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Historically, granulomatous inflammation has been described in association with tertiary syphilis. However, in recent years there have been increasing reports of granulomatous inflammation in patients with secondary syphilis. Here, we discuss two patients who presented with erythematous infiltrated papules and nodules and were eventually diagnosed with granulomatous secondary syphilis, with clearance of their rashes following treatment. We highlight important clues that can point clinicians and histopathologists toward a diagnosis of syphilis instead of differential diagnoses such as leprosy in reaction, cutaneous histiocytosis and lymphoma. Furthermore, after performing a literature review and from our own experiences, we wish to highlight that granulomatous syphilis is often palmoplantar-sparing and its presence may not necessarily be a feature of immunocompromised states, such as HIV infection. In this increasingly connected world, the recognition of an atypical presentation of an age-old disease in patients with different skin types must be underscored by close clinicopathological correlations., Competing Interests: Conflicts of interest: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Abstract: Syphilis is a sexually transmitted disease that can present a wide variety of clinical and histopathological manifestations. We present the case of a 75-year-old patient with a persistent maculopapular rash on the trunk and extremities, in which the biopsy showed an exclusively perifollicular granulomatous infiltrate. In the immunohistochemical staining with anti- Treponema pallidum antibodies, spirochetes scattered within the perifollicular inflammatory infiltrate were identified. These findings together with the serological analysis allowed the diagnosis of secondary syphilis. Folliculotropic nonalopecic syphilis is rare, and the pathogenic mechanisms that cause this specific tropism are unknown. On the other hand, granulomatous inflammation is a pattern typically described in tertiary syphilis but also occasionally found in secondary syphilis. We present a case of secondary syphilis with the combination of both histopathological findings, an uncommon constellation for dermatopathologists to consider., Competing Interests: The author declares no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A 44-year-old male presented with a 2-month history of erythematous ulcerative papules and plaques on the scalp, face, and bilateral lower legs. He had a 5-year history of well-controlled HIV on antiretroviral therapy and recurrent syphilis infections. His face had violaceous plaques, while bilateral ankles and calves had ulcerative lesions with necrotic centers and purple borders. The morphologies clinically mimicked pyoderma gangrenosum on the lower extremities and cutaneous lymphoma on the face. Biopsy and reactive rapid plasma reagin confirmed a diagnosis of lues maligna, and the patient was successfully treated with penicillin G benzathine., (© 2024 The Author(s). International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Syphilis is a sexually transmitted infection characterized by multiple stages. Cardiovascular involvement is a manifestation of tertiary syphilis, occurring between 10 and 40 years after the primary infection. The authors present a case of atypical presentation of tertiary syphilis in a 49-year-old male patient who was admitted to the hospital with bilateral transient loss of vision. Contrast-enhanced CT imaging revealed thoracic aortitis with carotid occlusion, coronary artery stenosis, ischemic stroke, myocardial infarction, and multiple intracardiac thrombi. A postmortem autopsy revealed positive laboratory results for syphilis, which was corroborated by medical autopsy findings of syphilitic aortitis. Keywords: CT-Angiography, Aorta, Cardiac, Vascular, Tertiary Syphilis © RSNA, 2024.

Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary Gastric syphilis is rare and presents in 1% of patients with syphilis. The most common presenting symptom is abdominal pain and fullness (92%), followed by nausea/vomiting (71%), weight loss (60%), and gastric bleeding (35%). Multisystem involvement may be seen, as with our patients who presented with a rash and chancre, but in up to two-thirds of patients, there may be no concurrent extraintestinal manifestation of syphilis. The endoscopic appearance typically consists of multiple annular ulcerations and erosions, sometimes with a purple/brown hue at the ulcer margin, as well as nodular mucosa, thickened gastric folds, and nondistensibility of the stomach. This presentation leaves the clinician with a broad differential diagnosis, including lymphoma, infiltrative tumors, Crohn’s disease, and tuberculosis, to name a few. Histologic examination can demonstrate a chronic gastritis with dense plasmacytic and lymphocytic infiltrate, proliferative endarteritis or endophlebitis, and perivascular cuffing. A high index of suspicion for T pallidum is needed to appropriately diagnose gastric syphilis with serologic testing and to detect spirochetes on gastric biopsy specimens with immunostaining, silver staining, dark field microscopy, or polymerase chain reaction. Treatment is prescribed based on the clinical stage of syphilis and results in full resolution of symptoms. The nonspecific clinical and endoscopic presentation of gastric syphilis indeed makes it “the great imitator” of other gastric diseases. Therefore, as highlighted in these cases, gastric syphilis should be suspected in high-risk patients who present with abdominal symptoms and unusual endoscopic findings. Early diagnosis can lead to prompt treatment and a significant decrease in syphilis-associated morbidity. Deepika Satish, MD, Assistant Professor of Medicine, Baylor College of Medicine, Houston, Texas, USA Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

