Skip to main content
Log in

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

  • Original Articles
  • Published:
Virchows Archiv A Aims and scope Submit manuscript

Summary

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Andres A-C, Schönenberger C-A, Groner B, Hennighausen L, Le-Meur M, Gerlinger P (1987) Ha-ras oncogene expression directed by a milk protein gene promoter: tissue specificity, hormonal regulation, and tumor induction in transgenic mice. Proc Natl Acad Sci USA 84:1299–1303

    Google Scholar 

  • Azuma M, Yoshida H, Kawamata H, Yanagawa T, Furumoto N, Sato M (1988) Cellular proliferation and ras oncogene of p21 21,000 expression in relation to the intracellular cyclic adenosine 3′:5′-monophosphate levels of a human salivary gland adenocarcinoma cell line in culture. Cancer Res 48:2898–2903

    Google Scholar 

  • Celis JE, Celis A (1985) Cell cycle dependent variations in the distribution of the proliferating cell nuclear antigen in cultured cells: subdivision of S phase. Proc Natl Acad Sci USA 82:3262–3266

    Google Scholar 

  • Chapnik JS (1983) The controversy of Warthin's tumor. Laryngoscope 93:695–716

    Google Scholar 

  • Cuthbertson RA, Klintworth GK (1988) Transgenic mice — a gold mine for furthering knowledge in pathobiology. Lab Invest 58:484–502

    Google Scholar 

  • Dardick I (1991) Histogenesis and morphogenesis of salivary gland neoplasms. In: Ellis GL, Auclair PL, Gnepp DR (eds) Surgical pathology of the salivary glands. WB Saunders, Philadelphia, PP 108–128

    Google Scholar 

  • Dardick I, Nostrand AWP van (1987) Morphogenesis of salivary gland tumors: a prerequisite to improving classification. Pathol Annu 22(pt.1):1–53

    Google Scholar 

  • Ellis GL, Auclair PL, Gnepp DR, Goode RK (1991) Other malignant epithelial neoplasms. In: Ellis GL, Auclair PL, Gnepp DR (eds) Surgical pathology of the salivary glands. WB Saunders, Philadelphia, pp 455–488

    Google Scholar 

  • Frith CH, Heath JE (1985) Adenomas, adenocarcinomas, salivary gland, mouse. In: Jones TC, Mohr U, Hunt RD (eds) Monographs on pathology of laboratory animals: digestive system Springer-Verlag, Berlin, pp 190–192

    Google Scholar 

  • Hanahan D (1986) Oncogenesis in transgenic mice. Oncogenes and growth control. In: Kahn P, Graf T (eds) Springer, Berlin Heidelberg New York, pp 349–363

    Google Scholar 

  • Hoffler H (1991) Oncogene and receptor expression. In: Seifert G (ed) Cell receptors. Morphological characterization and pathological aspects. Springer, Berlin Heidelberg New York, pp 435–456

    Google Scholar 

  • Jones JM, Keller SA, Samuelson LC, Osborn L, Rosenberg MP, Meisler MH (1989) A salivary amlyase transgene is efficiently expressed in liver but not in the parotid gland of transgenic mice. Nucleic Acids Res 17:6613–6623

    Google Scholar 

  • Kratochvil FJ (1991) Canalicular adenoma and basal cell adenoma. In: Ellis GL, Auclair PL, Gnepp DR (eds) Surgical pathology of the salivary glands. Saunders, Philadelphia, pp 202–224

    Google Scholar 

  • Leder A, Pattengale PK, Kuo A, Stewart TA, Leder P (1986) Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell 5:485–495

    Google Scholar 

  • Lewis JE, Olsen KD, Weiland LH (1991) Acinic cell carcinoma: clinicopathologic review. Cancer 67:172–179

    Google Scholar 

  • Muller WJ, Sinn E, Pattengale PK, Wallace R, Leder P (1988) Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 54:105–115

    Google Scholar 

  • Neilsen LL, Discafani CM, Gurnani M, Tyler RD (1991) Histopathology of salivary and mammary gland tumors in transgenic mice expressing a human Ha-ras oncogene. Cancer Res 51:3762–3767

    Google Scholar 

  • Pattengale PK, Stewart TA, Leder A, Sinn E, Muller W, Tepler I, Schmidt E, Leder P (1989) Pathology and molecular biology of spontaneous neoplasms occurring in transgenic mice carrying and expressing activated cellular oncogenes. Am J Pathol 135:39–61

    Google Scholar 

  • Seifert G (1991) Histological typing of salivary gland tumours. World Health Organization international histological classification of tumours, 2nd edn Springer, Berlin Heidelberg New York

    Google Scholar 

  • Seifert G, Brocheriou C, Cardesa A, Eveson JW (1990) WHO international histological classification of tumours: tentative histological classification of salivary gland tumours. Pathol Res Pract 186:555–581

    Google Scholar 

  • Semba K, Kamata N, Toyoshima K, Yamamoto T (1985) A v-erbB related oncogene, c-erbB-2 is distinct from c-erbB-1/epidermal growth factor receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc Natl Acad Sci USA 82:6497–6501

    Google Scholar 

  • Sinn E, Muller W, Pattengale P, Tepler I, Wallace R, Leder P (1987) Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell 49:465–475

    Google Scholar 

  • Spandidos DA, Lamothe A, Field JK (1985) Multiple transcriptional activation of cellular oncogenes in human head and neck solid tumors. Anticancer Res 5:221–224

    Google Scholar 

  • Stenman G, Sandros J, Nordkvist A, Mark J, Sahlin P (1991) Expression of the ERBB2 protein in benign and malignant salivary gland tumors. Genes Chrom Cancer 3:128–135

    Google Scholar 

  • Stewart TA, Pattengale PK, Leder P (1984) Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell 38:627–637

    Google Scholar 

  • Tsukamoto AS, Grosschedl R, Guzman RC, Parslow T, Varmus HE (1988) Expression of the int-1 gene in transgenic mice is associated with mammary hyperplasias and adenocarcinomas in male and female mice. Cell 55:619–625

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dardick, I., Burford-Mason, A.P., Garlick, D.S. et al. The pathobiology of salivary gland. Vichows Archiv A Pathol Anat 421, 105–113 (1992). https://doi.org/10.1007/BF01607042

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01607042

Key words

Navigation