Open Access

Warthin’s tumor of the larynx: a very rare case and systematic review of the literature

  • Lluís Nisa1, 2, 3,
  • Basile Nicolas Landis1, 4,
  • Cinzia Salmina1,
  • Angeliki Ailianou5,
  • Eva Karamitopoulou6 and
  • Roland Giger1Email author
Journal of Otolaryngology - Head & Neck Surgery201544:16

DOI: 10.1186/s40463-015-0067-5

Received: 3 December 2014

Accepted: 16 April 2015

Published: 12 May 2015

Abstract

Background

Warthin’s tumor or cystadenolymphoma (CAL) is a benign salivary gland tumor occurring almost exclusively in the parotid gland. CALs of other locations are rare.

Case presentation

We report a laryngeal CAL detected in a positron emission tomography/computed tomography (PET/CT) performed for breast cancer follow-up. The tumor was successfully treated by transoral surgery.

Discussion

Only 14 cases of laryngeal CAL are reported worldwide. These cases confirmed our experience of an uncomplicated and mostly successful transoral resection.

Conclusion

CALs of the larynx are very rare. They are characterized by hypermetabolism in PET/CT. The increasing use of PET/CT investigations in cancer patients could give rise to more incidental findings of CALs at unusual locations such as the larynx.

Keywords

Warthin’s tumor Cystadenolymphoma Papillary cystadenoma lymphomatosum Incidentaloma PET/CT Larynx

Background

Laryngeal tumors are predominantly malignant, with squamous cell carcinoma being the most frequent histopathological entity. Benign tumors represent around 5 % of all laryngeal tumors, and most of these are papillomas (more than 80 %).

Cystadenolymphoma (CAL) is a benign tumor of the salivary glands, also known as Warthin’s tumor or papillary cystadenoma lymphomatosum. CAL affects most often the parotid gland, and is the second most frequent benign salivary gland tumor following pleomorphic adenoma. CALs represent about 10 % of all salivary gland tumors, are most prevalent after the 6th decade of life, have a male predominance, and are more common in smokers. In general, salivary gland tumors of the larynx are rare and malignant forms prevail. Benign salivary gland tumors of the larynx are very rare and therefore poorly documented, despite claims that oncocytic lesions occur more frequently than previously thought [1].

The aim of the present article is to report a case of supraglottic CAL and review all cases of laryngeal CALs in the literature in order to discuss presentation, histological features, management and outcome.

Case presentation

A 61-year-old woman was treated for a lobular carcinoma of the left breast in 2010. She had been disease-free since the end of treatment, but the 2-year follow-up 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) showed increased uptake on the left supraglottic region (Fig. 1). With the exception of some intermittent episodes of hoarseness in the recent past, she was without symptoms. The patient is an active smoker and free of professional or environmental exposures.
Fig. 1

18F-FDG-PET/CT of the larynx. Intense FDG uptake in the left supraglottic region (arrowhead). a) axial, b) coronal

Transnasal fiberoptic laryngoscopy revealed a 2 x 1 cm expansive mass involving the left side of the supraglottis. Vocal fold mobility was unaffected. A direct laryngoscopy under general anesthesia was performed (Fig. 2) for biopsy, which revealed a CAL. Complete endoscopic examination of the upper aerodigestive tract was otherwise normal. An MRI showed a 2 × 1 × 3.5 cm multi-cystic lesion of the left supraglottic region (Fig. 3). Therapeutic excision was performed endoscopically under suspension microlaryngoscopy using CO2 laser. Histopathologic analysis of the resection specimen confirmed the diagnosis of a CAL (Fig. 4). The follow-up was complicated by edema of the involved aryepiglottic fold causing moderate dysphagia three months after surgery. A second CO2 laser resection under suspension microlaryngoscopy was performed in order to resect inflammatory and edematous tissue. Further follow-up was uneventful, without any symptoms or signs of recurrence after 2 years.
Fig. 2

Direct laryngoscopy. A 2 × 1 cm expansive mass on the left side of the supraglottis (arrowhead; asterisk = anterior commissure)

