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Cross-reactivity of Anti-Treponema Immunohistochemistry With Non-Treponema Spirochetes: A Simple Call for Caution

2016; American Medical Association; Volume: 140; Issue: 10 Linguagem: Inglês

10.5858/arpa.2016-0004-le

1543-2165

Sory J. Ruiz, Gary W. Procop,

Leptospirosis research and findings

Syphilis has different histopathologic presentations, and it can mimic a significant number of entities. The anti–Treponema pallidum immunohistochemical stain (Biocare/PP153AA, Concord, California) is useful in cutaneous biopsies from patients with secondary syphilis, and it is superior to the Warthin-Starry silver stain.1 At our institution, we have been asked about the possibility of syphilis involving oropharyngeal mucosa or the gastrointestinal tract. We are cautious when examining these biopsies because some non-Treponema spirochetes are present in the normal microbiota of the human oropharynx and gastrointestinal tract. It was our concern that these non-Treponema spirochetes may cross-react with the anti-Treponema antibody, potentially contributing to a misdiagnosis.Human intestinal spirochetosis is characterized by the presence of a layer of spirochetes adherent to the apical epithelial surface of the colorectal mucosa. The spirochete species most often associated with this finding in humans are Brachyspira pilosicoli and Brachyspira aalborgi. Brachyspira pilosicoli has been identified in other animals, such as pigs, rodents, and chickens, suggesting that the acquisition can be zoonotic.2 Higher prevalence rates are reported in developing countries, homosexual men, and HIV-positive patients, who are also at increased risk for syphilis.3The histopathologic findings of intestinal spirochetosis are different from those of syphilis. We are not suggesting that this differentiation is a diagnostic conundrum. Rather, we used biopsies from patients with intestinal spirochetosis to evaluate the potential of cross-reactivity of a commercially available polyclonal antibody directed against T pallidum.We searched the electronic archives at our institution for the diagnosis of "intestinal spirochetosis" from January 2005 to December 2014. Eight biopsies from patients with intestinal spirochetosis were found. Hematoxylin-eosin stains and Warthin-Starry stains were available in all cases. The slides were reviewed and the diagnoses confirmed. In all biopsies, the hematoxylin-eosin–stained sections revealed a thickened and shaggy basophilic band on the apical cell membrane of the colorectal epithelium; Warthin-Starry stain demonstrated numerous spirochetes (Figure, A and B). Immunohistochemistry for T pallidum (Biocare/PP153AA) was performed on 2-μm sections of paraffin-embedded tissues, and the tissues were incubated 16 minutes at 37°C. The protein-antibody complexes were located with a biotin/streptavidin–horseradish peroxidase/diaminobenzidine tetrahydrochloride (DAB) detection kit (iView DAB Detection; Ventana Medical Systems, Oro Valley, Arizona).All biopsies showed strong positivity for the polyclonal antibody for T pallidum (Figure, C). These findings are supportive of those described by De Brito and colleagues,4 who described the cross-reactivity of the spirochetes of intestinal spirochetosis with both anti–T pallidum and anti–Leptospira interrogans antibodies.4The potential for cross-reactivity of commercially available antibodies for T pallidum with other spirochete species poses a potential diagnostic pitfall when biopsies are taken from locations wherein spirochetes may be encountered. The anti–T pallidum immunohistochemical stain remains a significant advance in the detection of T pallidum spirochetes in the biopsies of patients with syphilis. It is important for the pathologist to be aware of this cross-reactivity with non-Treponema spirochetes. The histopathologic diagnosis of syphilis should not rest entirely on a positively staining spirochete. Rather, the diagnosis should be made based on the presence of the spirochetes with the appropriate histopathologic findings.