Metatypical Adenoid Cystic Carcinoma: A Variant Showing Prominent Squamous Differentiation With a Predilection for the Sinonasal Tract and Skull Base.

Adenoid cystic carcinoma is a malignant salivary gland neoplasm, commonly involving the major and minor salivary glands. Adenoid cystic carcinoma arising in the skull base region is considerably less common and is characterized by aggressive clinical behavior, perineural invasion, and intracranial extension. Classically, these tumors are composed of ductal and myoepithelial cells, arranged as tubules and cribriform structures, as well as in a solid pattern when higher in grade. The distinctive molecular findings in this tumor are the gene fusions involving the MYB/MYBL1 and NFIB genes. Squamous differentiation, trabecular, and macrocystic growth patterns are exceedingly rare in these tumors and when present can cause significant diagnostic challenges. Squamous differentiation, in particular, is considered by many to be an exclusion criterion for adenoid cystic carcinoma outside of cases with high-grade transformation. In addition, a similar-appearing tumor with squamous differentiation, namely human papillomavirus-related multiphenotypic sinonasal carcinoma, has recently been defined, further complicating this differential diagnosis. Recently, we have come across 3 cases of adenoid cystic carcinomas involving the sinonasal tract and skull base having extensive interconnecting trabecular growth, macrocysts, and squamous differentiation, yet demonstrating the signature fusions involving MYB-NFIB and MYBL1-NFIB by RNA sequencing. In this article, we describe the clinical, histomorphologic, and imaging findings of these cases and propose the appellation "metatypical adenoid cystic carcinoma" for this uncommon variant morphology.