Fig. 3

Fat-suppressed T2 weighted MRI of the larynx. Multi-cystic hyperintense lesion occupying the left supraglottic region (arrowhead). a) axial, b) coronal

Fig. 4

Histopathology of the laryngeal cystadenolymphoma. H&E staining of the laryngeal CAL showing oncocytic epithelium (arrowhead) surrounded by lymphoid stroma (asterisk) (magnification 40×)

Discussion

We report a case of CAL of the supraglottic larynx identified via PET/CT done within the frame of breast cancer follow-up. Additionally, in order to obtain more relevant information on this seemingly rare entity, we performed a literature review without language restriction. Articles were searched in PubMed (up to June 2014) with the following terms: [(adenolymphoma OR lymphomatous cystadenoma OR cystadenolymphoma OR papillary cystadenoma lymphomatosum OR Warthin) AND (larynx OR laryngeal)], and with available cross-linked references from the articles found. We identified 12 eligible articles that reported 14 cases of true laryngeal CAL, histologically defined by the presence of papillary cystic epithelium and lymphoid stroma (Warthin’s tumor). Available clinical data were extracted from these articles [2-13] and summarized in Table 1. Our case was added for analysis purposes.
Table 1

Summary of published cases of laryngeal cystadenolymphoma

Authors

Age (years)/ Sex

Presentation

Location/Histologic features

Maximal size (cm)

Other involved sites

Surgical approach

Nbr. of operations

Outcome

Time of follow-up (months)

Comments

Heinz (1951) [2]

80/F

NR

Supraglottic

2.5

None

Transoral debulking

1

Persistence

4

-

Barbaccia et al. (1956) [3]

NR/M

Dyspnea

Supraglottic

NR

None

Tracheotomy, transcervical resection

1

FR

1

-

Tiwari and Williams (1969) [4]

72/F

Neck swelling

Supraglottic/within a laryngocele

4.5

None

Transcervical resection

1

FR

NR

-

Drut et al. (1975) [5]

70/F

Hoarseness

Supraglottic

NR

None

Transoral resection

1

FR

NR

-

Foulsham et al. (1980) [6]

66/F

Hoarseness

Supraglottic

1

None

Transoral resection

1

FR

12

Melkersson syndrome 6 years before

Engel et al. (1987) [7]

61/F

NR

NR

NR

None

Transoral resection

1

NR

NR

-

Evans et al. (1989) [8]

45/F

Hoarseness

Supraglottic

NR

None

Transoral resection

4

Recurrence, persistent supraglottic edema

NR

-

Loennecken (1989) [9]

77/F

Hoarseness Dyspnea

Supraglottic/within a laryngocele

2

Parotid gland

Transoral resection

1

Persistent supraglottic edema

NR

-

Tomik et al. (1991) [10]

72/F

Hoarseness Dyspnea

Supraglottic – glottic

NR

None

Transoral resection

1

FR

6

-

van der Wal et al. (1993) [11]

54/M

NR

NR

NR

None

NR

NR

NR

NR

-

50/F

NR

NR

NR

NR

NR

NR

NR

NR

50/F

NR

NR

NR

NR

NR

NR

NR

NR

Pätz and Möbius (1997) [12]

74/F

Dysphagia

Supraglottic

NR

Parotid gland

Transoral resection

1

FR

NR

-

Jordan et al. (1999) [13]

67/F

Hoarseness Dysphagia

Supraglottic bilaterally/within a laryngocele

3 / 2

None

NR

1

FR

NR

-

Present report (2014)

