Nasopharyngeal actinomycosis on 18F-fluorodeoxyglucose positron emission tomography/computed tomography: A case report

Introduction

Actinomycosis is a rare, chronic and indolent progressive granulomatous infection that is typically caused by the bacteria, Actinomyces israelii (1–3). Classically, actinomycosis presents in three clinical forms: Cervicofacial, thoracic and abdominopelvic (1,2). Cervicofacial actinomycosis accounts for around 60% of cases, with the mandible being the most frequently affected anatomic site (1–3). Though the clinical manifestations vary, an abscess formation with subsequent draining sinus and fistula formation is most commonly observed (1–3). An adequate course of antibiotics is the cornerstone of treatment (1–3). Surgical debridement is necessary in certain circumstances (1). The prognosis is positive, providing that early diagnosis and treatment occurs (3). Sustained observation is mandatory for detection of recurrence. Occurrence of nasopharyngeal actinomycosis is rare, and infection can occur without prior mucosal injury or an immunocompromised status (1). Therefore, it is advisable to always maintain a high level of clinical suspicion when treating patients with a persistent nasopharyngeal mass that presents with vague symptoms. The present study described a case of this rare disease entity. The clinical course, microbiologic findings and images were also presented.

Case report

An otherwise healthy 46-year-old Asian female underwent a 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) whole-body cancer screening at the Kaohsiung Veterans General Hospital (Kaohsiung, Taiwan). Intense, focal 18F-FDG uptake (standard uptake value, 6.2) was identified over the nasopharynx (Fig. 1). The patient was transferred to the otolaryngology outpatient department following a suspected nasopharyngeal malignancy in March 2013. A detailed history identified no other symptoms affecting the four general areas of compliant: aural, nasal, neck, or miscellaneous accounted for by cranial nerve involvement. In addition, the medical history of the patient, in relation to maxillofacial trauma or dental manipulation, was unremarkable. Direct nasopharyngoscopy with a rigid telescope revealed an unclearly demarcated granular mass originating from the roof of the nasopharynx (Fig. 2). A biopsy was performed and a sample of the fluid from the mass was sent for comprehensive microbiology and pathology analysis. The results revealed that the sample contained Gram-positive filamentous rods, but was negative for acid-fast staining. Despite this, the culture medium failed to grow any colonies. Microscopic analysis at low magnification identified cauliflower-shaped sulfur granules in association with acute and chronic inflammation (Fig. 3A). Higher-power microscopic examination revealed that these granules were surrounded by a rosette of clubbed filaments (Fig. 3B). Furthermore, Grocott-Gomori methenamine silver staining revealed the presence of filamentous rods (Fig. 3C). Based on these findings, the patient was diagnosed with nasopharyngeal actinomycosis. After two months of oral antibiotic treatment with 500 mg amoxicillin four times per day, recovery was uneventful, with no evidence of recurrence over the following 17 months. Written informed consent was obtained from the patient prior to publication of the study, and the study was approved by the Ethics Committee of the Institutional Review Board of Kaohsiung Veterans General Hospital (Kaohsiung, Taiwan).

Figure 1. Coronal (A) PET and (B) fused PET/CT scans, as well as axial (C) PET, (D) CT and (E) fused PET/CT scans revealing a focal hot lesion (maximum standard uptake value, 6.2) located at the roof of the nasopharynx and measuring ~1 cm in size. PET, positron emission tomography; CT, computed tomography.

Figure 2. Nasopharyngoscopic examination revealing a granular mass originating from the nasopharynx.

Figure 3. (A) Pictomicrograph from the nasopharyngeal biopsy revealing typical sulfur granules (arrow; H&E staining; magnification, ×100). (B) The central core of the sulfur granules contained organized aggregates of filaments with club-like eosinophilic structures, referred to as the Splendore-Hoeppli phenomenon (arrow; H&E staining; magnification, ×400). (C) Grocott-Gomori methenamine silver staining of the specimen (magnification, ×400). H&E, hematoxylin and eosin.