Context.—: Syphilis, a reemerging disease caused by the spirochete Treponema pallidum, is becoming more frequent in surgical pathology and hematopathology practices. Hematopathologists typically receive lymph node biopsies from patients with syphilis who have localized or diffuse lymphadenopathy. Occasionally, syphilis infection in the aerodigestive tract can show a prominent lymphoplasmacytic infiltrate and mimic lymphoma. Besides the varying and occasional atypical morphology, the fact that clinical suspicion tends to be low or absent when histologic evaluation is requested adds to the importance of making this diagnosis., Objective.—: To summarize histologic features of syphilitic lymphadenitis and syphilis lesions in the aerodigestive tract, and to review differential diagnosis and potential diagnostic pitfalls., Data Sources.—: Literature review via PubMed search., Conclusions.—: Characteristic histologic findings in syphilitic lymphadenitis include thickened capsule with plasma cell-rich inflammatory infiltrate, reactive follicular and paracortical hyperplasia with prominent lymphoplasmacytic infiltrate, and vasculitis. Lymph nodes, however, can show a number of other nonspecific histologic features, which frequently makes the diagnosis quite challenging. In the aerodigestive tract, syphilis is characterized by plasma cell-rich infiltrates. Immunohistochemistry for T pallidum is the preferred method for detecting spirochetes; however, this immunohistochemical stain shows cross-reactivity with other treponemal and commensal spirochetes. Differential diagnosis of syphilis in lymph nodes and the aerodigestive tract is broad and includes reactive, infectious, and neoplastic entities. Pathologists should be aware of the histologic features of syphilis and keep this challenging entity in the differential diagnosis., (© 2024 College of American Pathologists.)

In this work, we determined that Treponema pallidum subsp. pallidum (TPA) DAL-1 (belonging to Nichols-like group of TPA strains) grew 1.53 (± 0.08) times faster compared to TPA Philadelphia 1 (SS14-like group) during in vitro cultivations. In longitudinal individual propagation in rabbit testes (n = 12, each TPA strain), infection with DAL-1 manifested clinical symptoms (induration, swelling, and erythema of testes) sooner than Philadelphia 1 infection, which resulted in a significantly shorter period of the experimental passages for DAL-1 (median = 15.0 and 23.5 days, respectively; p < 0.01). To minimize the confounding conditions during rabbit experiments, the growth characteristics of DAL-1 and Philadelphia 1 strains were determined during TPA co-infection of rabbit testes (n = 20, including controls). During two weeks of intratesticular co-infection, DAL-1 overgrew Philadelphia 1 in all twelve testes, regardless of inoculation ratio and dose (median of relative excess DAL-1 multiplication = 84.85×). Moreover, higher DAL-1 to Philadelphia 1 inoculum ratios appeared to increase differences in growth rates, suggesting direct competition between strains for available nutrients during co-infection. These experiments indicate important physiological differences between the two TPA strains and suggest growth differences between Nichols-like and SS14-like strains that are potentially linked to their virulence and pathogenicity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bosák et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Syphilis can mimic, clinically and microscopically, many other diseases. By microscopy, typically syphilis presents with plasma cell infiltration, admixed with lymphocytes and macrophages, in lichenoid and/or perivascular/perineural distribution pattern. When exuberant, this inflammatory infiltrate can mimic a lymphoproliferative disorder (LPD), notably plasma cell neoplasia or lymphoma. To date, about 12 cases of secondary syphilis, all but one in extraoral location, suggesting initially a LPD, have been published. Here, to our knowledge, we report an unusual case of intraoral primary syphilis initially suggesting LPD, notably lymphoid hyperplasia (pseudolymphoma); however, mucosa-associated lymphoid tissue (MALT) lymphoma and follicular lymphoma could not be disregarded. Polyclonality of plasma cells on immunohistochemistry, in strict clinical correlation, was essential to arrive at the correct diagnosis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Abstract: Tertiary syphilis may present a diagnostic challenge due to negative nontreponemal serologies in up to 30% of cases and frequent lack of identifiable spirochetes on histopathology or other direct detection tests. We report 2 cases of round bodies staining with Treponema pallidum immunohistochemistry by light microscopy in biopsies from cutaneous syphilitic gummata. In 1 case, the finding was validated 3 times by 2 independent laboratories; in the other case, T. pallidum was detected by polymerase chain reaction in the biopsy sample. Spirochete round bodies have previously been reported in the setting of electron microscopy and fluorography, but to the best of our knowledge, have not been reported by light microscopy in a routine skin biopsy. Although the clinical implications are unclear, this may represent a helpful new paradigm for the diagnosis of tertiary syphilis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Syphilis is a persistent sexually transmitted disease caused by infiltration of the elusive pathogen Treponema pallidum. Despite the prevalence of human polymorphonuclear neutrophils (hPMNs) within cutaneous lesions, which are characteristic of incipient syphilis, their role in T. pallidum infection remains unclear. Tp92 is the only T. pallidum helical outer membrane protein that exhibits structural features similar to those of outer membrane proteins in other gram-negative bacteria. However, the functional mechanism of this protein in immune cells remains unclear. Neutrophils are short-lived cells that undergo innate apoptosis in response to external stimuli that typically influence this process. In this study, we determined that Tp92 impedes the activation of procaspase-3 via the ERK MAPK, PI3K/Akt, and NF-κB signaling pathways, consequently suppressing caspase-3 activity within hPMNs, and thereby preventing hPMNs apoptosis. Furthermore, Tp92 could also modulate hPMNs apoptosis by enhancing the expression of the anti-apoptotic protein Mcl-1, stimulating IL-8 secretion, and preserving the mitochondrial membrane potential. These findings provide valuable insights into the molecular mechanisms underlying T. pallidum infection and suggest potential therapeutic targets for syphilis treatment., (© 2023 John Wiley & Sons Ltd.)