61/F

Hoarseness

Supraglottic

3.5

None

Transoral resection

2

Persistent supraglottic edema

24

-

Abbreviations: M – male; F – female; FR – full recovery; NR – not reported

Male to female ratio was 2:13, and patients’ mean age was of 64.2 ± 10.99 years (range: 45–80). The clinical presentation was not disease–but organ-specific, reflecting laryngeal involvement, with hoarseness as leading symptom in 7, dyspnea in 3, and dysphagia in 2 patients. One patient presented with neck swelling. The location was exclusively supraglottic, with glottic involvement in only one of the cases. One case showed a bilateral CAL. Two patients presented CAL within a laryngocele. Tumor size ranged between 1 and 4.5 cm. In 2 cases, synchronous CALs of the parotid gland were seen. Transoral resection was performed in 9 out of 11 patients, and 2 underwent open transcervical resection. In most cases (9 out of 11 reported) one surgical procedure was sufficient to eradicate the tumor, whereas in one case 4 operations were needed for recurrent disease and the second case showed tumoral persistence after 4 months. Our case underwent a second operation due to persistent supraglottic edema with no residual CAL during definitive histopathologic examination. Another 2 cases showed persistent laryngeal edema postoperatively.

In summary, laryngeal CAL is very rare and can most often be managed with transoral resection. Recurrence seems to be an exception in the larynx and only few complications or side effects of the treatment are reported. The unique feature of our reported case is that the patient’s CAL was detected incidentally due to regular PET/CT follow-up investigation for a previously treated breast cancer. Only retrospective inquiry showed minor laryngeal symptoms consisting of some hoarseness episodes. Accurate diagnosis requires nonetheless histopathologic examination of the resected specimens. Malignant degeneration of CALs, originating from both the epithelial and the lymphoid compartments, is a rare but possible event. In the specific case of laryngeal CALs, no case of malignant degeneration could be identified.

Workup with PET/CT has been shown to indicate false positive results in head and neck cancer patients showing a CAL within neck lymph nodes mimicking a metastasis [14]. There was similarity with our case, where FDG-uptake was found in the larynx, and initially mistaken for a breast cancer metastasis. Van der Wal et al. described the largest series of laryngeal CALs (3 cases) along with seven other cases of extraparotideal CALs (cheek, oropharynx, palate, buccal fold, lower lip, submandibular gland) [11]. As CALs show a hypermetabolism in PET/CT exams, which are increasingly performed, future PET findings might bring new insight regarding synchronous and multiple Warthin’s tumor locations and into pathogenesis of this particular tumor. While some authors have classically considered CAL to be more similar to a reactive process than to a true neoplasia, the views on pathogenesis have evolved over the last decades. Current techniques show that the epithelial portion of a substantial subset of CALs is monoclonal and frequently harbors a translocation between chromosomes 11 and 19 t (11;19), which in turn results in the fusion oncogene CRTC1-MAML2 [CREB(cAMP response element-binding protein)-regulated transcription co-activator 1–mastermind-like protein 2], which is a master key involved in several signaling pathways that contribute to cell survival and proliferation, primarily the Notch pathway [15]. Van der Wal et al. underlined the fact that laryngeal CALs are indeed rare tumors and pathologic diagnosis can be challenging, especially when it comes to distinguishing CAL from oncocytic hyperplasia or metaplasia, pointing out that the only basic difference between these entities is the lack of lymphoid stroma in oncocytic lesions [11].

Another interesting point is the potential multifocal presentation of CALs. We found 2 cases of concomitant involvement of the larynx and the parotid gland (Table 1) [9, 12]. This is not a new finding, as synchronous or metachronous development of CALs in both parotid glands is not a rare event, which raises the question if there is a need for long-term follow-up in patients with CALs in general. Although speculative in nature, we feel that careful workup in incidental PET/CT findings could reveal a previously underestimated amount of extra-salivary and multiple synchronous CAL cases. In light of the open questions regarding the pathogenesis of CALs, more cases as the present ones could bring further insight into the nature of this special benign tumor.

Conclusion

Warthin’s tumors of the larynx are very rare. Transoral resection seems to be feasible for most cases, has little side effects, and is most often curative. As Warthin’s tumors show increased FDG-uptake similar to malignant tumors, it is hypothesized that with increasing PET/CT use, the number of Warthin’s tumor case reports outside the salivary glands may augment.

Consent

The patient has given her consent for the Case report to be published.

