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American Journal of Dermatopathology:
doi: 10.1097/DAD.0b013e3181c22546
Letter to the Editor

Immunostaining for Treponema pallidum: Caution in its Evaluation

Fernandez-Flores, Angel MD, PhD

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Service of Cellular Pathology, Clinica Ponferrada, Ponferrada, Spain.

To the Editor:

We would like to report some examples that have made us evaluate the immunostaining for Treponema pallidum with extreme caution, especially out of an appropriate clinical context. Most laboratories use the antibody T. pallidum (Biocare), which has given good results in the diagnosis of mucocutaneous syphilitic lesions.1-6

With this antibody, we saw immunostaining of what seemed to be bacilli in cases in which acid alcohol resistant bacilli (AARB) had previously been demonstrated. We have observed this phenomenon in several cases. Figure 1 (top left), for instance, shows a biopsy from the larynx of an 82-year-old man who presented nodules in the larynx. Luetic serology was negative. The biopsy from the larynx showed necrotizing granulomas (Fig. 1, top left) with AARB which were easily found (Fig. 2, top left). After immunostaining for T. pallidum, some positive structures which were very similar to the AARB were found in the biopsy (Fig. 2, top right).

Figure 1
Figure 1
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Figure 2
Figure 2
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We have also observed the same phenomenon in cases of atypical mycobacteria infection. Figure 1 (bottom), for instance, shows a cutaneous infection by Mycobacterium marinum in a 50-year-old woman (swimming-pool granuloma). Clinically, the lesion shows a sporothricoid appearance (Fig. 1 bottom, left). The biopsy demonstrated a granulomatous dermatitis (Fig. 1, bottom right), with a central abscess in the granuloma. Under oil immersion examination, some AARB were seen among the neutrophils with Ziehl-Neelsen staining (Fig. 2, second row, left). The woman had an aquarium at home, and the lesion easily healed with a combination of trimethoprim-sulfamethoxazole and minocycline. Although no serologic investigation was made in this case for syphilis, we retrospectively performed an immunohistochemical study for T. pallidum. As Figure 2 (second row, right) shows, the antibody highlighted some positive long structures (nonspirochetae) which were very similar to the AARB.

Figure 1 shows (top right) another case which is more typical of what a general pathologist sees in cases of tuberculosis. A 51-year-old woman presented with hemoptoic sputum and some bronchial exophytic lesions which were biopsied. The biopsy showed a necrotic granuloma with caseum (Fig. 1, top right). In the central areas of the granuloma, several AARB were found with Ziehl-Neelsen staining (Fig. 2, third row, left). Figure 2 (third row, right) shows the immunostaining for T. pallidum in this case.

Given the difficulties in distinguishing these positive structures from bacilli (if they are not real bacilli), we suggest caution when evaluating a positive immunostaining for T. pallidum, especially out of a clinical context of syphilis. Some cases of nodal inflammatory pseudotumor caused by luetic infection have been reported,7 but in them, the microorganisms presented showed a typical corkscrew morphology, which could be a crucial requisite before interpreting any immunostaining for T. pallidum as positive. This is even more important, because it is well known how inflammatory pseudotumor can be associated to infections by mycobacterium. Examples have been reported in the spleen,6,8 the lung,9 the lymph nodes,10 and the soft tissues.11 A spindle-cell tumor due to mycobacterium has also been described in the skin.12,13

Furthermore, the antibody for T. pallidum immunostains Helicobacter pylori, which typically has a corkscrew morphology (Fig. 2, bottom right). However, these two microorganisms can be easily differentiated utilizing a Giemsa stain; Helicobacter are positive with this stain (Fig. 2, bottom left). Being aware of this fact is crucial, in order not to over diagnose gastritis due to Helicobacter as syphilitic gastritis, which is uncommon but it can occur.14-17

Angel Fernandez-Flores, MD, PhD

Service of Cellular Pathology, Clinica Ponferrada, Ponferrada, Spain

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REFERENCES

1. Buffet M, Grange PA, Gerhardt P, et al. Diagnosing Treponema pallidum in secondary syphilis by PCR and immunohistochemistry. J Invest Dermatol. 2007;127:2345-2350.

2. Dogru M, Kato N, Matsumoto Y, et al. Immunohistochemistry and electron microscopy of retrocorneal scrolls in syphilitic interstitial keratitis. Curr Eye Res. 2007;32:863-870.

3. Hoang MP, High WA, Molberg KH. Secondary syphilis: a histologic and immunohistochemical evaluation. J Cutan Pathol. 2004;31:595-599.

4. Martín-Ezquerra G, Fernandez-Casado A, Barco D, et al. Treponema pallidum distribution patterns in mucocutaneous lesions of primary and secondary syphilis: an immunohistochemical and ultrastructural study. Hum Pathol. 2009;40:624-630.

5. Quatresooz P, Piérard GE. Skin homing of Treponema pallidum in early syphilis: an immunohistochemical study. Appl Immunohistochem Mol Morphol. 2009;17:47-50.

6. Suster S, Moran CA, Blanco M. Mycobacterial spindle-cell pseudotumor of the spleen. Am J Clin Pathol. 1994;101:539-542.

7. Facchetti F, Incardona P, Lonardi S, et al. Nodal inflammatory pseudotumor caused by luetic infection. Am J Surg Pathol. 2009;33:447-543.

8. Androulaki A, Papathomas TG, Liapis G, et al. Inflammatory pseudotumor associated with Mycobacterium tuberculosis infection. Int J Infect Dis. 2008;12:607-610.

9. Yoganathan K, Elliott MW, Moxham J, et al. Pseudotumour of the lung caused by Mycobacterium malmoense infection in an HIV positive patient. Thorax. 1994;49:179-180.

10. Chen KT. Mycobacterial spindle cell pseudotumor of lymph nodes. Am J Surg Pathol. 1992;16:276-281.

11. Wood C, Nickoloff BJ, Todes-Taylor NR. Pseudotumor resulting from atypical mycobacterial infection: a “histoid” variety of Mycobacterium avium-intracellulare complex infection. Am J Clin Pathol. 1985;83:524-527.

12. Liou JH, Huang PY, Hung CC, et al. Mycobacterial spindle cell pseudotumor of skin. J Formos Med Assoc. 2003;102:342-345.

13. Shiomi T, Yamamoto T, Manabe T. Mycobacterial spindle cell pseudotumor of the skin. J Cutan Pathol. 2007;34:346-351.

14. Chung KY, Lee MG, Chon CY, et al. Syphilitic gastritis: demonstration of Treponema pallidum with the use of fluorescent treponemal antibody absorption complement and immunoperoxidase stains. J Am Acad Dermatol. 1989;21:183-185.

15. Kasmin F, Reddy S, Mathur-Wagh U, et al. Syphilitic gastritis in an HIV-infected individual. Am J Gastroenterol. 1992;87:1820-1822.

16. Lichtenstein JE. Case: syphilitic gastritis. Gastrointest Radiol. 1981;6:371-374.

17. Sachar DB, Klein RS, Swerdlow F, et al. Erosive syphilitic gastritis: dark-field and immunofluorescent diagnosis from biopsy specimen. Ann Intern Med. 1974;80:512-515.

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