Secondary actinomycosis in a recurrent odontogenic keratocyst: A clinicopathological diagnostic challenge with 5‐year follow‐up

Abstract

OKC is an odontogenic developmental cyst with a significant risk of recurrence. Secondary infections of the lesion with Actinomyces organisms are rare and may pose a dilemma in managing the recurrent lesion. A 20-year-old male patient reported to the outpatient department with a radiolucent multilocular lesion of the posterior right side of the mandible. A diagnosis of OKC was made based on histopathology, and a conservative approach involving decompression and marsupialisation with subsequent enucleation of the cyst and peripheral ostectomy was planned. The lesion healed without any complications. After one year, swelling occurred along with a radiolucent lesion in the same area. Re-examination revealed a case of recurrent OKC with cortical expansion and sequestration. Resurgery revealed a lesion with basophilic filamentous bacterial colonies, eosinophilic peripheral clubs with a sulfur granule, and marked inflammation, indicating secondary actinomycotic infection rather than colonization. Aerobic and anaerobic cultures were done. Postoperatively, the patient received antimicrobial therapy consisting of intravenous clindamycin for 7 days, followed by oral amoxicillin-clavulanate for 4 weeks and metronidazole for 7 days. followup was performed clinically and radiographically, with gradual improvement and healing of the disease without recurrence for 4 years after treatment of the recurrent lesion, constituting 5 years of followup from the first diagnosis. This case highlights the importance of re-evaluation through repeated histopathological examination of the recurrent OKC, especially when inflammatory or destructive changes are present.

Highlights

• •A recurrent odontogenic keratocyst can have an associated secondary infection with Actinomyces.
• •The presence of sulfur granules and the associated inflammatory reaction was instrumental in differentiating between infection and contamination.
• •Re-biopsy of the recurrent lesion can uncover an unanticipated complication of the lesion in the form of an infection.
• •Surgical intervention and antibiotic treatment were followed by 4 years without any recurrence of the lesion.

Introduction

Odontogenic Keratocyst (OKC) is a developmental odontogenic cyst that commonly occurs in the posterior mandible and is characterised by local aggressiveness and a tendency to recur. The recurrence of the cyst depends on the size of the lesion, multilocularity, residual epithelium, and method of treatment. Minimally invasive therapy may decrease the morbidity in young patients at the expense of extended clinical and radiographic followup [[1], [2], [3], [4]].

Actinomyces spp. is part of the oral flora; however, they can cause chronic cervicofacial infection when they invade deeper structures following mucosal disruption. The diagnosis of the disease may be challenging, since Actinomyces can be detected on the mucosal surface; thus, it is necessary to demonstrate inflammation and the presence of typical sulfur granules or filaments [5,6]. Secondary infection with Actinomyces spp. of an odontogenic cyst is rarely observed, while recurrent OKC associated with actinomycosis was described only occasionally [7].

Here, we describe a case of recurrent OKC with secondary actinomycotic infection, based on histopathological findings in a young patient, emphasising the importance of repeated tissue examination and followup.

Case presentation

A 20-year-old male patient was seen with complaints of progressive swelling in the posterior mandible region for three months, along with mild pain. The patient denied having fever, weight loss, or malaise. Past medical and surgical history was unremarkable. No history of tooth extraction, endodontic therapy, or any surgical procedure in the affected area.

On extra-oral examination, there was the presence of diffuse, firm, mildly tender swelling measuring 4 × 3 cm with facial deformity. No redness, ulcers, or sinus tract was noted. Intra-oral examination revealed buccal cortical thickening with obliteration of the buccal vestibule. Teeth were vital.

A panoramic radiograph revealed a distinct multilocular radiolucent lesion starting from the 44–48 region with inferior displacement of the mandibular canal, displacement of teeth 47 and 48, slight root resorption of tooth 47, and presence of a cortical window at 46 (Fig. 1). The CT scan revealed a mostly cystic lesion in the right posterior mandibular body, angle, and ascending ramus, with cortical expansion and thinning (Fig. 2). OKC was the primary diagnosis, but ameloblastoma and odontogenic myxoma were also differential diagnoses.

Fig. 1.

