Innocuous presentation of ameloblastic carcinoma

Abstract

Ameloblastic carcinoma is a rare malignant odontogenic neoplasm that exhibits diverse clinical and radiological presentations. In fact there are several differential diagnoses during histopathological evaluation too. Lack of adequate reports could not establish the predominant demographic, clinical and radiological presentations. For the same reasons, the role of adjuvant radiotherapy and chemotherapy is also unsubstantiated yet. This case discusses the innocuous clinical and radiological presentation of ameloblastic carcinoma in a 55-year-old man where the diagnostic confirmation was achieved through histopathological evaluation. The differential diagnoses, treatment and follow-up details of this case are discussed in light of the previous published case reports and systematic reviews of case reports in an attempt to increase the sensitisation among dentists towards ameloblastic carcinoma.

Background

Odontogenic neoplasms are neoplasms that are derived from odontogenic apparatus, presenting various architectural and cytological patterns. To facilitate better communication between the clinician and pathologists for the effective treatment strategy, WHO has developed and edited the classification of odontogenic tumours recently.¹ Malignant odontogenic tumours are relatively uncommon neoplasms accounting for approximately 4.3% of all tumours.² Ameloblastic carcinoma (AC) is the second most common² malignant odontogenic neoplasm that retains the characteristics of ameloblastic differentiation and simultaneously evidences cellular atypia.^{3 4} There are two forms of AC: primary type and secondary type. The 2005 WHO classification⁵ divided AC into three forms: primary type, which arises de novo; secondary intraosseous type, which arises due to the transformation from a pre-existing ameloblastoma; and secondary extraosseous type. Because of its rarity there seemed very little rationalisation to classify AC; therefore, it continues as a single entity in 2017 WHO classification.¹ The clinical manifestations of AC are often deceptive simulating benign odontogenic tumours and odontogenic cysts. Although signs such as pain, ulceration, paresthesia and mobility of teeth indicate malignancy, distinguishing AC from intraosseous squamous cell carcinoma and other malignant odontogenic tumours clinically is not possible. In fact the conventional radiographical features are also diverse, including both unilocular and multilocular radiolucency with or without cortical bone destruction.⁶ Therefore, histopathology always offers the diagnostic confirmation. This report describes a similar case of AC with deceptive clinical and radiological features.

Case presentation

A 55-year-old man reported with the chief complaint of pain and swelling in the lower anterior teeth region since last 6 months. His medical history was unremarkable. On clinical examination a non-tender firm swelling was palpable on the left parasymphysis region of mandible with no palpable lymph nodes (figure 1). Intraoral examination revealed presence of a swelling in the mandibular symphysis region further extending into the left parasymphysis region. The swelling measured approximately 2.5 cm × 3 cm in size with surface ulceration due to repeated trauma from the maxillary teeth (figure 2). Both the cortical plates were found expanded. Oral hygiene of the patient was very poor, with generalised attrition of teeth and gingivitis. Orthopantomograph presented a well-defined unilocular radiolucency involving mandibular symphysis and left parasymphysis region (figure 3). Resorption of alveolar border along with root resorption of the left mandibular central and lateral incisors was observed in the radiograph. The patient provided the history of spontaneous exfoliation of four teeth on the left side of mandible including canine, premolars and first molar. Since the patient could not afford to get advanced imaging techniques such as CT and MRI done, extent of bone resorption, distant metastasis and lymph node involvement were not evaluated. Based on the clinical and radiological evaluation, several diagnoses were done. Odontogenic cysts such as odontogenic keratocyst, odontogenic tumours such as unicystic ameloblastoma and fibro-osseous lesions such as central ossifying fibroma were the provisional diagnosis. Although well-corticated unilocular radiolucency pointed towards the benign nature of the lesion, resorption of roots and alveolar bone led to the diagnosis of malignant odontogenic tumour and primary intraosseous squamous cell carcinoma. Biopsy was taken and sent for histopathological evaluation. Microscopic features revealed odontogenic follicles comprises peripherally located ameloblast-like cells and centrally located stellate reticulum-like cells in the background of moderately collagenous densely inflamed connective tissue stroma (figure 4). Cellular pleomorphism, hyperchromasia and mitotic figures were noticed in both ameloblast-like cells and stellate reticulum-like cells. Squamous metaplasia was also observed in a few of the odontogenic follicles (figure 5). A diagnosis of AC was made.

Figure 1.

Swelling on the left parasymphysis region of mandible.

Figure 2.

Swelling in the mandibular symphysis region extending into the left parasymphysis region with surface ulceration.

Figure 3.