Declarations

Acknowledgements

The authors wish to thank Mrs. Irina Ciorba-Nisa, MS, and Mr. Krzysztof Szmigiel, scrub nurse, for their skillful assistance during production of this manuscript and translation of several articles.

Authors’ Affiliations

(1)
Department of Otorhinolaryngology—Head and Neck Surgery, Inselspital, Bern University Hospital
(2)
Department of Clinical Research, University of Bern
(3)
Department of Radiation Oncology, Inselspital, Bern University Hospital
(4)
Department of Otorhinolaryngology—Head and Neck Surgery, Geneva University Hospital
(5)
Department of Diagnostic Radiology, Geneva University Hospital
(6)
Clinical Pathology Division, Institute of Pathology, University of Bern

References

  1. Lundgen J, Olofsson J, Hellquest H. Oncocytic lesions of the larynx. Acta Otolaryngol. 1928;94:335–44.View ArticleGoogle Scholar
  2. Heinz I. The adenolymphomata. Aust N Z J Surg. 1951;2:47–51.View ArticleGoogle Scholar
  3. Barbaccia F, Micelli F, Tosci C. Adenolinfoma della laringe. Arch Ital Otol Rhino Laringol. 1956;67:87–96.Google Scholar
  4. Tiwari RM, Williams HI. Adenolymphoma in a laryngocele. J Laryngol Otol. 1969;83:1227–30.PubMedView ArticleGoogle Scholar
  5. Drut R, Di Rago C, Di Rago C. Cistoadenoma papilar linfomatoso (tumor de warthin) de laringe. An Otorinolaringol Ibero Am. 1975;2:29–33.Google Scholar
  6. Foulsham 2nd CK, Snyder 3rd GG, Carpenter 3rd RJ. Papillary cystadenoma lymphomatosum of the larynx. Otolaryngol Head Neck Surg. 1981;89:960–4.PubMedGoogle Scholar
  7. Engel P, Larsen SB, Francis D. Extraparotid occurrence of papillary lymphomatous cystadenoma-Warthin’s tumor. Ugeskr Laeger. 1987;149:1244–6.PubMedGoogle Scholar
  8. Evans RA, Cassidy MT, Russell TS. Adenolymphoma of the larynx. J R Coll Surg Edinb. 1989;34:47.PubMedGoogle Scholar
  9. Loennecken I. Multilokuläres vorkommen eines zystadenolymphoms (warthin-tumor) in parotis und larynx. Laryngorhinootologie. 1989;68:212–5.PubMedView ArticleGoogle Scholar
  10. Tomik J, Papla B, Olszewski E. A case of Warthin’s tumor (papillary adenolymphoma) of the larynx. Otolaryngol Pol. 1991;45:296–8.PubMedGoogle Scholar
  11. van der Wal JE, Davids JJ, van der Waal I. Extraparotid Warthin’s tumours – report of 10 cases. Br J Oral Maxillofac Surg. 1993;31:43–4.PubMedView ArticleGoogle Scholar
  12. Pätz S, Möbius H. Simultanes auftreten eines zystadenolymphoms. HNO. 1997;45:91–3.PubMedView ArticleGoogle Scholar
  13. Jordan J, Babiński D, Sova J. Adenolymphoma (Warthin’s tumor) of the larynx: coexistence with the bilateral laryngocele. Contribution to differential diagnosis with oncocytic papillary cystadenoma. Otolaryngol Pol. 1999;53:213–6.PubMedGoogle Scholar
  14. Schwarz E, Hürlimann S, Soyka JD, Bortoluzzi L, Strobel K. FDG-positive Warthin’s tumors in cervical lymph nodes mimicking metastases in tongue cancer staging with PET/CT. Otolaryngol Head Neck Surg. 2009;140:134–5.PubMedView ArticleGoogle Scholar
  15. O’Neill ID. New insights into the nature of Warthin’s tumour. J Oral Pathol Med. 2009;38:145–9.PubMedView ArticleGoogle Scholar

Copyright

© Nisa et al. 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Advertisement