Panoramic radiograph depicting multilocular radiolucency on the right posterior region of the mandible with window formation in the periapical region of 46. Distally displaced 47 and 48, and downward displacement of the inferior alveolar nerve canal. Mild root resorption of 47.

Fig. 2.

Contrast-enhanced CT of the maxillofacial region demonstrated a well-defined, predominantly hypodense intraosseous lesion located in the right posterior mandibular region, extending from the posterior mandibular body toward the angle and ascending ramus with relatively homogeneous cystic appearance.

The incisional biopsy revealed thin, parakeratinized stratified squamous epithelium with a roughened surface and palisading basal cells, confirming the diagnosis of OKC (Fig. 3). In view of the patient's age and the characteristics of the lesion, conservative treatment was opted for. The lesion was decompressed and marsupialized through an 8 × 6 mm bony window. A customized acrylic obturator was used to maintain the opening, and the patient was advised to rinse the cavity with saline. Successive radiographs showed a decrease in lesion size and new bone formation.

Fig. 3.

The photomicrograph shows a cystic structure composed of relatively uniform stratified squamous epithelium with a thick, eosinophilic, keratinized surface layer. The stratified squamous epithelium in the cyst wall is relatively thin and well organized; the basal cell layer at the epithelial-stromal junction is evident. The cyst wall consists of fibrocollagenous connective tissue stroma that harbors fibroblasts and minute vessels. No cellular atypia or pleomorphism has been detected in the present section.

The early postoperative period was uneventful. At 15 days, 3 months, 6 months, and 8 months, clinical and radiographical examinations revealed adequate healing without any signs of recurrence (Fig. 4, Fig. 5, Fig. 6, Fig. 7).

Fig. 4.

Postoperative(15 days after first surgery) panoramic radiograph depicting surgical defect in right posterior region of mandible with missing 44, 45, 46.

Fig. 5.

Postoperative (three months after first surgery) panoramic radiograph depicting the healing surgical site.

Fig. 6.

Postoperative (Six months after first surgery) panoramic radiograph depicting satisfactory healing of surgical defect in right posterior region of mandible. Radiopacities present in the coronal region of 43 and 47 are the clasps of the obturator.

Fig. 7.

Postoperative (Eight months after the first surgery) panoramic radiograph depicting satisfactory healing of the surgical defect in the right posterior region of the mandible.

One year following initial therapy, the patient presented with recurrence in the form of swelling and asymmetry in the face. (Fig. 8) The panoramic radiograph revealed a new radiolucent area in the previously treated area. (Fig. 9) Computed Tomography showed a poorly defined lesion with a size of 4.2 × 3.5 × 2.8 cm, buccal cortical expansion, slight inferior positioning of the mandibular canal, osteolysis, and sequestration. Management of the condition was repeated surgically. Cystic contents and lesion tissue were excised, and the area was irrigated and grafted with β-tricalcium phosphate. Histopathological examination of the tissue and cyst contents, and culture for aerobic and anaerobic organisms, were performed.

Fig. 8.

Extraoral presentation (8 A) Frontal view showing the localized swelling of the right lower face with facial asymmetry. (8B) Right lateral view showing swelling in the posterior mandibular region.

Fig. 9.

Postoperative (12 months after first surgery) panoramic radiograph depicting two separate ill-defined radiolucencies: first in the 44 45 region and second mesially to 47 in the right posterior region of the mandible.

Histopathology confirmed OKC. In addition, the cyst wall showed a significant inflammatory and suppurative infiltrate with necrosis and basophilic filamentous bacterial colonies. Eosinophilic peripheral club and sulfur granule were seen in hematoxylin and eosin staining (Fig. 10, Fig. 11). The presence of bacterial colonies, typical morphological features of a sulfur granule, and a significant host inflammatory reaction favored secondary actinomycosis infection rather than simple colonization of the mucosa. Bacterial cultures (aerobic and anaerobic) were performed. No specific bacteriological report for any species is provided, as the diagnosis is mostly based on histopathology.

Fig. 10.

Histological characteristics of the odontogenic cyst (H&E staining). (a) Photomicrograph depicting a cystic structure covered by stratified squamous epithelium, which is present on top of the fibrocollagenous stroma containing eosinophilic substance inside the cyst. (b) High-power view illustrating a thin and organized layer of stratified squamous epithelium lying on top of collagenous stroma. (c) High-power view depicting well-defined surface keratinization/parakeratinization with fibrocollagenous stroma underneath. (d) High-power view illustrating a stratified squamous epithelial lining with organized maturation and a collagenous stroma.

