Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 3134
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    
Year : 2011  |  Volume : 54  |  Issue : 1  |  Page : 167-169
Hyalinizing clear cell carcinoma of the base of tongue: A distinct and rare entity

1 Department of Pathology, Sri Ramachandra University, Porur, Chennai - 600116, India
2 Department of ENT, Head and Neck Surgery, Sri Ramachandra University, Porur, Chennai - 600116, India

Click here for correspondence address and email

Date of Web Publication7-Mar-2011


Hyalinizing clear cell carcinoma (HCCC) of tongue is a rare neoplasm originating from minor salivary glands. We present a case of HCCC involving the base of tongue, in a 73-year-old male, clinically diagnosed as fibroma. Laser excision of the mass was done. Histopathological examination showed an infiltrating lesion composed predominantly of clear cells. The differential diagnosis included other salivary gland lesions having a clear cell component and metastatic clear cell renal carcinoma. Immunohistochemistry was useful in ruling out these lesions exhibiting clear cell component from clear cell carcinoma. Imaging studies revealed no lesion in either kidney. Since, HCCC has a better prognosis and the adequate treatment is wide excision, it needs to be differentiated from other carcinomas with clear cells. No further therapy was given to the patient. One year after the surgery, the patient is symptom free without local recurrence and on regular follow up.

Keywords: Clear cell carcinoma, metastatic renal cell carcinoma, minor salivary gland

How to cite this article:
Masilamani S, Rao S, Chirakkal P, Kumar A R. Hyalinizing clear cell carcinoma of the base of tongue: A distinct and rare entity. Indian J Pathol Microbiol 2011;54:167-9

How to cite this URL:
Masilamani S, Rao S, Chirakkal P, Kumar A R. Hyalinizing clear cell carcinoma of the base of tongue: A distinct and rare entity. Indian J Pathol Microbiol [serial online] 2011 [cited 2020 Jan 18];54:167-9. Available from: http://www.ijpmonline.org/text.asp?2011/54/1/167/77393

   Introduction Top

Clear cell carcinoma, not otherwise specified (NOS) and otherwise called as clear cell adenocarcinoma/hyalinizing clear cell carcinoma (HCCC), is a malignant epithelial tumor composed predominantly of clear cells. It is frequently seen in hard/soft palate mucosa.

   Case Report Top

A 73-year-old male presented to the out-patient department with complaints of difficulty in swallowing for 6 months not associated with pain or change in voice. The patient was a chronic smoker and a diabetic on regular treatment. There were no palpable or enlarged neck nodes.

Local examination showed an indurated, firm mass [Figure 1] at the base of the tongue measuring 3 × 2 cm. The mucosa over the swelling was normal without any ulceration. The mass was firm and non tender. The clinical findings suggested a benign lesion, probably a fibroma. Laser excision of the mass was done and submitted for histopathological examination.
Figure 1: Endoscopic picture of posterior one-third of tongue showing a proliferative growth involving the base of tongue extending to vallecula and also crossing the midline. Epiglottis and tonsilo-lingual sulcus are free.

Click here to view

The excised mass measured 3 × 3 cm with ill-defined margins. The cut surface was uniformly firm and gray white. There were no obvious areas of hemorrhage or necrosis. Hematoxylin and eosin-stained tissue sections revealed an infiltrative lesion composed of tumor cells arranged in sheets, trabeculae and nests [Figure 2]a. Prominent hyalinized bands were seen throughout the lesion separating the nests of tumor cells [Figure 2]b. Occasional areas showed smaller cells with eosinophilic cytoplasm [Figure 2]c. Predominantly the cells had clear cytoplasm with bland nuclear features [Figure 2]d. There was no appreciable mitotic activity. The lesion was extending up to the mucosa with no surface ulceration [Figure 2]a.
Figure 2: (a) Section shows a tumor reaching the mucosal surface with cells arranged in sheets (H and E ×20); (b) tumor cells separated into nests by fibrous septae (H and E ×40); (c) minor population of smaller cells with eosinophilic cytoplasm (H and E ×100); (d) Cells show clear cytoplasm and bland vesicular nuclei (H and E ×200).