Discussion

Human actinomycosis was first described in 1878 by James Israel (4). Actinomycosis is a rare anaerobic bacterial infection, typically caused by Actinomyces israelii (1,2). The members of the pathogenic Actinomyces species do not exist freely in nature, but are commensals that normally inhabit the oropharynx (particularly the tonsillar crypts and the gingivodental crevices) (4), the abdominopelvic region or the female genitourinary organs (1). Antecedent tissue injury with coinfection by other pathogens that act in a synergistic manner may lead to infection at any site in the body. Orocervicofacial actinomycosis is the most common form of the disease, accounting for up to 60% of all cases (2). Lesions are frequently located at the angle of the jaw or in the submandibular region (1). Common presenting features include an acute painful abscess or chronic indolent soft-tissue swelling, from which sinus tracts can develop over time. At present, the clinical diagnosis of actinomycosis is challenging, and therefore the disease has been referred to as a ‘masquerader of head and neck’ disease (1–3).

Diagnosis is established most accurately by isolating the Actinomyces species in cultures of clinical specimens (1–3). However, previous studies have reported that <50% of cases highly suspected to suffer from actinomycosis lead to the growth of the organism in cultures (1–3). This is considered to be due to the requirement of strict anaerobic culturing conditions, previous antibiotic use or the overgrowth of a concomitant organism (1–9). Clinicians must be knowledgeable when submitting specimens in order to optimize the recovery of these fastidious anaerobic bacteria. Under microscopic examination, colonies of the organism form typical sulfur granules and present as round or oval basophilic masses on hematoxylin-eosin slides, the centres of which contain organized aggregates of filaments with club-like eosinophilic structures that are referred to as the Splendore-Hoeppli phenomenon (1–3). A Gram-stained smear of the specimen may exhibit beaded, branched Gram-positive filamentous rods (1–3). The utilization of specific stains, including Grocott-Gomori methenamine silver stain, MacCallum-Goodpasture stain, p-aminosalicylic acid or Brown-Brenn stain, may aid in the visualization of the bacilli (1). A specific differential consideration is a diagnosis of nocardiosis (9), which is positive for acid-fast staining. Therefore, the combination of clinical images, microbiological results and histological findings should enable a successful diagnosis of actinomycosis (1–3).

The treatment of actinomycosis involves prolonged antibiotic treatment and/or surgical resection (1–9). Surgery may be reserved for certain circumstances, such as the excision of the sinus tract, resection of necrotic tissue, sequestration of bone and drainage of abscesses (1). Although surgical intervention promotes recovery, it is not curative by itself. High-dose penicillin (18–24 million units per day) administered over a prolonged period is the standard form of therapy (1–3). Doxycycline, clindamycin and erythromycin may be used as effective alternative regimens, particularly for patients who are allergic to penicillin (1–3). However, previous data suggested that not all cases warrant long-term antibiotics. Sharkawy (2) and Oostman and Smego (3) stratified cases into mild and complicated infections, and concluded that the modern approach to treatment can be individualized depending on the site of infection, severity of disease and the patient's response to treatment. In addition, Daamen and Johnson (5) and Chiang et al (8) successfully treated patients with nasopharyngeal actinomycosis using a four-week administration of oral antibiotics.

To the best of our knowledge, nasopharyngeal actinomycosis resulting in a draining fistula has not been previously reported. Nasopharyngeal actinomycosis frequently presents as a non-tender virulent granuloma that is capable of expanding into contiguous tissue without regard for facial or anatomical barriers. In terms of its mass effect, it may cause unilateral otitis media with effusion (6), nasal airway obstruction (5) and carotid occlusion (7).

Since one of the hallmarks of nasopharyngeal carcinoma is its marked racial/ethnic and geographic distribution in Southeast Asia, recommendations for workup have changed over time as technologies have improved. PET scanning, albeit not routinely recommended, is not only capable of revealing the location of tumors, but also provides valuable information concerning metabolic tumor volume. Unlike in malignant disease, positive FDG uptake depends on the presence and activity of inflammatory leukocytes (10). In the present study, it was hypothesized that acute inflammation with direct actinomycetes invasion was the main cause of increased uptake of 18F-FDG.

In conclusion, although the occurrence of nasopharyngeal actinomycosis is extremely low, it is advisable to always maintain a high level of clinical suspicion when treating patients with a persistent nasopharyngeal mass that presents with only vague symptoms. Healthy individuals may be infected without any predisposing factors. A presumptive diagnosis is established by the presence of sulfur granules containing Gram-positive filamentous rods, but a negative result for acid-fast staining (1). The prompt initiation of an appropriate therapy is crucial for the eradication of this insidious disease. In addition, prolonged observation and follow-up are mandatory in order to detect recurrence. The present study fills a breach in the clinical literature regarding this unique disease entity. Future studies should aim to provide further innovative information regarding the clinical evaluation and management of nasopharyngeal actinomycosis.

References