An Integrated Cytologic and Histologic Approach to the Diagnosis of Salivary Gland Tumors
Section 3 -
Oncocytic Tumors (Dr. Powers)
William C. Faquin, M.D., Ph.D.
Celeste N. Powers, M.D., Ph.D.
A 71 year-old man with a 1.5 cm right non-tender submandibular mass that had been slowly increasing in
size for 1.5 years.
The smears were cellular and showed large polygonal cells in loosely cohesive clusters
and singly. Many clusters are 3-demensional rather than flat and some have transgressing blood vessels.
The cells have a low N/C ratio owing to the abundant delicate cytoplasm that in Romanowsky-stained
preparations shows small cytoplasmic vacuoles. The nuclei are cytologically bland, and round to oval
with small distinct nucleoli. The background is clean except for occasional naked nuclei. Based upon
these cytologic features, a diagnosis of acinic cell carcinoma was made. The patient had a total
submandibulectomy performed, and histologic examination confirmed the diagnosis of acinic cell carcinoma.
Discussion: Acinic Cell Carcinoma
Acinic cell carcinoma is the second most common salivary gland malignancy, representing approximately
4-6% of all salivary gland tumors and up to 17% of salivary gland malignancies. It is generally a
low-grade tumor although high-grade forms do occur. Acinic cell carcinoma typically presents as a
circumscribed, mobile, slowly growing mass which occasionally is painful. Acinic cell carcinoma is best
recognized in Diff-Quik stained specimens, which highlights its cytoplasmic
vacuoles distinguishing the tumor cells from oncocytes of Warthin tumor and oncocytoma.
Cytoplasmic zymogen granules are PAS positive diastase resistant and negative for PTAH…the opposite is
true of oncocytomas. When acinic cell carcinomas show well-defined features of serous acinar
differentiation, the tumor is easily recognized both cytologically and histologically. However, acinic
cell carcinoma can show features of intercalated duct cells or of a non-descript adenocarcinoma, in which
case, it is much more challenging to recognize the tumor specifically as acinic cell carcinoma. A
careful search for focal acinar differentiation, zymogen granules, and cytoplasmic vacuolization is
helpful. The cytoarchitectural patterns seen in acinic cell carcinomas include solid, microcystic,
papillary, and follicular patterns. Other oncocytic tumors besides oncocytoma in the differential
diagnosis include the oncocytic variant of mucoepidermoid carcinoma which in contrast to acinic cell
carcinoma has at least some mucin-positive cells; metastatic renal cell carcinoma, and rarely,
pleomorphic adenoma with oncocytic metaplasia.
Cytologic features of acinic cell carcinoma:
- Cellular smear of serous-type
acinar cells or intercalated duct cells
- Sheets and crowded 3-D
- Large polygonal cells with
abundant finely vacuolated to granular cytoplasm
- PAS+D resistant cytoplasmic
- Indistinct cell borders
- Bland nuclear cytologic
- Background naked nuclei
- Psammoma bodies may be
Histologic Features of Acinic Cell Carcinoma:
The cells of this tumor can exhibit a variety of patterns including acinar,
intercalated duct, vacuolated, clear, and non-specific glandular. The most classic appearance is of a
tumor comprised of polygonal cells with abundant delicate, vacuolated basophilic cytoplasm in solid
nests. The stroma consists of fibrovascular septae. Other architectural patterns that can be seen
include papillocystic, microcystic, and follicular. While they may be sparse, occasional dark-staining
zymogen granules can often be found in cells with acinar differentiation, and they can be highlighted
using a PAS + diastase stain.
Section 3 - Figure 5
Acinic cell carcinoma comprised of polygonal epithelial cells with serous acinar differentiation. The cells have abundant basophilic cytoplasm, and dark zymogen granules are apparent.
Differential Diagnosis of Oncocytic Salivary Gland Lesions:
In assessing an oncocytic lesion of the salivary gland, Diff-Quik stains for identification of
cytoplasmic vacuoles is helpful, and sometimes, histochemical stains for intracellular mucin, PAS +
diastase, and PTAH can be useful for narrowing the differential diagnosis.
- Warthin tumor
- Acinic cell carcinoma
- Metastatic renal cell
- Pleomorphic adenoma with
- Mucoepidermoid carcinoma,