Association between Chlamydia psittaci infection and extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT)-lymphomas

7568 Background: MALT-lymphomas are often associated with infectious organisms. Microbial species associated with MALT lymphomas are: Helicobacter pylori (H.pylori), Campylobacter jejuni, Borrelia burgdorferi, and Hepatitis C Virus. Recent studies showed evidence of Chlamydia psittaci (C. psittaci) infection in 80% of ocular adnexal lymphoma and tumor regression following eradication therapy. We studied the presence of C. trachomatis, C. pneumoniae, and C. psittaci DNAs in MALT lymphomas of various sites and in non-malignant controls. Methods: MALT lymphomas from the following sites were selected for analysis: salivary gland (n=13), thyroid gland (n=4), skin (n=2), ocular adnexa (n=2), stomach (n=6), intestinum (n=4). Samples of Sjoegren syndrome (n=10) and samples of H. pylori positive gastritis (n=7) were included as non-malignant controls. Macrodissected tissue containing >80% lymphoma cells from paraffin embedded tissue was processed for DNA isolation. For the presence of C. psittaci and C. pneumoniae DNA real time PCR assays were used. For C. trachomatis a commercially available PCR assay (Roche Molecular Diagnostics) was employed. All samples were tested twice. A sample was regarded as positive if at least one positive result was obtained. Results: C. psittaci was found at variable frequencies in MALT lymphomas of different sites: 4/13 (31%) salivary gland, 2/4 (50%) thyroid gland, 2/2 (100%) skin, 2/2 (100%) ocular adnexa, 1/6 (17%) gastric, and 0/4 intestinal MALT lymphomas. Among the non-malignant specimens, C. psittaci DNA was detected in 4/10 (40%) samples of Sjoegren syndrome and in 0/7 samples of H. pylori positive gastritis. All nongastric MALT lymphomas tested were negative for C. trachomatis and C. pneumoniae. Conclusion: Our data reveal a clear association of C. psittaci infection with extragastric MALT lymphoma. However, no evidence could be established for C. trachomatis and C. pneumoniae infection. Moreover, the high prevalence of Sjoegren syndromes - the most frequent precursor lesion for MALT lymphomas of salivary gland and ocular adnexa - may suggest an involvement of C. psittaci induced antigenic driven lymphomagenesis in a significant proportion of extragastric MALT lymphomas. No significant financial relationships to disclose.

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MALT lymphoma: epidemiology, clinical diagnosis and treatment

Journal of Medicine and Life ◽

10.25122/jml-2018-0035 ◽

2018 ◽

Vol 11 (3) ◽

pp. 187-193 ◽

Cited By ~ 13

Author(s):

Petruta Violeta Filip ◽

◽

Denisa Cuciureanu ◽

Laura Sorina Diaconu ◽

Ana Maria Vladareanu ◽

...

Keyword(s):

Helicobacter Pylori ◽

B Cell ◽

Malt Lymphoma ◽

Cell Lymphoma ◽

Gastric Lymphoma ◽

Eradication Therapy ◽

B Cell Lymphoma ◽

Gastric Malt Lymphoma ◽

H Pylori

Primary gastric lymphoma (PGL) represents a rare pathology, which can be easily misdiagnosed because of unspecific symptoms of the digestive tract. Histologically, PGL can vary from indolent marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) to aggressive diffuse large B-cell lymphoma (DLBCL). During the years, clinical trials revealed the important role of Helicobacter pylori (H. pylori) in the pathogenesis of gastric MALT lymphoma. Infection with Helicobacter pylori is an influential promoter of gastric lymphomagenesis initiation. Long-term studies revealed that eradication therapy could regress gastric lymphomas.

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Ocular Adnexal Lymphoma: A Clinicopathological Study of a Large Cohort of Patients with No Evidence for an Association with Chlamydia psittaci.

Blood ◽

10.1182/blood.v106.11.978.978 ◽

2005 ◽

Vol 106 (11) ◽

pp. 978-978

Author(s):

Manuel F. Rosado ◽

Gerald E. Byrne ◽

Feying Ding ◽

Keneth A. Fields ◽

Phillip A. Ruiz ◽

...

