Introduction

Ameloblastoma is a benign but locally invasive tumor of odontogenic epithelial origin which is devoid of hard tissue formation [1]. Ameloblastoma rarely cause diagnostic difficulties due to classic histopathological presentation [2]. However, variation in conventional histologic presentations is not unusual [3]. Brannon (1994) defined Adenoid ameloblastoma (AA) as a variant of ameloblastoma whose histopathological features include a follicular or plexiform ameloblastoma with tubular structures [2]. These tubular structures resemble those seen in Adenomatoid odontogenic tumor (AOT); thus, the name adenoid ameloblastoma. Evans et al. in 2004 first introduced the term “adenoid ameloblastoma with dentinoid” as a neoplasm with histopathological features similar to ameloblastoma and AOT along with hard tissue formation [4]. AA is a rare histological variant in the unusual presentation category which can pose problem in diagnosis due to the presence of cribriform architecture, adenoid structures and varying degrees of dentinoid. Adenoid structures in odontogenic tumors like AOT and calcifying epithelial odontogenic tumor is commonly seen, however glandular or ductal structures are unusual in ameloblastoma. Jayasooriya PR et al. in their recent paper stated that any tumor which is a variant of ameloblastoma, has AOT-like areas with presence of dentinoid could be diagnosed as AA [5]. The present cases depicted all the features listed by various authors for AA. We report two cases with varied histopathological presentation that revealed existence of follicular/plexiform ameloblastoma with adenoid and dentinoid changes. Through this paper we intend to highlight two institutional cases of AA. The review of previous cases diagnosed as AA have also been tabulated (Table 1).

Table 1 List of previous cases diagnosed as Adenoid ameloblastoma in the jaws along with present cases
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Case Presentation

Case 1

A 32 years old female reported to our institution with complaint of pain and swelling on right side face from past 8 months which was increasing in size. No history of trauma was elicited. The patient underwent biopsy in 2015 although the report was inconclusive. Swelling resolved and spontaneously re-occurred on the same site. Extraoral examination revealed bony hard, non-tender 5 × 5 cm swelling on right side which extended from infraorbital region to lower border of mandible (Fig. 1a). Intraoral examination revealed buccal and lingual cortical expansion which extended from 43 to 45 region. Radiographic examination revealed an expansile lesion with cortical perforation in the buccal cortex and condylar neck region (Fig. 1b-c). The incisional biopsy was reported as acanthomatous ameloblastoma due to areas of squamous metaplasia in the tumor islands. The stroma also showed the presence of numerous hemorrhagic areas. Based on this, hemi mandibulectomy with reconstruction was performed with the goal to eradicate pathology, prevention of recurrence and to restore form, function and esthetics of the patient (Fig. 1d). The excised tissue specimen revealed numerous cystic structures lined by odontogenic epithelium with peripheral ameloblast like and central stellate reticulum like cells (Fig. 2a-b). Odontogenic epithelium proliferated in the form of interconnecting strands with adjacent areas of abundant homogenous eosinophilic dentinoid like material deposition that stained positive (pink) for van gieson (Fig. 2c-d). Adjoining multiple ductal structures lined by cuboidal to low columnar cells were also evident. Intervening stroma showed moderate inflammation, extensive hemorrhagic areas and multiple small and large vascular channels engorged with red blood cells. Based on clinical, radiological and histopathological examination final diagnosis of follicular ameloblastoma with dentinoid/AA was made. This intriguing histopathological diagnosis led us to retrospect another case which had revealed similar findings.

Fig. 1
figure 1

 A collage of Case 1 with (a) Extraoral photograph revealing bony hard, non-tender swelling on right side of face, (b) Computed Tomography which shows an expansile lesion, (c) Radiographic examination (CT) reveals cortical perforation in the buccal cortex and condylar neck region, (d) Resected gross specimen after hemi mandibulectomy

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Fig. 2
figure 2

 A collage of the histopathologic findings of Case 1 with (a) Photomicrograph reveals numerous cystic structures lined by odontogenic epithelium with tall columnar peripheral palisading of ameloblast like cells [4x/H&E], (b) shows centrally placed network like arrangement recapitulating stellate reticulum formation[10x/H&E], (c&d) Photomicrographs of tissue sections showing odontogenic epithelium proliferating in the form of interconnecting strands with adjacent areas showing deposition of abundant homogenous eosinophilic dentinoid like material stained amorphous pink. [10x/Van Gieson]

