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Papillary cystadenoma of a minor salivary gland: report of a case involving cytological analysis and review of the literature

Cathy 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 South Wales, Australia
DAVIES CAMPBELL DE LAMBERT PATHOLOGY, SYMBION LAVERTY PATHOLOGY, AND WESTMEAD HOSPITAL

A 91-year-old man presented with an asymptomatic swelling in the roof of his mouth. Clinically the lesion was 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 ne-needle aspiration biopsy was suggestive of a minor salivary gland neoplasm. An excision biopsy showed papillary cystadenoma of the minor salivary gland, with numbers of psammoma bodies. A stepwise approach is demonstrated in the diagnosis of this rare minor salivary gland neoplasm. To the authors best knowledge, this is the 12th case of this tumor seen in the palate. Furthermore, no previous case has included a ne-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 epithelial tumors characterized by unicystic or more commonly multicystic growth, intraluminal papillary proliferations, and ductlike structures. Previously a poorly dened entity, it has been suggested to represent Warthin tumor without the lymphoid stroma1; however, the distinct histological features suggest otherwise. Its true occurrence in the minor salivary gland has occurred more commonly in the lip, and only rarely in the palate.2-5 Cystadenomas represent between 2.0% and 4.7% of all minor salivary gland neoplasms.6,7 The cytological and histological features of a case of papillary cystadenoma of the soft palate in a 91-yearold gentleman are described. This case represents the oldest patient in the literature thus far. In addition, no other case report has yet described the cytological features of this entity. A literature review of other palatal papillary cystadenomas is presented.

Pathology Registrar, Davies Campbell de Lambert Pathology. Anatomical Pathologist, Symbion Laverty Pathology, North Ryde. c Oral and Maxillofacial Surgeon, Westmead Hospital, Westmead. d Associate Professor, Head of Department, and Oral and Maxillofacial 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
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CLINICAL PRESENTATION A 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 signicantly increased in size. Eating was not associated with any pain. His past medical history included intermittent atrial brillation, transient ischemic attacks, a previous gastric ulcer, and carcinoma of the prostate, which was managed with medications. He had no allergies and was currently on pantoprazole, goserelin, and multivitamins. Clinical examination revealed a 3-cm-diameter cystic-type swelling at the junction of the right hard and soft palate. The lesion was nontender and the overlying mucosa appeared normal. No cervical lymphadenopathy was found. A computed tomography (CT) scan was undertaken of the maxilla, which demonstrated a smooth, welldened thickening of the right side of the soft palate. The lesion extended to the midline with no erosion of the posterior aspect of the hard palate. The lesion was well demonstrated on axial, coronal, and sagittal imaging (Fig. 1). The density was similar to the remainder of the soft palate and was thought to represent a form of retention cyst or tumor. The orthopantogram (OPG) showed no abnormality of the teeth and his chest radiograph was within normal limits. Blood tests including a full blood examination, erythrocyte sedimentation

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

Fig. 2. Cohesive groups of bland epithelial cells (Diff Quik stain; magnication 600).

rate and serum biochemistry were also within normal limits. Prior to denitive management, a ne-needle aspiration biopsy (FNAB) was taken, and dental impressions were made for the construction of a maxillary splint that could be used at the time of surgery to provide hemorrhage control, pain control, and secondary intention healing. DIFFERENTIAL DIAGNOSIS Clinically, the differential diagnoses included other cystic salivary gland tumors such as pleomorphic adenoma, cystic mucoepidermoid carcinoma, and the papillary cystic subtype of acinic cell carcinoma. In addition, as pleomorphic adenoma is the most common tumor in both the major and minor salivary glands, this was also considered in the differential diagnosis. As the palate is the most common site for malignant intraoral tumors of minor salivary gland origin,8 cystic mucoepidermoid carcinoma must also be entertained. Benign lesions such as mucous retention cyst, odontogenic cysts, lipoma, and palatal abscess of odontogenic origin may also be clinically indistinguishable. The palate is also the most common site for extranodal lymphomas, and this represents another clinical differential diagnosis.9 Schwannomas and neurobromas can arise from the palatine nerves in this area, and might be considered. Adenomatoid hyperplasia of minor salivary gland can clinically mimic salivary gland tumors, although histologically they appear similar to normal-appearing salivary glands.10 Although intraoral squamous cell carcinoma occurs most commonly in the tongue followed by the oor of the mouth,11 it remains an important differential diagnosis. Histologically, the differential diagnoses are broad, and include numerous other benign and malignant mi-

