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                    ORAL AND MAXILLOFACIAL SURGERY
                    A RARE CASE REPORT OF SYPHILIS MIMICKING AN
Case Report
                    OROPHARYNGEAL NEOPLASM
                    Sofia Kalantary1a, Christophe Politis2b* , Wouter De Vos1,3c, Sten Stevens1d, Maarten Van Genechten1,3e,
                    Herman Jr Vercruysse1,3f, Geert Van Hemelen1g
                    1
                     ZMACK / Associatie MKA, AZ Monica Antwerp, Belgium
                    2
                     Department of Maxillofacial Surgery, Hôpital Erasme, Université Libre de Bruxelles – ULB, Brussels, Belgium
                    3
                     Department of Cranio-Maxillofacial Surgery, Antwerp University Hospital, Z.M.A.C.K association of Antwerp

                    a
                      MD, DDS, Maxillofacial Surgery Resident; e-mail: kalantarysofia89@gmail.com;
                    b
                      MD, DDS, Maxillofacial Surgery Resident; e-mail: christophe.politis@gmail.com; ORCIDiD: https://orcid.org/0000-0002-1076-1327
                    c
                      MD, DDS, Maxillofacial Surgeon; e-mail: de.vos.w@gmail.com;
                    d
                      MD, DDS, Maxillofacial Surgeon; e-mail: sten.stevens@gmail.com;
                    e
                      MD, DDS, Maxillofacial Surgeon; e-mail: maartenvangenechten@telenet.be;
                    f
                     MD, DDS, Maxillofacial Surgeon; e-mail: juni90@hotmail.com;
                    g
                      MD, DDS, Maxillofacial Surgeon; e-mail: drvanhemelen@azmonica.be;


                    ABSTRACT                                                                                https://doi.org/10.25241/stomaeduj.2021.8(1).art. 8

                    Aim Syphilis is a widely spread, sexually transmitted disease that is often considered archaic, but it has been
                    on the rise in recent years. The oropharyngeal region is an uncommon location for treponema pallidum to
                    present itself. It is even more uncommon when, on a radiological evaluation, it is diagnosed as a neoplasm
                    or squamous cell carcinoma. This case report discusses a rare case of syphilis that mimics an oropharyngeal
                    carcinoma.
                    Summary The patient presented himself initially with cervical lymphadenopathies and an oropharyngeal
                    lesion. On the MRI scan, the lesion was suspicious for an oropharyngeal squamous cell carcinoma. Multiple
                    negative biopsies (2X) urged the search for an alternative diagnosis. After serologic testing, it became clear
                    the patient was suffering from syphilis. Syphilis is known as the “great pretender” and can present in a non-
                    specific manner.
                    Key learning points
                    i) Syphilis is known as the “great pretender”.
                    ii) Treponema pallidum infections need to be taken into account as a differential diagnosis in patients with
                    an oropharyngeal lesion.
                    iii) Syphilis is on the rise.
                    iv) Syphilis has the ability to mimic a malignancy upon clinical presentation.
                    v) Syphilis has the ability to mimic a malignancy on CT and MRI-imaging.

                    KEYWORDS
                    Syphilis; Cervical Lymph Node; Oropharyngeal Ulceration; Carcinoma; Mimicking.


                    1. INTRODUCTION                                                                   Since 2010, reports of syphilis incidence rates in the
                                                                                                      European Union (EU) have been ever increasing.
                    An increasing incidence of syphilis is inherently                                 This trend seems to be accelerating, predominantly
                    related to an increasing number of atypical presen-                               amongst male homosexuals [1]. Syphilis is a sexually
                    tations of the disease. Syphilis is on the rise and, with                         transmitted infection caused by Treponema palli-
                    the increase in cases, there has been an increase in                              dum, a well-known pathogen that can cause patho-
                    different and unusual presentations of the disease.                               logy in the maxillofacial area. Although there is little


                                   OPEN ACCESS This is an Open Access article under the CC BY-NC 4.0 license.
                                   Peer-Reviewed Article
                        Citation: Kalantary S, Politis C, De Vos W, Stevens S, Van Genechten M, Vercruysse Jr H, Van Hemelen G. A rare case report of syphilis mimicking an
                        oropharyngeal neoplasm. Stoma Edu J. 2020;7(4):78-82
                        Received: February 06, 2021; Revised: February 10, 2021; Accepted: February 13, 2021; Published: February 15, 2021
                        *Corresponding author: Dr. Christophe Politis, Department of Maxillofacial Surgery, Hôpital Erasme, Université Libre de Bruxelles – ULB,
                        Route de Lennik 808, B-1070 Bruxelles, Belgium
                        Tel: +32 (0)2 555 4474; Fax: +32 (0)2 555 4599; e-mail: Christophe.politis@gmail.com;
                        Copyright: © 2020 the Editorial Council for the Stomatology Edu Journal.




