Journal of Cranio-Maxillo-Facial Surgery 42 (2014) e301ee304

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Journal of Cranio-Maxillo-Facial Surgery

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Case report

Ameloblastoma with varied sites of metastasis: Report of two cases

and literature review
Yi Lin, Jian-feng He*, Zhi-yong Li, Jian-hua Liu
Department of Oral and Maxillofacial Surgery, The First Afliated Hospital, College of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou 310003,
Zhejiang, PR China

a r t i c l e i n f o

a b s t r a c t

Article history:
Paper received 23 June 2013
Accepted 8 October 2013

Objective: We report two rare cases of lung metastasis from maxillary ameloblastoma, in order to review
its risk and analyse the types of metastases that can present with this disease.
Methods: A 40-year-old male with multiple recurrences and a 46-year-old female, who had undergone
successful surgical treatment of a maxillary ameloblastoma, presented with metastatic lesions. The
primary tumour and metastases were benign in both patients. We reviewed and analysed 20 cases of the
same condition reported in recent years.
Results: Our initial treatment for the primary maxillary lesion was performed more than 10 years before
the pulmonary lesions presented. Due to the aggressive nature of this tumour, metastases in the lungs
and cervical lymph nodes (male patient) were conrmed.
Conclusion: These cases presented a diagnostic challenge due to the multiple and varied sites of recurrence, which indicate the natural behaviour of this tumour. Different routes of metastasis can occur,
including implanting, haematogenous, and lymphatic spread. CT-guided percutaneous transthoracic lung
biopsy is an important method to conrm metastatic ameloblastoma.
2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights
reserved.

Keywords:
Ameloblastoma
Metastases
Histopathology

1. Introduction

2. Case reports

Ameloblastoma is a benign tumour of odontogenic epithelial

origin, which accounts for approximately 1% of all mandibular tumours and cysts (Adebayo et al., 2011). It is a locally invasive
tumour with the tendency to recur. Although histologically benign
and clinically slow growing, ameloblastoma may metastasize to
regional lymph nodes and distant sites (Eckardt et al., 2009;
Dissanayake et al., 2011).
In the WHO classication system of 2005, a clear distinction
between ameloblastoma, malignant ameloblastoma, and ameloblastic carcinoma was made. Malignant ameloblastoma differs from
ameloblastoma because of the presence of distant metastasis;
although both share the same benign histology. Ameloblastic carcinoma has combined histologic features of ameloblastoma, with
cytologic atypia and with or without metastasis (Sciubba et al.,
2005). Successful treatment for malignant ameloblastoma remains elusive. We report two cases of maxillary ameloblastoma
with varied sites of metastasis.

2.1. Case 1

* Corresponding author. Tel.: 86 571 87236893; fax: 86 571 87236395.

E-mail address: lydabao@126.com (J.-f. He).

A 40-year-old male consulted his stomatologist because of two

bony hard lumps in the left maxillary alveolar bone in October
1996. An extended resection of left maxilla was performed, with a
histologic diagnosis of ameloblastoma. Subsequently, he experienced multiple frequent recurrences during the 10-year follow-up
period (February 1999eMarch 2009). Pathological features of
recurrent lesions were consistent with ameloblastoma, with
tumour nests comprising stellate cells and peripheral palisading.
In August 2009, computer tomography (CT) conrmed multiple
spherical lesions in both lungs without calcication. The largest
lesion (3.1 cm) was located in the right hilum (Fig. 1). CT-guided
percutaneous transthoracic lung biopsy was performed. Microscopic evaluation showed primarily ameloblastoma (Fig. 2). In
November 2011, multiple metastatic lymph nodes in the left neck
and superior mediastinum with second rib destruction were found
on CT (Fig. 3). Although the patient refused lymph node biopsy at
that point, the imaging characteristics and clinical presentation
were consistent with malignant ameloblastoma with metastases to
multiple lymph nodes.

1010-5182/$ e see front matter 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.jcms.2013.10.010

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Y. Lin et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) e301ee304

Fig. 1. Computed tomography shows metastatic nodules in both lungs.

Fig. 3. Computed tomography shows metastatic lymph nodes in the superior mediastinum with destruction of the second rib (arrow).

2.2. Case 2
A 46-year-old female underwent extended resection of the right
maxilla. 15 years later, in 2011, multiple nodules in both lungs were
found on routine chest X-ray. Thoracic CT (Fig. 4) and CT-guided
percutaneous transthoracic lung biopsy (Fig. 5) conrmed metastatic ameloblastoma. Second opinion consultation at the University of California, Los Angeles concurred with the diagnosis.
3. Discussion
Ameloblastoma is a histologically benign, but locally invasive
tumour with a high likelihood of recurrence, but rarely metastasizing. The incidence of malignancy/metastasis in relation to
ameloblastoma has been reported as 2%, but more realistically is far

Fig. 2. The lung metastasis is similar to the primary tumour, demonstrating islands of
epithelium with prominent basaloid and columnar peripheral cells and evidence of cell
streaming (H&E, 100).

less (Houston et al., 1993). Many cases of metastasis of ameloblastomas are linked to multiple operations or recurrences (Luo
et al., 2012), and furthermore, it is reported that malignant transformation was observed in patient with multiple recurrences (Lin
et al., 2013). Most reported cases of metastatic ameloblastoma
suggest haematogenous or lymphatic spread (Houston et al., 1993).
Another unusual mechanism (aspiration of tumour cells from the
primary lesion during surgery) was described by Vorzimer and
Perla in 1932, which may contribute to pulmonary, lymphatic, or
haematogenous spread (Vorzimer and Perla, 1932). This hypothesis
was supported by the presence of tumour in the bronchi and
bronchioles. Nonetheless, diffusely scattered metastatic lesions in
both lungs and in the surrounding vasculature is more likely the
result of haematogenous spread (Henderson et al., 1999).
The most common site of metastases in ameloblastoma is the
lung, followed by cervical lymph nodes, brain, and bone (Eliasson
et al., 1989). We analysed 20 cases in addition to our two cases
reported in the global literature from 1999 to 2013 (Table 1). We

Fig. 4. Computed tomography shows metastatic nodules in both lungs.