Fig. 11.

Histopathologic features of recurrent odontogenic keratocyst with actinomycotic infection secondary to it. (11.a) H&E-stained section at low power magnification (100 × total magnification). It shows the cyst lining composed of epithelium, with fibrocollagenous connective tissue beneath it and inflammatory exudate within. (11.b) H&E-stained section (100 × total magnification). It shows inflammation within fibrocollagenous connective tissue, along with a bacterial colony and adjacent osseous tissue. (11.c) H&E-stained section at intermediate magnification (200 × total magnification). It shows a dense inflammatory and suppurative infiltrate, along with necrotic debris and bacteria in aggregates. (11.d) H&E-stained high-power section (400 × total magnification). It shows a sulfur granule composed of an Actinomyces colony with a central basophilic filamentous bacteria with eosinophilic, club-shaped bacteria around them.

After diagnosing the condition, antibiotics were started, including intravenous clindamycin for 7 days, followed by oral amoxicillin-clavulanate 625 mg twice daily for 4 weeks and metronidazole 400 mg thrice daily for 7 days.

followup was done clinically and radiologically. The patient had no signs of recurrent lesions at 7 days, 3 months, 6 months, and 1 year after treatment of the recurrence. In addition, the patient had no symptoms, and imaging showed ongoing bone healing with no recurrence at 2, 3, and 4 years after treatment of the recurrence. (Fig. 12, Fig. 13, Fig. 14, Fig. 15, Fig. 16, Fig. 17, Fig. 18, Fig. 19) There was no recurrence up to 4 years after treatment of the recurrent lesion, with a total of 5 years of followup from diagnosis.

Fig. 12.

Postoperative followup panoramic radiograph (seven days after second surgery) showing granular radiopacity in the right posterior region of the mandible, suggestive of bone graft placement. Teeth missing: 44–48. Root canal filling seen in 43.

Fig. 13.

Post-operative followup panoramic radiograph (three months after second surgery) showing satisfactory healing in the right posterior region of the mandible. Teeth missing: 44–48. Root canal filling seen in 43.

Fig. 14.

Post-operative followup panoramic radiograph (six months after second surgery) showing satisfactory healing in the right posterior region of the mandible.

Fig. 15.

Extraoral frontal and right lateral profile of the patient showing complete healing (12 months follow-up after second surgery).

Fig. 16.

Post-operative followup panoramic radiograph (12 months after second surgery) showing satisfactory healing in the right posterior region of the mandible with no evidence of recurrence.

Fig. 17.

Post-operative followup panoramic radiograph (2 years after second surgery) showing satisfactory healing in the right posterior region of the mandible with no evidence of recurrence.

Fig. 18.

Post-operative followup panoramic radiograph (3 years after second surgery) showing satisfactory healing in the right posterior region of the mandible with no evidence of recurrence. Teeth missing: 38, 44, 45, 46, 47, 48.

Fig. 19.

Post-operative followup panoramic radiograph (4 years after second surgery) showing complete healing in the right posterior region of the mandible with no evidence of recurrence.

Discussion

The principal infectious-disease relevance of this case lies not merely in the identification of Actinomyces within an oral lesion, but in the clinicopathological evidence supporting a secondary actinomycotic process in a recurrent odontogenic keratocyst (OKC). Actinomyces spp. are known to be a regular component of the oral microflora. As such, it is extremely important not to take the mere presence of Actinomyces spp. in the mouth as a sign of invasive infection. Cervicofacial actinomycosis is usually characterized by a rather slow course and, clinically, can easily be mistaken for various tumor-like, inflammatory, cystic, and even chronic infectious processes [5,6].

