The pathobiology of salivary gland. II. Morphological evaluation of acinic cell carcinomas in the parotid gland of male transgenic (MMTV/v-Ha-ras) mice as a model for human tumours.

Abstract

In the transgenic TG.SH (mouse mammary tumour virus/v-Ha-ras) mouse, designed to develop mammary tumours, occasional spontaneous salivary gland tumours have been reported, predominantly in males. The incidence and histomorphology of salivary gland tumours in 73 TG.SH mice were surveyed and in total, 21.9% developed both overt and microscopic parotid tumours. The majority developed between 73 and 150 days of age. In 31.5% of the TG.SH mice, occasional unilateral, but more frequently bilateral exophthalmos due to hyperplasia of the intraorbital (Harderian) lacrimal gland was observed. In 70% of these animals, parotid tumours developed later. Since Harderian gland hyperplasia, occurring as early as 5 weeks of age, preceded the development of palpable salivary gland lesions, this stigma is useful for the early selection of animals likely to progress to tumour formation. Before tumour-bearing transgenic mice are considered to be suitable models of human neoplastic disease, morphological characterization is necessary to ensure that the tumours are histologically representative of the human lesions for which they are potential models. In this study, all parotid tumours consisted of acinar-like glandular structures with central lumina discernible by electron microscopy. Ultrastructurally, secretory granules evident in the apical cytoplasm of the tumour cells resembled the zymogen granules of the normal parotid acinar cell, and some cells had a prominent complement of rough endoplasmic reticulum. These features, along with focal amylase expression detected immunohistochemically in some parotid tumours, identified these neoplasms as acinic cell carcinomas that mimic the human salivary gland acinic cell carcinoma faithfully.