Introduction
Syphilis is a systemic infectious disease caused by Treponema pallidum. Gastric involvement is uncommon and may mimic gastric carcinoma, lymphoma, or other inflammatory and infectious gastric diseases because of its nonspecific clinical, endoscopic, and histopathologic findings. Histologically, syphilitic gastritis is classically associated with a prominent lymphoplasmacytic infiltrate, but the amount of plasma-cell infiltration may vary, creating a potential diagnostic pitfall in small gastric biopsies.
We report a 20-year-old woman with gastric syphilis presenting as multiple irregular gastric ulcers. The case highlights the diagnostic value of recognizing the combined pattern of mucosal injury, lymphoplasmacytic inflammation, vascular changes, positive syphilis serology, and direct demonstration of T. pallidum in tissue. A pre-existing dissociative (conversion) disorder, recorded as "hysteria" in the original clinical chart, is reported only as part of the patient's medical history and is not considered etiologically related to gastric syphilis.
This report was prepared in accordance with the CARE case report guidelines.
Case description
A 20-year-old woman presented to our hospital with a 1-month history of recurrent epigastric pain that had worsened over the preceding 2 days and was accompanied by nausea and acid reflux. The pain was cyclic and more severe when she was hungry. Three years earlier, she had been diagnosed with a dissociative (conversion) disorder (recorded as "hysteria" in the original clinical chart) after a self-inflicted knife injury to the left hand; a further self-inflicted upper-limb injury occurred 1 year before presentation.
She reported no known history of sexually transmitted infection. On examination, she appeared distressed and had a depressed mood. Multiple painless lesions were present at both oral commissures and on the oral and nasal mucosa, clinically consistent with mucous patches of secondary syphilis.
Epigastric tenderness was present without rebound tenderness. No succussion splash or other signs of gastric outlet obstruction were identified, and bowel sounds were normal.
Laboratory investigations revealed the following abnormalities (Table 1).Table 1Summary of key laboratory findings on admission.TestResultInterpretationT. pallidum-specific antibodyPositivePositiveRapid plasma reagin (RPR)Positive, titer 1:128Abnormal (high titer)Anti-thyroid peroxidase antibody80.82 IU/mLElevatedAST/ALT ratio0.64DecreasedCholinesterase4708.00 U/LDecreasedHigh-density lipoprotein cholesterol0.73 mmol/LDecreasedApolipoprotein A10.76 g/LDecreasedLipoprotein (a)990.00 mg/LIncreasedUrea2.5 mmol/LDecreasedCreatine kinase24.00 U/LDecreasedLymphocyte percentage20.2%DecreasedMonocyte percentage8.7%Increased
Gastroscopy showed multiple focal ulcers with irregular, elevated margins, yellow surface exudates, and surrounding mucosal congestion and edema (Fig. 1).Fig. 1Gastroscopic images (A-D) showing multiple focal gastric ulcers with irregular, elevated margins and yellow surface exudates, accompanied by congested and edematous surrounding mucosa.
Histologically, biopsy specimens from the gastric antrum and body showed mucosal erosion with a dense mixed inflammatory infiltrate in the lamina propria, composed predominantly of lymphocytes and plasma cells with admixed neutrophils. Small vessels showed wall thickening and fibrosis with prominent perivascular lymphoplasmacytic inflammation. Focally, gastric pits were dilated, some glands were damaged, and reactive epithelial atypia was present.
Neutrophils were identified within glands and glandular lumina. No malignancy was identified (Fig. 2).Fig.
2(A-D) Gastric mucosal erosion with dense lymphoplasmacytic and neutrophilic inflammation in the lamina propria, small-vessel wall fibrosis, focal glandular injury with reactive atypia, and neutrophilic infiltration of glands and glandular lumina (original magnification: x200).
Immunohistochemistry for T. pallidum demonstrated numerous spirochetes along the gastric mucosal surface and within the lamina propria and epithelium (Fig. 3). In the context of positive syphilis serology and compatible clinicopathologic findings, these results supported the diagnosis of gastric syphilis.Fig.
3(A-B) Representative immunohistochemical images showing T. pallidum organisms within the gastric mucosa (original magnification: x400). Immunohistochemistry for T. pallidum demonstrated numerous spirochetes along the gastric mucosal surface and within the lamina propria and epithelium (Fig. 3).
