Clear cell carcinoma of palatine salivary gland: A diagnostic challenge.

INTRODUCTION

Clear cell carcinoma is a rare low-grade salivary gland malignant neoplasm which represents approximately 1% of all salivary gland tumors. These tumors occur exclusively in minor salivary gland and are characterized by an indolent growth and less aggressive biological behavior. The clarity of cytoplasm of the clear cells has been attributed to accumulation of glycogen, loss of organelles, or as fixation artifact.[123] As a result, the differential diagnosis of intraoral clear cell neoplasms of includes a diverse group of tumors including primary salivary gland clear cell tumors, clear cell odontogenic tumors as well as few metastatic tumors. Therefore, the diagnosis of clear cell carcinoma is of exclusion.[12]

CASE REPORT

A 40-year-old female patient presented with a slow growing, painless swelling of 6–7 years’ duration on the right side of the face intraorally and extraorally. Habit history revealed smoking of 10 cigarettes per day for 7 years. Intraoral examination revealed a diffuse hard swelling measuring about 5 cm × 6 cm on the maxillary right posterior region, extending from the midline of the palate, from mesial aspect of 14 to the distal aspect of 18. Orthopantamograph and occlusal radiograph showed extensive bone loss and missing 16. The computed tomography at the level of the maxilla revealed a radiodense mass extending from the 14 region up to the maxillary tuberosity and also extension of the tumor mass into the maxillary antrum. A volume-rendered computed tomography showed erosion of the palatine bone on the right side of the maxilla [Figure 1]. Grossly, the tumor mass was yellowish cream in color with a reddish tinge, firm in consistency with an irregular surface texture. The cut surface was yellowish white with a few hemorrhagic foci at the periphery.

Figure 1

Occlusal radiograph (left) superficial erosion of the palatine bone, computed tomography (right) revealed the extent of the tumor mass

HISTOPATHOLOGIC FEATURES

Overlying orthokeratinized stratified squamous epithelium showed pseudoepitheliomatous hyperplasia, increased mitotic figures and individual cell keratinization [Figure 2]

Figure 2

Photomicrograph of overlying palatine epithelium with underlying connective tissue showing clear cells (H&E, ×40)

Connective tissue stroma showed sheets and strands of clear cells and small cells with eosinophilic cytoplasm with oval to round nucleus interspersed with dense, fibrocellular radiating collagen fibers [Figure 3]

Figure 3

Photomicrograph of clear cells and small eosinophilic cells in sheets and islands separated by fibrocellular connective tissue septa (H&E, ×40)

Some of the cells are arranged in nests and cords along with duct-like structures filled with mucoid material [Figure 4]

Figure 4

Photomicrograph of island of clear cells and eosinophilic cells with duct-like structures (H&E, ×200)

Clear cells appear to be pleomorphic with prominent hyperchromatic nuclei [Figure 5]

Figure 5

Photomicrograph of island of pleomorphic clear cells and eosinophilic cells (H and E, ×200)

At the periphery, palatine salivary glands were evident [Figure 6]

Figure 6

Photomicrograph of palatine salivary gland at the periphery of the mass (H&E, ×40)

Perineural invasion was also noted [Figure 7].

Figure 7

Photomicrograph of infiltration of nerve fiber bundles at the periphery of the tumor (H&E, ×100)

The presence of clear cells in hematoxillin and eosin sections justified the need to perform special stains and immunohistochemistry (IHC) to arrive at definitive diagnosis.

SPECIAL STAINS

Mucicarmine (residual salivary glands at the periphery showed positive stain) [Figure 8], alcian blue, periodic acid–Schiff reagent (PAS), phosphotungstic acid hematoxillin (PTAH), Congo red and oil red O stain showed a negative reaction for the tumor.

Figure 8

Photomicrograph of negative mucicarmine staining of the clear cells except the palatine salivary (H&E, ×40)

IMMUNOHISTOCHEMISTRY

Tumor cells showed positivity for cytokeratin panel CK, CK5/6 (CK5-basal cell marker with myoepithelial markers CK6) [Figure 9]

Figure 9

Photomicrograph of immunostaining of the clear cells by the cytokeratin 5/6 (×100)

P63-small eosinophillic cells showed positive reaction indicative of proliferation, whereas clear cells showed no reaction [Figure 10]

Figure 10

Photomicrograph of immunostaining of the small eosinophilic cells by the proliferative marker P63 (×100)

Eosinophilic cells showed S100-positive reaction [Figure 11]

Figure 11

Photomicrograph of immunostaining of the clear cells by the s100 (×100)

Negative reaction for CK8, CK19, smooth muscle actin (SMA), CD10 (metastasis) and Vimentin markers.

DIFFERENTIAL DIAGNOSIS

Clear cell variants of primary salivary gland tumors

Mucoepidermoid carcinomas – they show PAS positive, diastase-resistant cytoplasmic granules. Mucous cells demonstration by mucicarmine, alcian blue and IHC staining for MUC5AC helps in diagnosis[23]

Acinic cell carcinoma – degenerative clear cell changes account for < 95% of tumor cells. They show PAS positive, diastase-resistant cyplasmic granules, negative with mucicarmine and alcian blue. IHC staining for CK7 and CK 8 positive[23]

Oncocytoma – positive with PAS and PTAH (blue cytoplasmic granules under oil immersion). Negative with digested PAS and Alcian blue[2]

Epithelial-myoepithelial carcinoma – characteristic biphasic pattern with inner cell expressing epithelial markers (low-molecular-weight cytokeratin Cam 5.2, European medicines agency and AE1/AE3), surrounded by an outer layer of cells showing positive staining with myoepithelial markers such as SMA, calponin, vimentin and S-100. PAS-positive basement membrane separating the tumor island from stroma[123]

Myoepithelial carcinomas – clear cells negative with mucicarmine staining. Myxoid matrix is positive with alcian blue staining. Tumor cells are positive with myoepithelial markers calponin, vimentin, SMA, S-100, CK7 and CK14.[123]

Clear cell lesions of odontogenic origin

Clear cell odontogenic carcinoma shows lobulated growth pattern, presence of osteodentin, and more likely to be intraosseous in origin. The clear cells are PAS positive with diastase sensitive cytoplasmic granules. They are negative with mucin, vimentin and muscle actin. Positive with CK8 and CK19[4]

Clear cell variants of calcifying epithelial odontogenic tumor – presence of calcifications – Liesegang rings and Congo red stain positive for amyloid deposition in connective tissue.[4]

Metastatic clear cell lesions

Renal cell carcinoma shows pronounced cellular atypia, vascularity of the lesions, demonstration of intracytoplasmic fat, positivity with CD10 and vimentin.[23]

FINAL DIAGNOSIS

Based on clinicoradiological findings and immunohistochemical profile of the microscopic features, the diagnosis of clear cell carcinoma of minor salivary gland of hard palate was given.

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Conflicts of interest

There are no conflicts of interest.