Eye and Ocular Adnexa Manifestations of Warthin Tumor
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Warthin’s tumor (WT), also known as papillary cystadenoma lymphomatosis or adenolymphoma, is a benign neoplasm that primarily affects the parotid glands.[1] It is a rare extra-parotid lesion that can involve structures including the minor salivary glands, throat, mouth or eye.[1][2] WT affecting the ocular structures is known as WT of the eye (WTE).[1] Within the realm of ophthalmology, there are eight reported cases of WTE documented in the English literature. Four cases involve the caruncle, while there exists one case for each of the following: the plica semilunaris, the lacrimal gland, the lacrimal sac, and the eyelid.[1] [2][3] [4] [5] [6] [7] [8] Diagnosis of WTE heavily relies on histology of the excised tissue and, across all cases, treatment involves a local excision of the tumor with no recurrence reported following the procedure.
Disease Entity
D11.9 is the ICD-10 code associated with Warthin’s tumor of the salivary gland. However, there is no specific code for Warthin’s tumor of the eye and ocular adnexa.
History and Prevalence
WT accounts for approximately 4-11% of all salivary gland tumors and is the second most common tumor of the parotid glands.[6][9] [10] However, in rare cases, WT can occur in orbital spaces.[1] The first case of WTE was reported in 1963 by Oaks & Jenson in the American Journal of Ophthalmology.[3] [4] Upon review of the English literature, only seven other cases of WT have been reported involving the structures of the eye (Table 1).
Risk Factors and Primary Prevention
There is a strong association between Warthin’s tumor of the salivary glands and smoking.[8][11] However, the association between smoking and WTE is unknown and has not been studied.[6] As outlined in Table 1, four cases did not specify the smoking status of the patient with WTE, whereas the other four cases identified their patients as non-smokers.
Advanced age has been proposed as a risk factor, specifically for development of WT of the lacrimal gland.[2] Liu et al., 2019 hypothesized that the increase of age causes the lacrimal caruncle to become hypertrophied and lose its functional capacity, which in turn increases the risk of developing tumors.[1]
| Table 1: Eight reported cases of WTE.* (M: Male, F: Female, OD: right eye, OS: left eye, +/-: Positive for/Negative for) | |||||||
|---|---|---|---|---|---|---|---|
| Publication | Publication Year | Age | Gender
(M/F) |
Eye | Location | Smoking (+/-) | Treatment |
| Oaks & Jenson | 1963 | 65 | F | OD | Caruncle | Unknown | Surgery |
| Carden | 1983 | 70 | F | OD | Plica Semilunaris | Unknown | Surgery |
| Mathur et al. | 1989 | 60 | M | OS | Eyelid | - | Surgery |
| Gupta et al. | 1990 | 60 | F | OD | Lacrimal sac | Unknown | Surgery |
| Bonavolontà et al. | 1997 | 62 | F | OD | Lacrimal gland | Unknown | Surgery |
| Zepeda & Lai | 2013 | 90 | M | OD | Caruncle | - | Surgery |
| Liu et al. | 2019 | 71 | F | OD | Caruncle | - | Surgery |
| Iacob et al. | 2021 | 76 | M | OS | Caruncle | - | Surgery |
* Table data modified and derived from Liu et al., 2019 and Iacob et al., 2021.
Affected Patient Populations
Patients with WTE typically present with advanced age.[1] There is no clear association between gender and WTE.[2]
Pathophysiology
Warthin’s tumor (WT) is a slowly progressing, benign epithelial tumor.[1] WT frequently occurs in the parotid gland and rarely affects extra-parotid tissue.[1][12] These rare sites of localization include the eye, throat, mouth and lips.[2] [3] [6] [7][13] [14] [15] WT commonly demonstrates a history of growth and decline, which is a hallmark feature of the disease.[1] Malignant transformation of WT is extremely rare, with a malignancy rate of approximately 1%.[16] [17] A change in phenotype of cells through metaplasia to squamous cell differentiation is a well-known feature of WT.[18]
Presently, there remains debate around the pathophysiology underlying the distant extraparotid involvement of Warthin’s tumor. For periparotid and cervical involvement, however, the present pathophysiological understanding is that the delayed encapsulation of the parotid gland during embryogenesis permits undifferentiated lymphoid stromal tissue to interact with the developing meshwork of salivary ducts. Once encapsulation is complete, some of the salivary ducts and acini may be trapped within the differentiated extraparotid lymph nodes.[19] For the more distant extraparotid Warthin’s tumors (pharynx, larynx, sinuses, lacrimal gland), it is believed that ectopic proliferation of salivary gland tissue in lymph nodes or lymphatic tissue somewhat explains these manifestations.[1] In short, more research needs to be done to further elucidate the pathogenesis.[1]
Diagnosis
Clinical Presentation
Patients with WTE typically present with progressively growing, “fleshy”, painless mass that is partly solid and partly cystic on various sites of the eye, including the caruncle, lacrimal gland and eyelid.[4] [5] [8] Patients usually deny eye pain, eye discharge, vision changes or visual disturbances.[4] [5] [6] [8] The duration of onset is usually over the course of several months to several years[2] [6] [7].
