Periocular Mucosa-Associated Lymphoid/Low Grade Lymphomas: Treatment With Antibiotics

doi:10.1016/j.ajo.2005.03.060

American Journal of Ophthalmology

Volume 140, Issue 4, October 2005, Pages 729-730

https://doi.org/10.1016/j.ajo.2005.03.060 Get rights and content

Purpose

To report on the treatment of primary mucosa-associated lymphoid tumors (MALT)/low grade lymphomas of the conjunctiva/orbit treated solely with systemic antibiotics.

Design

Retrospective interventional case series.

Methods

Three adult patients with biopsy/marker proven MALT lymphomas of the conjunctiva/orbit were treated with systemic antibiotics and followed for signs of local or systemic relapse.

Results

All three patients showed a response to antibiotics based on clinical, ultrasonographic, and MRI/CT imaging studies. Two patients have had complete remissions (42 months follow-up) and one a partial remission (18 months). No systemic relapses have occurred.

Conclusion

MALT/low grade lymphomas of the conjunctiva/orbit respond to systemic antibiotic therapy and may have complete remissions.

Section snippets

Patient 1

Forty-six months ago, a 58-year-old white man had a biopsy of a salmon colored subconjunctival mass. Histology was a low grade, diffuse, B cell MALT lymphoma. He was treated with one course of systemic antibiotics with a PrevPak without complications. Repeated systemic examinations, MRI of the orbits, ophthalmic examinations, and B-scan ultrasound have revealed no recurrent disease.

Patient 2

Twenty-one months ago a 79-year-old white man had a biopsy of a salmon colored subconjunctival mass. Histology was a diffuse lymphoid population of small, round lymphocytes with clumped chromatin and small amounts of cytoplasm. Flow cytometry revealed monoclonal B-cells expressing surface immunoglobulin of the IgMk isotype. He received doxycycline 100 mg twice a day for one month. Follow-up clinical, ultrasound, and PET scanning revealed considerable reduction in local disease.

Patient 3

Sixteen months ago a 74-year-old woman had a biopsy of a salmon colored subconjunctival mass. The pathology was a low-grade B cell lymphoma (MALT) with medium sized lymphocytes with scant cytoplasm. A systemic evaluation revealed no other disease. She was treated with doxycycline 100 mg twice a day for one month. Five months later, there is no clinical or ultrasonographic evidence of recurrence.

Some MALT/low grade lymphomas have been shown to be caused by infections, and early treatment of

References (5)

H. Boot et al.
Gastric lymphomathe revolution of the past decade
Scand J Gastroenterol Suppl
(2002)
E. Zucca et al.
Are antibiotics the treatment of choice for gastric lymphoma?
Curr Hematol Rep
(2004)

There are more references available in the full text version of this article.

Cited by (47)

