LGCmain
Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 5737
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size
IJPM is coming out with a Special issue on "Genitourinary & Gynecological pathology including Breast". Please submit your articles for these issues


 
  Table of Contents    
LETTER TO EDITOR  
Year : 2019  |  Volume : 62  |  Issue : 3  |  Page : 501-503
Ameloblastic carcinoma: A diagnostic dilemma


Department of Pathology, Homi Bhabha Cancer Hospital, Sangrur, Punjab, India

Click here for correspondence address and email

Date of Web Publication26-Jul-2019
 

How to cite this article:
Sancheti S, Somal PK, Sarkar S. Ameloblastic carcinoma: A diagnostic dilemma. Indian J Pathol Microbiol 2019;62:501-3

How to cite this URL:
Sancheti S, Somal PK, Sarkar S. Ameloblastic carcinoma: A diagnostic dilemma. Indian J Pathol Microbiol [serial online] 2019 [cited 2019 Aug 17];62:501-3. Available from: http://www.ijpmonline.org/text.asp?2019/62/3/501/263464




Editor,

A 31-year-old male presented with difficulty in swallowing since 8 months. On examination, a growth was identified in the floor of the mouth and middle third of the alveolus. The magnetic resonance imaging (MRI) revealed a multiseptate, cystic mass involving the mandible with erosion of the bone and extension into the adjacent soft tissue. These findings were suggestive of a malignant lesion. Subsequently, the patient underwent a middle one-third mandibulectomy with bilateral modified neck dissection.

Gross examination revealed a 3.7 × 2.5 × 2.0 cm mass in the floor of mouth involving the underlying mandible. Microscopy showed an epithelial tumor composed of interconnecting islands and plexiform arrangement intermixed with solid epithelial sheets and islands. The epithelium had a columnar basal cell configuration bounding a stellate reticulum interior. Areas resembling classic ameloblastoma (AB) were also noted [Figure 1]a and [Figure 1]b. The tumor infiltrated into the mandible and adjacent soft tissue [Figure 1]d. Cellular pleomorphism was noted. The mitotic rate was 6/10 hpf [Figure 1]c. There were no lymphovascular emboli or perineural invasion. All the resection margins were free. Modified neck dissection revealed reactive lymph nodes. The immunohistochemistry (IHC) revealed the neoplastic cells to be diffusely positive for p63 [Figure 1]f and pancytokeratin. Ki-67 labelling index (LI) was nearly 20% in the highest proliferating areas [Figure 1]e. The stellate reticulum cells showed focal positivity for S100. Cytokeratin 18 (CK 18) was diffusely positive in all the layers in tumor cells [Figure 2]. A diagnosis of AC was made based on the cytological atypia, high Ki-67 LI, and infiltrative growth pattern. Patient was asymptomatic on follow up over the course of 4 months.
Figure 1: (a) Ameloblastic carcinoma exhibiting interconnected tumor nests and strands (H and E, ×40), (b) tumor nests with peripheral pallisading and central stellate reticulum (H and E, ×400), (c) tumor cells with nuclear pleomorphism and increased mitotic activity (arrows) (H and E, ×400), (d) tumor nests invading the underlying bone (H and E, ×400), (e) Ki-67 immunohistochemistry highlights increased proliferation rate, (f) immunohistochemistry for p63 shows diffuse positivity in the epithelial cells and weak positivity in the stellate reticulum cells

Click here to view
Figure 2: Immunohistochemistry with CK18 helps in differentiating AB from AC with CK 18 diffusely positive in all the layers in AC (a) and only in the selective stellate reticulum cells in AB (b)