Y. Lin et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) e301ee304

Fig. 5. Lung specimen shows metastatic ameloblastoma (H&E, 400).

found the most frequent site of metastasis to be the lungs (72.7%),

especially the patients undergoing multiple operations (80%).
Because of this high incidence of lung metastasis, the risk of
intraoperative implantation via endotracheal tube aspiration
Table 1
Patient demographics: 22 cases of malignant ameloblastoma.
Author/year
reported

Primary
site

Site of
metastasis

Number of
surgeries

First
metastasis
(years)

Henderson et al.
(1999)
Onerci et al.
(2001)
Ciment and Ciment
(2002)
Campbell et al.
(2003)
Zarbo et al.
(2003)
Hayakawa et al.
(2004)
Hasim et al.
(2007)
Gilijamse et al.
(2007)
Cardoso et al.
(2009)
Reid-Nicholson et al.
(2009)
Senra et al.
(2008)
Papaioannou et al.
(2009)
Devenney-Cakir et al.
(2010)
Dissanayake et al.
(2011)
Amzerin et al.
(2011)
Lai and Wang
(2011)
Golubovi
c et al.
(2012)
Luo et al.
(2012)
Berger et al.
(2012)
Lin et al. 2013
Present case 1

Mandible

Lungs

Multiple

33

Maxilla

Lungs

Multiple

12

Mandible

Lungs

29

Mandible

Lungs

19

Maxilla

Iliac

Multiple

15

Mandible

Lungs, kidney

Mandible

Lungs

Multiple

18

Mandible

Multiple

13

Mandible

Cervical
lymph nodes
Cervical
lymph nodes
Cervical
lymph nodes
Lungs

Primary
diagnosis
Primary
diagnosis
7

Mandible

Lungs

Multiple

27

Mandible

Lungs, skull

Mandible

23

Mandible

Cervical
lymph nodes
Lungs

Multiple

Maxilla

Lungs

Multiple

Mandible

Mandible

Cervical
lymph nodes
Lungs

Primary
diagnosis
29

Maxilla

Lungs

Maxilla
Maxilla

Multiple
Multiple

8
13

Present case 2

Maxilla

Lungs
Lungs, cervical
lymph nodes
Lungs

15

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cannot be ignored. It is impossible to determine whether surgery

for multiple recurrences increase the risk for pulmonary
metastasis.
Metastases to other regions such as the skull, iliac nodes, kidney,
and liver are even rarer. The most clinically signicant cases are the
two with cervical lymph node enlargement prior to surgery, with a
pathologic diagnosis of ameloblastoma; these cases afrm the
ability of ameloblastoma to spread via the lymphatics.
Although the longest reported survival after pulmonary
metastasis is 37 years (Hasim et al., 2007), the prognosis for
metastatic ameloblastoma is still poor. In 1981, Laughlin reviewed
43 patients with documented cases of metastatic ameloblastoma:
the disease-free interval from rst diagnosis to the appearance of
metastasis was 9 years; the median survival time after metastases was 2 years (Laughlin, 1989). In 1993, Sheppard (Sheppard
et al., 1993) reported the time from initial diagnosis to pulmonary metastases to range from 0.3 to 31 years. The mean diseasefree interval for pulmonary metastasis is 14.37 years and for
cervical lymph node metastasis is 12.96 years. This indicates that
cervical metastasis may precede lung metastasis (Duffey et al.,
1995). In our study, the mean disease-free interval from diagnosis of tumour to distant metastasis is 13 years. Thus, development of metastases is relatively slow, and long term follow-up
is recommended for patients with ameloblastoma (Adebayo et al.,
2011).
Since aggressive surgery is the only effective treatment for primary ameloblastoma, this therapy is often applied to metastatic
disease (Sheppard et al., 1993). If preoperative tissue diagnosis is
desired, transbronchial biopsy can be performed. Neck dissection is
recommended for patients with lymph node metastases. Radiotherapy and chemotherapy are reserved for the palliative setting
and for inoperable tumours (Laughlin, 1989). Platinum-based regimens are considered to be rst line treatment as far as chemotherapy is concerned (Amzerin et al., 2011). Campbell reported a
patient who received cyclophosphamide (50 mg t.i.d.), with
accompanying decrease in size of the left lung lesion (Campbell
et al., 2003). Nonetheless, the effect of these chemotherapy regimens is of limited value in the treatment of malignant
ameloblastoma.
4. Conclusion

Mandible
Mandible

From these ndings, it is important to note that multiple operations or recurrences are the risk factors for ameloblastoma
metastasis; meanwhile, patients without multiple recurrences of
ameloblastoma still have the potential to develop metastatic lesions. In order to detect metastases as early as possible, the postoperative review should be regular and for life, especially in patients with a history of relapse, as distant metastasis can occur
after a long time. For the diagnosis of metastases, CT-guided
percutaneous transthoracic lung biopsy and lymph node biopsy
are useful methods to conrm metastatic ameloblastoma. The
treatment of ameloblastoma metastasis requires further research
and practice.
Conict of interest
None.
Acknowledgements
This work was supported by grants from the National Natural
Science Foundation of China (No. 81001213) and the Zhejiang
Provincial Science and Technology Plan (No. 2012C33010).

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