Radiotherapy for localized gastric and orbital MALT lymphomas
2016, Cancer/Radiotherapie
Les lymphomes du Mucosa-Associated Lymphoid Tissue (MALT) gastrique et de la région orbitaire sont des lymphomes malins non hodgkiniens à cellules B de faible grade de malignité ou indolents. Ils sont radiosensibles et de pronostic favorable. De nombreuses études rétrospectives ont montré que la radiothérapie était un traitement efficace et bien toléré dans les lymphomes du MALT de la région orbitaire localisés, ainsi que de ceux gastriques de stades IE–IIE, en l’absence d’infection par Helicobacter pylori ou en cas de persistance du lymphome après éradication d’H. pylori.
Primary gastric and orbital MALT lymphomas are both low grade (indolent) B-cell non-Hodgkin's lymphomas. Traditionally, these tumors are radiosensitive and have a good prognosis. In localized orbital and stages IE–IIE gastric MALT lymphomas without Helicobacter pylori infection or in case of persistent H. pylori infection after eradication therapy, several retrospective studies have shown that radiotherapy was an effective and well-tolerated treatment.
Review article: Mucosa-associated lymphoid tissue (MALT)-type lymphoma of ocular adnexa. Biology and treatment
2016, Critical Reviews in Oncology/Hematology
Citation Excerpt :
Finally a further study reported that oral doxycycline led to a positive clinical response in 64% of C. psittaci DNA-positive and 38% DNA-negative OALs (Ferreri et al., 2006b) leading to the conlusion that results obtained in POAMLs with doxicycline are variable. In a recent review on the use of antibiotic therapy in non-gastrointestinal MALT lymphoma (Kiesewetter and Markus Raderer, 2013) were reported the cumulative results obtained with the use of doxycycline 100 mg BID for 21 days in a total of 8 studies (Ferreri et al., 2005, 2006b, 2008b, 2012; Abramson et al., 2005; Grünberger et al., 2006; Kim et al., 2010; Yeung et al., 2004). Only 3 of these studies were prospective (Ferreri et al., 2005, 2006b, 2012) and one was a case report (Yeung et al., 2004).
Over the last decades, we have witnessed an increase in the incidence of primary ocular adnexa lymphomas (POALs) probably because advances in imaging techniques have enabled precise biopsies of the tumors. The ocular tissue biopsy, before the initiation of the appropriate treatment, is mandatory and necessary for a correct diagnosis of POALs by the use of immunophenotyping and a correct molecular classification. Only in a minority of cases the ocular adnexa are secondarily affected by a systemic disease. Among the POALs, the most common is the primary extra nodal lymphoma of MALT-type (POAML). POAML is rarely symptomatic in the early phase of the disease. As a consequence, often we see a delay in ophthalmic consultations and diagnosis. The clinical manifestations are heterogeneous and its management requires a multidisciplinary approach involving ophthalmologists, hematologists and radiotherapists.
Antibiotic therapy in nongastrointestinal MALT lymphoma: A review of the literature
2013, Blood
Citation Excerpt :
In 2004, Ferreri et al11 were the first to report a possible association between CP and OAML and have consecutively contributed 4 further studies on CP eradication in such patients.14-17 We could identify a total of 9 studies14-22 published between 2004 and 2012 on antibacterial therapy in patients with OAML including Korean, Italian, Hungarian, US-American, Chilean, Spanish, Swiss, and Austrian study groups' experiences, providing a more or less “global” overview. Taken together, a total of 131 patients were enrolled in these 9 series, comprising 4 retrospective trials (number of patients = 58), 1 single case report, and 3 (initially 4) prospective trials including 81 patients.
Although antibiotic therapy has been established as the standard of care in patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, much less is known about the value of antibiotic therapy in nongastrointestinal (non-GI) MALT lymphomas. A computerized search (Medline) accompanied by a manual search to identify clinical reports on the topic of antibacterial therapy in patients with non-GI MALT lymphomas was performed. The majority of data were available for MALT lymphoma of the ocular adnexa (OAML) including a total of 131 patients in 4 retrospective studies, 3 prospective series (including 81 patients), and 1 case report. Treatment was exclusively targeting Chlamydophila psittaci (CP), using doxycycline in all but 2 studies. The median follow-up for these studies was 25 months, and both CP-positive as well as CP-negative patients responded. Complete remission was achieved in 23 patients (18%), 36 (27%) had a partial remission, 55 (42%) had stable disease, and 8 patients (6%) had progressive disease accounting for an overall response rate of 45%. In the largest study, a better response was suggested in CP-positive patients. By contrast, only scattered reports could be found for other non-GI localizations, allowing no conclusion about the benefit of antibiotic therapy and probably resulting in a publication bias toward positive cases. Based on these results, antibiotic therapy using doxycycline appears to be a reasonable first-line therapy for patients with OAML. Antibiotics, however, remain experimental for the time being in patients with other non-GI MALT lymphomas. Further preclinical studies as well as large-scale therapeutic trials are warranted to define the role of antibiotic therapy in such patients.
Extranodal marginal zone lymphoma of the ocular adnexa
2009, Blood
Citation Excerpt :