Click here to view


Odontogenic tumors are rare.[1] The classification of odontogenic tumors has been a controversial topic for decades. The term ameloblastic carcinoma (AC) was first used by Shafer in 1983 to describe AB cases with malignant transformation.[2] Metastasizing ameloblastoma (MAB) is diagnosed when metastasis of AB occurs. There is usually little atypia and presence of significant atypia should alert to the diagnosis of AC.[1] AC primarily affects middle-aged individual with mean age of 49–56 years and a male predilection.[2],[3],[4] The most common site involved is the mandible, followed by the maxilla.[2],[4] Majority of the tumors arise de novo and some arise from a pre-existing AB.[3],[4] Radiological examination often reveals a multilocular mass and with focal radiopacities. Root resorption can also be noted.[2] Perforation of the cortical plate and extension into surrounding soft tissue is usually indicative of AC.[5]

The differentiation of AC from AB is most important. AC is diagnosed when there is evidence of cytological atypia in a histological pattern of AB. An elevated mitotic rate is especially helpful as AB exhibit less mitosis.[6] IHC may be helpful in distinguishing the two entities. Ki-67 LI is found to be significantly higher in AC than in AB.[7],[8] Mean Ki-67 LI in AC has been reported to be approximately 20%, while in AB it is approximately 4%–5%.[7] The expression of certain CKs can also help to differentiate between AB and AC, with CK 18 being especially useful. While CK 18 is diffusely positive in all tumor cells in AC, it is only weakly positive in stellate reticulum in AB.[8] CK 14 and CK 19 are expressed in both the epithelium and stellate reticulum in AB and AC. CK 7 is negative in both AB and AC.[8],[9] Recently, SOX2 has been proposed as a sensitive and specific IHC marker for AC. It is negative in AB, but diffusely positive in AC.[10] Matrix metalloproteinase-2 (MMP-2) and MMP-9 have also been studied as potential markers for differentiation between AB and AC. MMP-2 is expressed in both the tumor cells and stroma, but AC shows a higher expression as compared to AB.[8],[11] The results of MMP-9 have been controversial with some studies reporting increased MMP-9 expression in stromal cells in AC as compared to AB, whereas others have found a higher expression of MMP-9 in tumor cells of AB rather than AC with no difference in the stromal expression.[8],[11] However, their diagnostic utility has not been well established.

The other differentials include basaloid squamous cell carcinoma, primary intraosseous carcinoma, squamous odontogenic tumor, and calcifying odontogenic tumor. The characteristic periodic acid–Schiff positivity in micro cystic spaces in basaloid squamous carcinoma helps to distinguish it from AC.[4] Primary intraosseous carcinoma and squamous cell carcinoma arising in lining of odontogenic cyst shows squamous differentiation but lacks an AB component.[5],[12] Squamous odontogenic tumors show benign squamous epithelium with microcystic changes and keratinization but lack the AB differentiation and cytological atypia.[5] Calcifying odontogenic tumors show features of squamous cell carcinoma along with characteristic amyloid deposition.[12] Keratoameloblastoma and acanthomatous ameloblastoma are benign variants of AB which can sometimes be confused with AC but the extensive squamous metaplasia, keratinizing cysts, and lack of cytological atypia help in differentiation.[5] Other rare differentials which can be confused with AC include metastatic carcinoma to the jaws from lung, breast, gastrointestinal tract, and salivary gland tumors. However, these can be reliably ruled out by clinical evaluation and immunohistochemistry.

Surgery is the most widely used treatment option, with the role of radiotherapy and chemotherapy still not very clear. There is a higher recurrence rate following curettage alone than following partial resection, and therefore a wide surgical resection, with clear margins, is recommended.[4] Radiotherapy has been used in cases with positive surgical margins, perineural infiltration, or soft tissue invasion.[4] Since AC has a high recurrence rate and frequent metastasis in the lung and regional lymph nodes, it is pertinent that the patients be followed long term.[3],[4],[5]

The 2005 World Health Organization (WHO) classification defined AC as an entity combining histological features of AB with cytological atypia, even in the absence of metastases and divided it into three types – primary type, secondary intraosseous type, and secondary peripheral type.[2] The latest WHO 2017 classification has somewhat simplified this classification and only one type of AC is now recognized.[1]