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literature describing oropharyngeal treponema              of the tonsils, mucosa, hard and soft palate, floor




                                                                                                                        Case Report
pallidum infections as mimicking an oropharyngeal          of the mouth, dentition, and tongue showed no
squamous cell carcinoma (OPSCC), it has been               abnormalities.
described in rare cases [2]. This case report presents
such a case.                                               3. RADIOGRAPHIC EXAMINATION
Ulcers of the oral cavity and the oropharynx are
frequently encountered in maxillofacial practices          A multi-slice computerized tomography scan (CT)
around the world. Consequently, the differential diag-     with iodine contrast revealed an irregular lining
nosis of oral and oropharyngeal ulcers is an important     on the left of the posterior wall of the oropharynx
one. A wide range of causes for oral or oropharyngeal      (Fig. 2). Furthermore, the scan showed a slight retro-
ulcers are reported, such as aphthous, traumatic,          pharyngeal gray area without any collection or fluid
malignant, tuberculosis, HIV and AIDS (Table 1).           build-up.
Ulcers can also present associated with skin lesions       There were multiple lymphadenopathies in the
[3]. Most of these ulcers are promptly diagnosed and       neck, at levels II to III on the left side and on level II
treated because the oral or oropharyngeal subsite          on the right side. In addition, a magnetic resonance
and the anamnesis are often positive indicators            imaging (MRI) scan was performed to further investi-
for diagnosis. An important differential diagnostic        gate this soft tissue lesion. The MRI scan showed
criterium for traumatic ulcerations is if healing occurs   an oropharyngeal lesion compatible with an
after removal of the probable cause. It is important       oropharyngeal carcinoma (Fig. 3). There was no
however to distinguish innocent solitary ulcerations       extranodal extension in the neck. As an oropha-
from malignant lesions, such as squamous cell              ryngeal squamous cell carcinoma was suspected,
carcinomas. Lesions that persist longer than 3 weeks       a diagnostic biopsy was performed.
should be considered as malignant until proven
otherwise.                                                 4. PATHOLOGY
A tuberculous ulcer is rare, almost always secondary
to lung tuberculosis and preferably located on the         Two negative biopsies were taken by an ENT surgeon
tongue (or lips). It is often not painful and regional     before referral. Because the clinical presentation
lymphadenopathy is usually present. A rare cause           was very suggestive for malignancy, a fiberoptic
of chronic solitary ulcers is syphilitic ulceration.       inspection under general anesthesia with biopsies
Ulcer usually develops on the lips and, rarely, on the     was performed at our center.
tongue, the pharynx, or the tonsils [4]. In even more      The biopsy showed mucosal ulceration and a dense
rare cases, the ulcer will present itself mimicking        chronic inflammation with mixed lymphoplasmacytic
a neoplasm in the oropharynx on a clinical and a           infiltrate. No monoclonal cell population was detec-
radiological basis. Hence, it has been named “the          table, and there was no evidence of dysplasia or
great pretender” [5].                                      epithelial malignancy.

