Journal of the National Cancer Institute Advance Access originally published online on September 11, 2007
JNCI Journal of the National Cancer Institute 2007 99(18):1418-1419; doi:10.1093/jnci/djm118
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© The Author 2007. Published by Oxford University Press.
CORRESPONDENCE |
A Woman and Her Canary: A Tale of Chlamydiae and Lymphomas
Affiliations of authors: Unit of Lymphoid Malignancies (AJMF, CD, PG, GPD, MP) and Medical Oncology Unit (AJMF, GPD), Department of Oncology, San Raffaele Scientific Institute, Milan, Italy; Cancer Bio-Immunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, IRCCS National Cancer Institute, Aviano, Italy (RD, EP); National Reference Laboratory for Animal Chlamydioses, Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna, Pavia, Italy (SM, NV); Pathology Unit (CD, MGC, LP, MP), Università Vita e Salute (PG, AD), and Ophthalmology Unit (AGR), San Raffaele Scientific Institute, Milan, Italy
Correspondence to: Andrés J. M. Ferreri, MD, Unit of Lymphoid Malignancies, Medical Oncology Unit, Department of Oncology, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy (e-mail: andres.ferreri{at}hsr.it).
Ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma is associated with chronic infection of Chlamydophila psittaci (Cp) (1), the etiologic agent of psittacosis, a human disease caused by infected bird exposure. Asymptomatic chlamydial infections are common in household animals (2), and human infections, including chronic conjunctivitis (3), may be underdiagnosed. Although 40% of patients with ocular adnexal MALT lymphoma report prolonged contacts with household animals and a history of chronic conjunctivitis (1), Cp transmission from an infected animal leading to asymptomatic Cp persistence and eventual development of a Cp-associated lymphoma in humans remains to be demonstrated. Here, we report the case of a patient with two metachronous Cp-associated lymphomas that provides the first evidence supporting this model.
In January 2000, a 60-year-old woman with ocular adnexal MALT lymphoma (in both lachrymal glands) was referred to our institution. Cp DNA in samples from diagnostic biopsy of the ocular adnexal MALT lymphoma was detected by touchdown enzyme time release–polymerase chain reaction (PCR) and sequencing (1). The patient underwent successive treatment regimens with rituximab, radiotherapy, and chlorambucil, all followed by relapse. At the third relapse, which occurred in the right lachrymal gland and cervical lymph nodes, she was treated with Cp-eradicating therapy with doxycycline (4), and this treatment was followed by a complete remission, which lasted beyond June 2007 (44+ months).
In September 2005, the patient complained of dyspnea, dysphonia, dysphagia, and cough. A neoplastic mass surrounding the right bronchus and multiple cervical and mediastinal lymphadenopathies of up to 5 cm were detected (Fig. 1, A). A fibrobronchoscopic biopsy revealed a diffuse large B-cell lymphoma (Fig. 1, C and D). Immunoglobulin heavy-chain variable region (IgHV) gene analysis (5) established that both lymphomas were clonally unrelated and showed that a single rearrangement occurred in the ocular adnexal MALT lymphoma (IgHV3-23 gene) and that two different rearrangements occurred in the diffuse large B-cell lymphoma of the bronchus (IgHV3-64 and IgHV4-34), thus confirming that the diffuse large B-cell lymphoma did not evolve from ocular adnexal MALT lymphoma.
Cp DNA was detected both in diffuse large B-cell lymphoma samples and in peripheral blood mononuclear cells collected simultaneously with bronchial biopsy. This led us to hypothesize that Cp reinfection occurred due to chronic exposure to a persistent source of the bacterium. A canary, present in the patient's house since 1998, was identified as a potential candidate. Cp DNA was found in the bird's feces and organs (lungs, spleen, liver, and bowel), and sequence analysis confirmed that both the patient and her canary were infected by the same chlamydial strain. Another Chlamydiaceae (Chlamydophila abortus) were excluded by PCR (6). The presence of Cp was confirmed by immunohistochemistry (Fig. 1, E) that showed scattered Cp-positive cells with macrophage-like morphology in tissue sections from ocular adnexal MALT lymphoma, diffuse large B-cell lymphoma, and the canary's organs.
The patient was treated again with doxycycline, achieving Cp eradication (DNA was no longer detected in post-antibiotic peripheral blood mononuclear cells) and complete lymphoma remission (Fig. 1, B), which lasted beyond June 2007 (19+ months). This finding suggests that, in an early phase, even aggressive lymphomas might be dependent on chronic antigenic stimulation and that regression of Cp-associated diffuse large B-cell lymphoma after antibiotic therapy should be further investigated.
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This case history adds new pathogenic and therapeutic perspectives to the association between Cp and lymphomas. To our knowledge, this was the first time that 1) the source of bacterial infection in a patient with Cp-related lymphoma was identified and 2) it was demonstrated that prolonged exposure to the infected bird resulted in continuous reinfection. Transmission from animals to humans mainly occurs through aerosols of fecal or feather dust, in which Cp remains viable for months (7). Thus, it is not surprising that both lymphomas in our patient arose in organs (ocular adnexa and bronchus) considered as "first barriers" to air-transported antigens. In patients with Cp-related lymphomas, sustained contact with potentially infected animals should be investigated. Either animal treatment or removal from contact with the patient may prevent Cp reinfection and eliminate subsequent risk of lymphoma development.
Funding
Italian Association for Cancer Research (to R. Dolcetti and C. Doglioni).
NOTES
A. J. M. Ferreri and R. Dolcetti contributed equally to this work.
The authors indicated no potential conflicts of interest.
The authors are thankful to Mrs M. B. E. and her family for their kind patience and continuous support. We appreciate the excellent technical assistance of Elena Dal Cin (Pathology Unit, San Raffaele Scientific Institute, Milan, Italy).
REFERENCES
(1) Ferreri AJ, Guidoboni M, Ponzoni M, De Conciliis C, Dell'Oro S, Fleischhauer K, et al. Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst (2004) 96:586–94.
(2) Nasisse MP, Guy JS, Stevens JB, English RV, Davidson MG. Clinical and laboratory findings in chronic conjunctivitis in cats: 91 cases (1983–1991). J Am Vet Med Assoc (1993) 203:834–7.[Web of Science][Medline]
(3) Lietman T, Brooks D, Moncada J, Schachter J, Dawson C, Dean D. Chronic follicular conjunctivitis associated with Chlamydia psittaci or Chlamydia pneumoniae. Clin Infect Dis (1998) 26:1335–40.[Web of Science][Medline]
(4) Ferreri AJ, Ponzoni M, Guidoboni M, Resti AG, Politi LS, Cortelazzo S, et al. Bacteria-eradicating therapy with doxycycline in ocular adnexal MALT lymphoma: a multicenter prospective trial. J Natl Cancer Inst (2006) 98:1375–82.
(5) Ghia P, Prato G, Scielzo C, Stella S, Geuna M, Guida G, et al. Monoclonal CD5+ and CD5– B-lymphocyte expansions are frequent in the peripheral blood of the elderly. Blood (2004) 103:2337–42.
(6) Hill JE, Goh SH, Money DM, Doyle M, Li A, Crosby WL, et al. Characterization of vaginal microflora of healthy, nonpregnant women by chaperonin-60 sequence-based methods. Am J Obstet Gynecol (2005) 193:682–92.[CrossRef][Web of Science][Medline]
(7) Grimes JE, Avian chlamydiosis. CRC handbook of zoonoses. Beran GW, Steele JH, eds. (1994) 2nd ed. Boca Raton (FL): CRC. Press. 389–402.
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