Ocular adnexal lymphoma---comparison of MALT lymphoma with other histological types

Cahill, Mark; Barnes, Colma; Moriarty, Paul; Daly, Peter A.; Kennedy, Susan

doi:10.1136/bjo.83.6.742

Cited by 84 publications

(65 citation statements)

References 29 publications

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“…The median diagnosis age in our study was 63 years, which is similar to a previously reported median age at diagnosis of POAML ranging from 41 to 72 years. [28][29][30][31] However, POAML can be seen in patients of any age, including children (the youngest patient in our cohort was 7 years old). We observed a higher incidence of preceding autoimmune disorders in POAML patients (12.4%) compared with previous reports (0% to 6%).…”

Section: Discussionmentioning

confidence: 99%

“…3,4,30,33,35 Only 20% of our POAML patients presented with more advanced disease, and BM was involved in 10 patients (9%) who underwent BM biopsy. BM biopsy upgraded patients' stage from Ann Arbor stage I to IV in only 6 cases.…”

Section: Discussionmentioning

confidence: 99%

“…30,33 Only few studies demonstrated conjunctival involvement as the most common anatomical location of tumor. 28,34 It is possible that there are some geographical changes in the anatomical predisposition of POAML.…”

Section: Discussionmentioning

confidence: 99%

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Long-term course of patients with primary ocular adnexal MALT lymphoma: a large single-institution cohort study

Desai

Joag

Lekakis

et al. 2017

Blood

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Key Points• POAML (specifically Ann Arbor stage I disease) has an excellent clinical outcome, with only a few patients succumbing to lymphoma.• POAML patients face a continuous risk of distant relapse, including in the central nervous system, and transformation to aggressive lymphoma.While primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML) is the most common orbital tumor, there are large gaps in knowledge of its natural history. We conducted a retrospective analysis of the largest reported cohort, consisting of 182 patients with POAML, diagnosed or treated at our institution to analyze long-term outcome, response to treatment, and incidence and localization of relapse and transformation. The majority of patients (80%) presented with stage I disease. Overall, 84% of treated patients achieved a complete response after first-line therapy. In patients with stage I disease treated with radiation therapy (RT), doses ‡30.6 Gy were associated with a significantly better complete response rate (P 5 .04) and progression-free survival (PFS) at 5 and 10 years (P < .0001). Median overall survival and PFS for all patients were 250 months (95% confidence interval [CI], 222 [upper limit not reached]) and 134 months (95% CI, 87-198), respectively. Kaplan-Meier estimates for the PFS at 1, 5, and 10 years were 91.5% (95% CI, 86.1% to 94.9%), 68.5% (95% CI, 60.4% to 75.6%), and 50.9% (95% CI, 40.5% to 61.6%), respectively. In univariate analysis, age >60 years, radiation dose, bilateral ocular involvement at presentation, and advanced stage were significantly correlated with shorter PFS (P 5 .006, P 5 .0001, P 5 .002, and P 5 .0001, respectively). Multivariate analysis showed that age >60 years (hazard ratio [HR] 2.44) and RT<30.6Gy (HR54.17) were the only factors correlated with shorter PFS (P 5 .01 and P 5 .0003, respectively). We demonstrate that POAMLs harbor a persistent and ongoing risk of relapse, including in the central nervous system, and transformation to aggressive lymphoma (4%), requiring long-term follow-up. (Blood. 2017;129(3):324-332)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Long-term course of patients with primary ocular adnexal MALT lymphoma: a large single-institution cohort study

Desai

Joag

Lekakis

et al. 2017

Blood

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“…94,95 Adnexal MALT lymphomas have been described in the context of chronic conjunctivitis, and particularly "inclusion conjunctivitis," which can be associated with Chlamydia infection. 96,97 The presence of Chlamydia psittaci DNA in biopsy material and peripheral-blood mononuclear cells from patients with ocular adnexal lymphomas 94 was demonstrated by targeted polymerase chain reaction (PCR), and C psittaci DNA was detected in 80% of ocular adnexal lymphoma samples.…”

