|Year : 2013 | Volume
| Issue : 2 | Page : 281-283
Post-radiotherapy locoregional recurrence of hyalinizing clear cell carcinoma of palate
Sonia Gon, Aditi Bhattacharyya, Bipasa Majumdar, Tushar K Das
Department of Pathology, R G Kar Medical College & Hospital, Kolkata, India
|Date of Web Publication||13-Jun-2013|
Flat 4J, Avani Orchid, 186 A, Raja Rammohan Roy Road, Kolkata - 700 041
Source of Support: None, Conflict of Interest: None
Clear cell carcinoma of the salivary glands is a rare tumor that represents less than 1% of all salivary tumors and is a new disease that is only recognized in recent years. It is rare and the standard treatment is still under investigation. This tumor often follows an indolent course and treatment includes wide surgical excision with or without adjuvant radiotherapy. Recurrence of the hyalinizing clear cell carcinoma (HCCC) after complete surgical resection is uncommonly documented. We hereby report a case of post-radiotherapy locoregional recurrence of HCCC of the palate and recommend further clinicopathological study and long-term follow-up to document the biological behavior of this entity along with highlighting the role of special stains and immunohistochemistry in its diagnosis.
Keywords: Hyalinizing clear cell carcinoma, locoregional recurrence, minor salivary gland, post-radiotherapy
|How to cite this article:|
Gon S, Bhattacharyya A, Majumdar B, Das TK. Post-radiotherapy locoregional recurrence of hyalinizing clear cell carcinoma of palate. J Can Res Ther 2013;9:281-3
|How to cite this URL:|
Gon S, Bhattacharyya A, Majumdar B, Das TK. Post-radiotherapy locoregional recurrence of hyalinizing clear cell carcinoma of palate. J Can Res Ther [serial online] 2013 [cited 2020 Jun 4];9:281-3. Available from: http://www.cancerjournal.net/text.asp?2013/9/2/281/113386
| > Introduction|| |
Clear cell tumors in the oral cavity constitute a heterogenous group of lesions which may be odontogenic, metastatic or salivary gland in origin. Hyalinizing clear cell carcinoma (HCCC) is a rare, low-grade neoplasm of the minor salivary glands, representing less than 1% of all salivary tumors. 
It is composed exclusively of epithelial cells with optically clear cytoplasm.  These cells are positive for cytokeratin and negative for S-100 protein and smooth muscle actin. This immunohistochemical staining differentiates it from other tumors of the oral cavity having a predominantly clear cell component and also indicates that HCCC is composed only of epithelial cells. 
The tumor often follows an indolent course and treatment includes wide surgical excision with or without adjuvant radiotherapy.  Recurrence of the HCCC after complete surgical resection is uncommonly documented. 
| > Case Report|| |
A 70-year-old female presented with chief complains of difficulty in the opening of mouth and swallowing along with a rapidly increasing painless submucosal mass on the palate. On local examination, noduloproliferative growth involving right tonsillar fossa, peritonsillar area and right side of the palate was seen. The growth measured 3 cm × 2 cm with erosion of the overlying mucosal surface [Figure 1]. A detailed examination of the head and neck revealed no other abnormal findings and no cervical lymphadenopathy was noted.
|Figure 1: Noduloproliferative growth involving right tonsillar fossa, peritonsillar area and right side of the palate|
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Patient had a past history of complete excision of similar type of tumor 6 years back which was histopathologically diagnosed as clear cell carcinoma - arising from minor salivary gland of the palate with all the surgical margins free from the neoplastic process. Patient also underwent three cycles of radiotherapy for the same.
At present, patient noticed a small swelling at the operative side, rapidly increasing in size. Punch biopsy from the swelling was taken and sent to the Department of Pathology for histopathological examination.
| > Pathological Examination|| |
Grossly, multiple small bits of grayish yellow tissue were present, and all of them were processed. On microscopic examination, the tumor composed of clear cells arranged in solid nests, cords and streaming columns of 2-3 cells width. The stroma shows abundant thick strands of fibrous tissue with hyalinization [Figure 2] and [Figure 3]. Mitotic figures with one to two mitoses per 10 high power fields were noted in only one area of the sections examined. The mass had no connection with the overlying squamous epithelium and was infiltrative at the margins. The tumor cells and the hyalinized fibrous bands were strongly periodic acid schiff (PAS) positive.
