This article has Open Peer Review reports available.
Bilateral multifocal Warthin's tumors in upper neck lymph nodes. report of a case and brief review of the literature
© Naujoks et al; licensee BioMed Central Ltd. 2012
Received: 16 January 2012
Accepted: 3 April 2012
Published: 3 April 2012
Cystadenolymphomas (Warthin's tumors) are the second most frequent lesions of the parotid gland. Due to their benign clinical behavior, the low rates of recurrence and malignant transformation they were classified as tumor-like lesions. In addition, a polyclonal growth of the epithelial components of the tumor could be detected. Warthin's tumors occur bilateral in 7-10%, whereas a multifocal appearance is extremely rare. Even if the pathogenesis is still unclear a heterotopia of salivary tissue during embryogenesis is the most likely explanation for the origin of these tumors in the upper neck and periparotideal region. Here we present a rare case of bilateral, multifocal, extraglandular Warthin's tumors in lymph nodes of the upper neck and give a brief review of the literature. If a primary malignancy can be excluded by a careful staging procedure prior to the operation an isolated excision of the lesions of the neck is the adequate treatment.
KeywordsWarthin's tumor Bilateral Multifocal Neck lymph nodes Treatment Pathogenesis
Cystadenolymphoma is the second most frequent benign tumor of the parotid gland representing 6 to 10% of all tumors of the salivary glands . In general, Warthin's tumors present as encapsulated lesions with cystic and solid areas which usually occur in the caudal pole of the parotid gland. Initially, tumors present as an asymptomatic, slowly growing masses, affecting predominantly men (10:1) in the 5th and 6th decade [2, 3]. Bilateral lesions occur in 7-10% of cases while multifocal lesions and recurrence occur in 2% of cases [4, 5]. Histopathologically, they consist of a double-layer of oncocytic epithelial cells capable of forming cysts and papillary projections and a variable lymphatic stroma component . Malignant transformation is very rare and the incidence of a carcinoma arising in a Warthin's tumor is approximately 1% . Although pathogenesis is still unknown there is an association with cigarette smoking [3, 6]. Since Honda et al. showed that the epithelial tumor components are polyclonal cell populations  these lesions cannot be classified as a true neoplasia anymore. This is supported by the fact that the tumors show a clinical behaviour that is typical for benign lesions and that there are only low rates for recurrence and malignant transformation [4, 5, 8]. Therefore, these lesions were classified as tumor-like-lesions [2, 9].
There are several theories to explain the origin and the development of the tumors. Only two of the theories remain, namely the hypothesis that the tumor is an adenoma with concomitant lymphocytic infiltration , and second the hypothesis of heterotopia of salivary tissue into peri- and intraparotideal lymph nodes . The latter theory is supported by the fact that during embryogenesis of the glandula parotis a penetration of epithelial cells of the oral mucosa into lymphocyte-rich tissue takes place. Due to the late encapsulation of the parotis the occurrence of intraparotideal lymph nodes and heterotopia of salivary tissue in parotideal and upper neck lymph nodes can be explained. Therefore, the origins of Warthin tumors are these epithelial inclusions [2, 11, 12]. This theory supports the heterotopia of salivary tissue in the upper neck and periparotideal region. It is unlikely to explain the origin of salivary tissue in the lower neck. Therefore, Youngs and Scofield suggested a relationship between a defective closure of the sinus of the His of the branchial apparatus with heterotopic salivary tissue .
There are only a few reports on the occurrence of extraglandular Whartin tumors, especially with a bilateral and multifocal appearance [11, 14–16]. Here we present a rare case of a simultaneous bilateral, multifocal Warthin's tumor in upper cervical lymph nodes and give a brief review of the literature.
A 85-year-old Caucasian man presented to our department in 2011 with a 4-year history of swelling on the mandibular angle of both sides. After initial slow and continuous growth, the masses now showed an accelerated enlargement in the last months, he indicated.
The patient was a non-smoker. He reported no pain, facial or trigeminal disorders. B-symptoms, a stay abroad and the presence of domestic animals were denied. Furthermore, the patient suffered from coronary heart disease, cardiac arrhythmia, barrett esophagus and hypertension.
The patient recovered from the operation very soon and showed no signs of recurrence during follow up so far.