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Case 2

A 60-year-old female had visited the college with complaint of swelling in the lower jaw for 5 years with no history of trauma (Fig. 3a). The swelling gradually increased to present size with referred pain to ear and head. Intraoral examination revealed solitary, firm, fluctuant and nontender swelling of size 14 × 12 cm that extended from right to left angle region obliterating the buccal vestibule (Fig. 3b). Radiographic findings revealed a well-defined multilocular radiolucency with radiopacity causing expansion and thinning of cortex. The biopsy tissue upon sectioning showed intraosseous odontogenic neoplasm with tumor cells proliferating as interconnected plexus. Peripheral cells were cuboidal to low columnar with central stellate reticulum like areas with perivascular hyalinization (Fig. 4a). Formation of dentinoid like material was also evident which stained positive for van gieson (Fig. 4b). Stroma showed rich vascularity with areas of cystic degeneration (Fig. 4c). Significant sheet like proliferation of epithelial cells was noted along with glandular and adenoid like areas (Fig. 4d). Thus, a diagnosis of plexiform ameloblastoma with dentinoid changes/ AA was recapitulated. In consideration of both cases, it is suggested that AA could essentially result from any variant of ameloblastoma whether follicular or plexiform due to inductive changes and dentinoid formation.

Fig. 3
figure 3

 A collage of Case 2 with (a) Extraoral photograph revealing large swelling on lower jaw, (b) Intraoral photograph revealing solitary, firm, fluctuant and nontender swelling of size 14 × 12 cm extending from right to left angle region obliterating the buccal vestibule

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Fig. 4
figure 4

 A collage of the histopathologic findings of Case 2 with (a) Photomicrograph revealing interconnected strands and cords of odontogenic epithelium with tall columnar peripheral palisading ameloblast like cells diagnosed as plexiform ameloblastoma [10x/H&E], (b) Photomicrograph showing deposition of abundant homogenous eosinophilic dentinoid like material stained amorphous pink. [10x/Van Gieson], (c) Photomicrograph depicting extensive decongested vessels [10x/H&E], (d) Photomicrograph showing proliferation of spindle shaped cells forming rosette like appearance[40x/H&E]

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Discussion

Ameloblastoma generally do not show any evidence of induction; however, rare cases associated with hard tissue formation have been reported [6]. Dentinoid is defined as non-mineralized substance that resembles dentin, but which neither contains tubules nor fulfils the criteria for atubular dentin. It is located in a close anatomical relationship to odontogenic epithelium [7]. It is also hypothesized that the excessive stimulation of angiogenesis during tumor development may also lead to an inductive process that might aid in dentinoid formation in the adjacent connective tissue [8]. At times, AOT-like areas predominate, which may overshadow the ameloblastomatous areas leading to benign diagnosis and conservative treatment, which will ultimately result in recurrence [3]. AA is considered as a neoplasm with potential for extension and recurrence. Thus, decision of proper patient care is determined by accurate diagnosis of the tumor. In consideration with the previous reports, the histologic findings of the present cases resembled strongly those reported by Orlowski et al., Matsumoto et al., and Evans et al. so new term “adenoid ameloblastoma with dentinoid” was coined. It is also intriguing to note that the reported cases of longstanding or recurrent ameloblastoma never exhibited the formation of dentinoid helping us to conclude that ameloblastoma with dentinoid formation is not a secondary phenomenon in a pre-existing conventional ameloblastoma rather it arises de novo [8]. AA is demographically similar to conventional ameloblastoma but with histopathological differences and a higher rate of recurrence. AOT shows mutation in KRAS p.G12V and p.G12R gene whereas ameloblastoma shows BRAF p V600 gene mutation which makes them genetically distinct. In a recent study, nine AA cases were screened by TaqMan allele-specific qPCR to assess BRAF p.V600E, ameloblastoma signature mutation, and KRAS p.G12V and p.G12R, AOT signature mutations. Neither BRAF nor KRAS mutations were identified in any of the case. The molecular outcome supported AA as an entity distinct from AOT and ameloblastoma [9]. Further both our cases revealed rich vascularity with endothelial lined blood vessels and areas of cystic degeneration resembling hemangiomatous ameloblastoma. Possible explanation for vascularity is similar to Lucas RB et al. findings which stated that vascular component is purely a secondary change and opined that cystic degeneration occurs in the stroma of plexiform ameloblastoma. During the cystic formation, some blood vessels persist and dilate instead of diminishing resulting in vascular component that can present as diagnostic dilemma [8]. Thus, we aimed to highlight these two cases of a newly recognized entity separate from the ameloblastoma group of tumors, defined as an epithelial neoplasm characterized by cribriform architecture and duct-like structures, with dentinoid presently diagnosed as AA [10].

Conclusion

The recently updated 5th edition WHO odontogenic tumor classification (2022) has also included AA as a separate entity in the benign tumor category. Our cases will add on to the already published cases depicting it as unique standalone tumor due to its rarity, unusual behavior and prognosis. Thus, it is pertinent to diagnose it accurately and further studies incorporating genetic analysis should be done to shed light on its biological aggressiveness.