In the current case, repeated histopathological analyses revealed basophilic filamentous bacterial colonies, eosinophilic peripheral clubs, and sulfur granules within a recurrent OKC lesion, along with significant suppurative and necrotic inflammation. Sulfur granules are dense clusters of filamentous organisms and are strong indicators of actinomycosis when seen in the appropriate clinical and histopathological context. However, sulfur granules are not completely specific and may sometimes be found in other infections involving filamentous bacteria or fungi. The significance of sulfur granules as a marker of disease is thus enhanced when they are found in combination with tissue inflammation and characteristic filamentous organism morphology [5,6]. In the current case, the organisms were observed in the recurrent OKC lesion along with significant tissue destruction and inflammation rather than being identified from a superficial mucosal biopsy. This scenario provides a stronger pointer towards clinically significant secondary infection with actinomycosis than mere identification of Actinomyces.

It should, however, be clearly stated that certain microbiological aspects must be acknowledged. Even though both aerobic and anaerobic cultures were done, the existing documentation does not contain species-level isolation of Actinomyces. Culturing for the diagnosis of cervicofacial actinomycosis is known to be quite complicated because Actinomyces species are very picky anaerobic bacteria, can be present in small amounts, and can be easily overgrown by other microflora found in the mouth. Previous literature on the topic has consistently noted that both direct microscopy and histopathology serve as good complements to culture. [5,6]. The existing diagnosis can therefore be referred to as histopathologically supported secondary actinomycotic infection.

The recurrent nature of the underlying OKC represents a second important component of the case. OKCs demonstrate clinically relevant recurrence due to their characteristic epithelial architecture, locally aggressive behavior, and potential for residual epithelial remnants after treatment. Contemporary evidence indicates that recurrence varies substantially by treatment modality and lesion characteristics, with simple enucleation generally associated with higher recurrence than approaches incorporating decompression or adjuvant techniques. A recent overview of systematic reviews reported a mean recurrence of approximately 16.2%, with the highest recurrence observed after simple enucleation, whereas the use of adjuvant approaches may reduce recurrence [[1], [2], [3], [4]]. These findings support the rationale for the initial conservative approach in this young patient, in whom decompression followed by enucleation and peripheral ostectomy was selected to reduce morbidity while preserving mandibular structures.

However, recurrence was noted approximately 1 year following treatment. The relatively early recurrence highlights the fact that radiologic reduction and postoperative healing do not necessarily result in complete resolution of the pathological process. Risk of recurrence depends on several factors, including lesion size, multilocularity, anatomical site, and epithelial remnants, among others [[2], [3], [4],[8], [9], [10]]. Current evidence also supports a more tailored approach to treatment as well as follow-up due to the importance of the issue of recurrence, even with apparently successful treatment [1,2]. In the present case, the recurrence was not merely radiological recurrence of a cystic lesion but involved bone destruction, bone expansion, and sequestration.

Reassessment of the histopathology was thus essential. While the first biopsy confirmed OKC, the second revealed a new pathological process involving bacteria, sulfur granules, and suppurative inflammation. This provides one of the key diagnostic principles in infections of the mouth and jaws: recurrence of a lesion should not necessarily be equated with recurrence of the original pathology when there has been a change in the clinical/radiographic appearance of the condition. A reassessment of the histopathology may reveal another disease, such as infection, a response to therapy, an inflammatory transformation, or a secondary pathological process. This is especially true for cervicofacial actinomycosis, which causes nonspecific swelling, inflammation, and destruction characteristic of several other oral and maxillofacial conditions [5,6].

In this case, the additional information from the recent report by Ma et al. on recurrent mandibular OKC occurring in the background of chronic actinomycotic osteomyelitis, which highlights the significance of histological analysis, needs to be taken into account [7]. This means the relationship between recurrent OKC and Actinomyces infection is not new and has been reported previously. The importance of the current case lies in a thorough clinicopathological demonstration of a sulfur granule-forming infection in the context of recurrent OKC, clear differentiation between colonization and clinically significant infection, the need for repeated biopsy to demonstrate the superimposed infection, and long-term results. The distinction is crucial, since the novelty of a contemporary case report should come from its diagnostic and clinical significance, not necessarily from being the first description of the problem.

OKC shows great diversity in its imaging characteristics, including multilocularity, corticoperiosteal expansion, tooth movement, and involvement of adjacent structures [8]. The recurrence in this case exhibited an ill-defined destructive pattern with sequestration, broadening the differential diagnosis beyond that of a simple recurrent cyst. Thus, the re-evaluation of the lesion on cross-sectional imaging became a catalyst for a second tissue diagnosis. The combination of imaging and histopathology proved significant in this case because neither diagnostic tool provided a sufficient answer on its own.

