Navigating small biopsies of salivary gland tumors: a pattern-based approach

Diagnosis of salivary gland tumors on small biopsy can be difficult because of overlapping morphology, limited tissue availability, and technical artifact. Although a specific diagnosis is not feasible in all cases, a cautious and thoughtful approach to the differential diagnosis and a keen awareness of clinical consequences can facilitate the most complete and useful classification possible. In this review, we present a general strategy for the evaluation of small salivary biopsies, including consideration of clinical and radiographic information, systematic assessment of histologic patterns, and judicious use of immunohistochemistry and molecular studies. We then focus on the distinctive differential diagnoses raised by 6 specific histologic patterns: tubular and cribriform architecture, squamous differentiation, mucin and other secretions, high-grade cytology, epithelial and lymphoid elements, and oncocytic features. Throughout this systematic and pattern-based approach, we focus on practical and cost-effective strategies to overcome the most common diagnostic challenges in limited material. •Diagnosis of salivary gland tumors on small biopsy can be challenging because of overlapping histologic and immunohistochemical features of various tumor types as well as technical limitations including crush artifact, sampling error, and limited size.•A general strategy for evaluation of small salivary biopsies should include consideration of radiographic information, histologic patterns, and ancillary studies, with a cautious approach informed by the clinical consequences of all possible diagnoses.•Recognition of specific histologic patterns including tubular and cribriform architecture, squamous differentiation, mucin and other secretions, high grade cytology, epithelial and lymphoid elements, and oncocytic features can help narrow the differential diagnosis.