Physical Examination Findings
On gross exam, patients typically present with a spherical, well-encapsulated fibrous nodule at affected site.[4] Across the reported cases of WTE, no consistent ophthalmic exam findings are specific or sensitive for WTE. One case report describing WT in the lacrimal caruncle reported diminished visual acuity of affected eye (0.1 in affected eye compared to 0.5 in unaffected eye).[1] Another case of WT of the lacrimal gland noted downward and inward proptosis of the affected eye with mechanical blepharoptosis, with an otherwise unremarkable ophthalmic exam.[7] However, the remaining cases of WT affecting the eye do not overtly describe visual acuity findings. With this in mind, ophthalmologists may possibly need to rely more heavily on histology for clinical diagnosis.
Imaging
Various imaging modalities can be useful in diagnostic work up for WTE. Magnetic resonance imaging (MRI) can be useful in visualizing any abnormality of the orbit and surrounding structures of the eye.[1] Computed tomography (CT) can also be used for lower resolution visualization of the orbit and adjacent structures.[4]
Histopathology
On histology, WTE is characterized by intertwined islands of bi-layered epithelial tissues with eosinophilic cytoplasm encircled by a background of lymphocytes that demonstrate occasional germinal center formation.[8] Biopsy samples of WTE typically demonstrate a lymphocytic component, consisting of lymphocytes and plasma cells, alongside an epithelial component.[5] [7] The lymphocytic component is focal with follicular organization, while the epithelial component is formed by solid nests and papillary infoldings of columnar cells.[5] [7]
Differential Diagnoses
Oncocytomas of the eye have been reported in the literature, with the highest prevalence occurring in the caruncle.[20] It is important to distinguish an oncocytoma from WTE as they are both benign tumors that have similar clinical presentations.[5] A histopathologic difference is noted where WTE presents both as epithelial cells lining cystic spaces and lymphoid tissue while an oncocytoma demonstrates large round epithelial cells with acidophilic cytoplasm.[7]
Management
Medical Management
No medications have been reported to treat WTE.[8]
Surgical Management
The most effective treatment to date for WTE is local excision. This provides patients with a favorable prognosis.[1][8]
Post-Operative Follow-Up
- The post-excision healing period typically lasts for approximately three weeks.[5] For all patients treated with local excision, there were no complaints of pain, discomfort, or tearing.[3] These patients were seen for several months after surgery for recurrence monitoring and no recurrence was documented.[3] [5] [7] [8]
Post-Surgical Complications
- No complications were reported.[8]
Prognosis
After surgical intervention, patients diagnosed with WTE had a good prognosis and made a full recovery.[1][8]
Concluding Remarks
WTE is extremely rare and poses very little risk for malignancy.[1][16] However, it is important to biopsy the tissue to confirm the diagnosis and differentiate between benign pathology versus malignant transformation.[1] Excision of tumor from ocular and adnexal parts of the eye has proven to be low-risk to the patient and has subsequently provided favorable outcomes to all treated.[1]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 Liu R, Wang L, Yang B, et al. A rare warthin tumor occurring in lacrimal caruncle: a case report. Clin Oncol. 2019;4:1659.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Mathur A, Mehrotra ML, Dhaliwal U. Warthin's tumor of the eye lid. Indian J Ophthalmol. 1989;37(4):193.
- ↑ 3.0 3.1 3.2 3.3 3.4 Oaks LW, Jenson MB. Warthin’s tumor. Papillary cystadenoma lymphomatosum occurring in a human caruncle. Am J Ophthalmol. 1963;56:459–461.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Gupta RK, Kumar S, Nath D, et al. Adenolymphoma of lacrimal sac. A case report. Indian J Cancer. 1990;27:116–118.
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 Carden R. An unusual case of papillary cystadenoma lymphomatosum of the plica semilunaris. J Am Optom Assoc. 1983;54:995–996.
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 Zepeda MR, Lai EM. Warthin’s tumor of the lacrimal caruncle. Taiwan J Opthalmol. 2013;3:82–84.
