Surgical pathology revealed granulation tissue with actinomycotic granules, with no evidence of malignancy (Figures 1 and 2). Gram stain revealed few WBCs but no organisms. Microbiology cultures grew rare Staphylococcus epidermidis, and light growth of Aggregatibacter actinomycetemcomitans. Based on these findings and the clinical picture, the patient was diagnosed with cervicofacial actinomycosis, or "lumpy jaw."
Actinomycosis is a chronic, indolent infection caused by the Actinomyces species, most often by Actinomyces israelii. This infection is characterized by the development subacute to chronic inflammatory mass lesions, which may develop draining sinus tracts, fistulae, abscesses, and tissue fibrosis. This infection can affect immunocompetent and immunocompromised patients (1). The most common location of actinomycosis is the oral-cervicofacial region, more specifically at the angle of the jaw or in the submandibular region. This is the origin of its colloquial nickname, "lumpy jaw." It can be difficult to recognize clinically, and is often confused with a neoplastic process or fungal infection.
Actinomyces are gram-positive filamentous bacilli. Their branching, filamentous morphology gives them a fungal-like appearance and is the origin of their name, from the Greek actis (ray or beam), and mykes (fungus). These bacterial filaments are much narrower than true fungal hyphae, however, allowing for their discrimination (2). On gram stain Actinomyces can stain irregularly, resulting in a beaded or banded appearance. It is important that this not be confused with gram positive cocci, which can look similar (3).
Actinomyces israelii are microaerophilic, and grow best under anaerobic conditions. They are fastidious, slow growing organisms. In culture, young colonies of Actinomyces israelii are characterized by branching filaments radiating from a central point, described as "spider colonies." Older colonies grow in more distinct clumps, and are often described as having a "molar tooth" appearance (3).
Actinomyces israelii is a normal constituent of the oral cavity and pharynx, and can be found in the gingival crevices and tonsillar crypts of healthy adults and children, as well as on carious teeth and in dental plaques. Other species of Actinomyces are found throughout the body, including in the distal esophagus, gastrointestinal, and genitourinary tract (4,1). Although A. israelii ordinarily behaves as a benign commensal, it can act as an opportunistic pathogen when the mucosal barrier is disrupted due to trauma, dental procedures, or oral surgery, leading to infectious actinomycosis (4-6).
The true incidence of actinomycosis is not known, and it is thought that there are likely to be many unrecognized cases of oral-cervicofacial disease that are treated empirically. Cervicofacial actinomycosis is more likely to affect males than females, with an incidence ratio of 3:1. The etiology of this gender disparity is not known, but it is hypothesized to be due to differences in dental hygiene habits between male and females, as well as due to increased incidence of oral trauma in male as compared to female patients. Although cervicofacial disease is the most common site of actinomycosis, it has also been reported in the abdominal, pelvic, and thoracic regions. Abdominal cases most often occur after surgery, such as for appendicitis or diverticulitis. Pelvic cases have been reported after prolonged use of intrauterine devices (7). Thoracic cases can cause cough, low-grade fever, and cavitary-like lesions which radiographically mimic tuberculosis, and are thought to be associated with aspiration of the organism from the oropharynx (8). In all sites, it is disruption of the mucosal barrier that allows this ordinarily benign organism to behave in a pathogenic manner.
On surgical pathology, actinomycosis is characterized by sulfur granules (Figure 1). These are composed of bacteria cemented together by a polysaccharide-protein complex and calcium phosphate. Grossly, these sulfur granules appear yellow. When patients develop draining sinus tracts from actinomycotic lesions, these granules can give the draining purulent discharge a distinctive yellow tint. Microscopically, these granules are composed of delicate, branched filaments of bacteria. These granules typically induce a local tissue response in immunocompetent individuals, characterized by palisading epithelioid macrophages, neutrophils, and granulation tissue (Figure 2). At the periphery of the granules, one can see radially oriented, eosinophilic filaments with clubbed ends; this is known as the splendore-hoeppli phenomenon. Although sulfur granules and the splendore-hoeppli phenomenon are often thought of in the context of actinomycosis, they are not specific to infection with Actinomyces, and can in fact be seen in cases of nocardiosis, botryomycosis, and other infections (1). On the other hand, sulfur granules may not always be seen or adequately sampled in cases of actinomycosis, so their absence cannot be used to exclude this infection. The most definitive way to diagnose actinomycosis is microbiologic culture (3).
Unfortunately, since only an aerobic culture was sent in this case, Actinomyces israelii was not identified in this patient's culture. However, his culture did grow Aggregatibacter actinomycetemcomitans.
Aggregatibacter actinomycetemcomitans is a gram-negative, fastidious, coccoid or rod-shaped bacillus. It can grow aerobically or anaerobically, and is capnophilic. In culture, Aggregatibacter actinomycetemcomitans produces small colonies (0.5-3 mm in diameter) after about 48-72 hours of incubation on blood agar, with subsequent growth into a star-like structure with pitting of the agar medium. In liquid media, the colonies form granules that adhere to the sides of the tube (3). The Aggregatibacter species have recently been reclassified based on DNA homology and 16S rRNA sequencing studies, which showed a close relationship between what were once Actinobacillus Actinomycetemcomitans, Haemophilus aphrophilus, and Haemophilus segnis. These species were found to be only distantly related to the type species of their former genera, but are sufficiently related to each other to warrant the creation of a the new genus Aggregatibacter, within the family Pasteurellaceae (9,10).
Aggregatibacter are perhaps best known as a member of the "HACEK" group of bacteria, including Haemophilus, Aggregatibacter (previously Actinobacillus), Cardiobacterium, Eikenella, and Kingella. These HACEK bacteria are rare causes of endocarditis, and are known for causing "culture negative endocarditis," as these organisms grow relatively slowly as compared to their more common endocarditis-causing counterparts, Staphylococcus and viridans group Streptococcus (11).
However - as its name suggests - Aggregatibacter actinomycetemcomitans was first isolated with Actinomyces israelii in cases of cervicofacial actinomycosis, and has since been identified in many cases of cervicofacial actinomycosis. Like Actinomyces, it is an oral commensal. However, the clinical impact of its presence in cases of actinomycosis is not well understood.
Ultimately, this patient was diagnosed with cervicofacial actinomycosis based on the growth and identification of Aggregatibacter actinomycetemcomitans, the surgical pathology findings of sulfur granules, and the clinical presentation. To effectively treat actinomycosis, long-term antibiotic therapy with a beta-lactam or tetracycline is required. Antibiotic treatment must be continued until complete resolution of the lesion. In some refractory cases, surgical drainage or excision is required. Accordingly, this patient was treated with amoxicillin, with a plan to continue treatment for 3-6 months, or until complete resolution of the lesion.
Contributed by Sarah B. Hugar and A. William Pasculle, ScD.