Cutaneous manifestations of syphilis are varied and may present with non-specific features. We describe a 45-year-old man who presented with erythematous scaly plaques and nodules on his scalp. In previously reported cases, there were only descriptions of nodules as well as tumors. However, in our case, the patient presented with plaques and nodules on his scalp that quickly resolved with treatment for syphilis. It is important to recognize and treat syphilis at an early stage.

Human monkeypox is a viral zoonosis that has recently emerged worldwide. Clinical cutaneous features include papules, vesicles, and pustules. However, atypical manifestations mimicking other infectious diseases are being reported more frequently. We present a 41-year-old man patient with untreated HIV with generalized rupioid crusted ulcerated plaques with perineal ulceration that were found to represent monkeypox and cytomegalovirus infections.

Syphilis is surging in Japan and worldwide among both homosexual and heterosexual individuals. Diagnosis can be challenging because syphilis is "the great imitator" and clinical manifestations are highly variable. Oral manifestations of syphilis are usually seen in the second stage and the primary syphilis in the oral cavity is rare. We describe a heterosexual man with isolated tonsillar lesions initially misdiagnosed as pharyngeal lymphoma and subsequently diagnosed as primary syphilis. Clinicians should be aware that isolated oropharyngeal involvement can occur in the primary syphilis and can mimic a neoplasm.

Syphilis is a sexually transmitted infection that causes serious health problems without treatment. Detection of syphilis is necessary to stop the spread of the infection. Cytological screeners and pathologists may experience fine-needle aspiration cytology (FNAC) for syphilitic lymphadenitis; however, its characteristic cytological features are rarely reported. We present FNAC cytological features of syphilitic lymphadenitis in a case of a 21-year-old man. He presented with a sore throat and painful neck lymphadenopathy. His swollen and painful neck persisted even with antibiotic treatment. Necrotizing lymphadenitis and lymphoma were clinically suspected. FNAC was taken from the swollen lymph node. Cytologic findings of the specimen showed various inflammatory cells with small-sized vessels arranged in a branching/arborizing fashion. The vessels were surrounded by inflammatory cells, including plasma cells, neutrophils, and macrophages. Perivascular plasma cell cuffing was focally seen along with inconspicuous granulomas. Neutrophils appeared to involve the vascular wall. The cytological findings suggested syphilitic lymphadenitis, and clinical findings and serological tests confirmed primary syphilis with concomitant human immunodeficiency virus infection. Branching/arborizing vessels associated with many plasma cells, vascular involvement of neutrophils, and granulomas may suggest syphilitic infection if the specimen is obtained via FNAC. (189 words)., (© 2023 Wiley Periodicals LLC.)

Background: The re-emergence of Monkeypox (MPX) and its related ophthalmic disease represent a clinical challenge in the initial stages because of the presence of lesions like those caused by varicella zoster, syphilis, and other infections due to other poxviruses. Human Immunodeficiency Virus (HIV) infection and secondary immunodepression raise the risk of severe and prolonged disease., Purpose: We present the case of a young immunosuppressed male patient with MPX, who presented with multiple skin lesions, also including risky ophthalmological manifestations due to extensive eyelid involvement., Conclusions: We describe a novel form of late-onset conjunctivitis and eyelid lesions, without active extraocular disease, highlighting the heterogeneous behavior of the new clinical form of MPX, that exhibits a wide spectrum of lesions in different stages of evolution.

