|Year : 2005 | Volume
| Issue : 4 | Page : 153-8
|Papillary cystadenoma lymphomatosum : Case report and review of literature
Karthikeya Patil, VG Mahima, Shalini Kalia
Department of Oral Medicine and Radiology, J.S.S. Dental College and Hospital, Mysore-570015, Karnataka, India
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| Abstract|| |
Papillary Cystadenoma Lymphomatosum or Warthin's tumour is a unique neoplasm arising almost exclusively in the parotid salivary gland and is composed of oncocytic epithelium with a prominent lymphoid infiltrate. The tumor is usually asymptomatic and may be associated with varying degrees of pain not necessarily an indication of malignant transformation in the tumour. The tumour is managed easily by surgical excision. This article presents a typical case arising in the right parotid gland of a 73-year-old male with review of literature of this rare tumour.
Keywords: Papillary Cystadenoma Lymphomatosumr, parotid gland neoplasms, tobacco, oncocytes
|How to cite this article:|
Patil K, Mahima V G, Kalia S. Papillary cystadenoma lymphomatosum : Case report and review of literature. Indian J Dent Res 2005;16:153
|How to cite this URL:|
Patil K, Mahima V G, Kalia S. Papillary cystadenoma lymphomatosum : Case report and review of literature. Indian J Dent Res [serial online] 2005 [cited 2022 Jan 19];16:153. Available from: https://www.ijdr.in/text.asp?2005/16/4/153/29904
| Introduction|| |
Papillary Cystadenoma Lymphomatosum or Warthin's tumor is a wellrecognized monomorphic adenoma constituting a minority of salivary gland tumours.  The tumour was first described by Aldred Scott Warthin, a professor of pathology, University of Michigan, Ann Arbor, MI, USAin 1939 .
The turner arouses interest owing to its dual structure of lymphoid tissue and epithelium . In spite of extensive work done, the tumor continues to provoke speculation regarding its histogenesis ,.
The tumour is relatively rare, involves the parotid gland of an elderly male patient in the fifth to seventh decade of life ,,,,. It is usually asymptomatic or presents as slowly growing, most often at the angle of the mandible . Warthin's tumour can hence, be identified as benign tumour by clinical inspection or palpation . We report a unilateral case involving the right parotid gland in an elderly male patient.
| Case report|| |
A 73-year-old male patient reported to the Department of Oral Medicine and Radiology, JSS Dental College and Hospital, Mysore with a complaint of swelling below the right ear since 7 years. It was insidious in onset and gradually increasing in size to the one at the time of presentation over the past seven years. The swelling was associated with mild, aching, intennittent pain localized to the area Pain was not associated with meal times and did not restrict neck movements. Patient denied any other swellings on his body. Further, no change in the texture or skin over the swelling was reported by the patient.
Medical history was non-contributory. Patient's family history was negative regarding similar complaints.
Patient was a known smoker consuming about twenty beedis daily since the past thirty years. He denied alcohol consumption and had a healthy appetite.
General physical examination revealed a moderately built and nourished patient with satisfactory vital signs. No signs of pallor, items, cyanosis, clubbing or wasting were detected. The face appeared asymmetric owing to the right upper cervical swelling
Local extraoral examination revealed a solitary, localized roughly oval swelling in the right infra-auricular region measuring about 3 centimeters supero inferiorly and 2 centimeters anteroposteriorly. It was situated just posterior to the right angle of the mandible extending posteriorly to the level in line with the right ear lobe. It extended from below the right ear lobe to the level about 1.5 centimeters from the inferior border of the mandible. The right ear lobe appeared slightly elevated [Figure - 1]. The skin over the swelling appeared normal with no evidence of scars, sinuses, discolorations or punctum.
On palpation of the swelling, there was mild tenderness. In spectory findings regarding shape, size and extent were confirmed. The swelling was felt to be discrete, smooth and well defined. It was mobile over the adjacent structures but appeared to be attached to the underlying tissue.
It was soft in consistency, fluctuant and non-reducible. The swelling was not affected on activating the stemocleido mastoid muscle.
Intraoral examination revealed normal mucosa and orifices of the parotid gland appeared to be normal. No swelling on the soft palate was detected. Stimulation of the parotid glands yielded normal salivary flow with normal consistency, quantity and colour. Other intraoral findings were non-contributory.
Based on the history and clinical examination, a provisional diagnosis of benign tumour was given. A differential diagnosis of pleomorphicadenofna, Warthin's tumour, a low-grade parotid malignancy (acinic cell adenocarcinoma, adenoid cystic carcinoma, mucoepidermoid carcinoma), lipoma and neurofibroma arising in the salivary gland were included.
Patient was investigated accordingly. Hematological investigation revealed no abnormal values.