Section: Malt Lymphomasmentioning

confidence: 99%

Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation

Suarez

2006

Blood

399

296

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IntroductionThe geographic heterogeneity in the incidence of B-cell nonHodgkin lymphomas (NHLs) suggests that environmental factors such as infections might have a role in lymphomagenesis. 1,2 Because of the inherent genetic instability of lymphocytes, lymphoid proliferation increases the risk of transformation, and sustained activation of the lymphoid system, which can be observed during chronic infection, immunodeficiency, and autoimmunity, constitutes a risk factor for lymphomas. [3][4][5] Congenital and acquired immunodeficiencies associated with HIV infection and solid organ or hematopoietic transplantation increase the risk of developing B-cell NHLs. 6,7 Similarly, Sjögren syndrome and other autoimmune conditions are also associated with an increased risk of lymphomas. 8,9 Certain types of lymphomas are associated with specific microbial infections, and infection-associated lymphomas currently fall in diverse histopathologic categories (Table 1). 10 Infections may contribute to lymphomagenesis by promoting favorable conditions for lymphocyte transformation, such a increased proliferation or decreased apoptosis of lymphoid cells. 11 Direct lymphocyte transformation by a given microbial agent is the simplest scenario accounting for infection-associated lymphomas. Lymphotropic transforming viruses such as Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), and human Tlymphotropic virus 1 (HTLV-1) directly infect a subset of lymphoid cells in which they express viral oncogenes. [12][13][14] An alternative scenario to direct transformation of lymphocytes has more recently emerged for microbial species associated with lymphomas but that do not directly infect or transform lymphoid cells. They have in common the ability to persist chronically in host tissues and trigger a sustained lymphoid proliferation, giving a selective advantage to lymphoid clones that still remain dependent upon antigen stimulation. 15,16 According to this model, the microbial pathogen is neither intrinsically transforming nor oncogenic, but can be viewed as a chronic source of antigens increasing the proliferative rate of lymphoid effectors, hence fueling the transformation process. This model has emerged with the description of several lymphomas developing in the context of chronic antigen-dependent immune stimulation, among which H pylori-associated gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the best characterized 15,17,18 (Figure 1). Precise elucidation of the mechanisms underlying this "indirect" lymphomagenesis as well as completion of the inventory of the microbial species driving these antigen-dependent lymphoproliferations may provide important clues for their early diagnosis and the rationalization of the therapeutic interventions for this subtype of lymphomas.This group of lymphomas often involves extranodal sitesnormally devoid of organized lymphoid tissue-and manifests initially as indolent low-grade proliferations, reminiscent of the normal lymphoid hyperplasia driven by a physiologic antigenic stimulation....

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“…Both ocular adnexal MALT lymphomas and gastric MALT lymphomas are characterized by an indolent course, a large prevalence of marginal zone B-cell histologic type, and a varying degree of infiltrating reactive T-cells. 29 The role of an infectious agent may further be elucidated by National Cancer Institute data that depict a rapid and steadily increasing incidence of ocular non-Hodgkin lymphomas from 1975-2001 (both intraocular and adnexal) in white men and women, with no evidence of peaking in recent years. 158 This is in distinct contrast to non-ophthalmic non-Hodgkin lymphomas, the incidence of which showed evidence of peaking in recent years.…”

Section: Chronic Antigen Stimulation In Ocular Adnexal Malt Lymphomamentioning

confidence: 99%

The Role of Infectious Agents in the Etiology of Ocular Adnexal Neoplasia

Verma

Shen

Sieving

et al. 2008

Survey of Ophthalmology

114

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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.

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Ocular adnexal lymphoma---comparison of MALT lymphoma with other histological types

Abstract: As a small percentage of these tumours recur, patients should be followed up indefinitely. (Br J Ophthalmol 1999;83:742-747)

Cited by 84 publications

References 29 publications

Long-term course of patients with primary ocular adnexal MALT lymphoma: a large single-institution cohort study

Long-term course of patients with primary ocular adnexal MALT lymphoma: a large single-institution cohort study

Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation

The Role of Infectious Agents in the Etiology of Ocular Adnexal Neoplasia

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