Case 6 -

Gastric syphilis Professor Fatima Carneiro Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP)

Clinical history: Man, 35-year-old, with long lasting dyspepsia. In January 2005 the patient was submitted to gastric endoscopies on two occasions at the Hospitais da Universidade de Coimbra in Portugal . He was found to have multiple, non-healing, gastric ulcers that failed to respond to Proton Pump Inhibitors (PPIs) therapy. Helicobacter pylori infection was not diagnosed and no antibiotic therapy was prescribed. Consecutively, diffuse gastric mucosal thickening was observed raising suspicion for a neoplastic process. A distal gastrectomy was performed on the patient at the same hospital. Case 6 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Clinicopathologic features: The surgical specimen was constituted by distal stomach (GC-24cm; LC-12-cm; duodenal segment- 1.5cm); lymph nodes (n=26) were isolated from both curvatures (the largest with 1.5cm in diameter); lymph nodes from the hepatic- and celiac-chain were sent also for examination. The antral mucosa appeared erythematous and edematous with irregular nodular masses. The body mucosa, however, had a normal appearance. By histology, no evidence of neoplasia was found but rather a diffuse inflammatory destructive gastritis. Notably, no parasite, viral inclusions or H. pylori were found on initial microscopic evaluation. Lymph nodes displayed reactive changes. The case was sent for consultation, initially to the University Hospital S.João, Porto , Portugal and later to the Gastrointestinal Pathology Service of the Massachusetts General Hospital , Boston , USA . The histological examination confirmed the presence of a dense, diffuse mucosal lymphoplasmacytic infiltrate with only scattered residual glandular elements with intraluminal abscesses. An ill-defined granulomatous process was also noted. Some inflammation spilled over into the superficial submucosa where an ill-defined perivascular distribution of the lympho-histocytic and plasma cell rich infiltrate raised the possibility of involvement by gastric syphilis. Based on this information, the patient was subsequently investigated and found to be HIV-negative but serologic testing revealed a reactive polyclonal hyper- gammaglobulinemia, a positive Venereal Disease Research Laboratory (VDRL) blood test of 1:16, and T. pallidum agglutination assay (TPHA) of 1:1,028. Despite a non-contributory Whartin-Starry stain, gastric syphilis was then strongly considered, and the paraffin-embedded thin sections of resected tissue were forwarded to the Laboratory Reference and Research Branch, Division of STD Prevention, Centers for Disease Control and Prevention in Atlanta, Georgia to perform direct fluorescent antibody staining specific for T. pallidum and polymerase chain reaction (PCR) for treponemal DNA detection (Two specific DNA targets: 47 kDa lipoprotein gene and DNA polymerase I gene (pol A) for T. pallidum were used in the real-time simplex PCR test). Direct immuofluorescent-antibody test results revealed the presence of numerous spirochetes that were immunologically specific for pathogenic treponemes. Real-time PCR probes detected positive signals from duplicated DNA samples extracted from two separate paraffin-embedded thin sections as well as from the positive DNA control. Diagnosis: Gastric syphilis Discussion: Reported cases of gastric involvement by T. pallidum have been rare in the medical literature. Ikebe et al. [1] reviewed 59 cases of gastric syphilis reported between 1971 and 1990. Since 1990, only 34 cases with 2 from HIV-infected patients have been documented [2]. The accurate mode of the syphilitic infection was not known in the present case. The patient was found to be HIV-negative on two occasions. Documented symptoms of gastric syphilis are usually non-specific and include nausea, vomiting, abdominal pain and weight loss. Complications including gastric hemorrhage, perforation, and gastric outlet obstruction have also been reported, but are less common [3]. Gastric syphilis may exhibit a variety of endoscopic and radiographic appearances including mucosal erosions, shallow ulcers, rugal hypertrophy, and nodularity that are indistinguishable from gastric lymphoma or linitis plastica. Routine staining with hematoxylin and eosin of the gastric biopsy typically shows marked, diffuse, chronic inflammation composed of a dense lympho-plasmacytic cell infiltrate with or without granulomas, often in a perivascular distribution. Endarteritis obliterans may also be present. The findings are etiologically non-specific and a high index of clinical suspicion is needed to prompt further evaluation and definitive diagnosis. Gastric syphilis remains a rare manifestation of the secondary and tertiary forms of the disease, which may affect young adults. It is exceedingly difficult to make a definitive diagnosis on the basis of biopsy findings, since spirochetes are seen infrequently and histopathologic findings are often nonspecific. Unless gastric syphilis is suspected and appropriate staining or molecular testing performed, the diagnosis cannot be made with certainty. The diagnosis has often been inferred in retrospect when examination of gastric lesion is negative for cancer, serologic tests are positive for syphilis, and the gastric lesion resolve after therapy with penicillin. Gastric syphilis should be considered in patients at risks for STD who complain of nausea, vomiting, weight loss, and abdominal pain and in whom unusual gastric lesions or presumed peptic ulcers unresponsive to standard therapy are encountered. Warthin-Starry silver stain is capable of demonstrating spirochetes and confirming the diagnosis. However, this method cannot differentiate T. Pallidum from contaminating oral or skin spirochetes. In the present case, we have employed the FITC-labeled anti-T. pallidum monoclonal antibody stain combined with the most recent molecular diagnostic testing, real-time PCR, to confirm the diagnosis of gastric syphilis. Both methods are specific for T. pallidum detection with higher sensitivity and a faster diagnosis achieved by the real-time PCR [4, 5]. After the diagnosis of gastric syphilis, the patient was treated by antibiotic therapy and has improved. No post-therapy specimens have been taken so far. References: Ikebe M, Oiwa T, Mori M, Kuwano H, Sugimachi K, Yao T: Gastric syphilis: case report and review of the literature. Radiat Med 12:171-175, 1994. Guerrero A F, Straight TM, Eastone J, Spooner K: Gastric syphilis in an HIV-infected patient. AIDS Patient Care STDs. 19:281-285, 2005. Winters HA, Notar-Francesco V, Bromberg K, Rawstrom SA, Vetrano J, Prego V, Kuan J, Raufman J-P: Gastric Syphilis: five recent cases and a review of the literature. Ann Intern Med 116:314-319, 1992. Norris S, Sell S: Role of polymerase chain reaction in the diagnosis of gastric syphilis. Human Pathol 27:749-750, 1996. Liu H, Rodes B, Chen C-Y, Steiner B: New tests for syphilis: rational design of a PCR method for detection of Treponema pallidum in clinical specimens using unique regions of the DNA polymerase I gene. J Clin Microbiol. 39:1941-1946, 2001.