The first description of adenolymphoma was done by Hildebrand in 1895  and in 1929 Warthin published a series of so called papillary cystadenoma lymphomatosum leading to the well known term 'Warthin's tumor' . Cystadenolymphomas are the second most frequent benign tumors of the parotid gland representing 6 - 10% of all tumors of the salivary glands . However, it is difficult to estimate the real incidence of Warthin's tumors since there are regional, national and racial differences [2, 3]. There is controversy about the origin and pathogenesis of cystadenolymphomas. One major hypothesis acts on the assumption of heterotopic salivary tissue. During the embryogenesis epithelial cells of the oral mucosa penetrate into lymphocyte-rich tissue and can be entrapped into parotideal lymph nodes. In addition, the late encapsulation of the parotid gland permits the occurrence of intraparotideal lymph nodes. Thus Warthin's tumors have their origin in these epithelial inclusions . This hypothesis puts Warthin's tumors in vicinity of lateral cervical cysts, who are thought to origin from proliferating heterotopic inclusions of tonsillar tissue in cervical lymph nodes . The hypothesis of heterotopia may explain the origin of salivary tissue in parotideal lymph nodes, in the periparotideal region and the upper neck, but fails to explain the origin of heterotopic salivary tissue in the lower neck or lymph nodes in the mediastinal cavity. Already in 1967 a relationship between a defective closure of the sinus of the His of the branchial apparatus with heterotopic salivary tissue was suggested by Youngs and Scofield  as a possible reason for heterotopic salivary tissue of the lower neck. Other authors propose that aberrant salivary tissue of the pharyngeal pouch may migrate downwards with the thyroid and parathyroid gland .
Beside the epithelial component these tumors consist of a stromal component with lymphocytic infiltrates and lymph follicles. One hypothesis about the origin of these lymphatic components is the proposal of Low et al., namely that the lymphatic component is a result of an immunological reaction to the epithelial growth . This suggestion is supported by recent findings of Teymoortash et al. who could prove evidence for a promotion of lymphangiogenesis by the epithelial tumor .
Since Honda et al. were able to prove that the epithelial components are polyclonal cell populations this lesion cannot be classified as a true neoplasia anymore . According to the WHO these lesions were classified as tumor-like-lesions . There are many arguments that support the tumor-like classification of these lesions. First, these tumors show a slow growth and do not affect the facial nerve. This clinical appearance of this tumor is similar to other benign lesions. In addition, the polyclonal origin of the epithelial components excludes an malignant growth pattern . In addition, there are low rates for recurrence and malignant transformation [4, 5, 8, 22].
The sonographic diagnosis of neck masses originating from heterotopic salivary gland tissue remains challenging due to their rarity. In the present case, first of all, metastastic tumor growth had to be taken into account, because the whole lymphatic tissue was depleted of the lymph nodes. Moreover, the simultaneousness of the occurrence of three similar bilateral lesions suggested the presence of a metastasizing malignant tumor. The absence of detectable intra- or perinodal vessels and the hyperechoic appearance of the presumptive metastatic tissue rather argued against this assumption, but histopathological investigation of the entire lesions was the only way to establish the correct diagnosis.
The management of neck masses secondary to heterotopic salivary tissue is complex and depends among other things on the dignity of the lesion. Due to the fact that the definitive diagnosis can finally be achieved by a histological examination it is still a challenge for the surgeon to balance the surgery appropriate. Unnecessary surgery of the salivary glands with its associated morbidity or missing a primary malignancy should be avoided. Therefore a careful search for any primary cancer should be performed prior to the operation as recommended by Ferlito et al. . In the presented case no primary malignancy could be detected by clinical examination, CT-scan and ultrasound. Afterwards the patient underwent a selective lymph node excision on both sides. This is consistent with the conclusion of Rodgers et al. namely that a local excision with close follow up is an appropriate management for benign neoplasms of cervical heterotopic salivary tissue . According to Ferlito et al. a cervical lesion should be considered as primary tumor and treated as mentioned above if the preoperative search for primary malignancies is negative . Consequently the exclusion of a major salivary gland neoplasm by clinical examination and radiographic imaging should preclude the removal of a major salivary gland . There was a controversial discussion about the position of fine needle aspiration cytology in the diagnosis of Warthin's tumors or lesions of the parotid gland in general. Meanwhile several studies could prove a high sensitivity and specificity for the diagnosis of Warthin's tumor with fine needle aspiration cytology (FNAC) [26, 27]. Risks like facial nerve lesions and infection can be disregarded because of their infrequency. Due to the fact that the final diagnosis cannot be established until histopathological study of the surgical sample has been performed, FNAC may be an option to close this gap of diagnosis and permit a detailed preoperative planning. In the presented case a FNAC was not performed because the masses were too far away from the parotid gland. Therefore a resection of the gland was beyond all questions. Nevertheless, a FNAC should be always performed for the preoperative diagnosis of lesions of the salivary glands if a resection of the gland is taken into account. Cytology, when coupled with clinical and image findings, may permit conservative tumor management .