Syphilis is a sexually transmitted infectious disease caused by the spirochete bacterium Treponema pallidum . A characteristic lesion of primary syphilis is chancre. It can develop over genital or extra genital sites, depending on the site of contact with the infectious agent. Cases of oral syphilis have been on the rise in the previous two decades, probably because of the involvement of the oral cavity in sexual practices. We here report an unusual case of primary syphilis who presented with a painless indurated oral ulcer over the lateral borders of the tongue.

Syphilis, caused by Treponema pallidum ( T. pallidum ), is associated with the oxidative stress due to its inflammation-like symptom, and detecting the reactive oxygen species (ROS) is crucial for monitoring the infectious process. Herein, we design and synthesize a perylene-based tunable fluorescent probe, PerqdOH, which can detect endogenous O 2 ˙ - during T. pallidum infection. The fluorescence peak shifted from 540 nm to 750 nm with increasing O 2 ˙ - levels. Besides, both decreased green fluorescence and enhanced red fluorescence could be observed simultaneously during the in vitro infection, providing the real-time monitoring of intracellular O 2 ˙ - caused by T. pallidum . Furthermore, the probe exhibited a remarkable signal in the treponemal lesions on the back of a rabbit model. Taken together, our synthesized PerqdOH holds great potential for application in clarifying the infectious process caused by T. pallidum in real time.

Abstract: Isolation of Treponema pallidum subsp. pallidum strains still relies on rabbit intratesticular inoculation of clinical samples. In this article, we report an alternative isolation approach based on the inoculation of fresh and frozen needle aspirates of primary experimental lesions into culture plates suitable for in vitro propagation of the syphilis agent., Competing Interests: Conflict of Interest: None declared., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

The main symptom in primary syphilis is a small, painless, sore or ulcer called a chancre on the penis, vagina, or around the anus, although chancres can sometimes appear in the mouth or on the lips, fingers, or buttocks. We present the case of a man in his early 60 s with a chief complaint of a painful tongue ulcer. An ulcerated, indurated, and hemorrhagic lesion (23 × 14 mm) was found on the ventral tongue surface, near the oral floor. Palpation identified several swollen, mobile, elastic cervical lymph nodes, with no tenderness. We initially diagnosed tongue cancer; however, during a subsequent detailed examination for a malignant tumor, including biopsy and obtaining additional history, his disease was finally identified as primary syphilis with multiple swollen cervical lymph nodes. Oral amoxicillin and probenecid were started, and after 14 days, there was partial reduction in the size of the submandibular lymph nodes and the ulcer on the left tongue margin. The number of patients with syphilis in Japan increased by eight times from 2012 to 2018. We suggest that dentists consider primary syphilis as a differential diagnosis for oral refractory ulcer with induration and obtain a detailed patient history.