2. CASE REPORT                                             5. DIAGNOSIS

A 35-year-old male with no significant medical             Although the clinical and radiologic presentation
history was referred to the Cranio-Maxillo-Facial          was very suspect for an oropharyngeal carcinoma,
department of the University Hospital of Antwerp,          multiple negative biopsies ruled out a malignancy.
Belgium with swallowing difficulty and minor pain          Alternative diagnoses were investigated and a
in the throat for the last two months. He suffered         differential diagnosis was made. After performing
from significant fatigue and unexplained weight            extensive laboratory tests, the diagnosis of an active
loss of 10 kg in the previous months. He noticed a         syphilis was confirmed.
swelling of the left oropharynx and multiple bilateral     Blood tests showed a positive Treponema pallidum
lumps in his neck. There was no history of smoking,        RPR (Rapid Plasma Regain) in combination with
oncological disorders, or a familial predisposition to     highly elevated titers in the Treponema Pallidum
cancer. The patient claimed to have no risk factors for    particle Hemagglutination Assay (TPHA). The TPHA
sexually transmitted diseases and no sexual contact        test is a very sensitive treponemal test (sensitivity
for a longer period of time.                               >95% and specificity >99%, qualitative mean
Clinical examination revealed an ulcerative mass           accuracy, 91.4%; range, 56.1 to 98.2%; quantitative
of 30 mm by 50 mm in size in the left oropharynx           mean accuracy, 75.4; range, 55.5 to 95.5%) [6].
(Fig. 1). The ulceration was associated with moderate      In this case, the TPHA was >20280 which indicated
pain complaints.                                           the presence of treponema pallidum. In addition
The patient had multiple swollen cervical lymph            to the TPPA result, a RPR (Rapid Plasma Regain,
nodes, which were painless. No facial deformities          nontreponemal test) was performed, with a positive
or any neurological abnormalities were noted. The          result (titer 2).
thyroid gland presented normal upon swallowing             The results of this nontreponemal test is
and was not enlarged. Further intra-oral examination       semiquantitative, reflecting the activity of the



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                    Kalantary S, et al.
www.stomaeduj.com

Case Report



                     Figure 1. Ulcerative lesion seen in the left oropharynx.                   Figure 2. Axial section of a CT scan of the head and neck showing an ir-
                                                                                               regular posterior wall of the oropharynx.

                     Table 1. Differential diagnosis for oral/oropharyngeal ulcers..

                     Traumatic                                                                Syphilis
                     Malignant                                                                Tuberculosis
                     Iatrogenic (radiotherapy, chemotherapy, antiresorptive                   Recurrent, painful ulcerations (Behçet’s disease, chemotherapy,
                     medication, etc.)                                                        radiotherapy, herpetic, aphtous, etc.)



                                                                                               7. DISCUSSION

                                                                                               Due to the rising number of cases of syphilis,
                                                                                               syphilitic lymphadenitis is an important differential
                                                                                               diagnosis for patients presenting with cervical
                                                                                               lymphadenopathy and oropharyngeal lesions [9].
                                                                                               Clinicians should be aware that syphilis can also
                                                                                               present as a squamous cell carcinoma-like lesion
                                                                                               in most oral subsites [10]. In this case, the patient
                                                                                               presented with weight loss, fatigue, cervical lympha-
                                                                                               denopathies, an oropharyngeal lesion, and an MRI
                                                                                               scan that suggested a possible oropharyngeal squa-
                                                                                               mous cell carcinoma. Because multiple biopsies were
                                                                                               negative for malignancy, an alternative diagnosis
                                                                                               was eventually made.
                                                                                               It has to be mentioned, that there are different techni-
                                                                                               ques to obtain an oropharyngeal biopsy, and
                                                                                               a false-negative result may be possible if the
                     Figure 3. Axial section of an MRI scan of the head and neck showing an    technique employed is not optimal. In case of
                    oropharyngeal lesion compatible with an oropharyngeal carcinoma.           doubt, a new biopsy should be taken and retaken
                                                                                               by the same surgeon, taking into account that an
                    infection [7]. Given the clinical presentation and                         incision biopsy at the exact location of the lesion
                    serologic testing, the diagnosis of a primary/early                        is the most sensitive. We advise against fine-
                    secondary active syphilis was made. HIV testing                            needle aspiration cytology of ulcerative lesions
                    was negative, as was the screening for Chlamydia,                          because of its lower sensitivity and specificity,
                    Hepatitis B and C, and gonorrhea.                                          which are respectively 71.4% and 97.8% [11].
                                                                                               Syphilis can evolve into four stages, each with certain
                    6. TREATMENT                                                               characteristics (Table 2). Given the absence of
                                                                                               mucous patches or maculopapular lesions, and the
                    The patient was referred to the infectious disease                         local presentation, a working diagnosis of primary
                    specialist and his general practitioner (GP) for                           syphilis was made [12].
                    treatment with benzathine penicillin intramuscular                         Tamura et al. (2008) described a case similar to the
                    (2.4 million IE, one day treatment) [8].                                   one presented in this report [13]. His patient presen-
                    After 3 weeks the patient was seen on consultation,                        ted with an oropharyngeal tumor and a cervical
                    and the lesion and the discomfort had disappeared.                         lymphadenopathy with the primary lesion being



