Actinomycosis of the Tongue: A Case Report and Review of Literature

Background: Actinomycosis of the tongue is an uncommon, suppurative infection of lingual mucosa, caused by actinomyces. The clinical diagnosis may present serious difficulties because of its ability to mimic other lesions, including both benign and malignant neoplasms. Methods: Here, we describe the case of a 52-years-old patient affected by an asymptomatic, tumor-like tongue swelling, then diagnosed as actinomycosis. A review of tongue localization of actinomycosis is also reported, with emphasis on clinical findings and therapy. Results and Conclusion: Early diagnosis and treatment, with pus drainage and systemic antibiotic therapy, are pivotal to avoid severe and life-threatening complications.


Introduction
Actinomycosis is an uncommon, chronic, suppurative bacterial infection affecting soft-tissues caused by an anaerobic, filamentous Gram-positive bacterium, Actinomyces israelii. It was recognized for the first time in humans in about 1845 by Von Langenbeck [1].
Actinomycosis is classified by location as cervicofacial (50-60%), abdominal (25%), or pulmonary (15%) lesions. Cervicofacial actinomycosis is the most frequent clinical form, and the "lumpy jaw syndrome", associated with odontogenic infection, is the most common clinical manifestation [2]. In the oral cavity, the infection commonly occurs in the mandibular area (submandibular region, ramus, and angle) in over 50% of cases [3,4], followed by cheek, parotid gland, tongue, nasal cavity, hypopharynx, gingival and oral space. Actinomycosis is associated with large abscesses and/or mandibular osteomyelitis, with or without the presence of the sinus tract [2]. Actinomyces spp. usually have a low pathogenicity and cause disease in a condition of poor oral hygiene, after surgical procedures and/or dental treatments such as extraction of a mandibular molar or as a complication of maxillofacial trauma.
In 1885, Von Hacker described the first case of actinomycosis of the tongue [5], which remains a very uncommon lesion of the oral cavity, representing less than 3% of all reported cases of actinomycosis in English literature [6,7]. Although it is a benign condition, if not treated, it can give, in later stages, osteomyelitis with extensive bone destruction [8,9]. Actinomycosis of soft tissues may extend to adjacent bone in up to 15% of cases [10,11].
Actinomycosis especially affects male patients aged 20 to 60 years [12]. The main predisposing factors include diabetes, alcohol abuse, malnutrition, and radiation therapy and immunosuppression [3]. Furthermore, patients affected by human immunodeficiency virus (HIV) had often shown to have poor outcomes [13,14].
The diagnosis of actinomycosis of soft tissues is based on clinical findings and on histological examination and staining of the lesion. The presence of sulphur granules in tissue sample or the pus drainage help during diagnosis, although nocardiosis may also present with sulphur granules [15][16][17]. The clinical diagnosis of tongue actinomycosis may present difficulties because of its ability to mimic other lesions, including both benign and malignant neoplasms. The histopathological examination is decisive to arrive to the final diagnosis and exclude other diseases.
Here, we describe the case of a patient who presented with a tumor-like lingual swelling, then diagnosed as actinomycosis of the tongue. A review of lingual actinomycosis cases is also reported.

