Acanthomatous ameloblastoma

+ General Considerations

Synonyms: Acanthomatous epulis, peripheral ameloblastoma

• Arises from remnants of odontogenic epithelium located in gingiva in tooth-bearing areas (Gardner 1996; Fulton 2012).
• Typically arises from gingival epithelium but may also arise from an intra-osseous location and break out of bone (Gardner 1993).
• Can occur in any part of the jaw but has a predilection for rostral mandible of adult large breed dogs (Thrall 1984; Fiani 2011).
• Golden Retrievers are over-represented (Fiani 2011; Goldschmidt 2017).

Conventional ameloblastoma is a non-canine acanthomatous ameloblastoma. Middle-aged dogs, with no apparent sex or breed predisposition. Distribution was equal between large and small dog breeds. Clinical appearance is mass causing focal swelling and expansion within jaw. This occurred more often in maxilla (13/20) compared to the mandible (7/20), and canine/premolars were most frequently involved. These typically had smooth surface of intact gingiva and/or mucosa with occasional cystic areas that were fluctuant and dark purple-blue. Radiographs and CT findings can demonstrate loculated intraosseous lesion. Conventional ameloblastoma and canine acanthomatous ameloblastoma also demonstrated bone lysis, tooth involvement, cortical bone involvement, contrast enhancement on CT, tooth displacement (Tjepkema 2020)

Clinical features:

• Proliferative gingival mass with an irregular surface causing tooth displacement.
• May sometimes be ulcerated with areas of necrosis.

Biologic behavior:

• Involvement of underlying bone is common causing severe cancellous and cortical bone destruction. It can also present with slow growth and minimal bone loss (Goldschmidt 2020).
• Metastasis has not been reported. Local recurrence can be noted after conservative local excision (Dubielzig 1982; Yoshida 1999).

Radiographic features:

• Bone lysis with displacement of teeth, periosteal reaction (reference?)
• Computed Tomography (CT) shows alveolar bone lysis, positive contrast enhancement, presence of cortical bone thinning are consistent findings. Some tumours were coupled with marked bone expansion, while some had minimal bone lysis. Predominantly intra-osseous locations were more often associated with aggressive biologic behavior. Intra-osseous locations were associated with a larger mean tumor size, presence of the following: tooth displacement, bone expansion, periosteal bone proliferation, cortical bone thinning, severity of bone lysis (severe to very severe bone lysis) (Goldschmidt 2020).

Cytologic features:

• Epithelial cell clusters and low number of individual spindle cells. Epithelial cells can demonstrate mild anisocytosis and anisokaryosis, round nuclei with finely stippled chromatin, no prominent nucleoli, high N:C ratios, low amounts of pale basophilic cytoplasm. Spindle cells appear slender with no oval nuclei and no prominent nucleoli, wispy cytoplasm (Munday 2017; Palic 2022)

Histopathologic features:

• Despite variability noted on advanced imaging, little variability on histopathology. Majority of tumors (70%) had no mitotic figures on 10 high power fields. Majority of histopathologic features did not significantly correlate with computed tomography features (Goldschmidt 2020).

+ Treatment

• Surgery: Curative-intent surgical treatment involves en bloc excision of the tumor and 1-2 cm of normal-appearing tissue. Marginal excision was associated with rapid recurrence (91% within an average of 32 days)(Yoshida 1999). Removal of gingival and bony aspect of canine acanthomatous ameloblastomas via curettage alone was associated with 100% recurrence (Dubielzig 1982). Wide local excision of at least 1 cm of adjacent bone resulted in consistent local cure and no local recurrence in 25 dogs (White 1989). A wider margin (2 cm intended surgical margins) resulted in 0% incomplete histopathological margin, while 1 cm intended surgical margin resulted in 1/3 of histopathological margins being incomplete (Goldschmidt 2017). Rim excision can also be considered as treatment for CAA in dogs where gingival mass was < 2 cm in the largest dimension and < 3 mm bone involvement of the adjacent tooth root with no evidence of local recurrence (Murray 2010).
• Radiation: May be an option for WHO stage T1 (< 2 cm maximum diameter) and T2 tumors (2 – 4 cm maximum diameter). Prescribed radiation dose was total dose of 48 Gy, over 4 weeks. Clinical stage (Stage T3, where tumor size was > 4 cm maximum diameter) was prognostic for risk of tumor recurrence (7.9 times risk of tumor recurrence compared to dogs with stage T1 tumors). Stage T1 and T2 had similar risk of recurrence. 4% of dogs had severe acute radiation reactions in the final week resulting in treatment discontinuation. 6.4% of dogs had chronic radiation reactions involving bone necrosis (Theon 1997). Skin effects may include epilation, dry to moist desquamation, change in skin pigmentation, hair loss (temporary or permanent) (Mayer 2007). There may also be a risk of radiation-induced carcinogenesis (McEntee 2004; Liptak 2007)
• Intralesional chemotherapy: Intralesional bleomycin can be administered from one to 16 treatments (dose range 10–20 U m-2). Side effects include wound formation with bone exposure, mild tissue reactions, local swelling, local infection (Kelly 2010).

