Clear cell carcinoma of soft palate- A case report

Abstract

Clear-cell carcinoma (CCC) of the salivary gland is a very rare malignancy. It is recently introduced in the WHO classification of salivary gland tumors. CCC is considered a low-grade tumor, which is commonly seen in elderly females. The most common intraoral sites affected by CCC are palate and tongue. CCC comprises 1% of all salivary gland tumors. CCC has a silent course and a limited nodal metastasis. A hyalinized variant of CCC has good prognosis and requires wide surgical excision with or without adjuvant radiotherapy. Microscopically, it is characterized by the presence of nests of glycogen-rich monomorphic clear cells within a hyalinized stroma. Immunohistochemistry analysis of CCC depicts tumor cells which are positive for epithelial markers and negative for S-100. Here, we report the case of a hyalinized CCC of minor glands of the palate which was misdiagnosed as poorly differentiated squamous cell carcinoma.

INTRODUCTION

Clear-cell carcinomas (CCCs) of head-and-neck region are rare; they form a heterogeneous group which include odontogenic, salivary gland and metastatic lesions.[1,2] The diagnoses of these malignancies need special concern as they give diagnostic dilemma and misinterpretation. The CCCs of the salivary gland are rare and usually occur in elderly females.[3] They are almost exclusively occurring in intraoral minor salivary glands and comprise 1% of all salivary gland tumors. The most common intraoral sites are palate and tongue.[4] Most CCCs are frequently asymptomatic and therefore attain a substantial size without causing much discomfort.[5] The diagnosis of CCCs is primarily based on the histopathological features and added immunological studies. Histologically, it is characterized by nests of glycogen-rich monomorphic clear cells within a hyalinized stroma. It follows an indolent course with limited metastatic potential as it is a low-grade carcinoma.[6] It is important to differentiate this entity from other more aggressive CCCs including mucoepidermoid carcinoma, epithelial–myoepithelial carcinoma, acinic cell carcinoma, odontogenic neoplasm and metastatic tumors like renal cell carcinoma.[7] Here, we report a rare case of a hyalinized CCC in an elderly female, which occurred on the palate and illustrated an indolent but locally infiltrative nature, which gives a false impression of poorly differentiated carcinoma.

CASE REPORT

A 50-year-old female presented to a private clinic with the complaint of swelling at the palatal vault. She gave a history of small swelling for 10 years without any symptoms and growth in size. Few months back, she noticed pain and a significant change in the appearance of the swelling. She gave a negative history of smoking and tobacco chewing. The regional lymph nodes were not palpable. Local examination revealed an indurated, firm, soft-tissue mass present on the posterior part of the palate [Figure 1]. The lesion extended to the right side of the alveolar bone causing expansion of the posterior maxillary jaw. The lesion had smooth, irregular surface with no area of hemorrhage and ulceration. Computed tomography scan showed indistinct palatal bone resorption with alveolar bone involvement [Figure 2]. Clinical features were suggestive of minor salivary gland tumor. The differential diagnosis included mucoepidermoid carcinoma, acinic cell carcinoma, carcinoma of the palate, odontogenic carcinoma and metastatic carcinoma. The lesion was excised and sent for histopathological examination. Microscopically, H and E-stained section illustrated an infiltrative lesion composed of tumor cells in the form of sheet, nests and trabeculae in a hyalinized stroma [Figure 3]. Most of the areas showed predominant cells with clear cytoplasm, distinct cell boundary and bland nuclei [Figure 4]. Mitotic activity was not appreciable. Periodic acid–Schiff (PAS) stain demonstrated positive tumor cells [Figure 5], but the tumor cells were negative for mucicarmine. Immunohistochemical analysis of the lesion showed positivity with pancytokeratin (CK) and lacking vimentin [Figures 6 and 7]. The lesion was negative, with smooth muscle actin and S-100 confirming the epithelial origin of cells. Based on the histopathological and immunohistochemistry (IHC) analysis, the diagnosis of hyalinized CCC of the intraoral minor salivary glands was confirmed. The patient was followed up for more than 6 months, and no recurrence or symptoms were recorded.

