ONLINE ONLY ARTICLES - CASE REPORT
|Year : 2021 | Volume
| Issue : 1 | Page : 204
Noncalcifying clear-cell variant of calcifying epithelial odontogenic tumor: A case report and review
Sangeeta Patankar, Sheetal Choudhari, Shubhra Sharma, Snehal Dhumal
Department of Oral and Maxillofacial Pathology and Microbiology, YMT'S Dental College and PG Institute, Navi Mumbai, Maharashtra, India
|Date of Submission||16-May-2020|
|Date of Acceptance||29-Jan-2021|
|Date of Web Publication||14-May-2021|
Department of Oral and Maxillofacial Pathology and Microbiology, YMT'S Dental College and PG Institute, Kharghar, Navi Mumbai - 410 210, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Clear-cell tumors of the head and neck are biologically diverse consisting of benign, malignant and metastatic lesions. These tumors pose a diagnostic challenge. In the oral cavity, these may be derived from odontogenic/nonodontogenic epithelium or from mesenchyme or can be metastatic. Odontogenic tumors with clear-cell change are rare. Calcifying epithelial odontogenic tumor (CEOT) is a rare, benign, locally aggressive odontogenic epithelial tumor affecting the jaw. Here, we report a case of clear-cell variant of CEOT with its histopathological differential diagnosis. A 43-year-old male patient with swelling in his lower right back tooth region showed a well-defined radiolucent lesion with smooth corticated periphery on radiograph. On incisional biopsy, tumor showed small sheets, cords and islands of odontogenic epithelium with nests of clear cells with no evidence of calcification. A final diagnosis of CEOT was established by differentiating other odontogenic and nonodontogenic lesions on the basis of clinical, radiographic, histopathologic and special stain features.
Keywords: Calcifying epithelial odontogenic tumor, clear-cell tumor, clear cells, Langerhans cells, noncalcifying clear-cell variant of calcifying epithelial odontogenic tumor, odontogenic tumor
|How to cite this article:|
Patankar S, Choudhari S, Sharma S, Dhumal S. Noncalcifying clear-cell variant of calcifying epithelial odontogenic tumor: A case report and review. J Oral Maxillofac Pathol 2021;25:204
|How to cite this URL:|
Patankar S, Choudhari S, Sharma S, Dhumal S. Noncalcifying clear-cell variant of calcifying epithelial odontogenic tumor: A case report and review. J Oral Maxillofac Pathol [serial online] 2021 [cited 2021 Jun 12];25:204. Available from: https://www.jomfp.in/text.asp?2021/25/1/204/316022
| Introduction|| |
Clear-cell tumors of the head and neck constitute around 1%–2% of all head-and-neck neoplasms. These tumors are biologically diverse consisting of benign, malignant and metastatic lesions. Cells appear clear in these tumors due to artifactual or degenerative changes, intracellular edema or due to presence of various cytoplasmic contents. Clear-cell tumors pose diagnostic challenge as these tumors can primarily consist of clear cells or clear-cell change may become more significant with progression of the tumor. In the oral cavity, they can be derived from odontogenic or nonodontogenic epithelium or from mesenchyme or can be metastatic. Cysts and tumors of odontogenic origin though have characteristic histopathological features; they may show clear-cell change and can pose a diagnostic challenge. Odontogenic tumors with clear-cell change are rare. Calcifying epithelial odontogenic tumor (CEOT) is a rare, benign, locally aggressive odontogenic epithelial tumor that affects the jaws. The most distinctive microscopic feature of classical CEOT is the presence of amyloid globules and Liesegang ring calcifications in the tumor tissue which makes the diagnosis easy. However, CEOT can show extensive clear-cell change which can make the diagnosis difficult. Here, we report a case of clear-cell variant of CEOT with its histopathological differential diagnosis.
| Case Report|| |
A 43-year-old male patient reported to the department of oral pathology and microbiology with chief complaint of swelling in his lower right back tooth region. Clinical examination did not divulge any obvious abnormality as stated by the patient and the medical history was noncontributory. The past dental history suggested that he underwent surgery in the same region 6 months back. Orthopantomogram revealed a well-defined radiolucent lesion with smoothly corticated periphery in the body of the mandible extending from the distal aspect of 43 to the mesial aspect of 47.