Keyword(s):

B Cell Lymphoma ◽

South Florida ◽

Response To Therapy ◽

Large Cohort ◽

Chlamydia Psittaci ◽

Comprehensive Cancer Center ◽

Primary Tumors ◽

Ocular Adnexa ◽

Geographical Regions

Abstract Ocular adnexal lymphomas (OALs) represent 6% of all primary extranodal NHL. However, they are among the most common primary tumors occurring in the ocular adnexa (26%). The etiology of OALs and the reason for the predominance of extranodal marginal zone lymphoma (EMZL) in this anatomical location are unknown. Ferreri et. al (J Natl Cancer Inst2004; 96:586) recently reported the presence of C psittaci DNA in 80% of the analyzed Italian ocular adnexa EMZL cases. Herein, we reviewed our 14-year single institution experience in a large cohort of patients with primary OALs and examined the association with C psittaci infection in South Florida. Clinicopathological characteristics, response to therapy, systemic dissemination and patients’ survival were analyzed in 62 patients with primary OALs treated and followed-up at the Sylvester Comprehensive Cancer Center. EMZL was the most frequent histological subtype (89% of OALs). Majority of EMZL patients (84%) presented with stage IE, however only 16% had an advanced stage. All stage IE patients were treated with local radiotherapy, while patients with disseminated disease received systemic therapy with or without local irradiation. All but one EMZL patient achieved CR. During a median follow up of 52 months (range 3–153), the estimated 5-year OS and FFP were 96% (95% CI: 90 to 100%) and 79% (95% CI: 65 to 92%), respectively. During the follow-up, 22% of patients relapsed, mainly in extranodal sites and 4% transformed to diffuse large B-cell lymphoma. None of the patients exhibited local orbital failure in the radiation field. To analyze the association between C psittaci infection and OALs in our patient population, C psittaci touchdown enzyme time release-PCR was used in 57 tumor specimens. DNA was extracted from 49 specimens of EMZL of ocular adnexa, 8 specimens of non- EMZL of ocular adnexa and 2 specimens from patients with reactive ocular lymphoid hyperplasia. C psittaci DNA was not detected in any of the 57 tumor DNA samples positive for either beta-globin or ApoE DNA quality control amplicons, while control reactions using DNA prepared form C psittaci strain 6 BC yielded amplicon of expected size. It is thus possible that there is a regional variation in EMZL etiology and association with infection pathogens. Additional studies evaluating the association between C psittaci and EMZL of ocular adnexa in other geographical regions are granted.

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Chlamydia Psittaci-Eradicating Antibiotic Therapy as a Potential Therapeutic Strategy Against Marginal Zone B-Cell Lymphoma of the Ocular Adnexa.

Blood ◽

10.1182/blood.v104.11.3274.3274 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3274-3274 ◽

Cited By ~ 1

Author(s):

Andres J. Ferreri ◽

Maurilio Ponzoni ◽

Massimo Guidoboni ◽

Antonia A. Lettini ◽

Laura Caggiari ◽

...

Keyword(s):

