Background and Objectives: Actinomycosis is a rare chronic contagion caused by Actinomyces spp. known for its ability to mimic malignant processes across various anatomical locations. Its clinical presentation can often resemble malignancies, Mycobacterium tuberculosis infections, nocardiosis, fungal infections, or other granulomatous diseases. This case series presents three patients diagnosed with Actinomyces spp., highlighting the diagnostic challenges and diverse clinical manifestations of the disease. Materials and Methods: We reviewed the clinical course, diagnostic procedures, and treatment outcomes of three patients with confirmed Actinomyces spp. The first case involved a 51-year-old male with a history of rhabdomyosarcoma in remission who presented with dysphagia. Magnetic resonance imaging identified an irregularly enhancing mass in the tonsil, and subsequent tonsillectomy confirmed Actinomyces spp. The second patient, an 80-year-old female, presented with dysphagia and a sublingual mass initially suspected to be diffuse large B-cell non-Hodgkin lymphoma; however, a histopathological analysis confirmed Actinomyces spp. The third case involved a 72-year-old male with abdominal pain and an ulcerated gastric lesion, where subtotal gastrectomy and histopathological examination confirmed the diagnosis of Actinomyces spp. Results: These three cases highlight the ability of Actinomyces spp. to closely mimic malignant lesions, which significantly complicates the diagnostic process. Although personalized interventions were required for each patient, diagnoses were ultimately confirmed through histopathology. Despite these challenges, timely recognition and appropriate treatment were achieved, underscoring the need to consider Actinomyces spp. in the differential diagnosis of similar presentations. Conclusions:Actinomyces spp. remains a diagnostic challenge due to its ability to mimic a variety of malignant and contagion conditions. This case series emphasizes the need for a thorough histopathological examination and a high index of suspicion when encountering lesions with atypical presentations. Given the potential for misdiagnosis, awareness and consideration of Actinomyces spp. are crucial in the differential diagnosis of chronic contagion and mass lesions. Further studies are warranted to refine diagnostic and therapeutic approaches.
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