When Sexually Transmitted Infection Treatment Fails: A Rare Dermatological Presentation of Lung Cancer - A Case Report.

Introduction
Cutaneous metastases are rare presentations of internal malignancies and may occasionally mimic other infectious or inflammatory dermatoses. In women, breast cancer is the leading cause of cutaneous metastases, whereas in men, lung cancer is most frequently observed. In rare cases, cutaneous metastasis can be present as the first clinical indication of lung cancer. Patients presenting with this condition generally have a poor outlook, with an average survival time of about 3 to 5 months [1, 2]. Ulcerative lesions localized to the genital and inguinal regions are predominantly attributable to sexually transmitted infections (STIs), with herpes simplex virus types 1 and 2 representing the most common etiologies. Other less frequent infectious agents include Klebsiella granulomatis (donovanosis), Haemophilus ducreyi (chancroid), Treponema pallidum (syphilis), and Chlamydia trachomatis serovars L1–L3 (lymphogranuloma venereum). Nonetheless, noninfectious causes such as Behçet’s syndrome, fixed drug eruption, and malignancies must also be carefully considered in the differential diagnosis [3]. Here, we report a unique case of cutaneous metastasis of lung adenocarcinoma (LUAD) initially suspected to be donovanosis or lymphogranuloma venereum due to its clinical presentation.

Case Presentation
A 46-year-old unmarried male was admitted to our clinic with a 1-month history of a painless ulcerative lesion in the right inguinal region. The lesion initially appeared as a small erythematous papule, which gradually enlarged and developed central erosion and ulceration. Multiple inguinal lymphadenopathies were noted and had been interpreted as reactive by ultrasonography. An excision of the inguinal lymph node had been performed at another hospital; however, the pathology report was not available to the patient and could not be retrieved from the hospital records.
Before presenting to our clinic, he had previously been hospitalized in the infectious disease department under the care of a specialist for further evaluation. As the presence of genital ulceration and lymphadenopathy initially suggested a STI, the patient was first treated with oral cephalosporin and quinolone; however, due to the lack of clinical improvement, intravenous cephalosporin and quinolone therapy were administered for 10 days, but the lesions did not regress. Upon presentation to our clinic, further evaluation was performed. Dermatological examination revealed a single, elliptical, sharply demarcated, slightly raised ulcer which bled easily on palpation. The surrounding lymph nodes were firm, mobile, and tender (shown in Fig. 1). Genital and perianal examinations were unremarkable. The patient denied any history of unprotected sexual intercourse.
Donovanosis (granuloma inguinale), lymphogranuloma venereum, and pyoderma gangrenosum were initially considered in the differential diagnosis. Serological tests for HIV and syphilis were nonreactive. Hepatitis serology revealed HBsAg, anti-HBc IgG, and HBV DNA positivity, with anti-HBs negativity.
A punch biopsy from the active margin of the ulcer demonstrated an infiltrative tumor composed of pleomorphic cells with prominent nucleoli, not connected to the epidermis (shown in Fig. 2). Immunohistochemical staining showed positivity for CK7 and TTF-1, consistent with metastatic LUAD (shown in Fig. 3).
For further systemic evaluation, the patient was referred to both pulmonology and oncology departments. Positron emission tomography identified increased metabolic activity corresponding to a mass in the anterior portion of the right lung’s middle lobe. Bronchoscopic biopsy confirmed non-mucinous ACC.

