Answer: Acinic cell carcinoma

Histology: Parotid tissue is present as is evidenced by the lobules of serous acini. The parotid parenchyma harbors a nodular mass comprised of a round to polygonal cells with abundant cytoplasm that ranges from eosinophilic to purple and granular. These cells form microcystic spaces. The tumor is surrounded and permeated by a lymphocytic infiltrate with germinal center formations, but a distinct lymph node capsule with subcapsular sinuses is not evident.

Discussion: Acinic cell adenocarcinomas are low-grade adenocarcinomas that demonstrate serous acinar differentiation. The vast majority arises from the serous-predominant parotid gland, but many examples involving the minor salivary glands have also been reported. Females are affected more frequently than males. The age distribution is fairly uniform from the third to the eighth decades of life, and acinic cell adenocarcinoma is the second most common malignant salivary gland tumor to involve children.
The microscopic features of acinic cell adenocarcinoma are extremely variable. Five different cell types are recognized: the acinic cell, the intercalated ductal cell, the clear cell, the non-specific glandular cell, and the vacuolated cell. As demonstrated in this case, the non-specific glandular cell may have abundant pink cytoplasm and be mistaken for the oncocytic cell of oncocytoma. Serous acinar differentiation is most fully developed in the acinic cell. These cells have granular purplish cytoplasm. The microscopic recognition of acinic cell adenocarcinoma also requires a strong appreciation for its diverse growth patterns. The pattern of growth may be solid, microcystic, papillary-cystic, or follicular. With the rare exception of a tumor that undergoes de-differentiation, acinic cell adenocarcinomas are uniformly regarded as low-grade tumors. Patient outcome does not consistently correlate with cell type or with architectural pattern.

When the histologic picture is dominated by some cell type other than the acinic cell, the diagnosis of acinic cell carcinoma may be difficult to establish. For example, a predominance of clear and vacuolated cell might be cause confusion with mucoepidermoid carcinoma, clear cell adenocarcinoma, and metastatic renal cell carcinoma. In such instances, the diagnostic acinic cells can be readily identified using a Periodic Acid-Schiff (PAS) stain: their cytoplasmic secretory granules are PAS positive and diastase resistant. At the architectural level, care must be taken not to misinterpret the solid pattern as normal parotid parenchyma, the papillary-cystic pattern as cystic mucoepidermoid carcinoma, or the follicular pattern as metastatic thyroid carcinoma.

A background histologic feature that easily lends itself to misinterpretation is this dense lymphoid infiltration that is commonly referred to as “TALP” – or Tumor Associated Lymphoid Proliferation. TALP simply represents an immune reaction to the tumor, but because of the way this reaction simulates a lymph node, TALP is often misinterpreted as tumor metastases to a lymph node. Even though this is an understandable error, it can result in inappropriate tumor staging leading to overly aggressive patient management.