Figure 1.

A firm, submucosal intraoral mass on the posterior palate involving the right alveolar ridge

Figure 2.

Computed tomography scan shows indistinct alveolar bone resorption

Figure 3.

Clear cells as nests in hyalinized stroma (H and E, ×10)

Figure 4.

Tumor cells with clear cytoplasm and distinct cell boundaries (H and E, ×40)

Figure 5.

Tumor cells showing periodic acid–Schiff positivity at ×40

Figure 6.

Tumor cells are negative for vimentin at ×10

Figure 7.

Tumor cells showing pancytokeratin positivity at ×40

DISCUSSION

CCC is less commonly reported malignancy in literature; therefore, this entity is considered a separate lesion because of its rarity and its pathognomonic histopathological features recently introduced in the WHO classification. From 1994 to 2004, only 13 cases of CCC in the salivary glands were published in English literature.[2] It was first reported by Milchgrub et al. in 1994.[1,3,8] The prevalence of CCC is 0.2%–1% of all salivary gland tumors. Females have been reported to be affected twice as common as men.[1] By definition, CCC contains a significant proportion of clear cells. The origin of this lesion is uncertain. Possibly, it arises from intercalated ducts as tumor cells stain positive for ck8 and ck18 and negative for myoepithelial markers and stratified squamous epithelial markers by IHC.[5,9]

The most common intraoral site includes the palate followed by lips and buccal mucosa. The natural course of the lesion is an indolent, painless, submucosal mass with limited metastatic potential.[6,10] CCC is typically evident on routine H and E-stained section, but special stains and IHC may be beneficial in differentiating it from other tumors with similar histomorphology.[3,5]

Hyalinizing CCC (HCCC) is a histological variant of CCCs and usually arises from intraoral minor salivary glands, with the most frequent site of occurrence being tongue, followed by palate. Hyalinizing nature of stroma can be a feature that is basis for the diagnosis of HCCC.[10] IHC and special stains can be extremely helpful in distinguishing HCCC from other tumors with clear cell features.[6] Microscopic diagnosis of HCCC is challenging as the spectrum of its microscopy overlaps those of salivary gland and other neoplasms which predominantly show clear cells.[10] HCCC could also be misdiagnosed as poorly differentiated carcinoma, acinic cell carcinoma epithelial–myoepithelial carcinoma and mucoepidermoid carcinoma.[11]

Clear-cell components in mucoepidermoid carcinoma have mucin in the cytoplasm and show positive staining with mucicarmine which helps in differential diagnosis. In acinic cell carcinoma, tumor cells are PAS positive and have zymogen granules. Neoplastic cells are positive with S-100 and smooth muscle antigen in epithelial–myoepithelial carcinoma and myoepithelioma. Odontogenic carcinoma with clear cells can be discriminated from CCC by biphasic growth pattern and positive staining by CK and S-100.[4,7] Metastatic tumor-like renal cell carcinoma needs systemic examination. A high degree of vascularity and pronounced atypia in addition to the lack of prominent hyaline stroma is generally regarded as a hallmark of renal cell carcinoma.[6,9]

HCCC has an excellent prognosis. Wide surgical excision is the treatment of choice. Further radiotherapy may not be required if clear surgical margins are obtained.[9] Postoperative radiotherapy is used to improve metastatic control in malignant salivary gland tumors.[10] According to the reported cases in literature, CCCs has 17% recurrence rate and 21% metastatic rate. Due to adverse biological behavior, close follow-up is therefore recommended.[1,3]

CONCLUSION

To understand the nature and biologic behavior of this tumor, more number of case series should be reported. Misinterpretation as other carcinomas can be evaded as special stains, and IHC techniques help in achieving a precise diagnosis. Predominant clear-cell component and hyalinizing stroma are characteristic features. Indolent nature and limited infiltration in surrounding tissue demands close follow-up after surgical intervention.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.