Incisional biopsy from the tumor showed bland connective tissue stroma with small sheets, cords and islands of odontogenic epithelium [Figure 1]. Odontogenic epithelial cells were with prominent intercellular bridges and hyperchromatic nuclei. A conspicuous feature of the lesion was the presence of nests of clear cells [Figure 2] and [Figure 3]. These cells were large round-to-oval exhibiting foamy cytoplasm with distinct borders. Globular eosinophilic amyloid-like material was admixed with epithelium in some areas. There was no evidence of calcification throughout the lesion.
|Figure 1: Histopathological image shows sheets of odontogenic epithelium in the stroma arranged in cords and small islands (H&E,×100)|
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|Figure 2: Histopathological image shows sheets of odontogenic cells with hyperchromatic nuclei and prominent intercellular bridges H&E ×400)|
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The following clear-cell tumors were included in the differential diagnosis of this central clear-cell jaw lesion.
Central mucoepidermoid carcinoma
Mucoepidermoid carcinoma is composed predominantly of cystic spaces and an epidermoid component in a fibrous stroma. It also consists of mucous cells and intermediate cells. Cellular pleomorphism and infiltrative growth is usually seen. The clear cells in MEC typically stain positively with PAS. Special staining for mucicarmine or alcian blue can readily identify the mucous cell population, which is considered diagnostic.
Metastatic renal cell carcinoma
Renal cell carcinoma shows solid masses of clear cells with small eccentric nuclei in an organoid or trabecular pattern. Blood vessels are dilated forming large sinusoids. In addition, the identification of a heterogeneous architecture and a rich dilated prominent sinusoidal vascular network favors metastatic renal cell carcinoma diagnosis. Similarly, the identification of hemorrhage and hemosiderin coupled with pronounced pleomorphism and cytological atypia should alert the clinician to the possibility of metastatic disease.
Unusual histologic biphasic patterns with areas of acceptable ameloblastoma (follicular, basaloid and acanthomatous) together with the conspicuous clear-cell component in the ameloblastic follicles warrant the diagnosis of clear-cell variant of ameloblstoma., Thus, the presence of typical ameloblastomatous areas will help in arriving at the diagnosis.
Clear-cell odontogenic carcinoma
This tumor is poorly circumscribed and consists of sheets of cells of uniform size with abundant clear cytoplasm and well-defined cell membranes. Tumor islands are separated by relatively dense fibrous tissue septa and may show peripheral palisading. Lesser dense areas of small basaloid epithelial cells with scanty cytoplasm or areas of hemorrhage may also be present.,,,
In our case, lack of clinical and radiographic evidence of malignant disease, absence of microscopic ameloblastomatous differentiation and the unequivocal presence of amyloid material and presence of sheets of odontogenic cells with hyperchromatic nuclei and presence of prominent intercellular bridges helped us to establish the diagnosis of CEOT. Special staining of amyloid-like material with Congo red helped us to confirm the diagnosis of CEOT [Figure 4]. Negative staining with mucicarmine ruled out the salivary gland origin of the tumor. However, the most characteristic feature of CEOT, that is calcifications, was not seen which made the diagnosis more challenging. The absence of calcification and presence of nests of clear cells in the present case were essential features to establish the final diagnosis of noncalcifying clear-cell variant of CEOT. The patient was then referred to the department of the surgery where he underwent excision of the lesion with peripheral ostectomy. The patient was followed-up for 6 months with no evidence of the recurrence.
|Figure 4: Histopathological image shows amyloid-like material admixed with epithelium (Congo red, ×100)|
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| Discussion|| |
CEOT is a rare, benign, locally aggressive odontogenic epithelial tumor that affects the jaws. First described in 1955 as a separate entity by Pindborg, it usually affects middle-aged individuals, with mandible being the most common site of occurrence. The most distinctive microscopic feature of classical CEOT is the presence of sheets of polyhedral cells, presence of amyloid globules and Liesegang ring calcifications in the tumor tissue. However, the presence of clear cells and absence of calcification in the present case posed a diagnostic challenge. Occurrence of clear cells with a complete absence of calcification has been a rarity being reported in approximately 8% of cases of CEOT., Some authors have also described it as a feature of cytodifferentiation., Absence of calcification may suggest less differentiation in the tumor. Our case was devoid of calcifications and there were nests of clear cells. Absence of calcification and presence of clear cell could be related here.
The authors have also described noncalcifying clear-cell variant of CEOT as Langerhans cell (LC)-rich variant of it.,,,, It is suggested that clear cells in noncalcifying CEOT could be LCs. According to Lin et al., the presence of amyloid stimulates LC migration from bloodstream to odontogenic epithelial nests due to antigenicity of amyloid. However, in conventional CEOT, calcifications in amyloid restrict the migration of LCs as mineralization in amyloid leads to a decrease or loss of its antigenicity. Thus, the presence of clear cells and absence of calcification can also be related to the presence of LCs in odontogenic nests of CEOT.