Case Report
A 52-year-old man was presented at our clinical unit (Oral Medicine Unit, Odontostomatologia II, ASST Santi Paolo e Carlo, Presidio Ospedaliero San Paolo) because of an asymptomatic, notulcerated swelling of the anterior part of the tongue. The patient reported a recent occurrence of the lesion. In his clinical history, the patient declared that, about 5 years before, a biopsy was performed approximately at the same location of the current lesion, with a diagnosis of benign squamous papilloma. He did not report any previous history of local trauma or abdominal, thoracic, or cervical abscesses.
Intraoral examination revealed a solid, fixed, bilobed submucosal nodule, located slightly on the right to the midline of the anterior part of the tongue ( Figure 1 a and b).   The lingual mucosa appeared normal in color, with two flat whitish spots and a small rounded erosion (about 2 mm in diameter). There was no restriction in tongue movement. Extraoral examination showed no evidence of cervical lymphadenopathy.
Hematological examination revealed neutrophilia, monocytosis, and a raised value of c-reactive protein (CRP), with a concentration of 3.5 mg/dL (normal range <0.5 mg/dL).
The clinical diagnosis was of a benign neoplasm, with a differential diagnosis including traumatic lesion, infective lesion or malignant neoplasm.
Under local anesthesia, two incisional biopsies of the lesion were taken for achieving the histopathological diagnosis-the first one of the epithelial layer and the other of the submucosa-in order to obtain a representative section. During the biopsy, a yellowish purulent drainage coming from the lesion was observed.
Three weeks after the biopsy, the patients received systemic antibiotic therapy because of a dental extraction. He was treated with oral intake of clarithromycin for one week (500 mg every 12 h), due to penicillin allergy.
Post-surgical healing was excellent, with the complete resolution of swelling at six weeks follow-up, when the histological result was given to the patient ( Figure 2). Antibiotics 2020, 9, x 3 of 8 The lingual mucosa appeared normal in color, with two flat whitish spots and a small rounded erosion (about 2 mm in diameter). There was no restriction in tongue movement. Extraoral examination showed no evidence of cervical lymphadenopathy.
Hematological examination revealed neutrophilia, monocytosis, and a raised value of c-reactive protein (CRP), with a concentration of 3.5 mg/dl (normal range <0.5 mg/dl).
The clinical diagnosis was of a benign neoplasm, with a differential diagnosis including traumatic lesion, infective lesion or malignant neoplasm.
Under local anesthesia, two incisional biopsies of the lesion were taken for achieving the histopathological diagnosis-the first one of the epithelial layer and the other of the submucosa-in order to obtain a representative section. During the biopsy, a yellowish purulent drainage coming from the lesion was observed.
Three weeks after the biopsy, the patients received systemic antibiotic therapy because of a dental extraction. He was treated with oral intake of clarithromycin for one week (500 mg every 12 hours), due to penicillin allergy.
Post-surgical healing was excellent, with the complete resolution of swelling at six weeks followup, when the histological result was given to the patient ( Figure 2). Histopathological examination of the biopsy specimen, indeed, showed a nodular mass deep into the muscularis propria of the tongue, showing colonies of actinomyces and a chronic and acute inflammatory process, including suppurative signs (Figure 3).
In humans, the etiological agent of this disease is mainly Actinomyces israelii, a filamentous Gram-positive bacilli, commensal of the flora of the oropharynx, gastrointestinal tract and urogenital tract. In the oropharynx, it is particularly present in gingival sulcus, tonsillar crypts, dental plaques, and periodontal pockets. Consequently, actinomycosis is considered an endogenous infection, where the trauma plays a catalytic role in starting the disease [6,7,29].
The microorganism is unable to penetrate healthy tissue, while, to become invasive, it requires the interruption of mucosal barrier to gain access to the submucosal tissue [31]. Actinomycosis of the tongue is an uncommon disease since lingual epithelial layer has a structure particularly resistant to local trauma and infection. The keratinized mucosal lining, vascular-rich parenchyma, great mobility, and mechanical cleansing by saliva make difficult for bacteria to adhere and multiply. Lingual actinomycosis is generally localized on the anterior two-thirds of the tongue, lateral to the medline [4], as occurred in this patient. When, after the trauma, such as self-biting (Table 1), the microorganism spreads deeply into the tissues and produces a massive fibrotic reaction surrounding the center of the lesion. Clinically, lingual actinomycosis appears as a hard nodular mass or swelling, slightly mobile on the adjacent layers, which can be rarely ulcerated and associated with necrotic tissue (Table 1). Although we could not retrieve specific information regarding recent traumas of the dorsum of the tongue, the patient reported a previous biopsy (with a diagnosis of squamous papilloma) at the same site of the current nodular lesion, which might have played a role in triggering the actinomycosis.
Pain, dysphagia, speech impairment, difficulty in moving the tongue can be reported by the patient (Table 1), although, in this report, the lesion was asymptomatic.
The gold standard for the final diagnosis is the histological examination including the histological staining to detect Actinomyces spp. colonies, whenever possible, also performed on purulent material. Bacterial culture is not recommended because it remains sterile in just about 50% of cases [2]. Typical microscopic findings include identification of Actinomyces spp. colonies and sulphur granules that are made of Gram-positive conglomeration of bacteria trapped in biofilm [2]. In our case, the diagnosis was achieved by the clinical findings and the identification of Actinomyces spp. colonies within the epithelial specimen.
The preferred treatment remains administration of antibiotics with surgical excision or incision of the lesion. The drainage of abscess or surgical excision, when the lesion is small, largely enhance the efficacy of antibiotic therapy [29]. The drug of choice is penicillin. The addition of beta-lactamase inhibitors or metronidazole gives benefits with recurrent and polymicrobial Actinimycosis infections [32]. Other therapies include administration of third-generation cephalosporin or, in case of patients allergic to amoxicillin, macrolides and clindamycin [2,3]. In literature, there is no agreement on the ideal duration of therapy. Some studies suggested the need of long therapies, from weeks to months. Recurrence may occur after the cessation of the antibiotic [30], especially when the therapy was incomplete or with insufficient duration. No studies described local or distant recurrence of lingual actinomycosis after being treated successfully with drainage and a complete cycle of antibiotics (Table 1). In this case, the patient showed complete resolution of the clinical picture, lasting one month from the biopsy with pus drainage and antibiotic 1-week treatment with clarithromycin.

Conclusions
Although lingual actinomycosis infections is a rare event, early diagnosis and treatment are pivotal to avoid severe and life-threatening cases. Because of its ability to mimic other diseases, especially neoplasms, actinomycosis can be a challenging problem for the clinician and always requires diagnostic investigations, including biopsy.
This infection must be considered in the differential diagnosis of any cervicofacial mass. Treatment should always include pus drainage and systemic antibiotic therapy.

Conflicts of Interest:
The authors declare no conflict of interest.