Update of Common Salivary Tumors
Moderators: Dr. John Eveson and Dr. Silloo Kapadia
Section 4 -
Oncocytic tumors are relatively rare, representing 1.9% of over 8000 parotid
consultations received at the AFIP.  A series of 68 patients with oncocytic salivary tumors,
84% occurred in the parotid, 11% in the submandibular gland and 5% were incidental findings within
cervical lymph node. 
There is no gender predilection.
A history of previous
radiation exposure has been documented in 20% of patients with oncocytic tumors, and these patients tend
to present two decades earlier.  Familial association, and association with Birt-Hogg-Dube
syndrome have been reported.
Bilateral oncocytomas may occur in 7% of cases, these are
usually associated with diffuse oncocytosis rather than single tumor nodules.
noted that bilateral oncocytomas occur more frequently than the coincidence of other bilateral salivary
On gross examination, parotid or submandibular oncocytomas may appear as single, small,
well-circumscribed, brown tumors, which may have central star-like fibrosis. Cyst formation may be
seen. Oncocytomas may also occur as part of a generalized process, oncocytosis, in which the entire
gland undergoes oncocytic metaplasia and hyperplasia. In this case the glandular architecture is
entirely replaced by multiple brown, tan nodules, some which central scarring, with some dominant tumor
Histologically, most oncocytic tumors are solid, with a variable cystic component. The
oncocytes form organoid nests and trabeculae. Cytologically, oncocytes can be cuboidal with abundant
bright pink granular cytoplasm and decreased ratio compared to normal parotid ductal cells. They can
also have a columnar shape, in which case the nuclear\cytoplasmic ratio remains relatively normal.
Oncocytic nuclei are typically very round and centrally placed, the nucleoli may be single and prominent.
"Pyknocytes", oncocytes with shrunken condensed nuclei, may be seen. The presence of tall oncocytes with
tapered ends, binucleated cuboidal oncocytes, and pyknocytes may be useful is distinguishing oncocytomas
from other salivary neoplasms (see below). Tumor hyalinization can be present entrapping nodules of
oncocytes and giving a false impression of invasion. Likewise, oncocytomas may be hypervascular with
dilated vessels, giving the false effect of vascular invasion.
Clear cell change within oncocytes, a seemingly contradictory concept, may cause
diagnostic confusion for clear cell oncocytomas may resemble acinic cell carcinomas.
association between clear cell oncocytosis, prior facial radiotherapy, bilateral multifocal disease, and
recurrence after parotidectomy has been seen.  Ultrastructural examination has shown that
glycogen accumulation may be responsible for this clear change.
examination reveals eosinophilic oncocytes scattered among the clear oncocytes. Oncocytosis of the
surrounding parotid gland is also very common; it produces a "checkerboard" pattern of parotid adipose
tissue and oncocytic nodules. This finding may also be helpful in establishing the diagnosis of
oncocytoma, as opposed to other clear cell entities.
The pathological differential diagnosis includes acinic cell carcinoma, clear cell carcinoma,
mucoepidermoid carcinoma, high-grade salivary duct carcinoma and metastatic renal cell carcinoma. The
balloon cell variant of melanoma is also a "clear cell" tumor and may metastasize to periparotid lymph
nodes. Identification of tapered oncocytes, binuclear oncocytes, pink granular cytoplasm, and
surrounding parotid oncocytosis is very helpful in establishing the correct diagnosis. Phosphotungstic
acid hematoxylin stain, incubated over for 48 hours (rather than the standard overnight incubation) is
also helpful; the mitochondria appear as cytoplasmic blue granules under oil immersion microscopy.
Electron microscopy (EM) may be the final arbitrator in distinguishing mitochondria from zymogen
The ultrastructural morphological alterations seen in oncocytomas suggest that tumorigenesis is
primarily due to mitochondrial alterations. There is a growing awareness of the significance of
mitochondrial DNA (mtDNA) deletions in various disease states, and point mutations in a number of
cancers, including head and neck carcinoma. Deletions in mtDNA have been associated with cigarette
smoking. Warthin's tumors, which are also characterized by abundant, morphologically altered
mitochondria, have been clearly associated with smoking.  Therefore it is logical to
investigate the role of mtDNA mutations in Warthin's tumors and oncocytomas.
deletion at 4977bp ("common deletion") was found in parotid tissues of both smokers and non-smokers, with
an age accumulation effect. However point mutations (specific base substitutions) were present in the
parotid tissue of 5 of 23 smokers, but not in any of the 16 non-smokers. 
The majority of parotid and submandibular oncocytomas behave in a benign fashion after resection, even
if rare aggressive features such as perineural invasion have been identified.  Local
recurrence is unusual and often the result of persistent multifocal oncocytosis in the remaining deep
parotid lobe. Malignant parotid or submandibular oncocytomas are very unusual, but have been
documented. These tumors may be either locally aggressive or infiltrative or can metastasize, either to
cervical lymph nodes or in a widespread fashion to CNS, bone, liver and lung.
many of these reports have short follow-up periods, some papers have documented a protracted course with
single or multiple local recurrences and distant metastases. Tumor related mortality might occur up to a
decade after the original diagnosis. Malignant parotid and submandibular oncocytomas usually appear
aggressive from the onset, only rarely may there be evidence of pre-existing benign oncocytoma or
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