Imaging included a panoramic and a 'puffed-cheek postero anterior skull radiograph [Figure - 2], both of which revealed no abnormalities.
Ultrasonographic findings were consistent with a right parotid mass with a well-defined hypoechoic mass situated in the lower pole of the gland. The mass measured about 3 x 1.5 centimeters. The rest of the parotid gland parenchyma was normal and there was no evidence of ductal dilatation. There was also moderate vascularity within the mass. This investigation confirmed the location of the swelling as arising within the parotid gland as well its encapsulated nature [Figure - 3].
Fine needle aspiration of the swelling yielded a hemorrhagic white material. Smears studied showed monolayered sheets of oncocytic cells with round nuclei and moderate cytoplasm. Background showed sheets of small lymphocytes, macrophages and granular debris. No evidence of malignancy or tuberculosis was detected. The microscopic features were suggestive of adenolymphoma or Warthin's tumour [Figure - 4].
Since the above finding apparently suggested a benign neoplasm of the parotid gland, a superficial parotidectomy was performed under general anesthesia and the specimen was sent for histopathologic examination. The gross specimen was brownish white in colour, oval in shape, soft in consistency and measured about 2 by 3 centimeters.
Microscopically, the sections showed papillary projections of ductal epithelium enclosing a cystic lumen and a lymphoid stroma The epithelium was bilayered with inner columnar luminal layer with centrally placed nuclei. Beneath were seen cuboidal to flattened cells. No mitotic activity was observed. The epithelium was supported by lymphoid rich stroma composed chiefly of lymphocytes interspersed with few macrophages and plasma cells. Few areas showed germinal centers. The lesion appeared to be well circumscribed with a thin capsule. The surrounding regions showed normal serous acinar glandular structures. Histopathologic findings were consistent with Papillary cystadenoma lymphomatosum or Wartbin's turnor [Figure - 5][Figure - 6].
| Discussion|| |
Papillary Cystadenoma Lymphomatosum or Warthin's tumour, a curious benign neoplasm with its intimidating histologic name, is the second most common salivary gland neoplasm , ,, . It was first reported in 1895 by Hildebrand. Albrecht and Artz in 1910 termed this salivary gland tumour papillary cystadenoma However, the eponym Warthin's tumour has been extensively used ever since Warthin reported two cases of this tumour in 1929.
The term adenolymphoma has been used but is objectionable according to some authors who feel thatthis term overemphasizes the lymphoid component and may give the mistaken impression that the lesion is a type of lymphoma , . The histogenesis of these tumours has long been disputed , ,, . Eveson JW and Cawson RA in their review have quoted Albrecht and Ariz who in 1910 first proposed the heterotropic theory of origin from neoplastic proliferation of salivary gland ducts present within intraparotid or paraparotid nodes.  This theory is widely accepted. ,,,, ,,,.
It is unclear whether the lymphoid tissue in Warthin's turnoor is that of anonnal lymph node, a cellular response to the epithelium or a combination of both.  It is further suggested that reactive changes follow, possibly in response to components of the neoplastic epithelium and the volume of lymphatic tissue increases , ,,.
Conversely, it may represent residual lymphoid tissue in lymph nodes partially replaced by ectopic, proliferative ductal epithelium , , . This theory may provide an explanation for the appearance of Warthin's tumour in locations in which lymph nodes are not commonly found .
Eveson JW and Cawson RA in their review have quoted Allegra who in 1971 suggested that the tumour was a type of delayed hypersensitivity disease. However, the highly organized structure of the lymphoid component, the predominance of IgA-producing plasma cells and the lack of circulating auto antibodies were proposed to be the strong evidence against auto innnune hypothesis .
EBV has been detected in Papillary Cystadenoma Lymphomatosum and is proposed to play a part in the development of the tumours, perhaps as an antigenic stimulus .
Tobacco smoking has been strongly associated with the development of the tumour , , , . Smokers have been estimated to have four to eight fold greater risk for Warthin's tumour than do non-smokers , , . Further, in a study, Asians were reported to have a40 times increased risk of developing Warthin's tumour if they smoke, compared with non-smokers . In our case, the patient gave a long history of cigarette smoking.
Papillary Cystadenoma Lymphomatosum represents 10 to 14 percent of all salivary tumours , . It accounts for 5 to 13.5 percent of all primary epithelial parotid tumours. ,,,.
The tumour usually occurs in the age range of 13 to 85 years, , ,, and exhibits male predilection , , , , ,. Themedian age ofpredilection is known to be between 40 to 70 years , , ,,.
The tumour shows predilection to patients of Caucasian origin , . However, there is considerable incidence among Asians, although Indian studies have not been reported . There are also reports of the incidence of equal predilection in both sexes since 1970 , , .
