Hyalinizing Clear Cell Carcinoma: Base of Tongue

Abstract

Hyalinizing clear cell carcinoma (HCCC) is a low grade, rare neoplasm originating from the minor salivary glands. It usually follows an indolent course and the main treatment modality is surgery. The prognosis of these tumours are good, hence it needs to be differentiated from other carcinomas with clear cells. Here we report a pathologically proven HCCC of the base of tongue.

Introduction

The term ‘hyalinizing clear cell carcinoma was proposed by Milchgrub et al. [1]. It is a malignant epithelial tumor composed predominantly of clear cells. These cells have a clear cytoplasm due to accumulation of glycogen. It is predominantly seen in hard and soft palate and very rarely seen in the base of tongue [2]. It is documentated to have female predominance. HCCC represents 1% of all salivary gland tumours. These tumour cells are characteristically positive for cytokeratin and negative for S-100 and smooth muscle actin (SMA).

Case Report

A 42 year old male presented to our outpatient department with complaints of swallowing difficulty for 5 months duration and feeling of choking sensation in the throat intermittently. There was no associated voice change or dyspnoea. The patient is a chronic smoker, who smokes 10–12 cigarettes per day. No comorbidities were present.

Local examination (Fig. 1) revealed a large smooth, broad based mass at the posterior one-third of tongue obstructing the laryngeal inlet, measuring approximately 3.0 × 2.0 cm. The mass was non-tender, smooth and non-ulcerated. No neck nodes were palpable. CT scan (Fig. 2) confirmed the size, margins and position of the mass and absence of neck nodes. The clinical appearance, thus, suggested a benign lesion.

Fig. 1.

Clinical picture of the mass in the oropharynx

Fig. 2.

CT scan image showing the mass in the oropharynx, with broad base

In view of the location and clinical appearance, preliminary biopsy or FNAC was not planned. Excision biopsy was directly planned under anesthesia. After requisite pre-operative investigations and anesthetic fitness, the patient was taken up for excision biopsy. Intubation was difficult and fibreoptic nasal intubation was done. With the patient in Rose position and using tonsillectomy mouth gag and tongue depressor, the mass was visualized. Using coblation, the mass was completely excised.

The excised mass was submitted for histopathological examination, which revealed squamous epithelium with infiltration by a tumour in the subepithelium, composed of polygonal cells arranged in solid nests, lobules and cords, separated by hyalinized fibrous septae (Fig. 3). The tumor cells had vesicular nuclei with conspicuous nucleoli, moderate amounts of clear cytoplasm and distinct cell borders. Mild nuclear pleomorphism and occasional mitotic figures were seen. There was no evidence of brisk mitotic activity or necrosis. Perineural invasion was not evident. Foci of myxoid degeneration and reactive lymphoid aggregates with germinal centres were also noted. Entrapped normal salivary gland ducts were also observed.

Fig. 3.

High power photomicrograph of tumour containing polygonal cells arranged in solid nests, lobules and cords (× 40)

Immunohistochemistry revealed positivity for pancytokeratin (CK AE1/AE3) for monoclonal antibodies AE1 and AE3 which recognize the acidic and basic subfamilies of cytokeratin and hence confirm the epithelial nature of the tumor. Patchy positivity was seen for CK 5/6 and p63. S-100 and CD 10 were negative, ruling out a metastatic clear cell renal cell carcinoma and clear cell myoepithelial carcinoma. With the histomorphology and the above mentioned immunophenotype, a diagnosis of primary hyalinizing clear cell carcinoma of salivary gland was made.

Blood urea nitrogen and serum creatinine were done to detect any renal abnormality. It was within normal limits.

Patient was followed up for almost a year and there was no local recurrence (Fig. 4). Option of radiotherapy was advised to the patient with need for regular and close follow-up.

Fig. 4.

Follow up photo 11 months after excision showing no local recurrence

Discussion

Tongue base tumours are generally squamous cell carcinoma as they arise from the mucosa. 0.5% or less of these malignancies arise from the salivary gland. More than 50% of salivary gland tumours are benign and the most common site is soft palate for minor salivary gland tumours. Minor salivary gland tumours are usually malignant as compared to parotid tumours [2]. Neoplasms of the salivary gland that occur at the tongue base include mucoepidermoid carcinoma, adenocarcinoma, adenoid cystic carcinoma and clear cell carcinoma.

Clear cell carcinoma (CCC) not otherwise specified (NOS) or hyalinizing clear cell carcinoma (HCCC) represents 1% of all salivary gland tumours. It is a rare, relatively newly described entity with predilection for palate, lips and buccal mucosa.

It is a low grade malignancy, whose origin is still unknown. It is thought to arise from intercalated duct and the tumour cells stain positive for CK8 and CK18. CCC is a distinct entity that was described by Batsakis et al. in 1980. It was histologically character-ized by Milgrub et al. in 1994 and Ellis in 1998. This entity was first published in 1968 in Germany as part of oral malignancies having clear cell populations. Milchgrub et al. (1994) first observed that the carcinoma has a prominent hyalinised stroma and a lack of myoepithelial differentiation [3]. HCCC is defined as a malignant epithelial neoplasm composed of monomorphous population of cells having clear cytoplasm. More recently it has been grouped as a distinct entity due to the presence of specific translocation (EWSR1–ATF1, Ewings sarcoma breakpoint region 1–activator transcription factor1) fusion-t (12:22) (q13:q12).