|Figure 2: Clear cells arranged in solid nests and cords along with abundant thick strands of fibrous tissue with hyalinization|
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|Figure 3: High power view of clear cells with abundant thick intervening fibrous tissue stroma with hyalinization|
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|Figure 4: epithelial membrane antigen EMA-positive clear cells highlighted by an arrow|
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On immunohistochemistry, the tumor cells were diffusely positive for epithelial membrane antigen (EMA) and consistently negative for S-100 [Figure 4]. Keeping all these information into consideration, a histopathological diagnosis of post-radiation locoregional recurrence of HCCC palate was made and the patient was referred to surgery and ear, nose & throat (ENT) outdoor for further investigations and management.
| > Discussion|| |
HCCC is a new and rare salivary gland neoplasm which occurs in the intraoral minor salivary glands.  It happens more commonly in the sixth and the seventh decades and women are affected twice as often as men. It is considered to be a low-grade indolent neoplasm, due to rare recurrence and metastasis. 
Clear cell occurs in several different tumors of the salivary gland, including benign tumors such as oncocytoma, myoepithelioma, and malignant tumors such as acinic cell carcinoma, mucoepidermoid carcinoma and myoepithelial epithelial carcinoma. Because of the lack of awareness, HCCC is often misdiagnosed as poorly differentiated carcinoma, squamous cell carcinoma, acinic cell carcinoma, mucoepidermoid carcinoma, and epithelial-myoepithelial carcinoma.  Clear cells in this tumor are glycogen rich and give a positive reaction with PAS stain and negative reaction with mucicarmine stain.  Thus, special stains and immunostains play a very important and definitive role to reach at a conclusive diagnosis of HCCC as documented in the present case.
The clear cells of mucoepidermoid carcinoma contain cytoplasmic mucin highlighted by mucicarmine stain. The clear cells in a clear cell oncocytoma contain glycogen, while the oncocytic cells contain abundant mitochondria, which stain with phosphotungstic acid hematoxylin. The tumor cells in acinic cell carcinoma contain zymogen granules, which are PAS positive and diastase resistant. Neoplastic myoepithelial cells in epithelial/myoepithelial carcinoma and malignant myoepithelioma express S-100 protein and smooth muscle antigen (SMA), which are not expressed by HCCC. 
Special stains are not much contributory in the odontogenic tumors with clear cell pattern such as odontogenic carcinoma, ameloblastoma, and calcifying epithelial odontogenic tumor, but they show a biphasic growth pattern with expression of cytokeratin and S-100 protein. 
Metastatic tumors in the oral cavity are derived from renal cell and thyroid cell carcinomas and rarely from the prostate, bowel or the liver. Neoplastic cells in renal cell carcinoma co-express cytokeratin and vimentin, whereas neoplastic cells in HCCC are negative for vimentin. 
As clear cell carcinoma is rare, few treatment protocols have ever been described. Being a tumor of low malignant potential, wide surgical resection is the treatment of choice with, or without, pre-/post-operative radiotherapy.  A few cases of the tumor metastasizing to the regional lymph nodes and two cases with metastasis to the lungs have also been reported in the literature. , Although increased mitosis was found in these cases, it is not a reliable feature in predicting tumor behavior as this feature was also seen in tumors with no metastasis.  Jin et al.,  has described a case of recurrence of clear cell carcinoma of salivary gland on tongue confirmed by the presence of EWSR1 gene rearrangement, and found that that the presence of "dedifferentiated" high grade HCCC may reoccur as low grade tumor even after undergoing extensive radiotherapy. The present case, though had all the surgical margins free from neoplastic process, developed locoregional recurrence after 6 years despite undergoing three cycles of radiotherapy. High grade of the tumor may have resulted in the locoregional recurrence. However, since the incidence of local recurrences is low, further clinicopathological study and long-term follow-up is necessary to document the biological behavior of this entity.
To conclude, clear cell morphology is not difficult to diagnose on routine histopathological sections but to document the cytoplasmic contents and origin of the clear cells, special stains, and immunohistochemistry is mandatory for the conclusive diagnosis. And, as the biological behavior of this rare tumor differs, as reported in various case reports in the literature, further clinicopathological study and long-term follow-up is necessary.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]