We presented a rare case of a multifocal bilateral cystadenolymphoma in upper cervical lymph nodes, the most frequent lesion of heterotopic salivary gland tissue. Even if there are several hypotheses the pathogenesis is still unclear. Recent studies were able to proof that these tumors are no true neoplasia and consequently were classified as tumor-like-lesions. The preoperative diagnosis to exclude primary malignancies and consequently the definition of a balanced surgery is still a major challenge for the surgeon. Careful clinical examination, radiography, ultrasound and in some cases fine-needle aspiration cytology should be performed. If a primary malignancy can be excluded the adequate therapy of these lesions is an isolated excision of the masses. In these cases surgery of the salivary glands with its morbidity should be avoided. Afterwards a close follow up is recommended.
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
- Chapnik JS: The controversy of Warthin's tumor. Laryngoscope. 1983, 93: 695-716.View ArticlePubMedGoogle Scholar
- Teymoortash A, Werner JA: Tissue that has lost its track: Warthin's tumour. Virchows Arch. 2005, 446: 585-588. 10.1007/s00428-005-1276-5.View ArticlePubMedGoogle Scholar
- Teymoortash A, Krasnewicz Y, Werner JA: Clinical features of cystadenolymphoma (Warthin's tumor) of the parotid gland: a retrospective comparative study of 96 cases. Oral Oncol. 2006, 42: 569-573. 10.1016/j.oraloncology.2005.10.017.View ArticlePubMedGoogle Scholar
- Seifert G, Bull HG, Donath K: Histologic subclassification of the cystadenolymphoma of the parotid gland. Analysis of 275 cases. Virchows Arch A Pathol Anat Histol. 1980, 388: 13-38. 10.1007/BF00430674.View ArticlePubMedGoogle Scholar
- Chung YF, Khoo ML, Heng MK, Hong GS, Soo KC: Epidemiology of Warthin's tumour of the parotid gland in an Asian population. Br J Surg. 1999, 86: 661-664. 10.1046/j.1365-2168.1999.01113.x.View ArticlePubMedGoogle Scholar
- Peter Klussmann J, Wittekindt C, Florian Preuss S, Al Attab A, Schroeder U, Guntinas-Lichius O: High risk for bilateral Warthin tumor in heavy smokers--review of 185 cases. Acta Otolaryngol. 2006, 126: 1213-1217. 10.1080/00016480600740605.View ArticlePubMedGoogle Scholar
- Honda K, Kashima K, Daa T, Yokoyama S, Nakayama I: Clonal analysis of the epithelial component of Warthin's tumor. Hum Pathol. 2000, 31: 1377-1380. 10.1016/S0046-8177(00)80007-6.View ArticlePubMedGoogle Scholar
- Foschini MP, Malvi D, Betts CM: Oncocytic carcinoma arising in Warthin tumour. Virchows Arch. 2005, 446: 88-90. 10.1007/s00428-004-1122-1.View ArticlePubMedGoogle Scholar
- Seifert G: Tumour-like lesions of the salivary glands. The new WHO classification. Pathol Res Pract. 1992, 188: 836-846.PubMedGoogle Scholar
- Thompson AS, Bryant HC: Histogenesis of papillary cystadenoma lymphomatosum (Warthin's tumor) of the parotid salivary gland. Am J Pathol. 1950, 26: 807-849.PubMedPubMed CentralGoogle Scholar
- Hilton JM, Phillips JS, Hellquist HB, Premachandra DJ: Multifocal multi-site Warthin tumour. Eur Arch Otorhinolaryngol. 2008, 265: 1573-1575. 10.1007/s00405-008-0622-z.View ArticlePubMedGoogle Scholar