Because these tumours have been associated with cigarette smoking, the change in sex ratio in females has been pointed by some authors to reflect the increased prevalence of smoking in females over the past few decades , . This association with smoking may also help explain the frequent bilaterality of the tumour as any tumour igenic effects of smoking might be manifested in bothparotids .
The tumour occurs almost exclusively in the parotid gland , , , , . However, tumours arising in the submandibular and sublingual salivary gland have also been reported , , . The intraoral accessory salivary glands are rarely involved , . Intraoral lesions have been reported on the palate, buccal mucoua and lips . Papillary Cystadenoma Lymphomatosum is the most common multifocal parotid tumour; 4 to 14 percent being bilateral , , . About 4 percent of cases have multiple unilateral tumours , , ,  and upto 12 percent of patients develop more than one lesion either synchronously or metachronously , , . Bilateral synchronous tumors are rare but have been reported , . The presence of the tumour in an extraparotid lymph node is well recognized , and occurs in about 20 percent of the cases .
The usual presentation is that of a painless, movable swelling at the lower pole of the parotid gland ,. The duration of the tumour onset has been reported to range from 3 weeks to 20 years ,.
Pain is an uncommon symptom and varies from mild discomfort and tenderness to very severe pain. Earache, deafness, tinnitus, variation in size of the swelling during eating, facial weakness, recent increase in size of the swelling have also been recorded .
The tumour usually shows a very slow growth and. is characterized by a well-circumscribed egg-shaped swelling of 1 to 3 centimeters in diameter , . However, a tumour exceeding 10 centimeters in diameter has been reported in the literature .
Compared with other imaging techniques such as plain radiography, sialography and computed tomography, ultrasonography is reported to be superior, not only in detecting tumourous lesions but also in describing the structure and even the vascularity of the lesions .
Papillary Cystadenoma Lymphomatosrmi has been reported as echogenic, strikingly hypoechoic or sonolucent with few internal focal echoes. Further, it shows the coarsest pattern among the benign salivary tumours, which is believed to reflect discrete septation of their cystic components (21).
The attenuation on plain CT is generally less in pleomorphic adenoma than in Papillary Cystadenoma Lymphomatosum. The former also tends to be more homogenous than Warthin's tumour, which has a more patchy appearance. This observation is only indicative of the tumour, but since the difference was not statistically significant, other types of changes have to be relied upon .
Conventional CT or CT sialography permit better definition of the tumour toward surrounding tissue. The relationship of the facial nerve may be of interest .
The scintigraphic examination is widely advocated by many authors for the diagnosis of Papillary Cystadenoma Lymphomatosum , ,.
This modality of imaging provides important information about the characteristic accumulation in the tumour and the function of the surrounding salivary gland at the same time . The tumour with a largeratio of epithelial tumour component to lymphoid component shows a remarkable accumulation of 99mTc-pertechnetate. This accumulation not only reflects the amount of epithelial tumour component but also the proportion of cystic space. The other features of this tumour that contribute to the scintigraphic results include a hypervascular flow which causes rising of 99mTc-pertechnetate levels in the early phase immediately after the injection  and a marked retention of 99mTc-pertechnetate in the wash-out image because the tumour is unconnected with the ductal system. ,  The wash-out image is important for diagnosing a Warthm's tumour, which accumulates and retains 99m Tc-pertechnetate because a normal parotid gland excretes on stimulation with ascorbic acid and most other benign tumours do not accumulate 99mTc-pertechnetate at all. 
The fluid aspirated from the tumour ranges from 3 to 4 ml and smears show clustered and dissociated oncocytes with lymphocytes and amorphous granular debris in the background. A fluid sample from the tumour can dilute the tumour cells, resulting in false negative diagnosis .
While elderly patients can be followed up without surgery the distinction of oncocytoma from Papillary Cystadenoma Lymphomatosum is important since the latter may occasionally behave in aggressive fashion ,,.
Smears from oncocyctomas are highly cellular, with a monotonous population of oncocytes in monolayers and three-dimensional fragments ,.
Macroscopically most of the tumours are round to oval encapsulated masses, 2 to 5 centimeters in diameter, arising in the great majority of cases in the superficial parotid gland. Transection reveals a pale gray surface punctuated by narrow cystic or cleft-like spaces filled with mutinous or serous secretion .
Microscopically, the tumour is usually discrete and surrounded by a thin capsule, which may be complete or incomplete ,. Asubcapsularsinus may be evident in about 47 percent of the cases .
The epithelial component forms a typical double layer of finely granular, oncocytic columnar or cuboidal cells with papillary projections protruding into the humma of macrocysts and microcysts , . Oncocytes are epithelial cells stuffed with mitochondria that impart to the cytoplasm the granular appearance . The luminal surface of outer cells may form small blebs resembling apocrine secretion .
In some cases, a ciliated type of epithelium is seen but this is limited in extent in maj ority of cases , .
