228 Tumours of the salivary glands

Definition

Clear cell carcinoma, not otherwise specified (NOS), is a malignant epithelial neoplasm composed of a monomorphous population of cells that have optically clear cytoplasm with standard haematoxylin and eosin stains. Because many types of salivary gland neoplasms commonly or consistently have a component of clear cells, clear cell carcinoma is distinguished by the absence of features characteristic of these other neoplasms and its monomorphous population of clear cells. ICD-O code 8310/3

 Synonyms

Clear cell adenocarcinoma; hyalinizing clear cell carcinoma. Clear cell carcinoma has been confused with epithelial-myoepithelial carcinoma (EMC), and EMC have been reported as clear cell carcinoma {407}.

Epidemiology

The peak occurrence is in patients in the 40-70 year age range, and they are rare in children {668,2658}. There is no sex predilection.

 Localization

Clear cell carcinomas are more frequent in the intraoral minor salivary glands than the major salivary glands {668,1728, 1931,2179,2369,2716}. The palate is most frequently involved, but buccal mucosa, tongue, floor of the mouth, lip, and retromolar and tonsillar areas are also affected.

Clinical features

The only sign in most cases is swelling, but mucosal ulceration and pain occur with some tumours. Patients have reported the durations of their tumours as 1 month to 15 years {2369}.

Macroscopy

Although the size of the primary tumour is usually 3.0 cm or less, the tumours usually are poorly circumscribed and infiltrate adjacent salivary gland, mucosa, soft tissues, bone, and nerves. The cut surface is greyish-white.

Histopathology

A monomorphous population of polygonal to round cells with clear cytoplasm characterizes clear cell carcinomas. In some cases, a minority of cells have pale eosinophilic cytoplasm. Nuclei are eccentric and round and frequently contain small nucleoli. PAS staining with and without prior diastase digestion of the tissue demonstrates cytoplasmic glycogen that varies from marked to not evident. The adjective glycogen-rich has been used by some to identify clear cell carcinomas with a prominent glycogen content {1028,2658}. With mucicarmine stain, intracytoplasmic mucins are usually absent. The tumour cells are arranged in sheets, nests, or cords, and ductal structures are absent. Mitotic figures are rare, but some tumours have a moderate degree of nuclear pleomorphism. In the hyalinizing type, the stroma is composed of thick bands of hyalinized collagen {727,1728}, but in other tumours it consists of interconnecting, thin fibrous septa that may be cellular or loosely collagenous. Clear cell carcinomas are unencapsulated and infiltrative. Immunoprofile

 While tumours are immunoreactive for cytokeratin, at least focally, immunohistochemical studies have given variable results for S100 protein, glial fibrillary acidic protein, actin, and vimentin {1028, 1728,1931,2348,2369,2658,2716}. Tumours that demonstrate histologic and immunohistochemical features of myoepithelial differentiation are best classified as clear cell variants of myoepithelioma or myoepithelial carcinoma {1719}.

Electron microscopy

Tight junctions, desmosomal attachments, tonofilaments, microvilli, and basal lamina are features of duct cell differentiation {399,1028,1728,1758,1931, 2369,2716}.

Histogenesis

 Ultrastructural investigations have found features of ductal but not myoepithelial differentiation .

Prognosis and predictive factors

Prognosis is excellent. A few tumours have metastasized to cervical lymph nodes and, rarely, the lung, but no patients have succumbed to this neoplasm {155,948,1728,2716}.