Abstract: We report a case of a 59-year-old man presenting with a widespread follicular-based papular rash with a several-month history of myalgias, lymphadenopathy, fatigue, and weight loss who was diagnosed with acute syphilitic folliculitis by tissue biopsy analysis with immunohistochemical demonstration of spirochetes in hair follicle epithelium. Serologic analysis also showed evidence of Treponema sp. infection. Owing to the rising number of syphilis cases in the last decade, it is important to recognize classic cutaneous findings of syphilis in addition to unusual presentations such as syphilitic folliculitis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: A 58-year-old man with large penile wound and enlarged regional lymph node was suspected of having disseminated penile cancer. FDG PET/CT for primary staging showed high FDG uptake on penis and in several enlarged lymph nodes. However, biopsies revealed no signs of malignancy, but ulceration, inflammation, fibrosis, and spirochetes. Furthermore, Wassermann test was positive. The patient was then treated for syphilis. To our knowledge, this is the first report on FDG PET/CT in a patient suspected of having penile cancer that turned out to be syphilis. Thus, syphilis can be added to the list of benign pitfalls in FDG PET/CT., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Syphilis is a sexually transmitted infectious disease caused by Treponema pallidum and characterized by a complex and variable clinical presentation. Cases of unexpected oral syphilis presenting as non-healing ulcers are uncommonly reported. We report 3 cases (one female and two males, aged 35, 35, and 56 years, respectively) in which patients presented with non-healing oral ulcers. Biopsies revealed surface ulceration and a significant neutrophilic infiltrate rather than the more conventional plasma cell infiltrate seen with most reported syphilis infections, potentially leading to an inaccurate diagnosis. Treponema pallidum immunohistochemistry highlighted spirochetes within the epithelium, with additional diagnostic confirmation by serum T. pallidum particle agglutination assay. Sexual history documentation by the clinician with nonspecific oral ulcers is paramount to aiding diagnosis and leading to proper management. Further, it is important to perform immunohistochemistry for T. pallidum in oral biopsies from non-healing ulcers, especially when clinical history raises the differential diagnosis or when other clinical manifestations may support this consideration., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Syphilis is an infectious disease that is at least discussed to be premalignant. This potential, combined with its general pathological impact, raises the question if syphilis increases mortality in oral cancer patients. The aim of the study was to assess if the five-year survival rates among patients suffering from oral squamous cell carcinoma (OSCC) with (cohort I) and without association with syphilis (cohort II) differ., Methods: Retrospective clinical data of patients diagnosed with OSCC (International Classification of Diseases [ICD]-10 codes C01-06) within the past 20 years from the access date September 25, 2021 were retrieved from the TriNetX network (TriNetX, Cambridge, Massachusetts, USA) to gain initial cohort 0. Subjects also diagnosed with syphilis (ICD-10 codes A51-53) were assigned to cohort I. Cohort II was comprised of the remaining individuals of cohort 0 by creating a group with the same number of patients as cohort I, and by matching for age and gender. Subsequently, Kaplan-Meier analysis and Cox proportional hazards regression were performed, and risk, odds and hazard ratios were calculated., Results: Of a total of 73,736 patients in cohort 0, 199 individuals were each assigned to cohort I and II. During the five-year period after tumor diagnosis, 39 and 30 patients in cohort I and II died. The five-year survival probabilities did not significantly differ between the cohorts (I vs. II = 74.19% vs. 75.01%; p = 0.52; Log-Rank test), nor the risk of dying (I vs. II = 19.6% vs. 15.08%; risk difference = 4.52%; p = 0.23). The calculated risk, odds and hazard ratios were 1.3 (95% confidence interval [CI] = 0.84; 2.00), 1.37 (95% CI = 0.81; 2.31) and 1.17 (95% CI = 0.73; 1.88), respectively., Conclusions: The obtained results indicate that the survival rate of individuals with OSCC might not be negatively influenced if syphilis is present/associated. However, the results need to be interpreted cautiously due to limitations related to the retrospective approach, especially as data on the tumor staging were not accessible., Trial Registration: Due to the retrospective nature of the study, no registration was necessary., (© 2022. The Author(s).)