Other variations seen are focal and mild squamous metaplasia, ,  mucous metaplasia and attenuation of the epithelium due to distension by the cysts .
The cysts usually contain eosinophilic secretions or amorphous material, while some may contain cholesterol clefts and epithelial and inflammatory cells , . Laminated bodies resembling corpora amylacea are seen in13percent ofthecases .
The lymphoid component consists of small lymphocytes with fewer plasma cells, macrophages and mast cells. Germinal follicles are present in 57 percent of the tumours. Mild and focal stromal fibrosis is common, as are focal areas of necrosis. The uncommon features that may be found are cholesterol clefts, associated multinucleatedgiant cells andepitheloidgranulomas .
Subclassification of Papillary Cystadenoma Lyrnphomatosum - Seifert and colleagues in 1980 analyzed 275 cases and proposed a histologic subclassification of Warthin's tumor. According to them, typical tumours had an equal ratio of epithelium to connective tissue, stroma-poor tumours had a lymphoid component of less than 30 percent and stroma-rich tumours had a lymphoid component of more than 70 percent of the tumour mass. A fourth type, characterized by large areas of squamous metaplasia was termed metuplastic.
Sunardhi-Widyaputra S and Van Darmne B in 1993 immunohistochemically studied the presence often acin, a molecule in the mesenchyme of salivary glands believed to play a role in embryogenesis and in development of tumours, in Papillary Cystadenoma Lymphomatosum and in oncocytorna. They found the protein to be abundant in Papillary Cystadenoma Lymphomatosum, prominent in the proximity of the basement membrane, beneath the oncocytic epithelial components. Tenacin staining in oncocytomawas focal although oncocytes are the actively proliferating cells in this tumour. The presence of oncocytic myoepithelial cells both in Papillary Cystadenoma Lymphomatosum and in oncocytoma surrounded by tenacin suggested that both tumours may arise from stem cells that are capable of differentiating into aberrant epithelial cells (oncocytes), myoepithelial cells invariable proportion or both .
Malignant transformation of Warthin's tumour or carcinoma ex papillary cystadenorna lymphomatosum is extremely rare , , . Whereas reports of transformation to malignant lymphoma within the lymphoid component are relatively numerous, there is a scarcity of carcinomas arising within pre-existing Warthin's tumour reported to date in the literature , , . Malignant tumours arising in this tumour include squamous carcinoma, undifferentiated carcinoma oncocytic adenocarcinoma andmucoepidermoidcarcinoma .
The diagnosis of malignant transformation of Warthin's tumour to carcinoma is based on three criteria: 1) the presence of pre-existing benign Warthin's tumour, 2) the presence of transitional zones from benign oncocytic to frankly malignant epithelium, 3) the exclusion of metastasis to lymphoid stroma from an extrasalivary primary carcinoma .
The majority of these tumours are benign. This tumour rarely invades the surrounding salivary gland and it is only a normal salivary gland displaced by tumour. The salivary gland usually retains its normal function and demonstrates only occasionally slight inflammation. Thus the salivary gland need not be removed completely .
Enucleation of the tumour is found to be satisfactory for Warthin's tumour . Some surgeons prefer local resection with minimal surrounding tissue; others opt for superficial parotidectomy to avoid violation of tumour capsule . A one to fifteen percent recurrence rate has been reported , , . However it is unclear whether these are trac recurrences or secondary tumour sites, as the tumour is known to be multicentric .
The case presented by us clearly illustrates the nature of Papillary Cystadenorna Lymphomatusurn as frequently reported in the literature. This tumour was presented by an Indian male patient in his seventh decade of life. The tumourous swelling was slowly growing over a period of 7 years, had caused minimal discomfort and was situated in the area so typical of the tumour, that is, the lower pole of the parotid gland. The history and clinical examination won half of the battle in diagnosis of this lesion. Ultrasonography aided in confirmation of the site as arising within the gland itself, its size, vascularity and encapsulated nature; which indirectly guided the fine needle aspiration. The cytological examination farther reinforced the diagnosis, hence guiding our treatment plan.
| Conclusion|| |
The understanding of salivary gland tumour pathology has increased in leaps and bounds. The paucity of this rarely reported benign salivary tumour especially among the Indians is the reason that the authors aim to document a case of the often studied and unique Warthin's tumour or Papillary CystadenomaLymphornatosum.
| Acknowledgements|| |
The authors thank Dr. K. Laxrnan, General Pathologist, Kannan Diagnostic Centre, Mysore and Dr. Sudheendra Oral Pathologist, Department of Oral Pathology, JSS Dental College and Hospital, Mysore for histopathological opinion.
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Department of Oral Medicine and Radiology, J.S.S. Dental College and Hospital, Mysore-570015, Karnataka
Source of Support: None, Conflict of Interest: None
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6]
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