using polymerase chain reaction (PCR) and GeneScan analysis. Clinical, histologic, immunohistochemical, PCR and GeneScan analysis findings are presented. A 58-year-old woman presented with a swelling of the left lower lid. Excisional biopsy of the tumour revealed a low-grade malignant B-cell Non-Hodgkin lymphoma (NHL) of MALT type. Despite localized radiochemotherapy, the patient developed recurrences occurring in the pharynx, in the right orbit, in the skin of the right foot, and in the bone marrow 1, 7, 11 and 14 years, respectively, after establishment of the first diagnosis. PCR for a rearrangement of the immunoglobulin heavy chains (IgH) and GeneScan analysis of the samples produced amplificates identical in size at most sites, indicating derivation from the same B-cell clone. It is generally assumed that ocular adnexal MALT lymphoma is associated with an indolent clinical course. Using IgH-PCR and GeneScan analysis, we demonstrate that the current case illustrates that these lymphomas do indeed require regular control examinations following treatment, as they often recur and disseminate in some patients in an unpredictable manner.

Primary ocular adnexal MALT lymphoma (POAML): A long-term follow up study of 114 patients (pts)

7593 Background: Although POAML is a recently recognized distinct entity, its natural history, prognostic factors, behavior of progression and death, and standard initial management have not been fully elucidated. Methods: 114 pts with a histologically verified POAML treated at our institution between 1970 and 2003 were retrospectively analyzed. Results: With a median follow-up duration of 5.7 years (0.6–34.0), estimated overall survival (OS) rate and progression-free survival (PFS) rate at 10 years was 89% and 57%, respectively. Older pts (&gt;60) showed significantly worse OS (p=0.002). However, other clinical factors did not affect significantly OS or PFS. 13 (11%) pts died, but only 3 (3%) due to progressive lymphoma. 31 (27%) pts progressed, 7(6%) at systemic diseases, 8 (7%) at contra lateral sites, and 16 (14%) at the same sites, and only 2 (2%) transformed high-grade lymphoma. All 8 pts who progressed at contra lateral sites were limited to those who had involved initially in the orbit (p=0.036) and their time to progression was significantly longer (p=0.039). Pts who received initially radiation-containing therapy were superior in PFS but not OS than those initially treated with other modalities (p=0.016 and 0.091, respectively). Moreover, when we compared the outcomes of no initial therapy cohort and immediate therapy cohort, there was no significant difference in OS and PFS (p=0.499 and 0.073, respectively). Conclusions: The majority of pts with POAML showed the behaviors of very indolent diseases, and only age was significant prognostic factor. Our preliminary observation suggesting that no initial therapy is an acceptable approach for selected pts (Ann Oncol 2006;17:135–40) was further confirmed in this study for all cohorts. Considering the possible heterogeneity of POAML among initial sites suggested by the present study and the genetic heterogeneity revealed by our previous study (Blood 2005;106:289a), further investigations on POAML are warranted. No significant financial relationships to disclose.

Bacteria-eradicating therapy for ocular adnexal MALT lymphoma: questions for an open international prospective trial

We read with great interest the article by Grünberger et al. on the ‘blind’ administration of doxycycline in a retrospective series of 11 patients with ocular adnexal lymphoma of MALT-type (OAL) [1]. Authors used this therapy on the basis that, in the Italian experience [2], most cases of OAL were shown to be related to chlamydial infection. However, a centralized molecular assessment of chlamydial infection was not performed, and no clinical responses were observed after a median follow-up of 9 months [1].

Chlamydia psittaci is variably associated with ocular adnexal MALT lymphoma in different geographical regions

Infectious agents play a critical role in MALT lymphoma development. Studies from Italy showed Chlamydia psittaci infection in 87% of ocular adnexal MALT lymphomas and complete or partial regression of the lymphoma after C. psittaci eradication in four of nine cases. However, C. psittaci was not demonstrated in ocular adnexal MALT lymphomas from the USA. This study was thus designed to investigate further the role of C. psittaci, and other infectious agents commonly associated with chronic eye disease, in the development of ocular adnexal MALT lymphoma. The presence of C. psittaci, C. trachomatis, C. pneumoniae, herpes simplex virus 1 and 2 (HSV1, HSV2), and adenovirus 8 and 19 (ADV8, ADV19) was assessed separately by polymerase chain reaction in 142 ocular adnexal MALT lymphomas, 53 non-marginal zone lymphomas, and 51 ocular adnexal biopsies without a lymphoproliferative disorder (LPD), from six geographical regions. C. psittaci was detected at similar low frequencies in non-LPD and non-marginal zone lymphoma groups from different geographical regions (0-14%). Overall, the prevalence of C. psittaci was significantly higher in MALT lymphomas (22%) than in non-LPD (10%, p=0.042) and non-marginal zone lymphoma cases (9%, p=0.033). However, the prevalence of C. psittaci infection in MALT lymphoma showed marked variation among the six geographical regions examined, being most frequent in Germany (47%), followed by the East Coast of the USA (35%) and the Netherlands (29%), but relatively low in Italy (13%), the UK (12%), and Southern China (11%). No significant differences in the detection of C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8, and ADV19 were found between lymphomas and controls from different geographical regions. In conclusion, our results show that C. psittaci, but not C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8 or ADV19, is associated with ocular adnexal MALT lymphoma and that this association is variable in different geographical areas.

Long-term follow-up results of no initial therapy for ocular adnexal MALT lymphoma

Background: The majority of lymphomas in the ocular adnexa are low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma). Although radiotherapy is the most frequently applied management, cataract and dry eye are problematic complications.Patients and methods: Between 1973 and 2003, the clinical features of 36 patients with ocular adnexal MALT lymphoma with no symptoms who were managed with no initial therapy after biopsy or surgical resection were retrospectively analyzed.Results: The median patient age was 63 years (range 22–84) and all patients had stage I disease, consisting of 31 unilateral cases and five bilateral cases. With a median follow-up of 7.1 years, 25 (69%) did not require treatment. The median time until the initiation of treatment in the remaining 11 patients (31%) was 4.8 years. Six patients (17%) died, and among them only two (6%) died due to progressive lymphoma. Seventeen patients (47%) progressed, but histologic transformation was recognized in only one (3%). The estimated overall survival rates of the 36 patients after 5, 10 and 15 years were 94%, 94% and 71%, respectively.Conclusions: In selected patients with ocular adnexal MALT lymphoma, no initial therapy might be an acceptable approach, because 70% of patients remained untreated at a median of 8.6 years, and their survival was comparable to that of reports on immediate therapy.