Unilocular well-defined radiolucency involving mandibular symphysis and left parasymphysis region.

Figure 4.

Photomicrograph (4×) showing odontogenic follicles comprises peripherally located ameloblast-like cells and centrally located stellate reticulum-like cells in the background of moderately collagenous densely inflamed connective tissue stroma.

Figure 5.

Photomicrograph (10×) showing squamous metaplasia of stellate reticulum-like cells of the odontogenic follicle.

Differential diagnosis

Because of the presence of ameloblast-like cells in the odontogenic follicles and squamous metaplasia of stellate reticulum-like cells, the microscopic differential diagnosis included benign neoplasms such as ameloblastoma particularly acanthomatous variant and keratoameloblastoma as well as squamous odontogenic tumour. The prominent cellular atypia excluded these benign neoplasms. Primary intraosseous squamous cell carcinoma was also considered due to the presence of squamous metaplasia of the stellate reticulum-like cells but later ruled out because of the peripheral palisading of ameloblast-like cells and stellate reticulum-like cells. The ameloblast-like cells and squamous metaplasia of the stellate reticulum also led to the diagnosis of basaloid squamous cell carcinoma, though it was eliminated later due to the presence of stellate reticulum-like cells. The exclusion of metastatic carcinoma from organs like the breast, lungs and gastrointestinal tract was due to the odontogenic components present in the tissue.

Treatment

The patient underwent segmental mandibulectomy followed by radiotherapy of 60 Gy localised to the mandible. The patient did not receive chemotherapy.

Outcome and follow-up

The patient was followed up for 1 year postsurgery, and there was no evidence of recurrence.

Discussion

The rarity and varied presentation of AC make such cases worth discussing. Only 206 cases have been reported in the latest systematic review,⁷ to which there have been approximately 11^8–18 case reports added up until now. Low numbers of cases may be attributed to the absence of pathognomonic clinical and radiological features and to the fact that not all cases undergo histopathological evaluation, which is essential for diagnosis. The mean age of presentation was found to be higher than 45.3 years, and a slight predominance for the mandible was found in men.⁷ The age, gender and site of the present case were concordant with the present findings. Nevertheless, AC is also known to occur in the paediatric age group. A review of literature conducted till 2014 revealed 22 paediatric patients presented with AC.¹⁹ The clinical signs are similar to most odontogenic cysts and tumours.⁷ Although a rapid increase in size, pain, ulceration and tooth mobility are signs of malignancy, it is difficult to diagnose AC clinically. Radiological presentation of AC varies widely. While it may destroy the cortical bones invading the adjacent tissues, well-defined unilocular or multilocular radiolucency simulating benign lesions can also be presented.⁷ The Orthopantomograph in the present case was masquerading benign lesions. Owing to the aggressive nature of AC, CT and MRI, PET/CT of every case should be undertaken to assess the bone resorption and rule out distant metastasis and lymph node involvement.^{4 20} Despite all advanced imaging techniques, histopathological evaluation is mandatory for the diagnosis. AC combines the microscopic features of ameloblastoma with cytological atypia. Few cases may require immunohistochemical markers such as Ki-67, Proliferatine cell nuclear antigen (PCNA), Minichromosome Maintenance (MCM) and alpha Smooth Muscle Actin (α-SMA) to distinguish AC from ameloblastoma^{21 22} although the present case did not require it due to the obvious presence of cellular atypia. Surgery with an adequate margin offers the best prognosis.²³ The effectiveness of radiotherapy is questionable except in cases with inadequate margins during surgery and local recurrences.²⁴ According to Giridhar et al,²⁵ adjuvant radiotherapy offers a survival advantage only in older patients with high-risk factors. The response rate as reported in another review²⁶ was found to be 100% for radiotherapy and chemoradiotherapy whereas only 86.7% for patients without chemotherapy or radiotherapy. The novel therapeutic strategies such as carbon ion therapy and Gamma knife stereotactic surgery are also suggested.²⁶ Distant metastasis, most frequently to lungs and less commonly to bone, liver and cerebrum,^{27 28} as well as recurrence are reported to occur in AC even after several years.^{28 29} Therefore, a long follow-up period in such rare cases is essential.

Learning points.

• Ameloblastic carcinoma is a rare odontogenic malignancy with high chances of metastasis to lymph nodes and distant organs.

• Since the clinical and radiological presentation masquerade many benign lesions, histopathology is mandatory for the confirmation.

• Due to the reported recurrence and distant metastasis even after several years follow-up for at least 5 years is essential.

• Although the literature evidence is uncertain it is advisable to institute postoperative radiotherapy in patients diagnosed with ameloblastic carcinoma.

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