    80              Stoma Edu J. 2021;8(1): 78-82                                                                  pISSN 2360-2406; eISSN 2502-0285
A rare case report of syphilis mimicking an oropharyngeal neoplasm
                                                                                                                                                    www.stomaeduj.com




                                                                                                                                                   Case Report
 Table 2. Most important characteristics of the four syphilitic stages.

 Stages                         Timing                                                 Characteristics
 Primary                        3-4 weeks incubation                                   Painless chancre at the site of infection
 Secondary                      4-10 weeks after infection                             Rash, systemic symptoms (fever, weight loss,
                                                                                       fatigue), headache, mucous membrane lesions
                                                                                       throughout body
 Latent                         Early latent (< 1 year after infection)                Asymptomatic, diagnosis through serologic testing
                                Late latent (> 1 year after infection)
 Tertiary                       1-10 years after infection                             Gummatous lesions, Cardiovascular issues, CNS
                                                                                       disorders

strongly suggestive for oropharyngeal cancer.                             the ‘great pretender’, in their ability to mimic a
Eventually this case was diagnosed with oropha-                           malignancy upon clinical presentation and on CT
ryngeal syphilis. As a FDG-PET scan was performed                         and MRI-imaging.
as part of a staging procedure, their work-up slightly
differed from ours. Since FDG is not specific for                         CONFLICT OF INTEREST
malignancy, it will also accumulate in many benign                        The authors declare that they have no competing interest.
processes such as inflammatory, post-traumatic or
benign tumours. Preferably incisional qualitative                         ACKNOWLEDGMENTS
biopsy should be taken before imaging FDG-PET
scan is considered.                                                       There are no conflicts of interest and no financial interests to be
                                                                          disclosed.
8. CONCLUSION
                                                                          AUTHOR CONTRIBUTIONS
Treponema pallidum infections need to be taken into
                                                                          SK, CP, HV wrote the manuscript in consultation with WD and
account as a differential diagnosis in patients with                      GV. All authors provided critical feedback and helped shape the
an oropharyngeal lesion when histopathological                            research and the manuscript. SS and MV aided in interpreting the
results exclude malignancy. Syphilis is known as                          results.




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Stoma Edu J. 2021;8(1): 78-82                                                                pISSN 2360-2406; eISSN 2502-0285                        81
                    Kalantary S, et al.
www.stomaeduj.com

Case Report                                                                                               Sofia KALANTARY
                                                                                         MD, DDS, Maxillofacial Surgery Resident
                                                                                                       ZMACK / Associatie MKA
                                                                                                  AZ Monica Antwerp, Belgium




                    CV
                    Dr. Sofia Kalantary is a resident in Oral and Maxillofacial Surgery at the University of Antwerp, Antwerp, Belgium. She has a clinical
                    focus in orthognathic and dento-alveolar surgery. During her training she spent two years at the St. Elisabeth Hospital, Tilburg in
                    the Netherlands where she was trained by JPO Scheerlinck. For the last two years of her residency she specialized in the field of
                    orthognathic surgery and 3D surgical planning at the ZMACK / MKA association of Antwerp, Belgium.




                    Questions
                    1. Syphilis is a sexually transmitted infection caused by
                    qa. Treponema pallidum;
                    qb. Actinomyces;
                    qc. Streptococcus salivarius;
                    qd. Neisseria gonorrhoeae.

                    2. Primary syphilis has an incubation time of
                    qa. 6 months;
                    qb. 3-4 weeks;
                    qc. 4-10 weeks;
                    qd. 1 day.

                    3. Syphilis has the ability to mimick
                    qa. Dental caries;
                    qb. Periodontal disease;
                    qc. Neuropathic pain;
                    qd. A malignancy on CT- and MRI-imaging.

                    4. An oral/oropharyngeal ulcer cannot be one of the following
                    qa. Syphilis;
                    qb. Traumatic ulcer;
                    qc. Malignant;
                    qd. Hemangioma.




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