Failure to detect Cp resulting from lack of sensitivity of PCR technique, the existence of different bacterial strains, or previous antibiotic therapy could, according to the authors, explain responses to doxycycline in Cp-negative patients. Abramson et al84 treated 3 patients with biopsy-proven conjunctival MALT lymphoma with antibiotic therapy, resulting in 2 complete remissions and 1 partial response. Given the variable prevalence of Cp infection in patients with OAML, empiric antibiotic treatment without prior testing for chlamydial infection cannot be generally recommended, as elaborated by Grünberger et al.85 To shed more light on the efficacy of antibiotics in the treatment of patients with OAML, Husain et al43 conducted a meta-analysis, identifying 4 studies with a total of 42 patients who had been treated with oral doxycycline.
Lymphomas of the ocular adnexa are a heterogeneous group of malignancies, composing approximately 1% to 2% of non-Hodgkin lymphomas (NHLs) and 8% of extranodal lymphomas. The most common subtype, accounting for up to 80% of cases of primary ocular adnexal lymphoma, is marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type. In the recent past, there have been significant advances in our understanding of the clinical characteristics, morphology and phenotype, etiology, pathogenesis, diagnosis, natural history, treatment approaches, outcome, and prognostic factors of this disease entity. Novel immunologic and molecular techniques have aided in the distinction between MALT lymphoma and other lymphoproliferative disorders and led to the identification of tissue markers of prognostic significance. Modern imaging modalities provide invaluable tools for accurate staging and treatment planning. Besides radiotherapy and chemotherapy, a variety of new treatment options have emerged in the management of patients with ocular adnexal MALT lymphoma, especially monoclonal antibody therapy and antibiotic therapy against Chlamydia psittaci, which has been associated with the pathogenesis of ocular adnexal lymphomas in some parts of the world. In this review, we present a state-of-the-art summary of ocular adnexal MALT lymphomas.
The Role of Infectious Agents in the Etiology of Ocular Adnexal Neoplasia
2008, Survey of Ophthalmology
Citation Excerpt :
The first study from Austria had a median follow-up of 9 months86 and revealed that 11 patients were given daily doxycycline 200 mg orally over 3 weeks, and none of the patients had an objectively measureable response. However, a study from the United States of three patients with conjunctival MALT lymphoma revealed that two patients had a complete remission (42 months follow-up) and the other patient had a partial remission (18 months follow-up).2 The small sample sizes of these studies is an obvious caution, but one that is not easily addressed given the rarity of ocular adnexal MALT lymphomas.
Given the fact that infectious agents contribute to around 18% of human cancers worldwide, it would seem prudent to explore their role in neoplasms of the ocular adnexa: primary malignancies of the conjunctiva, lacrimal glands, eyelids, and orbit. By elucidating the mechanisms by which infectious agents contribute to oncogenesis, the management, treatment, and prevention of these neoplasms may one day parallel what is already in place for cancers such as cervical cancer, hepatocellular carcinoma, gastric mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma. Antibiotic treatment and vaccines against infectious agents may herald a future with a curtailed role for traditional therapies of surgery, radiation, and chemotherapy. Unlike other malignancies for which large epidemiological studies are available, analyzing ocular adnexal neoplasms is challenging as they are relatively rare. Additionally, putative infectious agents seemingly display an immense geographic variation that has led to much debate regarding the relative importance of one organism versus another. This review discusses the pathogenetic role of several microorganisms in different ocular adnexal malignancies, including human papilloma virus in conjunctival papilloma and squamous cell carcinoma, human immunodeficiency virus in conjunctival squamous carcinoma, Kaposi sarcoma–associated herpes virus or human herpes simplex virus-8 (KSHV/HHV-8) in conjunctival Kaposi sarcoma, Helicobacter pylori (H. pylori,), Chlamydia, and hepatitis C virus in ocular adnexal mucosa-associated lymphoid tissue lymphomas. Unlike cervical cancer where a single infectious agent, human papilloma virus, is found in greater than 99% of lesions, multiple organisms may play a role in the etiology of certain ocular adnexal neoplasms by acting through similar mechanisms of oncogenesis, including chronic antigenic stimulation and the action of infectious oncogenes. However, similar to other human malignancies, ultimately the role of infectious agents in ocular adnexal neoplasms is most likely as a cofactor to genetic and environmental risk factors.
Uveal lymphoid hyperplasia: treatment with combination antibiotics and steroids
2023, British Journal of Ophthalmology

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Brief reportPeriocular Mucosa-Associated Lymphoid/Low Grade Lymphomas: Treatment With Antibiotics

Purpose

Design

Methods

Results

Conclusion

Section snippets

Patient 1

Patient 2

Patient 3

Gastric lymphomathe revolution of the past decade

Scand J Gastroenterol Suppl

Are antibiotics the treatment of choice for gastric lymphoma?

Curr Hematol Rep

Brief report
Periocular Mucosa-Associated Lymphoid/Low Grade Lymphomas: Treatment With Antibiotics