Since the present case showed areas resembling AB, we postulate that the AC arose in a background of AB. We also propose that AB and AC represent clinicopathological continuum in the natural history of this disease. However, more case studies and molecular work up needs to be encouraged to clearly define its biologic behavior and long-term prognosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Odell EW, Muller S, Richardson M. Odontogenic and maxillofacial bone tumours. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, editors. WHO Classification of Tumours – Pathology & Genetics: Head and Neck Tumours. 4th ed. Lyon: IARC Press; 2017. p. 203-60.  Back to cited text no. 1
    
2.
Moro A, Foresta E, Gasparini G, Pelo S, Forcione M, Cristallini EG, et al. Ameloblastic carcinoma of the maxilla: A case report and an updated review of the literature. Oncol Lett 2016;12:4339-50.  Back to cited text no. 2
    
3.
Li J, DU H, Li P, Zhang J, Tian W, Tang W, et al. Ameloblastic carcinoma: An analysis of 12 cases with a review of the literature. Oncol Lett 2014;8:914-20.  Back to cited text no. 3
    
4.
Yoon HJ, Hong SP, Lee JI, Lee SS, Hong SD. Ameloblastic carcinoma: An analysis of 6 cases with review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:904-13.  Back to cited text no. 4
    
5.
5. Avon SL, McComb J, Clokie C. Ameloblastic carcinoma: Case report and literature review. J Can Dent Assoc 2003;69:573-6.  Back to cited text no. 5
    
6.
Gardner DG. Some current concepts on the pathology of ameloblastomas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:660-9.  Back to cited text no. 6
    
7.
Casaroto AR, Toledo GL, Filho JL, Soares CT, Capelari MM, Lara VS, et al. Ameloblastic carcinoma, primary type: Case report, immunohistochemical analysis and literature review. Anticancer Res 2012;32:1515-25.  Back to cited text no. 7
    
8.
Yoon HJ, Jo BC, Shin WJ, Cho YA, Lee JI, Hong SP, et al. Comparative immunohistochemical study of ameloblastoma and ameloblastic carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:767-76.  Back to cited text no. 8
    
9.
Martínez-Martínez M, Mosqueda-Taylor A, Carlos-Bregni R, Pires FR, Delgado-Azanero W, Neves-Silva R, et al. Comparative histological and immunohistochemical study of ameloblastomas and ameloblastic carcinomas. Med Oral Patol Oral Cir Bucal 2017;22:e324-32.  Back to cited text no. 9
    
10.
Lei Y, Jaradat JM, Owosho A, Adebiyi KE, Lybrand KS, Neville BW, et al. Evaluation of SOX2 as a potential marker for ameloblastic carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117:608-160.  Back to cited text no. 10
    
11.
da Silva AD, Nóbrega TG, Saudades AW, Otero MI, Danilevicz CK, Magnusson AS, et al. Ameloblastic neoplasia spectrum: A cross-sectional study of MMPS expression and proliferative activity. Oral Surg Oral Med Oral Pathol Oral Radiol 2016;121:396-4010.  Back to cited text no. 11
    
12.
Huang JW, Luo HY, Li Q, Li TJ. Primary intraosseous squamous cell carcinoma of the jaws. Clinicopathologic presentation and prognostic factors. Arch Pathol Lab Med 2009;133:1834-40.  Back to cited text no. 12
    

Top
Correspondence Address:
Sankalp Sancheti
Department of Pathology, Homi Bhabha Cancer Hospital, Sangrur, Punjab
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_121_18

Rights and Permissions


    Figures

  [Figure 1], [Figure 2]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  


    References
    Article Figures

 Article Access Statistics
    Viewed41    
    Printed1    
    Emailed0    
    PDF Downloaded14    
    Comments [Add]    

Recommend this journal