Discussion
Globally, lung cancer continues to be the leading cause of cancer-related deaths in both sexes. Non-small cell lung cancer accounts for roughly 84% of lung cancer cases and is classified into three primary histological types: squamous cell carcinoma, adenocarcinoma, and large cell carcinoma [2, 4, 5]. Although any histological subtype of lung cancer has the potential to metastasize to the skin, research indicates that LUAD is the most frequently associated type and can occasionally be the initial manifestation of the disease [6]. Evidence also suggests that tumors originating in the upper lobes of the lung have a greater propensity for cutaneous metastasis [1]. In our case, the LUAD was located in the upper lobes, consistent with these findings. Cutaneous metastases predominantly localize to the chest, back, or scalp, with inguinal involvement representing an exceedingly rare manifestation. In a decade-long retrospective study by Ambrogi et al. [7], including 26 patients with cutaneous metastases secondary to lung carcinoma, no instances of inguinal region involvement were documented. To date, few reports describe LUAD metastasizing as genital ulcers, making this report a unique contribution to the literature [8].
Clinically, cutaneous spread of lung cancer commonly manifests as painless, firm nodular lesions that may rapidly grow and sometimes ulcerate and generally do not regress spontaneously. However, ulcerative lesions without any nodular component, as seen in our case, are quite rare and may easily be misinterpreted as infectious or inflammatory dermatoses [7]. Histopathologic and immunohistochemical analysis of skin biopsy specimens is essential for establishing an accurate diagnosis. Immunohistochemical markers such as TTF-1 and CK7 are critical for differentiating cutaneous metastases of lung origin from other visceral tumors. Their use is particularly valuable when the clinical picture is ambiguous as in our patient. As a differential diagnosis, granuloma inguinale (also known as donovanosis) is a chronic, progressive bacterial infection caused by Klebsiella granulomatis, typically characterized by painless genital ulcers. Treatment involves administration of doxycycline (100 mg twice daily), azithromycin (500 mg twice daily), or ciprofloxacin (750 mg twice daily) for a period of 3 weeks, or until complete resolution of all lesions is observed [9]. In our case, despite appropriate and effective antibiotic therapy, the lack of improvement in the lesion led to the exclusion of donovanosis.
Other bacterial etiologies such as chancroid (Haemophilus ducreyi) and syphilis (Treponema pallidum) were also considered in the differential diagnosis of genital ulcers. Chancroid typically presents with painful ulcers that have ragged, undermined edges and are often accompanied by tender, suppurative inguinal lymphadenopathy; in contrast, the ulcer in our patient was painless with sharply demarcated borders. Syphilis is usually characterized by a single, indurated, and well-defined painless ulcer (chancre) with a clean base, often accompanied by regional lymphadenopathy. In our patient, serologic tests for syphilis were negative, and the lesion’s clinical appearance did not correspond to a typical chancre. Therefore, these bacterial STIs were ruled out [3].
In addition to bacterial etiologies, other viral STIs such as condyloma acuminata (human papillomavirus infection), molluscum contagiosum, and herpes simplex virus types 1 and 2 should also be considered in the differential diagnosis of genital or inguinal lesions. These conditions typically present with characteristic clinical features such as verrucous papules or grouped vesicles rather than solitary ulcers. However, the clinical appearance of the lesion in our patient was not consistent with these infections. Therefore, these conditions were clinically excluded [3].

Conclusion
This case emphasizes that when investigating ulcerative lesions in the genital and inguinal region not only sexually transmitted diseases but also noninfectious conditions should be taken into consideration. Although cutaneous spread is uncommon, LUAD may resemble infections such as donovanosis and should be considered in the differential diagnosis. Especially in ulcers that do not heal for a long time and are resistant to treatment, cutaneous metastases should also be investigated and histopathological examination should be performed. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000549924).

Statement of Ethics
Ethical approval was not required for this study in accordance with local and national guidelines. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Conflicts of Interest Statement
The authors have no conflicts of interest to declare.

Funding Sources
This study was not supported by any sponsor or funder.

Author Contributions
M.D. and C.T.A. examined the patient, collected the clinical data, drafted the initial version of the manuscript, and were responsible for the clinical evaluation and case presentation. E.T.A. and S.D.P. contributed substantially to the critical review, editing, and refinement of the manuscript; provided academic supervision; improved the clarity and coherence of the text; and ensured that the discussion and conclusions were aligned with current dermatological literature. All authors contributed to the final revision, approved the submitted version, and agreed to be accountable for all aspects of the work.