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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 4  |  Issue : 1  |  Page : 34-37

Clear cell odontogenic carcinoma an enigmatic diagnostic challenge


Department of Oral Pathology and Microbiology, SCB Dental College and Hospital, Cuttack, Odisha, India

Date of Submission23-Feb-2020
Date of Decision30-Mar-2020
Date of Acceptance03-Apr-2020
Date of Web Publication20-Apr-2020

Correspondence Address:
Dr. Shanti Sudha Sahu
Department of Oral Pathology and Microbiology, SCB Dental College and Hospital, Cuttack - 753 007, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/oji.oji_10_20

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  Abstract 


Clear cell odontogenic carcinoma (CCOC) is an extremely rare odontogenic carcinoma with few cases reported in literature. In 2005, the WHO reclassified CCOC as a malignant odontogenic neoplasm, exhibiting an aggressive growth pattern with a propensity for regional, nodal, and distant metastasis. Being characterized histopathologically by sheets and islands of clear and vacuolated cells, it poses a diagnostic challenge to the clinician and pathologist to distinguish CCOC from other perplexing clear cell entities and requires immunohistochemical analysis. Here, we report a case of CCOC in a 50-year-old woman who presented with a solitary, diffuse, and tender swelling in the posterior aspect of the mandible for 1½ months. Wide local excision was performed for the case. The present case may aid to delineate its biological behavior along with shedding light on its histopathological and immunohistochemical character, thus contributing to the literature.

Keywords: Clear cell odontogenic carcinoma, diagnosis, immunohistochemistry, mandible


How to cite this article:
Sahu SS, Das SN, Rath R. Clear cell odontogenic carcinoma an enigmatic diagnostic challenge. Oncol J India 2020;4:34-7

How to cite this URL:
Sahu SS, Das SN, Rath R. Clear cell odontogenic carcinoma an enigmatic diagnostic challenge. Oncol J India [serial online] 2020 [cited 2020 Sep 22];4:34-7. Available from: http://www.ojionline.org/text.asp?2020/4/1/34/282831




  Introduction Top


Clear cell odontogenic carcinoma (CCOC) is a rare intraosseous jaw tumor of putative odontogenic origin, which was first described by Hansen et al. in 1985. He considered it as a low-grade carcinoma.[1] Initially, CCOC was heralded as clear cell odontogenic tumor or clear cell ameloblastoma. It was classified as a benign odontogenic tumor by WHO in 1992.[2] However, due to its locoregional metastasis, distant metastasis (pulmonary, bone), destructive growth pattern and recurrence,[3] CCOC was considered to be a malignant tumor of odontogenic origin in the WHO classification of 2005. It is still considered as a malignant tumor in the 2017 classification.[4]

Clear cells are rare in the head-and-neck region but can be observed in many benign or malignant tumors of epithelial, mesenchymal, melanocytic, and hematopoietic derivation as a part of the lesion.[5] However, when clear cells predominate in the lesion, they tend to obfuscate the pathologist in rendering a definitive diagnosis as these microscopic features are shared by many tumors of odontogenic, salivary, and metastatic origin.[6] Here, we report the case of CCOC in a 50-year-old female and the case was successfully treated.


  Case Report Top


A 50-year-old female patient presented with a complaint of swelling on the right side of face for the past 1½ months associated with localized pain for 15 days. On local examination, there was a diffuse extra oral solitary ovoid swelling over the right side of mandible, particularly mid ramus and angle area, measuring approximately 2.0 cm × 2.5 cm, the swelling being mildly tender and firm to hard in consistency. The overlying skin was apparently normal, pinchable with no rise in surface temperature. Regional lymph nodes were not palpable. On intraoral examination, a solitary, diffuse, mildly tender bony hard swelling with intact alveolar mucosa measuring about 1 cm in the retromolar region distal to 48 was found. 45 and 46 were absent, but there was no evidence of any carious tooth or vestibular tenderness. No history of trauma could be elicited. Systemic examination and hematological investigations yielded normal parameters.

