Papillary cystadenoma: a rare tumor of the minor salivary glands

ARTICLE

Benign cystadenoma [1] and certain malignant carcinoma (especially the well-differentiated cystic mucoepidermoid carcinoma and the papillary cystic type of acinic cell carcinoma) [1] of the minor salivary glands clinically resemble salivary gland cysts. However, in contrast to the latter, the former, although representing crucial differential diagnoses, are not well recognised in the dermatological literature. Furthermore, a rare secondary occurrence of real salivary gland neoplasms in preexisting salivary gland cysts has been reported [2].

Case report

A 39 year old female presented with an asymptomatic bluish tumor on the buccal mucosa which had grown slowly for one and a half years. A similar appearing lesion at the same location had been excised, 14 years previously. Its histological evaluation had confirmed a mucous retention cyst.

Physical examination revealed a 1.5 x 1 cm elastic, non-adherent multicystic bluish tumor on the buccal mucosa next to the first molar (Fig. 1). Lymphnodes and laboratory findings were unremarkable.

Total excision of the lesion was achieved. Histological examination revealed a multicystic tumor limited by a condensed lamina propria beneath the epithelium of the oral mucosa. The lining epithelium of the cystic lumen consisted in some areas of a bilayered, in others of a multilayered salivary duct epithelium with papillary projections into the cystic spaces, which contained secretory material. Epithelial cells with PAS-positive cytoplasmatic granules reminded us, to an extent, of apocrine secretion. Cellular atypia and mitoses were absent. A papillary cystadenoma was diagnosed. Unfortunately, the histological specimens from the first excision performed elsewhere were no longer available for reevaluation. The patient is being followed closely. No recurrence has occurred, so far.

Discussion

Salivary gland cysts are often observed in the oral cavity. They result from the presence of a circumscribed collection of mucus within the submucosal tissues. In most cases, an epithelium is absent and the mucin is directely enclosed by a wall of compressed and chronically inflamed connective tissue (extravasation type). Some mucous cysts (retention type) are true cysts and show a mucin-filled cavity surrounded by a thin distended layer of epithelium and a connective tissue wall [2, 3]. Less common, real epithelial neoplasms occur in the minor salivary glands [4-9]. The broad variety of benign and malignant tumor entities has been histologically classified by the WHO in 1972 [10] and revised in 1992 [1, 11, 12] (Table I). The clinical differential diagnosis of salivary gland cysts primarily has to take into account benign cystadenomas, the malignant well-differentiated cystic mucoepidermoid carcinoma [2] and the papillary cystic type of acinic cell carcinoma [1]. In our case, the histology was characteristic for a papillary cystadenoma. Histologically, it closely resembles the so-called Warthin tumor with absence of the lymphoid elements. The apical PAS-positive cytoplasmatic granules in our case recalled apocrine metaplasia providing evidence of a biological relationship between minor salivary glands and cutaneous apocrine glands. A phylogenetical context of these tissues has earlier been suggested by the expression of GCDF-15 (gross cystic disease fluid), they have in common [13, 14].

Most cases of papillary cystadenoma have occurred in the larynx. Manifestation in the major and minor salivary glands are rare [1]. The papillary cystadenoma mostly occurs between 6-9th decade without sex predominance [15]. In contrast, the similarly appearing benign mucinous cystadenoma is lined by mucous-producing cells or goblet cells. The differentiation of this tumor from its more common malignant counterpart, however, is difficult and is based on the tumor's circumscription and absence of cellular atypia [1, 2]. The mucoepidermoid carcinoma consists of mucous forming cells, epidermoid cells and sometimes of intermediate cells. In the well-differentiated type, however, there's no nuclear pleomorphism, mitoses are absent or extremely rare [1]. Some forms of acinic cell carcinoma may also present like our case. In general, the acinic cell carcinoma consists of four different cell types: large acinic cells, vacuolated cells, clear cells and non-specific glandular cells [1]. However, in the papillary cystic type of acinic cell carcinoma a configuration with papillae in cystic spaces is present [1] which may resemble papillary cystadenoma. Thus, salivary gland histology is extremely hard to interpret and requires special histological expertise [15].

Sporadic case reports mention the development of salivary gland tumors (e.g. mucoepidermoid carcinoma and basal cell adenoma) in preexisting salivary gland cysts [2]. It remains unclear, if, according to a long-standing hypothesis, our case represents an example of secondary tumor development in preexisting salivary gland cysts. In our case, 14 years prior to the excision of the papillary cystadenoma, at the same location a mucous retention cyst had been excised and histologically confirmed. These two tumors may have occurred independently or instead, the papillary cystadenoma may have developped in residuals of the mucous retention cyst. Recently, a study of 1,661 salivary gland cysts revealed epithelial metaplasia and proliferative activity in 3-10% of mucous retention cysts of the minor salivary glands and salivary duct cysts of the parotid gland [2]. Plump or papillary projections into the cystic spaces was regarded as possible early manifestation of true tumor growth [2]. Our case with manifest papillary cystadenoma and a past medical history of mucous retention cyst at the same location may support this suggestion.

Since fine needle aspiration is not unequivocal in cystic tumors [16, 17] and the prognosis of specific types of salivary gland tumors depends on their malignancy and adequate treatment measures [13, 18, 19], an early excision of all cystic tumors resembling mucous retention cysts is mandatory, since true adenomatous or carcinomatous tumor formation cannot be excluded clinically.

CONCLUSION

Acknowledgement

We thank Professor Gerhard Seifert, Institute of Pathology, University of Hamburg, Germany for histological co-evaluation.

REFERENCES

1. Seifert G, Brocheriou C, Cardesa A, Eveson JW. WHO international histologic classification of tumours. Tentative histological classification of salivary gland tumours. Pathol Res Pract 1990; 186: 555-81.

2. Seifert G. Mucoepidermoid carcinoma in a salivary duct cyst of the parotid gland. Contribution to the development of tumours in salivary gland cysts. Path Res Pract 1996; 192: 1211-7.

3. Spouge JD. Diseases of the salivary glands. In: Oral Pathology. Mosby, Saint Louis, 1973; 431-3.

4. Beckhardt RN, Weber RS, Zane R, Garden AS, Wolf P, Carrillo R, Luna MA. Minor salivary gland tumors of the palate: clinical and pathologic correlates of outcome. Laryngoscope 1995; 105: 1155-60.

5. Chau MN, Radden BG. Intra-oral salivary gland neoplasms: a retrospective study of 98 cases. J Oral Pathol 1986: 339-42.

6. Chou C, Zhu G, Luo M , Xue G. Carcinoma of the minor salivary glands: results of surgery and combined therapy. J Oral Maxillofac Surg 1996; 54: 448-53.

7. Eveson JW, Cawson RA. Tumours of the minor (oropharyngeal) salivary glands: a demogaphic study of 336 cases. J Oral Pathol 1985; 14: 500-9.

8. Isacsson G, Shear M. Intraoral salivary gland tumors: a retrospective study of 201 cases. J Oral Pathol 1983: 12: 57-62.

9. Loyola AM, de Araujo VC, de Sousa SO, de Araujo NS. Minor salivary gland tumours. A retrospective study of 164 cases in Brazilian population. Eur J Cancer B Oral Oncol 1995; 31B: 197-201.

10. Thackray AC, Sobin LH. Histological typing of salivary gland tumours. WHO international classification of tumours. World Health Organization, Genova, 1972.

11. Seifert G, Sobin LH. WHO histological classification of salivary gland tumours. A complementary on the second edition. Cancer 1992; 70: 79-85.

12. Seifert G. Histologic typing of salivary gland tumours. 2nd edn., Springer, 1991.

13. Mazoujian G, Pinkus GS, Davis S, Haagensen DE Jr. Immunohistochemistry of a gross cystic disease fluid protein (GCDFP-15) of the breast. A marker of apocrine epithelium and breast carcinomas with apocrine features. Am J Pathol 1983; 110: 105-112.

14. Swanson PE, Pettinato G, Lillemoe TJ, Wick MR. Gross cystic disease fluid protein-15 in salivary gland tumors. Arch Pathol Lab Med 1991; 115: 158-63.

15. Seifert G. Speicheldrüsentumoren. In: Doerr W, Seifert G, eds. Spezielle pathologische Anatomie. 2nd edn,Vol. 1/I. Berlin, Heidelberg, New York: Springer, 1996; 301-781.

16. Cohen MB, Liung BM, Boles R. Salivary gland tumors.Fine-needle aspiration vs frozen section diagnosis. Arch Otolaryngol Head Neck Surg 1986; 112: 867-9.

17. Orell SR, Nette WJ. Fine needle aspiration of salivary gland tumours. Problems and pitfalls. Pathology 1988: 20: 332-7.

18. Chilla R, Casjens R, Eysholdt U, Droese M. Maligne Speicheldrüsentumoren. Der Einfluþ von Histologie und Lokalisation auf die Prognose. HNO 1983; 31: 286-90.

19. Hickman RE, Cawson RA, Duffy SW. The prognosis of specific types of salivary gland tumors. Cancer 1984; 54: 1620-4.