The rate of syphilis in the United States has been increasing steadily in the past decade, but it remains an uncommon diagnosis in tissue biopsies. Most of the pathology literature on hepatic syphilis consists of older series or case reports. This study aimed to systematically characterize the histologic spectrum of hepatic syphilis in a contemporary cohort. Clinicopathologic features of 14 hepatic syphilis cases between 2012 and 2018 were analyzed to characterize the broad spectrum of histologic changes. Thirteen patients were men (age range: 19 to 59 y); 6 had known human immunodeficiency virus, 7 were men known to have sex with men, and no patient had known prior syphilis. Hepatic syphilis was the primary clinical suspicion in only 1 patient. Common symptoms included jaundice, rash, and abdominal pain. Thirteen had elevated transaminases, and 12 had elevated alkaline phosphatase. Pathologic changes were grouped into 5 histologic patterns: biliary-pattern injury (n=5), acute hepatitis (n=4), autoimmune hepatitis-like (n=1), fibroinflammatory mass-forming lesion (n=2), and no particular pattern (n=2). Nearly all showed portal and lobular lymphocytes and plasma cells; 12 had prominent histiocytes/Kupffer cells, 9 had ductular reaction, and 7 had duct inflammation. Occasional focal findings included dropout (n=7), phlebitis (n=7), and loose granulomata (n=5). Treponeme immunohistochemistry was positive in 10 and negative in 4, though treatment was given before biopsy in 3 of those 4. Thirteen patients had rapid plasma reagin testing either before or after biopsy, with 1:64 or higher titer. All patients who received treatment recovered. Hepatic syphilis is rare but likely underrecognized. It exhibits a variety of histologic appearances and therefore should be considered in several hepatic differential diagnoses, especially in men who have sex with men. Kupffer cells, granulomata, and phlebitis may suggest the diagnosis regardless of predominant histologic pattern. Negative treponeme immunohistochemical staining does not exclude the diagnosis, including in untreated patients., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Rationale: Syphilis is a contagious infectious disease caused by Treponema pallidum. Gastric involvement of syphilis is rare and has nonspecific gastrointestinal symptoms and endoscopic findings. To date, 16 cases have been reported in Korea. Here, we report 2 additional cases of gastric syphilis in men in their 30 second., Patients Concerns: Two 35- and 33-year-old men presented with epigastric pain., Diagnosis: The serum venereal disease research laboratory and fluorescent treponemal antibody absorption tests were positive. Esophagogastroduodenoscopy showed multiple variable-sized flat elevated lesions and geographic ulcers with whitish exudates in the antrum and body. Warthin-Starry silver staining of endoscopic biopsy specimens confirmed gastric syphilis., Interventions: The patients were treated with an intramuscular injection of 2.4 million units of benzathine penicillin once a week for 3 weeks., Outcomes: Clinical symptoms and gastric lesions were completely resolved., Lessons: First, gastric syphilis, despite its rarity and nonspecific symptoms and endoscopic findings, should be considered in a rare extracutaneous presentation of syphilis. Second, a high index of clinical suspicion and an accurate diagnosis based on a combination of clinical, radiological, endoscopic, serologic, and histopathologic findings provide an opportunity to identify and treat patients with gastric syphilis., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Syphilis incidence has exponentially increased in recent decades, particularly among men who have sex with men (MSM). Primary syphilis is characterised by a chancre appearing at the site of Treponema pallidum (TP) inoculation. Atypical morphological variants of syphilitic chancre are frequent. Clinical suspicion must be confirmed either by the demonstration of TP within the lesion through direct tests, such as dark field microscopy (DFM) or T. pallidum nucleic acid amplification technique (TP-NAAT), or by serological tests., Objectives: To analyse the clinical features, the sexual behaviour and the role of diagnostic tests in a cohort of men with primary syphilis in Milan., Methods: Epidemiological, clinical and laboratory data of male patients with primary syphilis seen at the STI Center of the University of Milan between 2015 and 2019 were retrospectively evaluated. Diagnosis was confirmed by at least one positive diagnostic test of either DFM, TP-NAAT or serology., Results: Among a total of 244 patients, 160 (65.6%) were MSM and 32 (13.1%) were living with HIV. One hundred twenty-four (50.8%) patients had a clinically atypical chancre. Chancres were exclusively extragenital in 30 (12.3%) patients, with MSM being more commonly affected (MSM vs heterosexuals: 16.3% vs 4.8%, respectively; p=0.012), and anal region the most frequently involved site. Chancres were multiple in 68/242 (28.1%) patients and morphologically atypical in 76/244 (31.1%). Diagnosis was obtained by (1) both serology and direct methods in 158/244 patients (64.7%), (2) serology solely in 47/244 (19.3%) and (3) direct methods solely in 39/244 (16%). DFM yielded positive results in 83/139 (59.7%) patients, while TP-NAAT gave positive results in 114/121 (94.2%) patients., Conclusions: Patients with primary syphilis frequently present with morphologically atypical chancres. Furthermore, MSM commonly exhibit extragenital involvement. A combined diagnostic approach including both direct and indirect tests is needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We evaluated 23 years of data for cornea donors at the Istanbul Faculty of Medicine Lions Eye Bank., Materials and Methods: Annual statistics of corneal donors between 1996 and 2019 were reviewed retrospectively. Records for 2008 and previous years were compared with records for 2009 and years thereafter,to assess donor demographics and reasons for discard of corneas., Results: A total of 3849 corneas were obtained from 2018 donors during a 23-year period. Of these, 26 donors (11.2%) were registered, whereas 1792 (88.8%) did not register any decision for donation. There were 210 (5.46%) corneas discarded for positive serology and 291 (7.56%) for unsuitable tissue morphology, and 3348 (86.98%) corneas were determined to be suitable for transplant. For the cause of death in 2009 and subsequent years, the incidence of trauma was lower (P = .001) compared with the years previous to 2009, whereas incidence of cardiac pathology (P = .014) was higher. The number of donors older than 50 years was higher for 2009 and years thereafter, compared with data from earlier years (P = .024). The rate of discarded corneas for unsuitable tissue morphology (P = .004) and total discarded corneas (P = .027) decreased in 2009 and years thereafter. The rate of discarded corneas for HIV was higher after for 2009 and years thereafter (P = .047), whereas the rate of discarded corneas for syphilis was significantly higher for 2015 and years thereafter (P = .001)., Conclusions: This study evaluated the most extensive eye bank data in Turkey and found that advances in lamellar surgery techniques and improvements in specular microscopic facilities have expanded the pool for cornealtransplants to include tissues from older donors. Moreover, the incidence rates for HIVpositive and syphilis-positive serology tests in discarded corneas have increased over time.