Routine orthopantomography revealed a mixed multilocular radiolucent lesion showing focal radiopacity, measuring 2.0 cm × 1.5 cm with poorly demarcated borders involving the apical areas of 47 and 48, extending from distal aspect of 44 anteriorly to the angle of mandible posteriorly [Figure 1]. Computed tomography (CT) scan revealed a heterogeneous expansile destructive lesion with focal areas of high density in the right mandibular body and ramus area. Based on the above findings, a clinico-radiological diagnosis of ameloblastoma was made.
Figure 1: Orthopantomograph shows mixed multilocular radiolucent lesion showing focal radiopacity, with poorly demarcated borders

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Histopathological examination (HPE) of the incisional biopsy specimen revealed a tumor with the predominant follicular arrangement of the tumor cells with biphagic pattern. The center of the follicles comprised round-to-polygonal cells having a clear to eosinophillic cytoplasm with eccentric nuclei. At the periphery, the follicles exhibited small dark vacuolated basaloid cells [Figure 2]a. Few peripheral cells exhibited palisading appearance with hyperchromatic vesicular nuclei and reverse polarity [Figure 2]b. The clear cell islands were separated by mature fibrous connective tissue stroma. Nuclear pleomorphism and mitotic activity were insignificant. With the above microscopic findings, a diagnosis of CCOC was made. Metastatic carcinoma, particularly renal primary was ruled out due to the absence of prominent sinusoidal vascular network with hemorrhagic foci. The ultrasonography of the abdomen and chest X-ray reports were within the normal limits, which further helped exclude the possibility of any metastatic carcinoma. Further special stains and immunohistochemical analysis were done to rule out other clear cell entities.
Figure 2: (a) Multiple follicular areas having peripheral small dark basaloid cells with hyperchromatic vesicular nuclei (red arrow) and central round-to-polyhedral cells with abundant clear cytoplasm (black arrow) (H and E, ×40), (b) peripheral cells showing palisading pattern (blue arrow) in few follicles (H and E, ×40), and (c) clear cells showing Periodic acid-Schiff with diastase sensitivity (×40)

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The cytoplasm of the clear cells demonstrates Periodic Acid Schiff (PAS) positive diastase sensitive materials [Figure 2]c, which was negative for mucicarmine stain. Immunohistochemical analysis showed strong positivity to cytokeratin (CK) 19 [Figure 3]a, diffuse positive for epithelial membrane antigen (EMA) [Figure 3]b, and focal positivity for S100 [Figure 3]c. Negative reactions to vimentin and smooth muscle actin (SMA) further aided to confer the diagnosis of CCOC. Following immunohistochemical confirmation, the patient underwent wide local excision with segmental mandibulectomy and supra-omohyoid neck dissection. HPE of the operated specimen was consistent with the features of incisional biopsy. All the surgical margins were free of malignancy. Lymphovascular and perineural invasions were absent. All the regional lymph nodes were found to be negative for malignancy. The case is under regular follow-up without any evidence of recurrence or metastasis for the past 16 months after the resection.
Figure 3: Immunohistochemical analysis (×40) showing (a) strong positivity to cytokeratin 19; (b) tumor cells showing moderate immunoreactivity to epithelial membrane antigen, (c) immunoreactivity to S100 indicating the presence of dendritic cells

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  Discussion Top


Odontogenic neoplasms with a significant clear cell component are extremely rare. With the Pubmed and Springer databases search, a total of 107 CCOC cases have been reported between 1985 and 2018.[7] The presence of clear cells in odontogenic cysts and tumors is due to their origin from the dental lamina. The epithelial rests of Malassez and reduced enamel epithelium around the crowns of impacted teeth are the two major embryonal tooth germ remnants located in the jaw. Usually, clear cells are the result of intracellular accumulation of products such as glycogen, lipid, mucin, and secretory products like zymogen granules. The scarcity of organelles due to hydropic degeneration or the occurrence of artifacts during tissue fixation or processing could also result in cells appearing clear. When these clear cells predominate in a tumor, arriving at a definitive diagnosis becomes challenging.[8]

