Case Report Head and Neck Oncology
Hyalinizing clear cell carcinoma of the base of tongue
K. Pujary, S. Rangarajan, D. R. Nayak, R. Balakrishnan, V. Ramakrishnan:
Hyalinizing clear cell carcinoma of the base of tongue. Int. J. Oral Maxillofac. Surg.
2008; 37: 93–96. # 2007 Published by Elsevier Ltd on behalf of International Association of Oral and Maxillofacial Surgeons.
K. Pujary1, S. Rangarajan2, D. R. Nayak1, R. Balakrishnan1, V. Ramakrishnan1
1Department of ENT – Head & Neck Surgery, Kasturba Medical College & Hospital, Manipal, India;2Department of Pathology, Kasturba Medical College & Hospital, Manipal, India
Abstract. Hyalinizing clear cell carcinoma is a rare, low-grade neoplasm of the minor salivary glands. It is composed exclusively of epithelial cells with optically clear cytoplasm. There are only a few isolated cases reported in the literature involving the base of tongue. The treatment of choice is wide excision and selective neck dissection, with or without radiotherapy. The prognosis of these tumours is good.
A 57-year-old male patient presented with a lesion in the base of tongue, which was well enhanced on contrast computerized tomography scan. Once confirmed by biopsy, the hyalinizing clear cell carcinoma was resected via a transcervical approach. The patient underwent postoperative radiotherapy. There was no evidence of locoregional recurrence or distant metastasis at 18 months of follow up.
Accepted for publication 12 June 2007 Available online 5 September 2007
Hyalinizing clear cell carcinoma (HCCC) is a rare tumour affecting the oral cavity, more commonly in adult females7. The tumour cells have a clear cytoplasm, which is due to the accumulation of gly- cogen. In some instances, it may be due to a fixation artefact. The tumour cells are characteristically positive for cytokeratin and negative for S-100 and smooth muscle actin (SMA). This emphasizes the fact that the tumour originates from epithelial cells and not myoepithelial cells7. The term
‘hyalinizing clear cell carcinoma’ was proposed by MILCHGRUB et al.7. They described the low-grade nature and epithe- lial origin of the tumour. This tumour needs to be differentiated from other sali- vary gland tumours having a significant proportion of clear cells and a relatively aggressive behaviour.
Case report
A 57-year-old male presented with a his- tory of foreign body sensation in the throat for 1 month. There was no history of smoking or intake of alcohol. On exam- ination by indirect laryngoscopy, a 3 cm 3 cm smooth submucosal mass was seen towards the left side of the base of tongue, extending to the tonsillolingual sulcus and vallecula (Fig. 1). On palpa- tion, the mass was firm, not tender and did not bleed. The tongue movement was normal. There was no palpable cervical lymphadenopathy.
The computerized tomography scan of the neck (axial cuts) with contrast showed a well defined heterogeneously enhancing mass at the base of tongue towards the left (Fig. 2). It involved the ipsilateral mylo-
hyoid muscle and bilateral genioglossus muscles. The lesion was extending to the left vallecula and abutting the epiglottis, displacing it posteriorly. There was no evidence of enlarged cervical lymph nodes.
A chest radiograph was normal. A biopsy was taken under general anaesthesia, which was suggestive of clear cell carcinoma. An ultrasound of the abdomen was normal. The patient was taken up for excision of the mass via a transcervical approach under general anaesthesia following nasotracheal intubation. On exposure of the hyoid bone, the muscles attached to its superior border were cut and retracted to expose the tumour. The tumour was removed in toto by blunt dissection. An extended suprao- mohyoid neck dissection was done. The wound was closed after achieving haemos- tasis and placing a vacuum drain.
Int. J. Oral Maxillofac. Surg. 2008; 37: 93–96
doi:10.1016/j.ijom.2007.06.014, available online at http://www.sciencedirect.com
0901-5027/01093 + 04 $30.00/0 # 2007 Published by Elsevier Ltd on behalf of International Association of Oral and Maxillofacial Surgeons.
Grossly, the tumour was partly cir- cumscribed, measuring 3 cm 2 cm 1.5 cm. It was solid and grey white on cut surface. Microscopically, the tumour was partly encapsulated with infiltrative margins, and was composed of large poly- gonal cells with clear cytoplasm and dis- tinct cell borders (Fig. 3a). In some areas, these cells were admixed with smaller cells having amphophilic cytoplasm. The nuclei were large, oval to slightly irregular
with coarse chromatin. The neoplastic cells were arranged in nests and trabecu- lae, surrounded by fibrous stroma showing hyalinization (Fig. 3a). Periodic acid–
Schiff (PAS) stain with and without dia- stase showed intracytoplasmic glycogen in some of the tumour cells (Fig. 3b).
There was no evidence of intracytoplas- mic mucin or fat. No atypical mitosis or necrosis was seen. Immunohistochemistry showed the tumour cells to be positive for
cytokeratin (AE1/AE3; Dako) (Fig. 3c).
S-100 (Dako) and vimentin (Dako) were negative. The light microscopic and immunohistochemical features were diag- nostic of hyalinizing clear cell carcinoma.
The resected margins and the lymph nodes were free of tumour.
Three weeks after surgery, the patient received postoperative radiotherapy of 60Gy in 30 fractions over 6 weeks. When seen on follow up after 18 months there was no evidence of recurrence or distant metastasis.
Discussion
Hyalinizing clear cell carcinoma (HCCC) is a distinct clinico-pathological entity.