Context.—: Aldred Scott Warthin, MD, PhD, was professor of pathology and director of the pathological laboratory at the University of Michigan during the first third of the 20th century., Objective.—: To explore the life and accomplishments of Dr. Warthin and his impact on academic anatomic and clinical pathology., Design.—: Available primary and secondary historic sources were reviewed., Results.—: After studying music, biology, and botany, Warthin attended medical school at the University of Michigan, graduating in 1891; he remained in Ann Arbor for 40 years, almost single-handedly transforming a rundown department into a top academic department. He was a dedicated teacher who produced 2 important pathology textbooks. His research interests were diverse. In 1913, he published one of the first papers unambiguously documenting heritability of cancers; subsequent research on one of his cancer families resulted in the description of Lynch Syndrome. He published extensively in the fields of surgical pathology and experimental pathology. He was a recognized expert on syphilis and pathology of aging., Conclusions.—: Warthin's name is eponymously associated with Warthin-Finkeldey giant cells in measles, Warthin's tumor of the parotid, and Warthin-Starry stain for the diagnosis of syphilis as well as Warthin's sign in the clinical diagnosis of pericarditis.

Background: Syphilis is a sexually-transmitted infectious disease caused by Treponema pallidum. Cases of primary and secondary syphilis are on the rise in the United States, with a 14.4% increase in new cases noted from 2017 to 2018 and an escalation of 71% between the years 2014 and 2018. Fulfilling its nickname of "the great imitator," oral manifestations of syphilis may mimic a variety of infectious, neoplastic, or immune-mediated processes, both clinically and histopathologically. This large spectrum of appearances can create a diagnostic challenge to the clinician and/or pathologist, leading to delay in diagnosis or misdiagnosis., Methods: A database of oral syphilis cases was created from archives at the University of Kentucky, University of Pittsburgh, LIJMC, Columbia University MC, and University of Tennessee. The age, sex, race, location, duration, and clinical description were recorded. Cases without positive reaction upon immunohistochemistry or serologic tests were excluded., Results: We identified 19 new cases of oral syphilis (17 males, one female, and one case unknown sex) and described the clinical and histopathological features of this re-emerging and potentially fatal disease. All cases demonstrated dense lymphoplasmacytic inflammation, often with inflammatory exocytosis or ulceration at the surface, and perivascular inflammation., Conclusions: Early recognition of the histopathologic and clinical manifestations of oral syphilis is imperative for prompt diagnosis, improved patient outcomes, and disease prevention., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: The clinical manifestations of recent syphilis can be variable, with typical and atypical patterns. Several conditions may cause atypical clinical aspects, including human immunodeficiency virus (HIV) co-infection. Besides the clinical features, co-infections may completely alter syphilis serological tests, causing interpretative difficulties and diagnostic delays. Aim of the work is to describe the difficulties encountered during the diagnostic evaluation of atypical skin manifestations and of the serology for syphilis of an HIV-infected patient who had contracted it several times., Case Presentation: In 2020, a 52-year old HIV-positive bisexual male patient was admitted to our department with a 4-month history of moderately itchy cutaneous lesions localized at his neck, trunk and arms. In 2013, the patient presented with a classic syphilitic roseola of the trunk and a secondary syphilis was diagnosed, with increased levels of rapid plasma reagin (RPR), Treponema pallidum hemagglutination assay (TPHA), anti-Treponema pallidum IgM and IgG Index. A second episode occurred in 2018, as a primary syphilis with multiple ulcerative lesions of the penis, and increased levels of RPR, IgG and IgM. In 2019, a further episode of secondary syphilis was treated with Doxycycline. In 2020, erythematous and papular lesions with vesicular components and urticarial erythema multiforme (EM)-like lesions were present at the neck, trunk and arms. Serological tests and Nucleic Acid Amplification Test (NAAT) for Treponema Pallidum were performed, as well as a cutaneous biopsy with histological and immunohistochemical evaluation of one lesion. NAAT was negative for T. pallidum. Serological test results were discordant with a new syphilis infection, showing only increased levels of RPR and anti-Treponema IgG. The cutaneous biopsy revealed a non specific histological pattern, while the immunohistochemical evaluation with anti-spirochetal antibodies was mandatory for the diagnosis of recent syphilis, showing clusters of rod-shaped elements, some of which with spiral form, focally present at the epidermis and adnexal structures., Conclusions: Nowadays, syphilis may present with atypical clinical and serological features. Physicians should be aware of these possible alterations and consider syphilis even in case of uncommon clinical aspect and unclear serological tests. Cutaneous biopsy and immunohistochemical exam may be mandatory for the diagnosis.

Competing Interests: The authors declare no conflicts of interest.

Syphilis is an increasingly common infectious disease caused by the bacterium Treponema pallidum . Atypical clinical presentations occur that may delay its diagnosis and treatment. Regional enlargement of lymph nodes is seen in both primary and secondary stages. Such lymph nodes very rarely become abscesses. Antibiotics should be administered in this situation; however, if this fails, the lymph nodes should be surgically excised.