CCOC shows marked female predilection with a ratio of 1:1.8, mainly affecting older patients with a mean age at the time of diagnosis being 54.2 years, ranging from the 2nd to 8th decades of life. Anatomically, there is a greater mandibular (77%) preponderance than maxilla, with the posterior region (48%) of the jaw being the more frequent site of occurrence. Classic clinical presentation is that of painless swelling of the lesion, and there may be occasional tooth mobility and paraesthesia of the lip.[9] It often manifests as a radiolucent or mixed radiolucent–radiopaque lesion, demonstrating both well and poorly delineated margins. The present case of CCOC is seen in a female, having posterior mandibular location and mixed radiolucent–radiopaque feature supporting literature.

Histopathologically, CCOC consists chiefly of epithelial cells with clear to faintly eosinophilic cytoplasm and a small dark staining nucleus. Biphasic, monophasic, and ameloblastomatous are the three distinct patterns exhibited by this tumor. The biphasic pattern being the most common among them as in our case and is characterized by nests or sheets of clear cells intermixed with islands of small basaloid appearing cells seen in the periphery of these nests or follicles or may form duct-like structures. The monophasic pattern shows epithelial islands comprising a monotonous population of clear cells. The third variant, i.e., the ameloblastomatous pattern is the least common type and consists of clear cell nests with a peripheral palisading cuboidal to columnar cells with reverse polarity.[8],[9] The present case exhibited biphasic pattern showing nests and sheets of central clear cells with basaloid polygonal cells at periphery separated by fibro-collagenous hyalinized stroma.

Immunohistochemical findings of CCOC are still inconsistent. The clear and eosinophilic tumor cells are reactive to CK, particularly CKs 8, 13, 18, and 19 and EMA. They are negative for vimentin, S-100-protein, desmin, SMA, human melanoma black-45, alpha (1) chymotrypsin, CD31, CD45 and Glial Fibrillary Protein.[8],[10] Xavier et al. in a report found that the immunoreaction of tumor cells to pan-CKs (AE1/AE3), CK 14 was intense, and CK 8, 18, and 19 varied from mild to moderate, whereas negative for S100 protein, CK 13, vimentin, SMA, laminin, and Type IV collagen.[8]

Clear cells are not pathognomonic of CCOC, thus giving rise to a broad range of differential diagnoses, such as clear cell variant of calcifying epithelial odontogenic tumor (CEOT), clear cell variant of muco-epidermoid carcinoma, hyalinising clear cell carcinoma (HCCC) of salivary gland, clear cell ameloblastoma, epithelial myoepithelial carcinoma, and metastatic renal cell carcinoma.[9],[11]

The PAS-positive with diastase sensitivity determined the presence of glycogen in clear cells in the present case, negating the presence of mucin by giving a negative reaction to mucicarmine ruling out the possibility of clear cell variant of mucoepidermoid carcinoma, HCCC of salivary gland and epithelial myoepithelial carcinoma. CK 19 positive reaction indicated its strong odontogenic origin.[5],[8] The S100 was positive only in the spindle or dendritic cells that resemble Langerhans cells, which could have migrated into odontogenic tumor epithelium nest as both oral and odontogenic epithelia emanate from same oral ectoderm and serve as antigen-presenting cells.[8],[12] Further histopathologically, the absence of amyloid material and calcifications in the tumor cells or the intercellular space ruled out the possibility of clear cell variant of CEOT.[8],[12] Clear cell salivary gland tumors express positive results for S-100 protein, CK, vimentin, and muscle actin, whereas odontogenic tumors with clear cell differentiation are negative for vimentin and muscle actin. A metastatic lesion can be ruled out with clinical and radiological assessments. Prominent sinusoidal vascularity and intratumoral hemorrhage that characterize metastatic renal clear cell carcinoma are absent in CCOC.[9]

Surgical resection with wide margins is the treatment of choice in CCOC cases. The role of lymph node dissection is unclear. Adjuvant radiotherapy may be helpful for cases with extensive soft tissue or perineural invasion, positive nodes and/or extracapsular spread or where tumor-free margins are not possible.[9] Wide local excision with segmental mandibulectomy and lymph node dissection was performed in our case, and adjuvant radiotherapy was not advised due to the absence of any risk factors. CCOC exhibits an aggressive growth pattern with low survival rate, regional nodal recurrence and distant metastasis, warrants close surveillance and long-term follow-up.


