Section 3 -

Oncocytic Tumors (Dr. Powers) William C. Faquin, M.D., Ph.D. Celeste N. Powers, M.D., Ph.D.

Clinical History: 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. Cytologic Findings: 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. Section 3 - Figure 1 Section 3 - Figure 2 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 clusters Large polygonal cells with abundant finely vacuolated to granular cytoplasm PAS+D resistant cytoplasmic zymogen granules Indistinct cell borders Bland nuclear cytologic features Background naked nuclei + lymphocytes Psammoma bodies may be seen Section 3 - Figure 3 Section 3 - Figure 4 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: Oncocytoma Warthin tumor Acinic cell carcinoma Metastatic renal cell carcinoma Pleomorphic adenoma with oncocytic metaplasia Mucoepidermoid carcinoma, oncocytic variant 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.