Diagnostic Value of MAML2 Rearrangements in Mucoepidermoid Carcinoma

Abstract

Mucoepidermoid carcinoma (MEC) is often seen in salivary glands and can harbor MAML2 translocations (MAML2+). The translocation status has diagnostic utility as an objective confirmation of the MEC diagnosis, for example, when distinction from the more aggressive adenosquamous carcinoma (ASC) is not straightforward. To assess the diagnostic relevance of MAML2, we examined our 5-year experience in prospective testing of 8106 solid tumors using RNA-seq panel testing in combinations with a two-round Delphi-based scenario survey. The prevalence of MAML2+ across all tumors was 0.28% (n = 23/8106) and the majority of MAML2+ cases were found in head and neck tumors (78.3%), where the overall prevalence was 5.9% (n = 18/307). The sensitivity of MAML2 for MEC was 60% and most cases (80%) were submitted for diagnostic confirmation; in 24% of cases, the MAML2 results changed the working diagnosis. An independent survey of 15 experts showed relative importance indexes of 0.8 and 0.65 for “confirmatory MAML2 testing” in suspected MEC and ASC, respectively. Real-world evidence confirmed that the added value of MAML2 is a composite of an imperfect confirmation test for MEC and a highly specific exclusion tool for the diagnosis of ASC. Real-world evidence can help move a rare molecular-genetic biomarker from an emerging tool to the clinic.

Mucoepidermoid carcinoma may be devoid of squamoid cells by immunohistochemistry: expanding the histologic and immunohistochemical spectrum of MAML2‐ rearranged salivary gland tumours

“…For example, it is now recognised that very bland, cystic cases previously regarded as Warthin tumours that lack a well-formed bilayer of oncocytes are usually Warthin-like MEC. 16,17,24 While many of these subtypes do not show squamoid differentiation morphologically, all previous variants of MEC have demonstrated evidence of squamous differentiation at least at an immunohistochemical level. Here, we expand the immunohistochemical spectrum of MEC with 10 cases that unexpectedly were negative for p63 and p40 despite confirmation of the presence of MAML2 fusions.…”

“…Far from being a molecular‐only diagnosis, each described MEC variant has also refined the morphologic boundaries between MEC and other tumours. For example, it is now recognised that very bland, cystic cases previously regarded as Warthin tumours that lack a well‐formed bilayer of oncocytes are usually Warthin‐like MEC 16,17,24 . While many of these subtypes do not show squamoid differentiation morphologically, all previous variants of MEC have demonstrated evidence of squamous differentiation at least at an immunohistochemical level.…”

Cystic Salivary Gland Neoplasms: Diagnostic Approach With a Focus on Ancillary Studies

“…MEC may harbor MAML2 (mastermind-like transcriptional coactivator 2) rearrangement. MALM2 rearrangement is the most common gene fusion that can be found in 35% to 77% of MEC cases 12. MAML2 rearrangement is recognized as a distinguishing feature in diagnosis of MEC by WHO tumor classification 13.…”

“…MAML2 rearrangement is recognized as a distinguishing feature in diagnosis of MEC by WHO tumor classification 13. The sensitivity of MAML2 for MEC is reported 60% by a large multi-institutional study 12. MAML2 testing has become particularly useful as multiple morphologic variants of MEC are now known 14–16.…”