  Conclusion Top


CCOC due to its meager contribution as an entity to literature, variable histopathological appearance, and immunophenotypic pattern, it becomes crucial on the part of clinicians and pathologists to segregate this lesion from other such lesions with clear cell component in the head and neck. In our case, perplexing immunoprofile showing the rare positivity to S100 protein possibly due to Langerhans cells, which mandates the need of further study to find the true pathologic significance of these cells in CCOC.

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.

Conflict of interest

There are no conflict of interest.



 
  References Top

1.
Hansen LS, Eversole LR, Green TL, Powell NB. Clear cell odontogenic tumor – A new histologic variant with aggressive potential. Head Neck Surg 1985;8:115-23.  Back to cited text no. 1
    
2.
Kramer IR, Pindborg JJ, Shear M. WHO Histological Typing of Odontogenic Tumor. 2nd ed. Berlin, Germany: Springer Verlag; 1992.  Back to cited text no. 2
    
3.
Kumar M, Fasanmade A, Barrett AW, Mack G, Newman L, Hyde NC. Metastasising clear cell odontogenic carcinoma: A case report and review of the literature. Oral Oncol 2003;39:190-4.  Back to cited text no. 3
    
4.
El-Naggar AK, Chan JK, Grandis JR, Takata T, Slootweg P, editors. Odontogenic and Maxillofacial Bone Tumours. WHO Classification of Head and Neck Tumours. 4th ed. Lyon: IARC; 2017. p. 205-60.  Back to cited text no. 4
    
5.
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.  Back to cited text no. 5
    
6.
Seijas BP, Franco FL, Sastre RM, García AA, López-Cedrún Cembranos JL. Metastatic renal cell carcinoma presenting as a parotid tumor. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:554-7.  Back to cited text no. 6
    
7.
Guastaldi FP, Faquin WC, Gootkind F, Hashemi S, August M, Iafrate AJ, et al. Clear cell odontogenic carcinoma: A rare jaw tumor. A summary of 107 reported cases. Int J Oral Maxillofac Surg 2019;48:1405-10.  Back to cited text no. 7
    
8.
Xavier FC, Rodini CO, Ramalho LM, Sarmento VA, Nunes FD, de Sousa SC. Clear cell odontogenic carcinoma: Case report with immunohistochemical findings adding support to the challenging diagnosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:403-10.  Back to cited text no. 8
    
9.
Swain N, Dhariwal R, Ray JG. Clear cell odontogenic carcinoma of maxilla: A case report and mini review. J Oral Maxillofac Pathol 2013;17:89-94.  Back to cited text no. 9
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10.
Werle H, Blake FA, Reichelt U, Schmelzle R, Heiland M. Clear-cell odontogenic carcinoma: A new case and long-term follow-up of an old case, and review of the literature. J Oral Maxillofac Surg 2009;67:1342-8.  Back to cited text no. 10
    
11.
Kwon IJ, Kim SM, Amponsah EK, Myoung H, Lee JH, Lee SK. Mandibular clear cell odontogenic carcinoma. World J Surg Oncol 2015;13:284.  Back to cited text no. 11
    
12.
Muramatsu T, Hashimoto S, Inoue T, Shimono M, Noma H, Shigematsu T. Clear cell odontogenic carcinoma in the mandible: Histochemical and immunohistochemical observations with a review of the literature. J Oral Pathol Med 1996;25:516-21.  Back to cited text no. 12
    


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