nor salivary gland tumors. These include pleomorphic adenoma, trabecular basal cell adenoma, reticular variant of myoepithelioma, low-grade mucoepidermoid carcinoma, and papillary cystic acinic cell carcinoma. Oncocytic variants of papillary cystadenoma exist, and aspirations of these can be confused with Warthin tumor or oncocytoma. In addition, other salivary gland tumors featuring prominent cytoplasm as seen in smears would need to be considered. MANAGEMENT In March 2004, the tumor was excised with an uneventful postoperative recovery. The patient is currently well and has had no recurrence at 2-year follow-up. DIAGNOSIS An FNAB of the uctuant swelling was undertaken using a 25-gauge needle. Serous blood-stained uid (1.5 mL) was aspirated and a residual nodule was palpable from which 2 further passes were made. DiffQuikstained smears and alcohol-xed papanicolaoustained smears were prepared. The smears were paucicellular with scant cohesive groups of epithelial cells showing a complex folded appearance in a cystic proteinaceous background. The nuclei were bland looking with mild variation in size (Figs. 2 and 3). In view of these ndings, the possibility of a minor salivary gland neoplasm was raised. Histology from the excision biopsy showed a papillary cystadenoma. The lesion was composed of 1 large cyst lined by uniform cuboidal to low columnar epithelium showing numbers of small papillary ingrowths, some of which were cystic and multiloculated (Figs. 4 and 5). Several cysts were lled with proteinaceous uid (Fig. 6). There were focal areas of mucus produc-

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Fig. 3. Scattered cells in a proteinaceous background (Diff Quik stain; magnication 20).

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

Fig. 4. A unilocular cyst with papillary ingrowths. There are adjacent juxtaposed minor salivary glands (top left) (hematoxylin and eosin [H&E], 20).

Fig. 6. Cystic spaces lled with proteinaceous uid and lined by bland cuboidal epithelium (H&E, 40).

tion with islands of mucus-secreting accessory salivary tissue present in the thin brous capsule of the cyst. Numbers of psammoma bodies were present (Fig. 7). Scattered areas of hemorrhage but no necrosis was seen. There were no malignant features. DISCUSSION The classication of papillary cystadenomas has previously been clouded. The resemblance to Warthin tumor, intraduct papilloma, and low-grade mucoepidermoid tumor has been previously suggested.1,12 The true incidence is difcult to estimate as it may have previously been misdiagnosed as intraductal hyperplasia.12 Originally it was placed in the category of monomorphic adenoma by Kerpel et al.12 The term salivary duct adenoma was later proposed for monomorphic adenomas

characterized by ductlike structures, which included papillary cystadenoma, sialadenoma papilliferum, and intraductal papilloma.13 The second edition of the World Health Organizations classication of salivary gland tumors denes cystadenoma as a distinct entity that is divided into papillary and mucinous types.14 The papillary cystadenoma is predominantly a tumor of minor salivary glands, where it appears most commonly in the lip.14 Several cases have occurred in the palate.2-5 In the major salivary gland, it can occur in the parotid and submandibular glands. Case reports of papillary cystadenomas of salivary gland origin have also been described in the larynx, lacrimal glands, body of the mandible, and nasopharyx.14,15 Similar lesions have also been described in other anatomic sites such as the epididymis,16 ovary,17 and kidney.18

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Fig. 7. Cystic spaces with papillary projections lined by uniform cuboidal epithelium with focal, scattered psammomatous calcication (H&E, 400).

Previous reports have shown an age range from 12 to 89 years, and an average age at diagnosis of 57 years. This case appears to be in the oldest patient in the literature. Previous series have shown a female predominance.15,19 In addition, the cases in the literature have not had prior FNABs. Based on the FNAB ndings of cohesive bland epithelial cells in a proteinaceous background, a denitive diagnosis could not be made, although the ndings were suggestive of a minor salivary gland neoplasm. Although not seen, a feature that may have been more suggestive of a denitive diagnosis of cystadenoma would be an arrangement of cells in a papillary conguration. Squamous metaplastic elements can also be seen.20 In a recent analysis of 21 cystic salivary gland lesions by FNAB, the authors suggested that FNAB could lead to a correct diagnosis in more than 70% of cases, which corresponded to their accuracy rate.20 In these cases, there was histological follow-up that was carried out at the same institution. We agree with the authors that there is a need for a stepwise approach and recognition of the difculties in interpretation of cystic salivary gland lesions. The histological features of this case were characteristic of the lesion. Cystadenomas are usually well circumscribed and are described as having cystic spaces with intracystic papillary projections. Glandular elements exist between the cystic spaces and consist of small cuboidal cells arranged around a central lumen. The lumen may contain eosinophilic uid, scattered inammatory cells, and rarely calcications. The cells lining the cystic spaces are attened or cuboidal and vary from one to several layers thick. Variations in this lining include focal areas of mucous or oncocytic cells,