Click here to view

Periodic acid Schiff (PAS) stain and PAS-diastase stains demonstrated the presence of glycogen in the clear cells. Immunohistochemical stains showed positivity for cytokeratin (CK) [Figure 3]a and vimentin [Figure 3]b and negativity for smooth muscle actin (SMA) [Figure 3]c and S-100 [Figure 3]d, confirming the epithelial nature of these cells. Histopathological and immunohistochemical findings suggested the possibility of primary clear cell carcinoma of minor salivary gland or metastatic renal cell carcinoma. During post-operative consultation, ultrasound abdomen was done which revealed no renal mass. Renal parameters (blood urea nitrogen and serum creatinine) were normal. Finally a diagnosis of HCCC of the tongue was rendered. The patient is under close follow up and 1 year after surgery, he is symptom free with normal findings at the site of excision and no recurrence of tumor.
Figure 3: (a) Cytoplasmic positivity noted in tumor cells (cytokeratin immunostain ×100); (b) tumor cells are negative for vimentin (Vimentin immunostain ×40); (c) tumor cells are negative for SMA (note the in-built positivity in the wall of blood vessels) (SMA immunostain ×40); (d) tumor cells are also negative for S100 protein (S100 immunostain ×40)

Click here to view

   Discussion Top

HCCC of tongue is a rare salivary gland neoplasm and only a few cases have been reported in the literature. [1],[2] Most of the cases show involvement of the oral cavity, particularly the palate. The origin of this tumor is still uncertain. Possible explanation of it arising from intercalated duct has been suggested as tumor cells stain positively for CK8 and CK18, and negatively for myoepithelial markers and multilayer squamous epithelial markers (CK10 and CK high molecular weight) by immunohistochemistry. [3] The behavior of these lesions seems to indicate a low grade malignancy and only follow up is usually recommended.

HCCC usually presents as a slow growing and painless submucosal mass without surface ulceration. Histopathology of clear cell carcinoma of oral cavity show monomorphic population of round cells with clear cytoplasm arranged in sheets, nests, cords, or ductal structures. The hyalinizing subtype show thick bands of collagen-separating clusters of tumor cells into solid lobules. Clearing of cytoplasm is due to the presence of glycogen, a feature well demonstrated by PAS stain with and without diastase. Tumor cells are negative for mucicarmine stain ruling out the possibility of mucin in the clear cells. This tumor is immunoreactive to CK and show variable results with S 100, glial fibrillary acidic protein (GFAP), actin, and vimentin. A variety of salivary gland neoplasms need to be considered in the differential diagnosis when a clear cell lesion is encountered in the oral cavity. [4] These include pleomorphic adenoma, myoepithelioma, and low grade mucoepidermoid carcinoma. Carefully looking for specific features of these neoplasms on histology and utilization of immunostains would help in differentiating HCCC from other clear cell-rich salivary gland tumors.

Pleomorphic adenoma, the most common salivary gland tumor, is easily identified by the distinct chondro/fibromyxoid stroma even in an unusual setting of prominent clear cell component. Myoepithelioma is a benign tumor with clear cells, spindle cells, and hyaline cells. The nuclear features are bland and borders are usually well circumscribed. Further, immunostains demonstrating myoepithelial origin like SMA and S 100 may be helpful in cases with doubtful histology. HCCC usually consists of a pure population of clear cells while mucoepidermoid carcinoma consists of mucin containing cells, squamous cells, and intermediate cells. Rarely, in mucoepidermoid carcinoma clear cells are also seen. Another important differential diagnosis that needs to be considered is metastatic clear cell renal carcinoma, especially if the lesion occurs in the older age group. The usual rich delicate vascularity of renal cell carcinoma is not seen in HCCC. Renal cell carcinoma shows immunopostivity for CK, vimentin, and CD10. [5] A thorough search for renal mass with imaging studies must be done before a diagnosis of primary HCCC of tongue is made.

HCCC has an excellent prognosis. The literature search reveals only few cases with metastasis to regional lymph nodes and occasional systemic metastasis. [3] Wide excision is the treatment of choice for this neoplasm with indolent behavior. [3] Further, even radiotherapy may not be required if a clear surgical margin is obtained.

   Conclusion Top

HCCC is a rare distinct histological subtype of clear cell adenocarcinoma encountered in minor salivary glands which can be confused with a variety of clear cell-rich tumors. This entity should be considered in tumors with a monotonous clear cell population in view of its low malignant potential.

