Background

Warthin's tumor is a benign neoplasm of the salivary glands. An older name is papillary cystadenoma lymphomatosum. It accounts for 4-15% of salivary gland neoplasms and is more common in men during their 6-7th decades. It almost exclusively occurs in the parotid gland and bilateral or multifocal tumors. The tumors present as a painless swelling, usually within the lower portion of the salivary gland.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Papillary cystadenoma lymphomatosum
INCIDENCE	4-11.2% of all salivary gland tumors Second most common benign salivary gland tumor
AGE RANGE-MEDIAN	Average age 62 years 60% occur between 50-79 years
SEX (M:F)	Slight male predominance but there has been an increased incidence in women
GEOGRAPHY	Low incidence in African Americans
EPIDEMIOLOGIC ASSOCIATIONS
Tobacco smoking	Smokers have 8x increased risk

 

DISEASE ASSOCIATIONS	CHARACTERIZATION
Malignancy	Rarely lymphoma or carcinoma may arise

 

PATHOGENESIS	CHARACTERIZATION
Clonal analysis of the epithelial component	Hum Pathol 2000;31:1377-1380 Analysis of 7 cases showed a polyclonal pattern using a PCR method based on the trinucleotide repeat polymorphism of the X-chromosome linked human androgen receptor gene (HUMARA) and on random gene inactivation of the gene by methylation
Reactive condition?	Some have suggested this is a reactive condition with extensive metaplasia and a secondary lymphoid response
Molecular assessment of allelic loss in Warthin tumors. Arida M, Barnes EL, Hunt JL. 1Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.	Mod Pathol. 2005 Jul;18(7):964-8 Abstract quote.   Warthin's tumors are benign lesions of the head and neck that have a characteristic morphologic appearance. The etiology of Warthin's tumors is controversial and whether they are true neoplasms or developmental malformations continues to be debated. In this study, we examined 12 Warthin tumors with a molecular and immunohistochemical approach. Immunostains for p53 and p16ink were performed. The epithelial and lymphoid components of each lesion were microdissected and PCR was performed for 13 microsatellite markers at or near common tumor suppressor genes. The results were analyzed semiquantitatively using capillary electrophoresis. Frequency of allelic loss was calculated. The epithelial component of all tumors was negative for p53 and p16ink. By molecular genotyping there was only one case that had one locus with allelic imbalance, while the remainder had no evidence of clonal allelic loss. The immunohistochemical and molecular results in this study lend support to the hypothesis that Warthin tumors are non-neoplastic, as there was no evidence of aberrant staining for tumor suppressor gene protein products and no evidence of consistent clonal allelic losses.

 

LABORATORY/ RADIOLOGIC	CHARACTERIZATION
Radiographs	Can concentrate 99mTc so scintigraphic examination can be performed Can also concentrate radioactive iodine

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
General	Well circumscribed averaging about 2-4 cm Usually cystic with brown fluid and papillary excrescences 10% occur in the deep lobe 8% occur in the periparotid lymph nodes, often found incidentally
VARIANTS
Bilateral or multifocal tumors	10-12% of cases
Papillary cystadenoma lymphomatosum syndrome	Acute onset of pain with sudden increase in size of the tumor May be secondary to leakage of fluid into surrounding tissues and retrograde infection from the oral cavity through Stenson's duct
Extraparotid Warthin's tumor Synderman C, Johnson JT, Barnes EL.	Otolaryngol Head Neck Surg 1986;94:169-175 Review of 176 Warthin's tumors accessioned over a 22 year period at U. of Pittsburgh 14 (8%) were extraparotid and occurred in high cervical lymph nodes adjacent to the parotid gland Occurred in 13 patients between 41-77 years (average 63 years) 7 M:6 F
Extraglandular Warthin's tumours: clinical evaluation and long-term follow-up. Ellies M, Laskawi R, Arglebe C. Department of Otorhinolaryngology, University of Gottingen, Germany.	Br J Oral Maxillofac Surg 1998 Feb;36(1):52-3 Abstract quote Nine patients with extraglandular cystadenolymphoma (Warthin's tumour) were treated between 1965 and 1995 at the Department of Otorhinolaryngology, University of Gottingen. This number corresponds to 2.7% of all Warthin's tumours treated at our clinic so far. Although this rare tumour is well documented by case reports, a controlled follow-up study has not yet been published to the best of our knowledge. The retrospective investigation presented here gives the patients' clinical data and documents therapeutic success. Our results show the complete absence of recurrences after surgical excision of extraglandular cystadenolymphomas.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
General	Hum Pathol 1984;15:361-367 Characteristic appearance and is usually cystic. The cysts are lined by epithelial cells with oncocytic features extending as papillary structures, surrounding an abundant lymphoid stroma with germinal centers. Ratio of B-T cells is 0.8:1 50% of the B lymphocytes contain IgG and 33% contain IgA 77% of tumors are typical subtype
Typical	Epithelial component 50%
Stroma poor	Epithelial component of 70-80%
Stroma rich	Epithelial component of 20-30%
Metaplastic forms
VARIANTS
Metastases	Rarely the lymphoid stroma acts as a lymph node receiving metastases from various carcinomas

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Metastatic carcinoma	Extraparotid Warthin's tumor may occur in high cervical lymph nodes This does not represent a metastasis
Sebaceous lymphadenoma
Lymphoepithelial lesions

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Prognostic Factors	Benign
Survival	Benign
Recurrence	Range from 2-12% Some recurrences may represent multifocal occurrence
Metastasis	J Surg Oncol 1980;15:7-10 Hum Pathol 1980;11:80-83 Lymphomas and carcinomatous transformation have been to known to arise
Treatment	Simple excision

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Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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Last Updated July 15, 2005

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