Microscopically, it is composed exclu- sively of a monomorphic population of undifferentiated cells with optically clear cytoplasm11. It is a rare entity accounting for less than 1% of all salivary gland tumours6. They arise from the minor sali- vary glands within the oral cavity and are commonly located in the palate, lips and buccal mucosa5,7. Base of tongue1, hypo- pharynx4, larynx4, nasal cavity8 and jaw bones2are the other rare documented sites of tumour occurrence. The tumour is more common in women between the fifth and seventh decades of life3,7. Clinically, as in this case, HCCC presents as a slow grow- ing and painless submucosal mass3.
The World Health Organization has not included HCCC as a separate entity in its classification of salivary gland neo- plasms12. Prior to its description by MILCH- GRUB et al.7, a few cases of the same tumour had been reported in the literature under various synonyms, such as clear cell carcinoma, glycogen-rich clear cell ade- nocarcinoma and glycogen-rich clear cell carcinoma. At present, it has the status of a distinct clinico-pathological entity, with the behaviour of a low-grade neoplasm with a low propensity towards recurrence, nodal and distant metastasis1,11. A few cases of the tumour metastasizing to the regional lymph nodes7 and two cases with metastasis to the lungs4,5, have also been reported in the literature. Although increased mitosis was found in these cases7, it is not a reliable feature in pre- dicting tumour behaviour, as this feature was also seen in tumours with no metas- tasis.
Histologically, the tumour has infiltra- tive borders, with the neoplastic clear cells arranged in thick trabeculae, nests, cords or solid sheets with a hyalinizing stroma3,7. Eosinophilic cells, as seen in the present case, may also be a component of the tumour2. The clear cells have distinct cell 94 Pujary et al.
Fig. 1. Rigid telescopic view of the submucosal mass in the base of tongue.
Fig. 2. Computed tomgraphy scan with contrast (axial cuts) showing an enhancing mass in the base of tongue.
borders with uniform small nuclei, which may show mild nuclear pleomorphism, as in this case. The special stain, PAS with and without diastase, shows variable amounts of PAS-positive diastase-sensitive mate- rial, representing glycogen, in the cyto- plasm of the tumour cells3,7. The tumour cells do not contain mucin. Immunohisto- chemistry shows expression of epithelial markers especially cytokeratins, and nega- tivity for vimentin, S-100 and SMA3,7. The differential diagnosis of HCCC on histo- pathology includes mucoepidermoid carci- noma, acinic cell carcinoma, clear cell oncocytoma, epithelial myoepithelial car- cinoma, malignant myoepithelioma, sebac- eous carcinoma, odontogenic tumours and metastatic renal cell carcinoma, all of which show a significant proportion of clear
cells3,7,9. The use of special stains and immunohistochemistry, along with careful histological examination of the tumour, for identifying the typical features found in each of these neoplasms, help in arriving at a correct diagnosis1–3,7. The clear cells of mucoepidermoid carcinoma contain cyto- plasmic mucin highlighted by mucicarmine stain. In sebaceous carcinoma, the presence of cytoplasmic lipid which is lost in routine histological processing accounts for the optically clear cytoplasm, and is demon- strated by fat stain on frozen tissue. The clear cells in a clear cell oncocytoma con- tain glycogen, while the oncocytic cells contain abundant mitochondria, which stains with phosphotungstic acid haema- toxylin. The tumour cells in acinic cell carcinoma contain zymogen granules,
which are PAS positive and diastase resis- tant. Neoplastic myoepithelial cells in epithelial/myoepithelial carcinoma and malignant myoepithelioma express S-100 protein and SMA, which are not expressed by HCCC. The odontogenic tumours show a biphasic growth pattern with expression of cytokeratin and S-100 protein2. Neoplas- tic cells in renal cell carcinoma co-express cytokeratin and vimentin, whereas neoplas- tic cells in HCCC are negative for vimentin.
Radiological imaging studies are also help- ful in ruling out the possibility of a meta- static renal cell carcinoma. Clinical differential diagnosis of the lesion at the base of tongue would include epithelial malignancies, granulomatous conditions, lingual thyroid, prominent lingual tonsils and cysts.
As these tumours are rare, there is no standard treatment protocol. There is con- troversy as to the appropriate surgical margins, the role of radiotherapy and the management of the neck. The indolent clinical course suggests that wide local excision is the treatment of choice. Large tumour size and nodal metastasis may alter the prognosis. An aggressive variant has been reported10. Postoperative radio- therapy is reserved for large tumours (>3 cm) and for positive surgical margins.
In conclusion, HCCC is a rare minor salivary gland tumour exhibiting the beha- viour of a low-grade malignancy. It has a better prognosis than the other salivary gland tumours showing clear cells. Wide local excision achieves adequate locore- gional control of small primary tumours.
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Fig. 3. (a) Neoplastic cells having mildly pleomorphic nuclei and abundant optically clear cytoplasm with distinct cell borders arranged in trabeculae surrounded by hyalinized stroma (haematoxylin and eosin;200). (b) Neoplastic tumour cells showing variable glycogen in the cytoplasm highlighted by PAS stain which dissolved on diastase digestion (PAS stain without diastase;100). (c) Tumour cells expressing cytokeratin highlighted by immunohistochemistry (cytokeratin AE1/AE3;100).
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Address:
Dipak Ranjan Nayak
Department of ENT – Head & Neck Surgery Kasturba Medical College & Hospital Manipal 576104
Karnataka India
Tel: +91 820 2922143 Fax: +91 820 2570061 E-mail:drnent@rediffmail.com 96 Pujary et al.