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 8.9 Iacob SI, Keyhani KK, Farhat NA. Warthin Tumor of the Caruncle: A Rare Case Report and Review of the Literature. Ophthalmic Plast Reconstr Surg. 2021 Jul-Aug 01;37(4):e133-e134.
- ↑ Auclair PL, Ellis GL, Stanley MW. Major and minor salivary glands. In: Silverberg SG, editor. Silverberg’s principles and practice of surgical pathology and cytopathology, vol. I. Philadelphia: Elsevier; 2006. p. 1214e9.
- ↑ O’Neill ID. New insights into the nature of Warthin’s tumor. J Oral Pathol Med 2009;38:145e9.
- ↑ Loy AH, Putti TC, Tan LK. Cyclooxygenase-2 expression in Warthin’s tumour. J Laryngol Otol. 2005;119:515–518.
- ↑ 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(1):43-44. doi:10.1016/0266-4356(93)90098-h.
- ↑ Duek I, Paker M, Gil Z, Cohen JT. Warthin tumor of the larynx: A case report and review of the literature. Ear Nose Throat J. 2018;97(7):E8-E11.
- ↑ Saunders S, Igbokwe U, Harmse D. Warthin tumor of the buccal mucosa. Br J Oral Maxill Surg. 2008;46(4):332-3.
- ↑ Petrocelli M, Sbordone C, Salzano G, Orabona GD, Cassandro FM, Fusetti S, et al. Incidental finding of upper lip Warthin tumor. Ann Ital Chir. 2017;14(6):1-4.
- ↑ 16.0 16.1 Therkildsen MH, Christensen N, Andersen LJ, Larsen S, Katholm M. Malignant Warthin's tumour: a case study. Histopathology. 1992;21(2):167-171. doi:10.1111/j.1365-2559.1992.tb00366.x.
- ↑ Thackray AC, Sobin LH: Histological Typing of Salivary Gland Tumours. WHO, Geneva, 1972.
- ↑ 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(1):13-38. doi:10.1007/BF00430674.
- ↑ Astor FC, Hanft KL, Rooney P, Benson CA, Flores CT, Lavertu P. Extraparotid Warthin's tumor: clinical manifestations, challenges, and controversies. Otolaryngol Head Neck Surg. 1996 Jun;114(6):732-5. doi: 10.1016/S0194-59989670094-3. PMID: 8643295.
- ↑ Say EA, Shields CL, Bianciotto C, Eagle RC Jr, Shields JA. Oncocytic lesions (oncocytoma) of the ocular adnexa: report of 15 cases and review of literature. Ophthalmic Plast Reconstr Surg. 2012 Jan-Feb;28(1):14-21. doi: 10.1097/IOP.0b013e31822dd236. PMID: 21956543.
- Yu G, Zou Z, Ma D. Comprehensive study on Warthin tumor of parotid gland. Chinese J Oral Med. 1995;34(5):187-9. 16.
- Gallo O, Bociolini C. Warthin’s tumor associated with autoimmune diseases and tobacco use. Acta Otolaryngol. 1997;117(4):623-7.
- Sato T, Ishibashi K. Multicentric Warthin tumor of the paraparotid region mimicking lymph node metastases of homolateral oral and oropharyngeal squamous cell carcinoma: reports of two cases. J Oral Maxillofac Surg. 1998;56(1):75-80.
- Yinuo J, Hongyan W, Yuan D, Zhe Y. Clinical and pathological observation of Warthin tumor epithelium into mucoepidermal carcinoma in 2 cases. J Diagnostic Pathol. 2016;23(3):186-9.
- Lennox B, Timperley WR, Murray D, et al. Adenolymphoma-like tumours of the lacrimal caruncle and the larynx. J Pathol Bacteriol. 1968;96:321–326.
- Deutsch AR, Duckworth JK. Onkocytoma (oxyphilic adenoma) of the caruncle. Am J Ophthalmol. 1967;64:458–461.
- Biggs SL, Font RL. Oncocytic lesions of the caruncle and other ocular adnexa. Arch Ophthalmol. 1977;95:474–478.
- Thompson AS, Bryant HC JrHistogenesis of papillary cystadenoma lymphomatosum (Warthin’s tumour) of the parotid gland. Am J Pathol. 1950;26:807–849.
- Yinuo J, Hongyan W, Yuan D, Zhe Y. Clinical and pathological observation of Warthin tumor epithelium into mucoepidermal carcinoma in 2 cases. J Diagnostic Pathol. 2016;23(3):186-9.
- Schulte, H. W.: Studies in cancer and allied subjects: II. The development of the human salivary glands. New York, Columbia University Press, 1913, vol. 4.