The case series reported by Milgrub et al. [1] and O’Sullivan-Mejia et al. [4] have reported female preponderance up to 75% but isolated case reports have an equal number of male (including this case) and female cases. Refer Table 1.

Table 1.

Review of literature

	Our case	Milchgrub et al.	Daniele et al.	O’Sullivan-Mejia et al.	Masilamani et al.	Farooq et al.	Suzuki et al.	Pujary et al.
Age	42		63	25-86, pred > 70	72	60	66	57
Sex	Male	Predominantly female	Female	6 F out of 8	Male	Male	Female	Male
Duration	5 months		4 years		6 months	2 years
Clinical size	3 × 2		4 × 4.5 × 6	1.2–4.5	3 × 2		4 × 3
Smoker	Yes				Yes
Location	Tongue base	Minor salivary glands	PNS	Tongue base, floor of mouth, malar, buccal mucosa, orbit, anterior tongue	Tongue base	Tongue base
Nodes	No	2 of 11	No	No	No	Yes
Route	Per oral		Trans nasal		Per oral	Trans cervical	Trans madnibular	Trans cervical
Tracheostomy			No			No	Yes	No
Neck dissection	No		No		No	Yes	Yes	No
Excision	Coblation		Endoscopic surgery		Laser	Conventional surgery	Conventional surgery
Radiotherapy			No	1 out of 8		Yes		Yes
Follow up	10 months	6 months to 11 years		1 to 10 years	12 months	4 months	21 months	18 months

As per O’Sullivan-Mejia et al. [4], HCCC is more commonly seen in the seventh decade though the tumour has been reported in all adult age groups. Our patient was in the fifth decade.

HCCC presents as a slow growing, painless submucosal mass without surface ulceration. Thus the patients usually present late—typically a few months after onset. And by this time, most of the reported tumours have reached a large size of 3–4 cm in diameter.

Though smoking has not been reported as a risk factor, our case and the case reported by Masilamani et al. [5] had a history of smoking.

Most of the reported lesions are in the oral cavity and base of tongue except for one case in the para nasal sinus reported by Daniele et al. [3].

CT scan/MRI is useful for making a diagnosis. The tumours appear as locally invasive lesion with adjacent bony lysis. MRI will show a diffusely enhancing T2 hyperintense lesion.

Cervical nodes have been reported in only a few cases [1, 6]. Our patient did not have any nodes clinically or radiologically.

There is no specific evidence-based treatment regimen but for solitary early stage lesions, wide local excision with radiographic surveillance is advocated.

The trans oral approach was used in our case. Some cases, in literature, needed trans-mandibular [7] or trans-cervical [6, 8] approaches. There is a report of tracheostomy being needed too. And at least two reported cases needed neck dissection [7].

Most of the reported cases were excised by conventional surgery. Laser was used in one [5] and the PNS tumour was excised endoscopically [3]. This case is the first to use coblation for excision.

Patients who present with loco-regional metastasis are recommended post-operative radiotherapy. Two cases have been reported that were given post operative radiotherapy. Only approximately 16% cases report loco-regional or distant metastasis [4].

It is necessary to distinguish HCCC from more aggressive tumours with clear cell features to en-sure proper treatment and management [4]. HCCC shows thick bands of collagen separating clusters of tumour cells into solid lobules with clearing of cytoplasm due to presence of glycogen. This feature is demonstrated by Periodic acid Schiff (PAS) stain [5]. Many head and neck tumours demonstrate clear cell changes on histology namely metastatic clear cell renal carcinoma, pleomorphic adenoma, myoepithelioma, low grade mucoepidermoid carcinoma, acinic cell carcinoma and clear cell odontogenic carcinoma. Metastatic clear cell renal carcinoma is an important diagnosis especially in older age group, which will be immunopositive for CK, vimentin and CD10. Pleomorphic adenoma has a distinct chondro-fibromyxoid stroma with clear cell component. Myoepithelioma is a benign tumour which has clear cells, spindle cells and hyaline cells. Calcifying epithelial odontogenic tumour is a benign tumour which histologically has abundant amyloid within its hyalinized stroma with concentric calcifications. Detection of EWSR1-ATF1 fusion by FISH is confirmatory of HCCC. This tumour has excellent prognosis.

Limitation of the Study

Due to technical limitations, the operative procedure could not be photographed or recorded.

Conclusion

To conclude, HCCC is a rare minor salivary gland tumor which behaves as a low grade malignancy. This tumor has better prognosis than other clear cell salivary gland tumours. Wide local excision achieves adequate loco-regional control of small primary tumours.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed Consent

Formal consent is not required for this type of study (clinical report). Informed consent was obtained from the patient for the surgical procedure.

Ethical Standards

All procedures performed in the study were in accordance with the ethical standards of the institution and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.