some of which may predominate. This case also showed numbers of psammoma bodies. Eleven previous cases have described papillary cystadenoma occurring in the palate (Table I). Although Waldron et al.7 described 4 cases in the palate, no histological photomicrographs were presented, and the pathological description was more suggestive of Warthins tumor. For this reason, we have not included those cases in this literature review. From analysis of the cases in the literature including the present case, the majority of palatal cases of papillary cystadenoma were male (58%), and occurred more commonly in the soft palate (33%), although in 5 cases, the part of palate was not specied. The recurrence rate was difcult to estimate, as 4 previous cases did not specify follow-up; however, out of the remaining 8 cases, only 2 cases experienced recurrences. In 1941, korpil21 reported the rst 2 documented cases of papillary cystadenoma in the palate. Both of these cases occurred in the soft palate, 1 of which experienced 2 recurrences. In a series of 33 cases of intraoral mucous and salivary gland tumors, Hobock22 described one case called papillary cystic adenoma, in the palate treated by radiotherapy. This case was classied as semi-malignant. Castigliano and Gold23 reported a case in the hard palate that was highly suggestive of papillary cystadenoma. This was called intraductal papilloma. From their analysis of 129 salivary gland tumors, Velios and Davidson24 described a case they called intraductal papillary adenoma, which histologically resembled papillary cystadenoma. The papillary projections were compared to the intraductal papilloma of the breast. Brooks et al.3 described 2 cases that were excised, 1 of which experienced a recurrence. Both cases were characterized by cystic spaces with papillary projections, lined by sheets and cords of ovoid cells. In 1967, Goldman5 described an interesting variant that displayed melanin, hence their designation, melanogenic papillary cystadenoma. This was attributed to the fact that melanoblasts can be found in minor salivary tissue.5 In a report of 38 cases, Crocker et al.,8 described a total of 3 papillary cystadenomas. One of these occurred in the palate, while the other 2 cases occurred in the upper lip and buccal mucosa. No clinical data were given. Guccion et al.4 described a single case with comprehensive histological photomicrographs, and an ultrastructural study. Ultrastructurally, their case showed that the lining cells were densely ciliated, a phenomenon rarely described in salivary gland neoplasms. In addition, the bilayered oncocytic epithelium was tightly packed with mitochondria. The most recently reported case, except for the present case, was one described in 2003 by Tsurumi et al.2 Although designated as papillary oncocytic cystade-

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Table I. Reported cases of papillary cystadenoma of the palate


Case korpil (1941)21 Hobock (1949)22 Castigliano & Gold (1954)23 Vellios & Davidson (1955)24 Brooks et al.3 (1956) Goldman5 (1967) Crocker et al.8 (1970) Guccion et al.4 (1997) Tsurumi et al.2 (2003) Present case Age, y 78 28 45 58 31 63 58 62 80 91 Sex M M F M M M F M F M Part of palate Soft Soft Palate Hard Palate Hard Soft Soft Palate Palate Hard Palate Classied as Papillary cystadenoma Papillary cystadenoma Papillary cystic adenoma Intraductal papilloma Intraductal papillary adenoma Papillary cystadenoma Papillary cystadenoma Mellanogenic papillary cystadenoma Papillary cystadenoma Papillary cystadenoma Papillary oncocytic cystadenoma Papillary cystadenoma Previous cytology No No No No No No No No No No No Yes Treatment Excision Excision Radiation Excision Excision Excision Excision Excision Excision Incision biopsy, then excision Excision Recurrence (followup, y) Yes 2 (16 & 18) No (2) Yes (1.2) No (2) No (?) No (3) No (2.5) No (2)

noma, they discussed how the most recent World Health Organizations classication subdivided salivary gland cystadenoma into papillary and mucinous types. This is the 12th reported papillary cystadenoma occurring in the palate. The cytological and histological features are highlighted. This patient appears to be the oldest in the literature to date. In addition, to the authors best knowledge, no previous case report has documented the cytological features. This case shows a systematic approach in the diagnosis of an unusual minor salivary gland tumor. The use of FNAB before biopsy aided the clinician in tailoring a suitable treatment plan. We recommend prior FNAB for future diagnosis of salivary gland lesions. This can preclude unnecessary surgery in inappropriate surgical candidates.
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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 Lambert 2 Leeds Street Rhodes, NSW 2138 Australia shusanlim@gmail.com

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