+ Prognosis

• Surgery: Reported recurrence rates following curative intent surgery ranges from 0 – 11% (Goldschmidt 2017, Murray 2010, White 1989, Kosovsky 1991, Sarowitz 2017, Wallace 1992). In Goldschmidt 2017, 23 patients that were diagnosed with CAA and had adequate post-surgical follow-up revealed no evidence of local recurrence regardless of post-surgical histopathological margins, including margins that were incomplete (less than 1 mm tumor free margins).
• Radiation: 3-year progression free survival was 80%. Tumor recurrence in 7 out of 39 (~17.9%) dogs treated. Median overall survival for death due to any cause was 48 months (Theon 1997).
• Intralesional chemotherapy: Complete response achieved within a median of 1.5 months from initial intralesional injection. No local recurrence was observed during study period (median follow-up 842 days) (Kelly 2010).

+ References

Dubielzig RR, Thrall DE. Ameloblastoma and keratinizing ameloblastoma in dogs. Vet Pathol 1982;19:596–607.

Fiani N, Verstraete FJM, Kass P, Cox DP. Clinicopathologic characterization of odontogenic tumors and focal fibrous hyperplasia in dogs: 152 cases (1995-2005). J Am Vet Med Assoc 2011;238:495-500.

Fulton A, Arzi B, Murphy B, Naydan DK, Verstraete FJM. The expression of calretinin and cytokeratins in canine acanthomatous ameloblastoma and oral squamous cell carcinoma. Vet Comp Oncol 2012;12:258-265.

Gardner DG, Baker DC. The relationship of the canine acanthomatous epulis to ameloblastoma. J Comp Pathol 1993;108:47–55.

Gardner DG. Epulides in the dog: a review. J Oral Pathol Med 1996;25:32–37.

Goldschmidt S, Bell CM, Hetzel S, Soukup JW. Clinical characterization of canine acanthomatous ameloblastoma (CAA) in 264 dogs and the influence of post-surgical histopathological margin on local reoccurrence. J Vet Dent 2017;34:241-247.

Goldschmidt S, Bell C, Waller K, Hetzel S, Soukup JW. Biological behavior of canine acanthomatous ameloblastoma with computed tomography and histopathology: A comparative study. J Vet Dent 2020;37:126-132

Kelly JM, Belding BA, Schaefer AK. Acanthomatous ameloblastoma in dogs treated with intralesional bleomycin. Vet Comp Onc 2010;8:81-86

Liptak JM, Withrow SJ. Oral tumors. In: Withrow SJ, MacEwen EG, eds. Small animal clinical oncology. 4th ed. Philadelphia, PA: WB Saunders Co; 2007:455–472.

Mayer MN, Anthony JM. Radiation therapy for oral tumors: Canine acanthomatous ameloblastoma. Can Vet J 2007;48:99-101

McEntee MC, Page RL, Theon A, Erb HN, thrall DE. Malignant tumor formation in dogs previously irradiated for acanthomatous epulis. Vet Radiol Ultrasound 2004;45:357–361.

Munday JS, Löhr CV, Kiupel M. Tumors of the alimentary tract. In:

Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, IA: Wiley Blackwell;2017:499-601.

Murray RL, Aitken ML, Gottfried SD. The use of rim excision as a treatment for canine acanthamatous ameloblastoma. J Am Anim Hosp 2010;46:91-96.

Palić J, Heier A, Wohlsein P. Cytologic features of an acanthomatous ameloblastoma in a dog. Vet Clin Pathol 2022;51:258–262

Sarowitz BN, Davis GJ, Kim S. Outcome and prognostic factors following curative-intent surgery for oral tumours in dogs: 234 cases (2004 to 2014). J Small Anim Pract 2017;58:146–153.

Theon AP, Rodriguez C, Griffey S, Madewell BR. Analysis of prognostic factors and patterns of failure in dogs with periodontal tumors treated with megavoltage irradiation. J Am Vet Med Assoc 1997;210:785–788.

Tjepkema J, Bell CM, Soukup JW. Presentation, Diagnostic Imaging, and Clinical Outcome of Conventional Ameloblastoma in Dogs. J Vet Dent 2020;37:6 – 13.

Thrall DE. Orthovoltage radiotherapy of acanthomatous epulides in 39 dogs. J Am Vet Med Assoc 1984;184:826-829.

Wallace J, Matthiesen DT, Patnaik AK. Hemimaxillectomy for the treatment of oral tumors in 69 dogs. Vet Surg 1992;21:337–341.

White RA, Gorman NT. Wide local excision of acanthomatous epulides in the dog. Vet Surg 1989;18:12–14.

Yoshida K, Yanai T, Iwasaki T, et al. Clinicopathological study of canine oral epulides. J Vet Med Sci 1999;61:897–902.