Together with positive syphilis serology and compatible clinicopathologic findings, these results supported the diagnosis of gastric syphilis.
The patient received psychological counseling, antidepressant therapy, and anti-treponemal treatment with benzathine penicillin G (2.4 million units intramuscularly once weekly for 3 weeks). Her gastrointestinal symptoms resolved within 5 days after treatment was initiated. Repeat endoscopy, serologic follow-up of the RPR titer, and long-term clinical assessment were not available because she was lost to follow-up after discharge.
Written informed consent was obtained from the patient for publication of this report and the accompanying images.
Discussion
Gastric syphilis is an uncommon manifestation of systemic T. pallidum infection and remains a diagnostic challenge because it can closely resemble more common inflammatory disorders as well as gastric carcinoma and lymphoma. The diagnostic difficulty is particularly relevant in endoscopic biopsy specimens, in which the histologic findings may be striking but are not pathognomonic. In the present case, the combination of multiple irregular ulcers, active chronic mucosal injury, lymphoplasmacytic inflammation, small-vessel wall fibrosis, high-titer syphilis serology, and abundant T. pallidum organisms on immunohistochemistry established the diagnosis and prevented interpretation of the lesion as a gastric malignancy.
Gastric syphilis is most often reported during secondary syphilis [1], [2], [3], [4], [5]. In a published review, affected patients ranged from 20 to 57 years of age, with a mean age of 31.7 years [6]. Epigastric pain or discomfort is the most frequent presentation, while nausea, vomiting, dyspepsia, anorexia, melena, and weight loss may also occur [6].
Endoscopic abnormalities are similarly nonspecific and include mucosal edema, erosions, irregular ulcers, thickened folds, and nodular or mass-like lesions [7], [8], [9], [10], [11]. The antrum and gastric body are commonly involved [8]. In our patient, multiple ulcers with irregular elevated margins and surface exudates raised concern for malignancy, illustrating the well-recognized endoscopic mimicry of this infection.
The patient's pre-existing dissociative (conversion) disorder was an accompanying medical condition rather than a proposed risk factor or cause of syphilis. Her current gastrointestinal symptoms were associated with objective endoscopic, serologic, and histopathologic abnormalities. We therefore mention this history for clinical completeness but do not infer a causal relationship between the psychiatric disorder and T. pallidum infection or gastric involvement.
The histopathologic spectrum of syphilitic gastritis deserves particular attention. Previous reports have described a destructive active chronic gastritis with mucosal injury, gland loss or destruction, prominent lymphohistiocytic inflammation, lymphoid aggregates, and variable numbers of plasma cells [12], [13], [14]. In the largest detailed histopathologic series to date, Assarzadegan et al. examined eight cases and found prominent lymphohistiocytic inflammation in all cases, whereas prominent plasma cells were present in only five, emphasizing that pathologists should not rely exclusively on plasma-cell prominence as a diagnostic clue [14].
Vascular abnormalities, including vessel-wall thickening or fibrosis and perivascular inflammation, may provide additional support [12], [13], [14]. Our case is concordant with this expanded spectrum: lymphocytes were more conspicuous than plasma cells, with mucosal erosion, focal glandular injury, neutrophilic inflammation, and small-vessel wall fibrosis. Rather than representing a novel histologic pattern, these findings reinforce an important practical diagnostic pitfall already recognized in the literature.
These histologic findings overlap with several important differential diagnoses. Helicobacter-associated gastritis and other infectious gastritides may produce active chronic inflammation, while the intense lymphohistiocytic infiltrate and lymphoid aggregates described in syphilitic gastritis can prompt evaluation for extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue or other lymphoproliferative disorders [14]. Reactive glandular atypia adjacent to ulceration may also contribute to concern for carcinoma.
In this setting, the value of the biopsy lies not in any single microscopic feature but in recognition of the overall destructive inflammatory pattern and appropriate clinicopathologic correlation. When compatible clinical or serologic findings are present, organism-specific testing should be pursued.
Serologic testing is central to the diagnosis of syphilis, but direct demonstration of T. pallidum in gastric tissue provides strong supportive evidence that the gastric lesion is related to the infection. Warthin-Starry staining and immunohistochemistry can be used to demonstrate organisms, although immunohistochemistry is generally easier to interpret in routine histopathologic practice [15]. Direct immunofluorescence and molecular methods, including polymerase chain reaction, have also been used [16].