- Singer MI, Applebaum EL, Loy KD: Heterotopic salivary tissue in the neck. Laryngoscope. 1979, 89: 1772-1778.View ArticlePubMedGoogle Scholar
- Youngs LA, Scofield HH: Heterotopic salivary gland tissue in the lower neck. Arch Pathol. 1967, 83: 550-556.PubMedGoogle Scholar
- Chae SW, Sohn JH, Shin HS, Choi JJ, Kim YB: Unilateral, multicentric Warthin's tumor mimicking a tumor metastatic to a lymph node. A case report. Acta Cytol. 2004, 48: 229-233. 10.1159/000326322.View ArticlePubMedGoogle Scholar
- Nishikawa H, Kirkham N, Hogbin BM: Synchronous extra-parotid Warthin's tumour. J Laryngol Otol. 1989, 103: 792-793.View ArticlePubMedGoogle Scholar
- Handschel JG, Depprich RA, Zimmermann AC, Braunstein S, Kubler NR: Adenomatoid odontogenic tumor of the mandible: review of the literature and report of a rare case. Head Face Med. 2005, 1: 3-10.1186/1746-160X-1-3.View ArticlePubMedPubMed CentralGoogle Scholar
- Hildebrandt O: Uber angeborene epitheliale Zysten und Fisteln des Halses. Arch Klin Chir. 1895, 49: 167-206.Google Scholar
- Warthin A: Papillary cystadenoma lymphomatosum. J Cancer Res. 1929, 13: 116-125.Google Scholar
- Jernstrom P, Prietto CA: Accessory parotid gland tissue at base of neck. Arch Pathol. 1962, 73: 473-480.PubMedGoogle Scholar
- Low WK, Ng SB: Synchronous parotid and nasopharyngeal Warthin's tumors: first report of a case. Ear Nose Throat J. 2002, 81: 839-841.PubMedGoogle Scholar
- Teymoortash A, Schrader C, Shimoda H, Kato S, Werner JA: Evidence of lymphangiogenesis in Warthin's tumor of the parotid gland. Oral Oncol. 2007, 43: 614-618. 10.1016/j.oraloncology.2006.07.006.View ArticlePubMedGoogle Scholar
- Handschel J, Herbst H, Brand B, Meyer U, Piffko J: Intraoral sebaceous carcinoma. Br J Oral Maxillofac Surg. 2003, 41: 84-87. 10.1016/S0266-4356(03)00036-6.View ArticlePubMedGoogle Scholar
- Ferlito A, Bertino G, Rinaldo A, Mannara GM, Devaney KO: A review of heterotopia and associated salivary gland neoplasms of the head and neck. J Laryngol Otol. 1999, 113: 299-303.PubMedGoogle Scholar
- Rodgers GK, Felder H, Yunis EJ: Pleomorphic adenoma of cervical heterotopic salivary gland tissue: case report and review of neoplasms arising in cervical heterotopic salivary gland tissue. Otolaryngol Head Neck Surg. 1991, 104: 533-536.View ArticlePubMedGoogle Scholar
- Daniel E, McGuirt WF: Neck masses secondary to heterotopic salivary gland tissue: a 25-year experience. Am J Otolaryngol. 2005, 26: 96-100. 10.1016/j.amjoto.2004.08.009.View ArticlePubMedGoogle Scholar
- Veder LL, Kerrebijn JD, Smedts FM, den Bakker MA: Diagnostic accuracy of fine-needle aspiration cytology in Warthin tumors. Head Neck. 2010, 32: 1635-1640. 10.1002/hed.21382.View ArticlePubMedGoogle Scholar
- Viguer JM, Vicandi B, Jimenez-Heffernan JA, Lopez-Ferrer P, Gonzalez-Peramato P, Castillo C: Role of fine needle aspiration cytology in the diagnosis and management of Warthin's tumour of the salivary glands. Cytopathology. 2010, 21: 164-169.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.