Background: Penicillin G, the current standard treatment for syphilis, has important drawbacks, but virtually no preclinical or clinical studies have been performed to identify viable alternatives. We tested, both in vitro and in vivo, three marketed antibiotics with adequate pharmacological properties to treat syphilis., Methods: We used an in vitro culturing system of T. pallidum to perform drug susceptibility testing and applied quantitative PCR targeting the tp0574 gene to measure bacterial growth. To confirm in vivo efficacy, fifteen rabbits were infected intradermally with T. pallidum at eight sites each and randomly allocated to an experimental treatment (linezolid, moxifloxacin, clofazimine) or a control arm (benzathine penicillin G [BPG], untreated). The primary outcome was treatment efficacy defined as the time to lesion healing measured from the date of treatment start. Secondary outcomes were absence of treponemes or treponemal mRNA in injection sites, absence of seroconversion, and cerebrospinal fluid (CSF) abnormalities and negative rabbit infectivity tests (RIT)., Findings: Linezolid showed in vitro bactericidal activity at concentrations of 0.5 µg/mL or higher. When administered orally to experimentally infected rabbits, it induced healing of early lesions at a time similar to BPG (hazard ratio 3.84; 95% CI 2.05-7.17; p < 0.0001 compared to untreated controls). In linezolid-treated animals, dark-field microscopy and qPCR assessment showed no presence of treponemes after day 3 post-treatment start, serologic test did not convert to positive, CSF had no abnormalities, and RIT was negative. Moxifloxacin and clofazimine failed to inhibit bacterial growth in vitro and could not cure the infection in the rabbit model., Interpretation: Linezolid, a low-cost oxazolidinone, has in vitro and in vivo activity against T. pallidum, with efficacy similar to BPG in treating treponemal lesions in the animal model. Our findings warrant further research to assess the efficacy of linezolid as an alternative to penicillin G to treat syphilis in human clinical trials., Funding: European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant agreement No. 850450)., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract: Elastophagocytosis is a characteristic finding of granulomatous and elastolytic disorders. It is defined by phagocytosed elastic fibers within histiocytes, multinucleated giant cells, or both. This finding has also been associated with certain medications, malignancies, inflammatory conditions, and infectious disorders. Although Drs Ragaz and Ackerman reported elastophagocytosis in a secondary syphilis lesion in a review of actinic granuloma in 1979, more recent publications have not recognized this finding. We present a case of elastophagocytosis within a lesion of secondary syphilis in a 65-year-old man. Biopsy from his left forearm demonstrated features of secondary syphilis including subtle vacuolar alteration with mild superficial and mid perivascular lymphoplasmacytic inflammation. There were interstitial giant cells with phagocytosed elastic fibers within the superficial dermis. Spirochete immunostain was positive with confirmatory Treponema pallidum IgG antibody and RPR titer. In this report, we present a unique case of secondary syphilis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The lichenoid tissue reaction pattern generally signifies cytotoxic damage to the epithelium. When such reaction pattern occurs on vulvar skin or mucosa, the effects can result in considerable morbidity. None of the entities discussed in this review are entirely unique to the vulva, however, some entities may classically occur at this site, while others tend to be widespread diseases that may incidentally affect vulvar skin and mucosa. Given the complex anatomy of the vulva and the bridging of a site showing both keratinizing squamous epithelium and non-keratinizing squamous mucosa, histopathologic features may display variation in presentation. Although identification of a "lichenoid reaction pattern" alone may provide insight into the disease process, understanding of clinical presentation and specific sites of involvement, along with recognition of the nuanced features of the disease entities can help establish a specific diagnosis. Accurate histopathologic diagnoses by pathologists can improve the ability for treating clinicians to implement timely and effective treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Massive perivillous fibrin deposition (MPFD) and the related entity of maternal floor infarction (MFI) are uncommon placental disorders of unknown etiology, associated with adverse obstetric outcome and a significant risk of recurrence. We describe a 19-year-old mother with untreated syphilis who delivered a male neonate with low birth weight, skin desquamation, and pneumonia. Placenta examination showed the expected changes for syphilis but unexpectedly, also showed MPFD. To our knowledge, this is the first report of MPFD associated with placental syphilis, thus expanding the list of etiologies that may be related to MPFD/MFI. It is postulated that the syphilis infection in our case led to a hypercoaguable state, eventually resulting in MPFD. In the right clinical setting, syphilis might be considered in the differential diagnosis when MPFD/MFI is observed on placental examination. The recurrence risk of MFPD/MFI associated with infections is believed to be lower than idiopathic cases and, by extrapolation, this lower risk should apply to syphilis as well.