Antibiotic Therapy ◽

B Cell ◽

Marginal Zone ◽

Mononuclear Cells ◽

Cell Lymphoma ◽

Objective Response ◽

B Cell Lymphoma ◽

Chlamydia Psittaci ◽

Ocular Adnexa

Abstract Background: Chlamydia psittaci (Ch.ps.) DNA has been detected in tumor tissue of 80% of patients with ocular adnexal lymphoma (OAL) and in peripheral blood mononuclear cells (PBMCs) of 40% of them [Ferreri AJM, et al. J Natl Cancer Inst 96:586, 2004]. Chronic antigenic stimulation provided by Ch.ps. persistent infection may favor the development and sustaining of OAL. Removal of this stimulation with antibiotic therapy could result in lymphoma regression. Aim: To assess the rate of Ch.ps. eradication and anti-lymphoma activity of antibiotic therapy in OAL patients. Methods: Twelve patients with Ch.ps.-positive marginal zone B-cell lymphoma of the ocular adnexa, at diagnosis (n=5) or relapse, were treated with doxycycline 100 mg, bid orally, for three weeks. The presence of Ch.ps. DNA in lymphoma samples was assessed by multiplex touchdown PCR. Specificity of the amplified PCR fragments was confirmed by direct sequencing of both sense and anti-sense strands. The presence of Ch.ps. DNA in PBMCs collected before and one and 12 months after antibiotic therapy was evaluated in 11 cases. Six of these patients had Ch.ps.-positive PBMCs and were assessable for bacterial eradication rate. Nine patients had measurable disease at the time of therapy and were evaluable for objective response; a lymphomatous lesion of ocular adnexa was detected in all 9 evaluable patients: unilateral in three, bilateral in three, associated with regional lymphadenopathies in two, and with multiple subcutaneous nodules in one. Objective response was assessed one, three and six months after therapy conclusion and every six months during follow-up. Observation period after doxycycline ranged from 1 to 29 months (median 25). Results: All patients but one completed antibiotic therapy, with excellent tolerability. At one month from doxycycline assumption, Ch.ps. DNA was no longer detectable in PBMC of the six positive patients; these results were confirmed at one year of fw-up in all the three assessable cases. Objective response was complete in two patients (26+ and 9+ months), partial in two (29+ and 6+ m.) and lower than 50% in two (3+ and 5+ m.), whereas one patient had stable disease at one month of fw-up. Two patients experienced progression and received salvage treatment. Importantly, two patients showed lymphoma regression in previously irradiated orbit, and the two patients with regional lymphadenopathies achieved complete response; doxycycline was the 4th-line treatment in one of them. Time to the best response ranged from 3 to 24 months. All patients are alive and well (median fw-up: 54 m.). Conclusions: Ch.ps.-eradicating antibiotic therapy is followed by tumor regression in OAL patients, even after multiple relapses. Estimation of response rate requires a longer follow-up. A large phase II trial is warranted to confirm whether this fast, cheap and well-tolerated therapy may be a valid alternative to conventional, more aggressive strategies against OAL.

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Regression of Ocular Adnexal Lymphoma AfterChlamydia Psittaci–Eradicating Antibiotic Therapy

Journal of Clinical Oncology ◽

10.1200/jco.2005.07.083 ◽

2005 ◽

Vol 23 (22) ◽

pp. 5067-5073 ◽

Cited By ~ 143

Author(s):

Andrés J.M. Ferreri ◽

Maurilio Ponzoni ◽

Massimo Guidoboni ◽

Carlo De Conciliis ◽

Antonio Giordano Resti ◽

...

Keyword(s):

Antibiotic Therapy ◽

Mononuclear Cells ◽

Tumor Regression ◽

Objective Response ◽

B Cell Lymphoma ◽

Chlamydia Psittaci ◽

Peripheral Blood Mononuclear ◽

Ocular Adnexal Lymphoma ◽

Before And After ◽

Duration Of Response

PurposeSome infectious agents contributing to lymphomagenesis have been considered targets for new therapeutic strategies. Chlamydia psittaci DNA has been detected in 80% of ocular adnexal lymphomas. The present pilot study was carried out to assess whether C psittaci–eradicating antibiotic therapy is associated with tumor regression in ocular adnexal lymphomas.Patients and MethodsNine patients with C psittaci–positive marginal-zone B-cell lymphoma of the ocular adnexa at diagnosis or relapse were treated with doxycycline 100 mg, bid orally, for 3 weeks. The presence of C psittaci DNA in peripheral-blood mononuclear cells (PBMCs) was also assessed before and after treatment in seven patients. Objective lymphoma regression was assessed 1, 3, and 6 months after therapy conclusion and every 6 months during follow-up.ResultsAll patients completed antibiotic therapy with excellent tolerability. At 1 month from doxycycline assumption, chlamydial DNA was no longer detectable in PBMCs of all four positive patients. Objective response was complete in two patients, partial response (> 50%) was observed in two patients, and minimal response (< 50%) was observed in three patients. Duration of response in the seven responders was 12+, 29+, 31+, 8+, 7+, 2+, and 1+ months, respectively.ConclusionC psittaci–eradicating antibiotic therapy with doxycycline is followed by objective response in patients with ocular adnexal lymphoma, even after multiple relapses of the disease. A confirmatory, large, phase II trial is warranted to confirm whether this fast, cheap, and well-tolerated therapy could replace other more aggressive strategies as first-line treatment against ocular adnexal lymphomas.

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