the morphologically similar appearing clear cells are ambiguous in nature and believed to be originated from different cell lineages such as epithelial , mesenchymal , melanocytic , or hematopoietic . clear cell odontogenic carcinoma ( ccoc ) is one among the rare neoplasm with only 74 reported cases in the literarure . it was first described by hansen et al . and later by waldron et al . , in 1985 , as clear cell odontogenic tumor . in 2005 , the world health organization ( who ) had reclassified as ccoc owing to its high rate of recurrence , local and distant metastasis , and tumor - related deaths . ccoc usually present with a variable degree of pain and mobility of regional teeth with or without the involvement of bone . approximately 60% of patients show evidence of soft tissue involvement in the anterior portion of the mandible as lesion perforates bone . radiographically , a poorly delineated , unilocular or multilocular radiolucent lesion with prominent bone destruction is observed . histopathologically , ccoc may show one or more architectural patterns such as biphasic , monophasic , and ameloblastomatous . the undetermined source of clear cells makes the diagnosis based on conventional histology nearly impossible . they require special attention to be differentiated from other clear cell lesions either by means of special stains such as mucicarmine , congo red and periodic acid schiff 's ( pas ) or immunohistochemical staining such as cytokeratin ( ck ) , epithelial membrane antigen ( ema ) , s-100 protein , and vimentin . expression of ck-19 and ema is a consistent finding in ccoc whereas the tumor shows negativity for vimentin , s-100 protein , desmin , and smooth muscle actin . this article presents another unique case of ccoc with varied clinicopathological , radiological , and histopathological findings affecting the symphyseal region of the mandible in a middle - aged patient . a male patient aged 46 years reported to outpatient department with the chief complain of swelling in the lower front tooth region since 45 months . intraorally , firm , nontendered , and exophytic lesion measuring 2.5 cm  4 cm was observed involving mandibular anterior jaw region with exfoliation of 31 , 32 and 41 , 42 . orthopantomogram revealed the presence of an ill - defined radiolucent destructive lesion in the mandibular anterior region [ figure 2 ] . computed tomography view showed well - defined hypodense area with the complete loss of buccal cortical plate and severe thinning of the lingual cortical plate in mandibular symphysis region [ figure 3 ] . intraoral view showing lesion in lower alveolar ridge orthopantomogram and computed tomography scan showing bone destruction in the symphysis region h and e stained section showing ( a ) islands of clear cells in fibrous connective tissue stroma ( 40 ) , ( b ) clear cells mixed with columnar cells with eosinophilic cytoplasm ( 100 ) keeping the clinical and radiological features in view , the provisional diagnosis of squamous cell carcinoma was made . the incisional biopsy was performed after obtaining informed consent from the patient , and the tissue sections were stained with hematoxylin and eosin ( h / e ) for microscopic evaluation . h / e staining of tissue sections revealed the presence of islands and sheets of round or polyhedral shaped hyperchromatic clear cells with the distinct cytoplasmic membrane . the tumor cells adjacent to the fibrovascular septa were cuboidal to columnar with reversed polarity of the nucleus and eosinophilic cytoplasm whereas central cells were large , round to polygonal with clear cytoplasm . mitotic figures were insignificant without any fibrous capsule at the periphery of the tumor [ figure 4 ] . photomicrograph showing ( a ) congo red stain , ( b ) mucicarmine stain and ( c ) periodic acid - schiff stain . congo red and mucicarmine are negative while periodic acid - schiff stain has taken up by cytoplasmic granules special stains such as mucicarmine , congo red , and pas were done to check the content of clear cells for mucin , amyloid , and glycogen deposition , respectively . mucicarmine and congo red were negative while pas was strongly positive suggesting the glycogen content of clear cells [ figure 5 ] . ck-19 and ema showed strong immunoreation to the tumor cells whereas s-100 protein and vimentin were nonreactive . photomicrograph showing ( a ) cytokeratin , ( b ) epithelial membrane antigen , ( c ) vimentin , ( d ) s-100 . the tumor shows strong positivity for keratin ( cytokeratin ) and epithelial islands ( epithelial membrane antigen ) . the vimentin immunoreactivity is positive for fibrous tissue stroma only while s-100 was negative the histopathological features confirmed the odontogenic origin of tumor and diagnosis of ccoc of the biphasic pattern was made . further , the patient was referred to oral surgery department for surgical excision of the lesion . the postoperative recovery was uneventful , and no recurrence was observed in 3 years follow - up period . initially , it was considered to be a benign neoplasm , but later due to its aggressive nature , spread , and recurrence , it is redesignated by the who as ccoc in 2005 . clear cells appear to be clear due to the presence of an intracellular accumulation of nonstaining compounds , such as glycogen , mucopolysaccharides , lipids , and mucin . the derivatives of the dental lamina or cell rests of malassez have been suggested to be the origin of clear cells in jaws . it is believed that during late bell stage , cells of inner enamel epithelium undergo histodifferentiation to presecretory ameloblast . electron microscope shows the presence of lysosomes , mitochondria , tonofilaments , and desmosomes . it is now known that bone morphogenetic protein ( bmp-2 ) plays a crucial role in regulating ms  1 and ms  2 along with dl  2 . the combined effect of ms  1 , ms  2 , and dl  2 influences dl  3 , which normally help ameloblast cell to differentiate . absence of these two homobox genes may be due to dysregulation of bmp-2 expression affecting the terminal differentiation of ameloblast cell . in addition to this , the genomic analysis also revealed a polypoid population of cells with dna index of 1.93 and overall s - phase of 10.2% suggesting chromosomal alterations in cases of ccoc . a wide age range from 14 to 89 years has been described with the peak incidence noted in the sixth decade of life . females out numbers males with the ratio of 2:1 . more than 80% of the lesions developed in the anterior portion of the mandible . the conventional radiological findings usually show poorly delineated , unilocular or multilocular radiolucent lesion that occurs with prominent bone destruction . the light microscopic features of ccoc reveal three histological patterns : biphasic , monophasic , and ameloblastomatous . the most common biphasic pattern shows two sets of cellular population arranged in sheets and islands . center cells are clear , round to polygonal in shape mixed with another population of cuboidal to columnar cells with eosinophilic cytoplasm at the periphery . the ameloblastomatous pattern is least common , characterized by the presence of clear cells inside the follicular network . it has a higher tendency for the invasion to the medullary bone , muscle , and the neural tissue . differential diagnoses include calcifying epithelial odontogenic tumor , mucoepidermoid carcinoma , myoepithelial carcinoma , hyalinising clear cell carcinoma , epithelial - myoepithelial carcinoma , amelanotic melanoma , and metastatic renal cell carcinoma [ table 1 ] . differential diagnosis of ccoc we could demonstrate intracellular glycogen by means of pas - positive , diastase - sensitive granule accumulation within the tumor cells whereas mucin and amyloid were excluded by negative mucicarmine and congo red staining . ccoc is differentiated from calcifying epithelial odontogenic tumor due to the absence of calcifications and amyloid deposition ( congo red negative ) . lack of intermediate cells , squamous differentiation , and mucin ( mucicarmine negative ) production excluded mucoepidermoid carcinoma . metastatic lesion is differentiated from ccoc microscopically as later lacks the prominent sinusoidal vascularity and intramural hemorrhage that characterize metastatic renal carcinoma . immunohistochemically , the tumor cells showed positive staining for wide spectrum ck and ema , but negative staining for vimentin and s-100 protein . the histochemical staining profile clearly spells the odontogenic nature of neoplasm excluding the possibility of salivary gland origin . the treatment should aim at wide surgical resection with tumor - free margins adjunct to radiotherapy . a long - term follow - up is necessary to look for any loco - regional recurrence and distant metastasis . conspicuous nature of clear cells in ccoc poses a great challenge to a pathologist to diagnose and differentiate from other clear cell lesions . these type of lesions demands diagnosis based on conventional histopathology adjuvant to special staining and immunohistochemistry for optimal management considering the risk of recurrence and metastases .