Primary syphilis of the oropharynx mimicking a neoplasm

Introduction

Syphilis is a re-emerging infection worldwide, including in Japan.^1,2 In the past, most cases of syphilis were reported in men who have sex with men. However, recently, the reported number of infections through heterosexual contact have exceeded those through homosexual contact.^2,3 Known as “the great imitator,” ⁴ syphilis has highly variable of clinical manifestations, especially in the early stage. Herein, we present a case of primary oropharyngeal syphilis without any genital or skin lesions that was differentiated from malignancy based on the specific pathological findings.

Case summary

A 56-year-old man was referred to our internal medicine clinic by his primary physician with suspected oropharyngeal lymphoma. The patient had a 3-months history of mild dysphagia. He reported no fever, night sweats, or weight loss. At the previous clinic, which was an ear, nose, and throat clinic, the doctor had observed bilateral white oropharyngeal lesions with surface irregularities, and a tonsillar biopsy had revealed lymphoid tissue proliferation.

The patient had an unremarkable medical history and was not on any daily medications. He had smoked one pack-per-day of cigarettes for 10 years but had quit 25 years ago, and he did not consume alcohol. He reported sexual contact with one female partner over the previous year, was not a commercial sex worker and had never had sex with men. Clinically, his pharynx showed a “butterfly appearance,” with white lesions spread over both tonsils (Figure 1). There was no cervical lymphadenopathy, skin rash, or genital ulcers. Blood tests showed no obvious signs of inflammation (peripheral leukocyte count, 5280 cells/L; neutrophils, 61.0%; basophils, 0.5%; eosinophils, 1.0%; monocytes, 9.5%; lymphocytes, 28.0%; and C-reactive protein level, 0.17 mg/dL) or renal or liver impairment. Lactate dehydrogenase, soluble interleukin-2 receptor, and squamous cell carcinoma antigen levels were within the normal range (200 U/L [reference range, 124–220 U/L], 542.9 U/mL [reference range, 204–587 U/mL] and 1.58 ng/mL [reference range, 0.6–2.3 ng/mL], respectively).OPEN IN VIEWER

The tonsils were re-biopsied. The histology showed neutrophil and plasma cell infiltration, enlarged capillary endothelium, and lymphoid hyperplasia (Figures 2(a) and (b)), with no alteration in the lymphoid population immunophenotype for CD3, CD5, CD20, or CD79a antibodies, and no evidence of malignancy. However, immunohistochemistry for Treponema pallidum showed multiple spirochetes in the squamous epithelium (Figure 2(c)). Subsequently, although an enzyme immunoassay was not performed, an automated latex turbidimetric immunoassay for serum rapid plasma reagin (RPR) revealed positive nontreponemal flocculation (129.7 RU; reference range, 0–1 RU) and T. pallidum agglutination, confirming the diagnosis of oropharyngeal syphilis. There were no signs of other sexually transmitted infections, including human immunodeficiency virus infection. Polymerase chain reaction (PCR) tests of oropharyngeal samples for Neisseria gonorrhoeae and Chlamydia trachomatis were negative. The patient was treated with oral amoxicillin and probenecid for two weeks because intramuscular benzathine penicillin is not available at our institution and this combination has reported to be highly effective. ⁵ At the 1-month follow-up visit, the pharyngeal lesions and dysphagia had resolved. The serum RPR level after 3 or 6 months was unavailable.OPEN IN VIEWER

Discussion

Oral involvement is said to be one of manifestations of secondary syphilis. ⁶ A recent case series revealed that only 7.5% of oral syphilis were consistent with primary syphilis. Because most primary lesions are asymptomatic and self-limiting, oropharyngeal lesions can be discovered incidentally with other syphilitic lesions during the secondary stage. ⁷ Therefore, the epidemiology of oropharyngeal syphilis remains unclear.

Oropharyngeal syphilis typically causes bilateral tonsillar lesions, which need to be differentiated from other conditions including neoplasms and viral, fungal, mycobacterial, and protozoal infections. ⁶ Presence of syphilis-related oropharyngeal lesions without other lesions such as rash or genital ulcers can be mistaken for a sign of underlying malignancy, including lymphoma.^4,8 Pathological findings of oropharyngeal syphilis show marked submucosal lymphoplasmacytic infiltration. ⁹ However, if syphilis is not clinically suspected and the lesions are biopsied and submitted for histopathology as suspected neoplasms, pathological diagnosis can be challenging. Mucosal lesions with plasma cell infiltration may be key findings for clinicians to suspect syphilis and should be evaluated using immunostaining for T. pallidum or PCR.^9,10

Immunohistochemistry for T. pallidum reveals in which layers spirochetes are present, thereby helping to differentiate the stage. In primary syphilis, immunostaining shows a mixed epitheliotropic and vasculotropic pattern of spirochetes, whereas in secondary syphilis, the spirochetes are restricted to the lower epidermal layers and have an intercellular distribution. ¹¹ The histopathology findings in our patient, showing most spirochetes in the upper epidermal layer, were characteristic of primary syphilis.

When clinicians encounter subacute oral lesions, they should consider syphilis in the differential diagnosis, even if the patient does not have any obvious risk factors. Isolated oropharyngeal manifestations are occasionally present in the primary stage and can be easily misdiagnosed if not suspected. ⁴ This is particularly important as the rates of syphilis continue to increase in many regions worldwide.