   References Top

1.Balakrishnan R, Nayak DR, Pillai S, Rao L. Hyalinising clear cell carcinoma of base of the tongue. J Laryngol Otol 2002;116:851-3.   Back to cited text no. 1
2.Chao TK, Tsai CC, Yeh SY, Teh JE. Hyalinising clear cell carcinoma of the hard palate. J Laryngol Otol 2004;118:382-4.   Back to cited text no. 2
3.Sun ZJ, Zhao YF, Zhang LU, Zhang WF, Chen XM, Wu SG. Hyalinizing clear cell carcinoma in minor salivary glands of maxillary tuberosity. Oral Oncology Extra 2005;41:306-10.  Back to cited text no. 3
4.Wang B, Brandwein M, Gordon R, Robinson R, Urken M, Zarbo RJ. Primary salivary clear cell tumors-a diagnostic approach: A clinicopathologic and immunohistochemical study of 20 patients with clear cell carcinoma, clear cell myoepithelial carcinoma, and epithelial-myoepithelial carcinoma. Arch Pathol Lab Med 2002;126:676-85.  Back to cited text no. 4
5.Rezende RB, Drachenberg CB, Kumar D, Blanchaert R, Ord RA, Ioffe OB, et al. Differential diagnosis between monomorphic clear cell adenocarcinoma of salivary glands and renal (clear) cell carcinoma. Am J Surg Pathol 1999;23:1532-8.  Back to cited text no. 5

Correspondence Address:
Suresh Masilamani
Department of Pathology, Sri Ramachandra University, Porur, Chennai -600 116
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.77393

Rights and Permissions


  [Figure 1], [Figure 2], [Figure 3]

This article has been cited by
1 Hyalinizing Clear Cell Carcinoma: Base of Tongue
Nataraj Pillai,Partheeban Balasundaram,Nehla Isaac
Indian Journal of Otolaryngology and Head & Neck Surgery. 2019;
[Pubmed] | [DOI]
2 Hyalinizing clear cell carcinoma of salivary gland origin in the head and neck: clinical and histopathological analysis
X.-H. Yang,L. Liu,Y.-Y. Shi,Y.-J. Hu,Q.-G. Hu,P. Zhang
International Journal of Oral and Maxillofacial Surgery. 2018; 47(6): 692
[Pubmed] | [DOI]
3 Reappraising hyalinizing clear cell carcinoma: A population-based study with molecular confirmation
Juan C. Hernandez-Prera,Ricky Kwan,Joseph Tripodi,Simion Chiosea,Carlos Cordon-Cardo,Vesna Najfeld,Elizabeth G. Demicco
Head & Neck. 2017; 39(3): 503
[Pubmed] | [DOI]
4 Clear cell carcinoma, not otherwise specified/hyalinising clear cell carcinoma of the salivary gland: The current nomenclature, clinical/pathological characteristics and management
Luca Daniele,Dimitrios Nikolarakos,Jonathon Keenan,Nathan Schaefer,Alfred King-yin Lam
Critical Reviews in Oncology/Hematology. 2016; 102: 55
[Pubmed] | [DOI]
5 Hyalinizing clear cell carcinoma of the head and neck: Case series and update
W. Greer Albergotti,Elizabeth A. Bilodeau,J. Kenneth Byrd,Mark M. Mims,Stella Lee,Seungwon Kim
Head & Neck. 2016; 38(3): 426
[Pubmed] | [DOI]
6 Clear Cell Carcinoma of the Base of the Tongue
Kenichi Watanabe,Yuri Okumura,Ken Hashimoto,Takashi Suzuki
Annals of Otology, Rhinology & Laryngology. 2015; 124(1): 55
[Pubmed] | [DOI]
7 Two Rare Entities in the Same Palate Lesion
Rabia Bozdogan Arpaci,Tuba Kara,Canan Porgali,Ebru Serinsoz,Ayse Polat,Yusuf Vayisoglu,Cengiz Ozcan
Journal of Craniofacial Surgery. 2014; 25(3): e235
[Pubmed] | [DOI]
8 Hyalinizing clear cell carcinoma of the tonsil and its treatment
Shadi B. Hijjawi,Shaad E. Abdullah,Kareem Abdelhadi,Eduardo Eyzaguirre,Maurice Willis,Nihal E. Abdulla
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 2012; 114(2): e32
[Pubmed] | [DOI]
9 A large swelling of the tongue
Ray, J.G., Bhattacharya, S., Mahato, B., Mukherjee, S., Chaudhuri, K.
BMJ Case Reports. 2011;


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

    Case Report
    Article Figures

 Article Access Statistics
    PDF Downloaded159    
    Comments [Add]    
    Cited by others 9    

Recommend this journal