Warthin's Tumor

Warthin�s Tumor (WT) has also been referred to as

cystadenolymphoma, adenolymphoma, and papillary
cystadenoma lymphomatosum.

It is the second most common benign salivary gland

tumor after pleomorphic adenoma. It accounts for 5% to
6% of all neoplasms of salivary glands and up to 12% of
benign parotid tumors.

WT occurs in 3rd to 7th decades of life with a slight male

predominance. Risk factors include smoking (8-fold
higher risk than non-smokers) and radiation exposure. 

WT predominantly involves the parotid gland and

presents as a painless mass. Rare cases involving the
submandibular gland and minor salivary glands have been
reported. 

Bilateral and multifocal WT are not uncommon. This

gross image of a WT shows solid and cystic components.
The pearly white nodules in the cyst wall are hyperplastic
lymphoid follicles covered by oncocytic epithelium.
Fine needle aspiration of Warthin�s tumor
shows cohesive sheets and clusters of
epithelial cells with oncocytic
features and background of lymphocytes (as
seen here; Diff-Quik stain).

The oncocytic cells are characterized by abundant

granular eosinophilic cytoplasm and round
centrally located nuclei.

The background may show mucus or thick fluid associated

with lymphoid cells.
Fine needle aspirate (FNA) smear of a Warthin�s tumor
(WT) showing cohesive sheets and clusters of oncocytic
cells arranged in a honeycomb pattern.

The background usually shows scattered lymphocytes,

although they are not seen in this image (PAP stain). 

Prior manipulation or FNA can cause secondary

changes in WT.

They include cytologic atypia, metaplasia (squamous and

mucous), hemorrhage, infarction, necrosis, acute and
chronic inflammation, fibrosis, granulation tissue formation
and changes of pseudoinvasion.
Grossly Warthin�s tumor (WT) ranges in size from 1.0
� 8.0 cm and has smooth encapsulated outer
surface.

The cut surface is usually shows solid and cystic

areas filled with mucoid, brown material.

The cystic areas may demonstrate papillary

projections.

This low power view of WT shows papillary structures

lined by oncocytic epithelium (left side) and dense
lymphocytic infiltrate with germinal center
formation (right side).
Warthin�s tumor (WT) has a distinct morphologic
appearance composed of papillary structures lined
by bi-layered oncocytic
epithelium forming cystic spaces and the stroma
with lymphoid component (as seen in this low
power micrograph).

Other inflammatory cells such as plasma cells, mast

cells, histiocytes and giant cells can be seen. 

Mucous cells and sebaceous glands can also be

seen and their presence may raise the possibility of
mucoepidermoid carcinoma.
This low power micrograph shows Warthin�s Tumor
composed of papillary and tubular
structures lined by bi-layered oncocytic
epithelium and the dense lymphocytic
infiltrate with prominent germinal center
formation.

The eosinophilic granular appearance of the

cytoplasm of oncocytic cells is due to abundant
mitochondriawhich can be demonstrated
by phosohotungstic acid-hematoxylin
stain (PTAH stain; appear as blue-black cytoplasmic
granules).
The epithelial component of Warthin�s tumor
is cytokeratin positive (CK7, 8, 18, and 19) and
the lymphoid stroma consists predominantly of IgA-
producing polyclonal B-cells with a few T-cells,
mast cells, and S-100-positive dendritic cells.

This high magnification view of the previous image shows

dense lymphocytic infiltrate with prominent germinal
center formation.

The epithelial component consists of tubular and papillary

structures lined by bi-layered epithelium composed of tall
columnar luminal cell layer and cuboidal oncocytic cells on
outer side.
High power view of Warthin�s tumor showing papillary
structures lined by bi-layered oncocytic
epitheliumcomposed of tall columnar luminal
cell layer and a discontinuous layer of basally
locatedcuboidal cells.

The stroma shows dense lymphocytic

infiltrate with germinal center formation.

The cystic spaces are filled with eosinophilic granular

material.
Higher magnification image of Warthin�s tumor
demonstrates papillary structures lined by bi-
layered epithelium.

The inner layer (basally located) is discontinuous and

composed cuboidal cells with eosinophilic granular
cytoplasm and vesicular round nuclei.

The columnar cells are located on the luminal aspect. The

stroma is well demarcated and composed of benign
lymphocytic infiltrate.
Warthin�s tumor (WT) is believed to develop
from neoplastic transformation of salivary
duct epithelium that is entrapped in intra-
parotid lymph nodes during embryonic
development.

The presence of subcapsular sinuses in some cases of

WT, the occurrence of WT in periparotid lymph nodes, and
the presence of B- and T-cells in the lymphoid component
of WT appear to support this theory.

This high power image of WT shows bi-layered oncocytic

epithelium and the stroma composed of dense
lymphocytic infiltrate with prominent germinal center
formation.
This image of Warthin�s Tumor shows tubular structures
composed of bi-layered oncocytic epithelium surrounded
by stroma with dense lymphocytic infiltrate.
The diagnosis of Warthin�s tumor (WT) is straight-
forward in most cases.

Cases with a predominant oncocytic cell component may

raise suspicion for oncocytoma, mucoepidermoid
carcinoma, oncocytosis or acinic cell
carcinoma.

When squamous and mucinous cell metaplasia is present

in WT, its distinction from mucoepidermoid carcinoma may
be challenging. 

Mucoepidermoid carcinomas often
carry translocations
t(11;19) and t(11;15)resulting in CRTC1-
MAML2 and CRTC3-MAML2 fusion genes � a
finding not seen in Warthin�s tumor.

This image shows classic appearance of Warthin�s

tumor with oncocytic epithelium arranged in tubules and
nests with associated lymphoid infiltrate.
Higher magnification image of Warthin�s tumor showing
oncocytic cells with eosinophilic granular cytoplasm and
vesicular round nuclei with prominent nucleoli.

The background shows benign lymphocytes and a few

plasma cells.
The tumor has multicystic appearance here
with oncocytic epithelium lining fluid-filled
spaces.

The cystic areas may contain cholesterol crystals,

cellular debris, or laminated bodies.

The lymphoid stroma is deficient in this focus.

Complete surgical excision with adequate surgical
margins is usually curative.

Local recurrence may follow an incomplete excision of

Warthin�s tumor. 

Malignant transformation is seen in less than

0.1% cases and can occur in either epithelial
component (squamous cell carcinoma, oncocytic
carcinoma, adenocarcinoma NOS, mucoepidermoid
carcinoma) or lymphoid component (Non-Hodgkin�s
lymphoma).

The image shows papillary structures lined by bi-layered

oncocytic epithelium and enclosing scant amount of
lymphocytic infiltrate.
Higher magnification image of the previous image showing
papillary structures lined by bi-layered oncocytic
epithelium and enclosing scant amount of lymphocytic
infiltrate.