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Chlamydia Infection and Lymphomas: Association Beyond Ocular Adnexal Lymphomas Highlighted by Multiple Detection Methods

Authors' Affiliations: ¹ Pathology and ² Medical Oncology Units, and ³ Unit of Lymphoid Malignancies, Department of Oncology, San Raffaele Scientific Institute, Milan, Italy; ⁴ Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, IRCCS National Cancer Institute, Aviano, Italy; ⁵ Department of Animal Biology, University of Pavia and ⁶ National Reference Laboratory for Animal Chlamydioses, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Pavia, Italy

Requests for reprints: Maurilio Ponzoni, Pathology Unit, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy. Phone: 39-02-26432544; Fax: 39-02-26432409; E-mail: ponzoni.maurilio{at}hsr.it.

Purpose: Chlamydia psittaci (Cp) has been associated to ocular adnexal lymphomas (OAL) with variable geographic distribution. Herein, we used multiple Chlamydia detection tools to identify Cp elementary bodies–containing cell and to assess Cp prevalence in both nodal and extranodal lymphomas.

Experimental Design: TETR-PCR, immunohistochemistry, immunofluorescence, electron microscopy, and laser-capture microdissection were done in 35 OALs to define their effect in Chlamydia detection and, moreover, to identify the Cp cellular carrier. Cp prevalence was screened by TETR-PCR in 205 extraorbital lymphomas and 135 nonneoplastic controls.

Results: Twenty-six (74%) OALs were associated with Cp infection: immunohistochemistry, immunofluorescence, and laser-capture microdissection-assisted PCR showed that monocytes/macrophages were the Cp carriers; electron microscopy showed the presence of intact Cp elementary bodies into these cells. Immunohistochemistry and TETR-PCR showed a 70% concordance rate (P = 0.001). Cp DNA was equally prevalent in non-OAL, nodal, and extranodal lymphomas: among the latter, it was more common in diffuse large B-cell lymphomas of the skin (P = 0.03) and Waldeyer's ring.

Conclusions: This multiparametric approach shows, for the first time, that monocytes/macrophages are the carriers of Cp, Cp seems preferentially associated with lymphomas arising in organs primarily exposed to antigens. The clinical implications of these findings deserve to be prospectively investigated.