Cervicofacial actinomycosis treatment usually involves both source control and antibiotic therapy, especially when the infection occurs with necrotic or damaged tissues. β-Lactam drugs still play an essential role in treating the disease. However, it is recommended to tailor the use of antimicrobials based on parameters such as the extent of infection, clinical response, drug susceptibility test results, and the adequacy of surgery [5,6]. The surgical procedure may be required for excision of necrotic tissues, drainage of abscesses, and treatment of the primary pathological process. In the present case, surgical treatment of the recurrent lesion was followed by postoperative antimicrobial therapy and the patient's recovery. Such a positive result indicates the importance of considering two aspects of the disease – the recurrent dental lesion and the infection.

This should, however, be considered in light of the limitation of having a case report. Without species-level confirmation, it is not possible to determine whether this case could provide a susceptibility pattern or optimal antibiotic treatment for the recurrence of OKC-related actinomycosis. It is also not possible to show that any particular antibiotic had a positive effect. The most important conclusion to be drawn from this case is the successful management through surgery, antibiotics, and follow-up.

Long-term follow-up is yet another strong point about the case. In addition, recurrence of OKC can occur years after the procedure. It is proven by the current literature that there should be a long period of monitoring, especially among those patients who have a recurrent OKC and those who underwent the conservative approach [[1], [2], [3], [4],9,10]. The nonrecurrence of OKC for 4 years after treatment of the recurrent OKC means 5 years of total monitoring.

All these considerations suggest a more general diagnostic guideline applicable to the management of infectious diseases. The mere presence of Actinomyces within an oral mucosa lesion does not mean either that there is a colonization or that an invasive infection took place. Confirmation can be achieved if the above-mentioned factors, including organism morphology, formation of sulfur granules, necrosis, purulent inflammation, behavior of the lesion, and imaging results, are present all at once. For a recurrent OKC with signs of inflammation or destruction, repeating the tissue biopsy will be crucial, as it will allow reassessment of the underlying lesion and identification of any accompanying infectious condition.

Thus, the main lesson of this case for IDCases is that the presence of a secondary actinomycotic infection in a recurrent odontogenic lesion requires a clinicopathological approach. Ignorance of this rule can lead to both underdiagnosis and overdiagnosis of a clinically significant infection.

Conclusion

Secondary actinomycotic infection is rare in cases of recurrent OKC. In this case, the presence of recurrent OKC, along with sulfur granules, bacterial colonies, and significant tissue inflammation, indicated an actinomycotic infection. Histopathologic evaluation was thus essential for making an accurate diagnosis. A combination of surgery and antimicrobial treatment led to the healing of the lesion. Recurrent OKC with signs of inflammation or destruction requires repeated tissue examination and follow-up.

Patient perspective

According to the patient, his first conservative therapy was reassuring because he did not want a lot of surgery. Upon recurrence of swelling approximately one year later, he was again treated when histological examination showed recurrent OKC with secondary actinomycosis. The patient reported relief of pain and swelling following treatment and was pleased with the subsequent clinical and radiological follow-up.

List of abbreviations

OKC- odontogenic keratocyst.

Author contributions

MK conceived the case report, collected and organized the clinical, radiographic, histopathological, and follow-up information, conducted the literature review, and drafted and revised the manuscript. VL contributed to clinical diagnosis and management and critically reviewed the manuscript. RK contributed to the histopathological evaluation and interpretation of the primary and recurrent lesions and critically reviewed the manuscript. All authors approved the final manuscript.

CRediT authorship contribution statement

Mohini Kadam: Writing – review & editing, Writing – original draft, Conceptualization, Investigation. Vidya Lohe: Writing – review & editing, Supervision. Ravindra Kadu: Writing – review & editing, Supervision.

Consent for publication

Written informed consent was obtained from the patient and his parents for publication of the clinical information and images.

Ethics approval and consent to participate

Ethics approval was not required for this single-case report. The authors confirm that all applicable patient consent requirements were fulfilled.

Funding

No funding was received.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability

The data supporting the findings of this case report are available from the corresponding author on reasonable request.