We reviewed cases of LC-rich variant of CEOT by typing keywords such as LC-rich variant of CEOT; CEOT with LCs; CEOT without calcifications; LC-rich variant of Pindborg tumor; noncalcifying LC-rich variant of CEOT and noncalcifying CEOT with LCs. We found 12 cases of noncalcifying LC-rich variant of CEOT through standard databases. Of these, two cases occurred extraosseously [Table 1]. This variant is commonly seen in the anterior maxilla with unilocular radiolucency without radiopaque foci and root resorption as common radiographic presentation. These cases were not associated with impacted teeth. Based on this finding, Chen et al. proposed that LC variant of CEOT may not be derived from reduced enamel epithelium and can have other odontogenic sources for origin such as the rests of Malassez as this variant was found to cause root resorption of the apical part of the involved tooth. Histopathologically, this variant shows smaller islands and cords of odontogenic cells with the presence of abundant amyloid substance. These cases show no evidence of calcifications and presence of clear cells, unlike conventional CEOT. Odontogenic origin of epithelial cells can be confirmed by positive cytokeratin staining. Further, the presence of LC can be confirmed with positive expression of S-100, langerin and CD1a., In our case, after through sectioning of the entire specimen, we found no evidence of calcification and there were nests of clear cells. However, we could not immunohistochemically confirm the presence of LCs.
|Table 1: Review of cases of noncalcifying Langerhans cell-rich variant of calcifying epithelial odontogenic tumor|
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The authors suggest that noncalcifying LC-rich variant of CEOT can behave differently. According to some authors, this variant of CEOT can have an aggressive behavior as the absence of calcifications suggests less tumor differentiation. In our case also, the present lesion was a recurrent lesion though details regarding earlier treatment modality are lacking. However, none of the cases reported in literature have shown recurrence. According to Asano et al., LCs may play a role in the regression of CEOT as it is found in halo nevi, keratoacanthomas and benign lichenoid keratosis. However, more cases are required to be studied to determine the relation between the absence of calcification and presence of LC in CEOT and its biologic behavior with longer follow-ups.
| Conclusion|| |
Noncalcifying clear-cell variant of CEOT represents a rare subset of neoplasms. The occurrence of clear cells in a field devoid of calcification and minimal features of the conventional CEOT can lead to a diagnostic dilemma which needs careful histopathological evaluation. The need to identify these lesions is attributed to its biologic behavior and implementation of appropriate therapy.
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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 initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Premalatha BR, Rao RS, Patil S, Neethi H. Clear cell tumors of the head and neck: An overview. World J Dent 2012;3:344-9.
Said-Al-Naief N, Klein MJ. Clear cell entities of the head and neck: A selective review of clear cell tumors of the salivary glands. Head Neck Pathol 2008;2:111-5.
Benton DC, Eisenberg E. Clear cell odontogenic carcinoma: Report of a case. J Oral Maxillofac Surg 2001;59:83-8.
de Oliveira MG, Chaves AC, Visioli F, Rojas EU, Moure SP, Romanini J, et al
. Peripheral clear cell variant of calcifying epithelial odontogenic tumor affecting 2 sites: Report of a case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:407-11.
Rangel AL, da Silva AA, Ito FA, Lopes MA, de Almeida OP, Vargas PA. Clear cell variant of calcifying epithelial odontogenic tumor: Is it locally aggressive? J Oral Maxillofac Surg 2009;67:207-11.
Simon D, Somanathan T, Ramdas K, Pandey M. Central Mucoepidermoid carcinoma of mandible - A case report and review of the literature. World J Surg Oncol 2003;1:1.
Flanigan RC, Campbell SC, Clark JI, Picken MM. Metastatic renal cell carcinoma. Curr Treat Options Oncol 2003;4:385-90.
de Aguiar MC, Gomez RS, Silva EC, de Araújo VC. Clear-cell ameloblastoma (clear-cell odontogenic carcinoma): Report of a case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:79-83.
Eversole RL. Malignant epithelial odontogenic tumors. Semin Diagn Pathol 1999;16:312-24.
Anavi Y, Kaplan I, Citir M, Calderon S. Clear-cell variant of calcifying epithelial odontogenic tumor: Clinical and radiographic characteristics. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:332-9.
Mesquita RA, Lotufo MA, Sugaya NN, De Araújo NS, De Araújo VC. Peripheral clear cell variant of calcifying epithelial odontogenic tumor: Report of a case and immunohistochemical investigation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:198-204.
Kumamoto H, Sato I, Tateno H, Yokoyama J, Takahashi T, Ooya K. Clear cell variant of calcifying epithelial odontogenic tumor (CEOT) in the maxilla: Report of a case with immunohistochemical and ultrastructural investigations. J Oral Pathol Med 1999;28:187-91.