In the present case, immunohistochemistry demonstrated numerous spirochetes along the mucosal surface and within the lamina propria and epithelium. Together with an RPR titer of 1:128, compatible mucocutaneous findings, and the characteristic gastric injury pattern, this finding established the diagnosis.
Recognition of this diagnostic pattern has practical clinical consequences. Gastric syphilis is treatable and may improve rapidly after appropriate antitreponemal therapy, whereas misinterpretation as carcinoma or lymphoma may lead to unnecessary invasive investigations or treatment. Benzathine penicillin G remains standard therapy for syphilis, with the regimen determined by clinical stage and duration of infection.
For primary and secondary syphilis, benzathine penicillin G 2.4 million units is recommended as a single dose in the 2021 CDC guidelines [17] and once weekly for one to two doses in the 2020 Chinese national guideline [18], whereas three weekly doses are recommended for late latent or unknown-duration syphilis [17], [18]. Although our patient's mucous patches and high-titer RPR were consistent with secondary syphilis, she received three weekly doses, a regimen more intensive than that recommended for secondary syphilis. The treating team selected this regimen because of the very high RPR titer and concern for visceral or deep-tissue involvement in a patient with gastric lesions.
Additional doses have not been shown to improve efficacy in primary and secondary syphilis [17], and whether extended therapy confers any benefit in gastrointestinal syphilis remains uncertain. Previous reports describe rapid improvement in gastrointestinal symptoms after treatment, with endoscopic abnormalities resolving more gradually [6]. In our patient, gastrointestinal symptoms resolved within 5 days after benzathine penicillin G was initiated.
HIV status is particularly relevant in unusual gastrointestinal syphilis and in interpreting disease severity and follow-up requirements; our patient tested negative for HIV, hepatitis B surface antigen, and hepatitis C antibody. The concurrently treated dissociative disorder was a separate comorbidity and was not considered part of the pathogenesis or treatment of gastric syphilis.
This report has limitations. The patient was lost to follow-up after symptom resolution; therefore, decline in the RPR titer, endoscopic healing, and long-term clinical outcome could not be documented. Guidelines recommend clinical and serologic follow-up after treatment of early syphilis, at 6 and 12 months in the CDC guideline [17] and at 3-month intervals during the first year in the Chinese guideline [18], which was not possible here.
Treatment response could therefore be assessed only clinically, which limits confirmation of cure. The route and timing of T. pallidum infection also could not be established. Nevertheless, the concordance of serology, mucocutaneous findings, gastric histology, and abundant T. pallidum organisms in the biopsy provides strong evidence for the diagnosis.
Conclusion
Gastric syphilis is a rare but important mimic of gastric malignancy and lymphoproliferative disease. This case does not establish a new histologic subtype; rather, it reinforces the increasingly recognized spectrum of syphilitic gastritis and a clinically relevant diagnostic pitfall. A destructive gastric inflammatory pattern with lymphohistiocytic and lymphoplasmacytic inflammation, glandular injury, and vascular changes should prompt consideration of syphilis even when plasma cells are not striking.
Integration of histology with syphilis serology and direct demonstration of T. pallidum in tissue can establish the diagnosis and help prevent unnecessary aggressive management.
Case Reports
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CRediT authorship contribution statement
Wen Han: Writing – review & editing. Qian Zhang: Data curation. Hongwei Ye: Resources.
Jin Ma: Resources. Chun Wang: Supervision. Hailiqiemu Maimaiti: Resources.
Lihong Chen: Investigation. Yuhuan Wang: Data curation. Xinlan Song: Resources.
Ethics declaration
Written informed consent to take part in the study and to publish the article has been obtained from all participants or their legal representatives. The privacy rights of participants have been observed.
This study included organ or tissue donors. This study includes human biological material and consent was obtained by donors, or their next of kin or legal representatives, for use in this study and for publication of the article. The samples used in this research were not sourced from executed prisoners or prisoners of conscience.
This study was performed in compliance with relevant laws, regulatory frameworks and guidelines where the research took place. This study was approved by the 1.eople's Hospital of Xinjiang Uygur Autonomous Region, Tianshan District, No. 91, Tianchi Road, Urumqi, 830001, Xinjiang, China.
(Approval No. KY2026102001)
Declaration of Competing Interest
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Reports a relationship with that includes: Has patent pending to. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper