Papillary cystadenoma of a minor salivary gland: report of acase involving cytological analysis and review of theliteratureCathy S. Lim, BSc (Med), MBBS, MPH (Hons),a Irene Ngu, FRACP,b

Ann P. Collins, BDS (Lond), LDSRCS (Eng), MDS (Syd), FRACDS FRACDS (OMS),c

Geoff M.W. McKellar, BDS (Qld), MDSc (Melb), FRACDS FRACDS (OMS),d New SouthWales, AustraliaDAVIES CAMPBELL DE LAMBERT PATHOLOGY, SYMBION LAVERTY PATHOLOGY, ANDWESTMEAD HOSPITAL

A 91-year-old man presented with an asymptomatic swelling in the roof of his mouth. Clinically the lesionwas nontender and appeared cystic. A CT scan showed a soft tissue swelling of his palate with no bony involvement.An orthopantogram and blood tests were noncontributory. A fine-needle aspiration biopsy was suggestive of a minorsalivary gland neoplasm. An excision biopsy showed papillary cystadenoma of the minor salivary gland, with numbersof psammoma bodies.

A stepwise approach is demonstrated in the diagnosis of this rare minor salivary gland neoplasm. To theauthors’ best knowledge, this is the 12th case of this tumor seen in the palate. Furthermore, no previous case hasincluded a fine-needle aspiration biopsy in the work-up, the cytological features of which will be described. (Oral

Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:e28-e33)

Cystadenomas of salivary gland are rare benign epithe-lial tumors characterized by unicystic or more com-monly multicystic growth, intraluminal papillary pro-liferations, and ductlike structures. Previously a poorlydefined entity, it has been suggested to represent War-thin tumor without the lymphoid stroma1; however, thedistinct histological features suggest otherwise. Its trueoccurrence in the minor salivary gland has occurredmore commonly in the lip, and only rarely in thepalate.2-5 Cystadenomas represent between 2.0% and4.7% of all minor salivary gland neoplasms.6,7

The cytological and histological features of a case ofpapillary cystadenoma of the soft palate in a 91-year-old gentleman are described. This case represents theoldest patient in the literature thus far. In addition, noother case report has yet described the cytological fea-tures of this entity. A literature review of other palatalpapillary cystadenomas is presented.

aPathology Registrar, Davies Campbell de Lambert Pathology.bAnatomical Pathologist, Symbion Laverty Pathology, North Ryde.cOral and Maxillofacial Surgeon, Westmead Hospital, Westmead.dAssociate Professor, Head of Department, and Oral and Maxillo-facial Surgeon, Westmead Hospital, Westmead.Received for publication Feb 7, 2007; returned for revision Jul 2,2007; accepted for publication Jul 16, 2007.1079-2104/$ - see front matter© 2008 Mosby, Inc. All rights reserved.

doi:10.1016/j.tripleo.2007.07.019

e28

CLINICAL PRESENTATIONA 91-year-old man presented in December 2003 with

a 6-week history of swelling in the roof of his mouth.The lesion was asymptomatic and had not significantlyincreased in size. Eating was not associated with anypain.

His past medical history included intermittent atrialfibrillation, transient ischemic attacks, a previous gas-tric ulcer, and carcinoma of the prostate, which wasmanaged with medications. He had no allergies andwas currently on pantoprazole, goserelin, and multivi-tamins.

Clinical examination revealed a 3-cm-diameter cys-tic-type swelling at the junction of the right hard andsoft palate. The lesion was nontender and the overlyingmucosa appeared normal. No cervical lymphadenopa-thy was found.

A computed tomography (CT) scan was undertakenof the maxilla, which demonstrated a smooth, well-defined thickening of the right side of the soft palate.The lesion extended to the midline with no erosion ofthe posterior aspect of the hard palate. The lesion waswell demonstrated on axial, coronal, and sagittal imag-ing (Fig. 1). The density was similar to the remainder ofthe soft palate and was thought to represent a form ofretention cyst or tumor. The orthopantogram (OPG)showed no abnormality of the teeth and his chest ra-diograph was within normal limits. Blood tests includ-

ing a full blood examination, erythrocyte sedimentation

OOOOEVolume 105, Number 1 Lim et al. e29

rate and serum biochemistry were also within normallimits. Prior to definitive management, a fine-needleaspiration biopsy (FNAB) was taken, and dental im-pressions were made for the construction of a maxillarysplint that could be used at the time of surgery toprovide hemorrhage control, pain control, and second-ary intention healing.

DIFFERENTIAL DIAGNOSISClinically, the differential diagnoses included other

cystic salivary gland tumors such as pleomorphic ade-noma, cystic mucoepidermoid carcinoma, and the pap-illary cystic subtype of acinic cell carcinoma. In addi-tion, as pleomorphic adenoma is the most commontumor in both the major and minor salivary glands, thiswas also considered in the differential diagnosis. As thepalate is the most common site for malignant intraoraltumors of minor salivary gland origin,8 cystic muco-epidermoid carcinoma must also be entertained. Benignlesions such as mucous retention cyst, odontogeniccysts, lipoma, and palatal abscess of odontogenic originmay also be clinically indistinguishable.

The palate is also the most common site for extran-odal lymphomas, and this represents another clinicaldifferential diagnosis.9 Schwannomas and neurofibro-mas can arise from the palatine nerves in this area, andmight be considered. Adenomatoid hyperplasia of mi-nor salivary gland can clinically mimic salivary glandtumors, although histologically they appear similar tonormal-appearing salivary glands.10 Although intraoralsquamous cell carcinoma occurs most commonly in thetongue followed by the floor of the mouth,11 it remainsan important differential diagnosis.

Histologically, the differential diagnoses are broad,

Fig. 1. Sagittal view showing a soft tissue mass on theposterior aspect of the hard palate.

and include numerous other benign and malignant mi-

nor salivary gland tumors. These include pleomorphicadenoma, trabecular basal cell adenoma, reticular vari-ant of myoepithelioma, low-grade mucoepidermoidcarcinoma, and papillary cystic acinic cell carcinoma.

Oncocytic variants of papillary cystadenoma exist,and aspirations of these can be confused with Warthintumor or oncocytoma. In addition, other salivary glandtumors featuring prominent cytoplasm as seen insmears would need to be considered.

MANAGEMENTIn March 2004, the tumor was excised with an unevent-

ful postoperative recovery. The patient is currently welland has had no recurrence at 2-year follow-up.

DIAGNOSISAn FNAB of the fluctuant swelling was undertaken

using a 25-gauge needle. Serous blood-stained fluid(1.5 mL) was aspirated and a residual nodule waspalpable from which 2 further passes were made. Diff-Quik–stained smears and alcohol-fixed papanicolaou-stained smears were prepared.

The smears were paucicellular with scant cohesivegroups of epithelial cells showing a complex foldedappearance in a cystic proteinaceous background. Thenuclei were bland looking with mild variation in size(Figs. 2 and 3). In view of these findings, the possibilityof a minor salivary gland neoplasm was raised.

Histology from the excision biopsy showed a papil-lary cystadenoma. The lesion was composed of 1 largecyst lined by uniform cuboidal to low columnar epithe-lium showing numbers of small papillary ingrowths,some of which were cystic and multiloculated (Figs. 4and 5). Several cysts were filled with proteinaceous

Fig. 2. Cohesive groups of bland epithelial cells (Diff Quikstain; magnification � 600).

fluid (Fig. 6). There were focal areas of mucus produc-

OOOOEe30 Lim et al. January 2008

tion with islands of mucus-secreting accessory salivarytissue present in the thin fibrous capsule of the cyst.Numbers of psammoma bodies were present (Fig. 7).Scattered areas of hemorrhage but no necrosis wasseen. There were no malignant features.

DISCUSSIONThe classification of papillary cystadenomas has pre-

viously been clouded. The resemblance to Warthintumor, intraduct papilloma, and low-grade mucoepider-moid tumor has been previously suggested.1,12 The trueincidence is difficult to estimate as it may have previ-ously been misdiagnosed as intraductal hyperplasia.12

Originally it was placed in the category of monomor-phic adenoma by Kerpel et al.12 The term “salivary duct

Fig. 3. Scattered cells in a proteinaceous background (DiffQuik stain; magnification � 20).

Fig. 4. A unilocular cyst with papillary ingrowths. There areadjacent juxtaposed minor salivary glands (top left) (hema-toxylin and eosin [H&E], �20).

adenoma” was later proposed for monomorphic adenomas

characterized by ductlike structures, which included pap-illary cystadenoma, sialadenoma papilliferum, and intra-ductal papilloma.13 The second edition of the WorldHealth Organization’s classification of salivary glandtumors defines cystadenoma as a distinct entity that isdivided into papillary and mucinous types.14

The papillary cystadenoma is predominantly a tumorof minor salivary glands, where it appears most com-monly in the lip.14 Several cases have occurred in thepalate.2-5 In the major salivary gland, it can occur in theparotid and submandibular glands. Case reports of pap-illary cystadenomas of salivary gland origin have alsobeen described in the larynx, lacrimal glands, body ofthe mandible, and nasopharyx.14,15 Similar lesions havealso been described in other anatomic sites such as the

Fig. 5. Close up of papillary projections that show focalproliferation resulting in a complex folded architecture (H&E,�400).

Fig. 6. Cystic spaces filled with proteinaceous fluid and linedby bland cuboidal epithelium (H&E, �40).

epididymis,16 ovary,17 and kidney.18

OOOOEVolume 105, Number 1 Lim et al. e31

Previous reports have shown an age range from 12 to89 years, and an average age at diagnosis of 57 years.This case appears to be in the oldest patient in theliterature. Previous series have shown a female pre-dominance.15,19

In addition, the cases in the literature have not hadprior FNABs. Based on the FNAB findings of cohesivebland epithelial cells in a proteinaceous background, adefinitive diagnosis could not be made, although thefindings were suggestive of a minor salivary glandneoplasm. Although not seen, a feature that may havebeen more suggestive of a definitive diagnosis of cys-tadenoma would be an arrangement of cells in a pap-illary configuration. Squamous metaplastic elementscan also be seen.20 In a recent analysis of 21 cysticsalivary gland lesions by FNAB, the authors suggestedthat FNAB could lead to a correct diagnosis in morethan 70% of cases, which corresponded to their accu-racy rate.20 In these cases, there was histological fol-low-up that was carried out at the same institution. Weagree with the authors that there is a need for a stepwiseapproach and recognition of the difficulties in interpre-tation of cystic salivary gland lesions.

The histological features of this case were character-istic of the lesion. Cystadenomas are usually well cir-cumscribed and are described as having cystic spaceswith intracystic papillary projections. Glandular ele-ments exist between the cystic spaces and consist ofsmall cuboidal cells arranged around a central lumen.The lumen may contain eosinophilic fluid, scatteredinflammatory cells, and rarely calcifications. The cellslining the cystic spaces are flattened or cuboidal andvary from one to several layers thick. Variations in this

Fig. 7. Cystic spaces with papillary projections lined byuniform cuboidal epithelium with focal, scattered psammo-matous calcification (H&E, �400).

lining include focal areas of mucous or oncocytic cells,

some of which may predominate. This case alsoshowed numbers of psammoma bodies.

Eleven previous cases have described papillary cysta-denoma occurring in the palate (Table I). Although Wal-dron et al.7 described 4 cases in the palate, no histologicalphotomicrographs were presented, and the pathologicaldescription was more suggestive of Warthin’s tumor. Forthis reason, we have not included those cases in thisliterature review. From analysis of the cases in the litera-ture including the present case, the majority of palatalcases of papillary cystadenoma were male (58%), andoccurred more commonly in the soft palate (33%), al-though in 5 cases, the part of palate was not specified. Therecurrence rate was difficult to estimate, as 4 previouscases did not specify follow-up; however, out of theremaining 8 cases, only 2 cases experienced recurrences.

In 1941, Škorpil21 reported the first 2 documentedcases of papillary cystadenoma in the palate. Both ofthese cases occurred in the soft palate, 1 of whichexperienced 2 recurrences. In a series of 33 cases ofintraoral mucous and salivary gland tumors, Hobock22

described one case called “papillary cystic adenoma,”in the palate treated by radiotherapy. This case wasclassified as semi-malignant. Castigliano and Gold23

reported a case in the hard palate that was highlysuggestive of papillary cystadenoma. This was called“intraductal papilloma.” From their analysis of 129 sal-ivary gland tumors, Velios and Davidson24 described acase they called “intraductal papillary adenoma,” whichhistologically resembled papillary cystadenoma. Thepapillary projections were compared to the intraduc-tal papilloma of the breast. Brooks et al.3 described 2cases that were excised, 1 of which experienced arecurrence. Both cases were characterized by cysticspaces with papillary projections, lined by sheets andcords of ovoid cells. In 1967, Goldman5 described aninteresting variant that displayed melanin, hencetheir designation, “melanogenic papillary cystade-noma.” This was attributed to the fact that melano-blasts can be found in minor salivary tissue.5 In areport of 38 cases, Crocker et al.,8 described a totalof 3 papillary cystadenomas. One of these occurredin the palate, while the other 2 cases occurred in theupper lip and buccal mucosa. No clinical data weregiven. Guccion et al.4 described a single case withcomprehensive histological photomicrographs, andan ultrastructural study. Ultrastructurally, their caseshowed that the lining cells were densely ciliated, aphenomenon rarely described in salivary gland neo-plasms. In addition, the bilayered oncocytic epithe-lium was tightly packed with mitochondria. The mostrecently reported case, except for the present case,was one described in 2003 by Tsurumi et al.2 Al-

though designated as “papillary oncocytic cystade-

ry cyst

OOOOEe32 Lim et al. January 2008

noma,” they discussed how the most recent WorldHealth Organization’s classification subdivided sali-vary gland cystadenoma into papillary and mucinoustypes.

This is the 12th reported papillary cystadenoma oc-curring in the palate. The cytological and histologicalfeatures are highlighted. This patient appears to be theoldest in the literature to date. In addition, to the au-thors’ best knowledge, no previous case report hasdocumented the cytological features. This case shows asystematic approach in the diagnosis of an unusualminor salivary gland tumor. The use of FNAB beforebiopsy aided the clinician in tailoring a suitable treat-ment plan. We recommend prior FNAB for futurediagnosis of salivary gland lesions. This can precludeunnecessary surgery in inappropriate surgical candi-dates.

REFERENCES1. Anderson WAD, Kissane JM, editors. Pathology. 7th ed. St

Louis: The CV Mosby Company; 1977. p. 1269.2. Tsurumi K, Kamiya H, Yokoi M, Kameyama Y. Papillary on-

cocytic cystadenoma of palatal minor salivary gland: a casereport. J Oral Maxillofac Surg 2003;61:631-3.

3. Brooks HW, Hiebert AE, Pullman NK, Stofer BE, Kan W.Papillary cystadenoma of the palate: a review of the literatureand report of two new cases. Oral Surg Oral Med Oral Pathol1956;9:1047-50.

4. Guccion JG, Redman RS, Calhoun NR, Saini N. Papillary cys-tadenoma of the palate: a case report and ultrastructural study.J Oral Maxillofac Surg 1997;55:759-64.

5. Goldman RL. Melanogenic papillary cystadenoma of the softpalate. Am J Clin Pathol 1967;48:49-52.

6. Auclair PL, Ellis GL, Gnepp DR. Other benign epithelial neo-plasms. In: Ellis GL, Auclair PL, Gnepp DR editors. Surgicalpathology of the salivary glands. Philadelphia: Saunders; 1991.p. 252-68.

Table I. Reported cases of papillary cystadenoma of t

Case Age, y SexPart ofpalate

Škorpil (1941)21 78 M Soft Papilla28 M Soft Papilla

Hobock (1949)22 45 F Palate PapillaCastigliano & Gold (1954)23 58 M Hard IntraduVellios & Davidson (1955)24 – – Palate Intradu

adenBrooks et al.3 (1956) 31 M Hard Papilla

63 M Soft PapillaGoldman5 (1967) 58 F Soft Mellan

cystCrocker et al.8 (1970) – – Palate PapillaGuccion et al.4 (1997) 62 M Palate PapillaTsurumi et al.2 (2003) 80 F Hard Papilla

cystPresent case 91 M Palate Papilla

7. Waldron CA, el-Mofty SK, Gnepp DR. Tumors of the intraoral

minor salivary glands: a demographic and histologic study of 426cases. Oral Surg Oral Med Oral Pathol 1988;66:323-33.

8. Crocker DJ, Cavalaris CJ, Finch R. Intraoral minor salivarygland tumors: report of thirty-eight cases. Am Acad Oral Pathol1970;29:60-8.

9. Marx RE, Stern D, editors. Oral and maxillofacial pathology: arationale for diagnosis and treatment. Chicago, IL: QuintessencePublishing Co.; 2003. p. 833.

10. Buchner A, Merrell PW, Carpenter WM, Leider AS. Adenoma-toid hyperplasia of minor salivary glands. Oral Surg Oral MedOral Pathol 1991;71:583-7.

11. Chen JK, Katz RV, Krutchkoff DJ. Intraoral squamous cellcarcinoma. Epidemiologic patterns in Connecticut from 1935 to1985. Cancer 1990;66:1288-96.

12. Kerpel SM, Fredman PD, Lumerman H. The papillary cystade-noma of minor salivary gland origin. Oral Surg Oral Med OralPathol 1978;46:820-6.

13. Seifert G, editor. World Health Organization. Histological typing ofsalivary gland tumours. 2nd ed. Berlin: Springer-Verlag; 1991 p. 16-7.

14. Cohen MA, Batsakis JG. Oncocytic tumors (oncocytomas) ofminor salivary glands. Arch Otolaryngol 1968;88:71-3.

15. Chaudhry AP, Vickers RA, Gorlin RJ. Intraoral minor salivarygland tumors: an analysis of 1414 cases. Oral Surg Oral MedOral Pathol 1961;14:1194-1226.

16. Zhou WQ, Gao JP, Wu B, Zhou SS. Papillary cystadenoma ofthe epididymis accompanied by testicular atrophy: a case report.Zhonghua Nan Ke Xue 2003;9:389-90.

17. Fatum M, Rojansky N, Shushan A. Papillary serous cystadeno-fibroma of the ovary—is it really so rare? Int J Gynaecol Obstet2001;75:85-6.

18. Davidov MI, Ponomareva TB, Liadov AA. Multiple bilateralpapillary cystadenoma of the kidney. Urologiia 2003;3:60-1.

19. Ellis GL, Auclair PL. Atlas of tumor pathology: tumors of thesalivary glands. Washington, DC: Armed Forces Institute ofPathology; 1995. p. 115-20.

20. Edwards PC, Wasserman P. Evaluation of cystic salivary glandlesions by fine needle aspiration: an analysis of 21 cases. ActaCytol 2005;49:489-94.

21. Škorpil FL. Uber das cystadenoma papillare der grossen undkleinen speicheldrüsen, Frankfurt. Ztschr Path 1941;55:39-50.

ate

ed asPreviouscytology Treatment

Recurrence (follow-up, y)

adenoma No Excision Yes � 2 (16 & 18)adenoma No Excision –ic adenoma No Radiation No (2)pilloma No Excision –pillary No – –

adenoma No Excision Yes (1.2)adenoma No Excision No (2)papillarya

No Excision No (?)

adenoma No Excision –adenoma No Excision No (3)cytica

No Incision biopsy,then excision

No (2.5)

adenoma Yes Excision No (2)

he pal

Classifi

ry cystry cystry cystctal pactal paomary cystry cystogenicadenomry cystry cystry oncoadenom

[German.]

OOOOEVolume 105, Number 1 Lim et al. e33

22. Hobock A. Intraoral mucous and salivary gland mixed tumours.Acta Radiol 1949;32:229-47.

23. Castigliano SG, Gold L. Intraductal papilloma of the hard palate:case report of an undescribed lesion of a minor salivary gland.Oral Surg Oral Med Oral Pathol 1954;7:232-8.

24. Vellios F, Davidson D. The natural history of tumors peculiar to

the salivary glands. Am J Clin Path 1955;25:147-57.

Reprint requests:

Cathy S. Lim, BSc (Med) MBBS, MPH (Hons)Davies Campbell de Lambert2 Leeds StreetRhodes, NSW 2138Australia

shusanlim@gmail.com