Afrogheh A, Schneider J, Mohamed N, Hille J. Calcifying epithelial odontogenic tumour with clear langerhans cells: A novel variant, report of a case and review of the literature. Head Neck Pathol 2014;8:214-9.
Singh N, Sahai S, Singh S, Singh S. Calcifying epithelial odontogenic tumor (Pindborg tumor). Natl J Maxillofac Surg 2011;2:225-7.
] [Full text]
Habibi A, Saghravanian N, Zare R, Jafarzadeh H. Clear cell variant of extraosseous calcifying epithelial odontogenic tumor: A case report. J Oral Sci 2009;51:485-8.
Schmidt-Westhausen A, Philipsen HP, Reichart PA. Clear cell calcifying epithelial odontogenic tumor. A case report. Int J Oral Maxillofac Surg 1992;21:47-9.
Yamaguchi A, Kokubu JM, Takagi M, Ishikawa G. Calcifying odontogenic tumor: Histochemical and electron microscopic observation of a case. Bull Tokyo Med Dent Univ 1980;27:129-35.
Krolls SO, Pindborg JJ. Calcifying epithelial odontogenic tumor. A survey of 23 cases and discussion of histomorphologic variations. Arch Pathol 1974;98:206-10.
Ganatra S, Castro H, Toporowski B, Hohn F, Peters E. Non-calcifying Langerhans cell-associated epithelial odontogenic tumor. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;116:E506-7.
Lee W, Myung NH, Kim CH. Calcifying epithelial odontogenic tumor: Report of three cases with immunohistochemical study. Int J Clin Exp Pathol 2016;9:5733-9.
Chi AC, Neville BW. Odontogenic cysts and tumors. Surg Pathol Clin 2011;4:1027-91.
Fumio Ide F, Matsumoto N, Miyazaki Y, Kikuchi K, Kusama K. What is the non-calcifying Langerhans cell-rich variant of calcifying epithelial odontogenic tumor? Head Neck Pathol 2019;13:489-91.
Lin HP, Kuo YS, Wu YC, Wang YP, Chang JY, Chiang CP. Non-calcifying and Langerhans cell-rich variant of calcifying epithelial odontogenic tumor. J Dent Sci 2016;11:117-22.
Takata T, Ogawa I, Miyauchi M, Ijuhin N, Nikai H, Fujita M. Noncalcifying Pindborg tumor with Langerhans cells. J Oral Pathol Med 1993;22:378e83.
Wang L, Wang SZ, Chen XM. Langerhans cells containing calcifying epithelial odontogenic tumor: Report of two cases and review of the literature. Oral Oncol Extra 2006;42:144e6.
Tseng CH, Wang YP, Lee JJ, Chang JY, Tseng YP, Wang JJ. Noncalcifying variant of calcifying epithelial odontogenic tumor with Langerhans cells. J Formos Med Assoc. 2015 Aug 1;114(8):781-2.
Kaushal S, Mathur SR, Vijay M, Rustagi A. Calcifying epithelial odontogenic tumor (Pindborg tumor) without calcification: A rare entity. J Oral Maxillofac Pathol 2012;16:110-2. [Full text]
Afroz N, Jain A, Maheshwari V, Ahmad SS. Noncalcifying variant of calcifying epithelial odontogenic tumor with clear cells e first case report of an extraosseous (Peripheral) presentation. Eur J Gen Dent 2013;2:80e2. [Full text]
Chen Y, Wang TT, Gao Y, Li TJ. A clinicopathologic study on calcifying epithelial odontogenic tumor: With special reference to Langerhans cell variant. Diagn Pathol 2014;9:37.
Tseng CH, Wang YP, Lee JJ, Chang JY. Noncalcifying variant of calcifying epithelial odontogenic tumor with Langerhans cells. J Formos Med Assoc 2015;114:781-2.
Taneeru S, Guttikonda VR, Korlepara R, Gaddipati R, Kundoor VK. Non calcifying type of calcifying epithelial odontogenic tumor: An unusual case report with special emphasis on histogenesis of calcifications. J Maxillofac Oral Surg 2017;16:253-7.
Santosh N, McNamara KK, Kalmar JR, Iwenofu OH. Non-calcifying langerhans cell-rich variant of calcifying epithelial odontogenic tumor: A distinct entity with predilection for anterior maxilla. Head Neck Pathol 2019;13:718-21.
Asano M, Takahashi T, Kusama K, Iwase T, Hori M, Yamanoi H, et al
. A variant of calcifying epithelial odontogenic tumor with Langerhans cells. J Oral Pathol Med 1990;19:430-4.
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