Clinicopathologic Comparison of Lynch Syndrome-associated and "Lynch-like" XXXX Identified on Universal Screening Using Mismatch Repair Protein Immunohistochemistry.

@entity1 @entity6756 @entity1204 @entity4309 @entity5 @entity4311 @entity14437 @entity4638
UNASSIGNED: Expanded testing for @entity4309 ( @entity4309 ) is increasingly recommended for @entity1 with @entity1204 , and immunohistochemistry (IHC) for @entity5 loss of mismatch-repair (MMR) protein expression is the most common primary screen. This has led to the recognition of MMR-IHC-deficient cases without identifiable mutations on directed germline sequencing. The clinical implications of such " @entity5 are unclear. We here report the clinicopathologic features of putative familial @entity1204 identified on universal MMR-IHC screening with attention to cases with discordant IHC and germline results. The files of the University of Virginia Pathology Department were retrospectively searched for all MMR-deficient @entity1204 identified on screening. Cases were categorized as likely sporadic ( @entity6756 / @entity14437 loss, evidence of @entity6756 promoter hypermethylation) or @entity4309 ( @entity4309 ) (loss of @entity4311 / @entity4638 , @entity4638 , or @entity14437 ). @entity4309 cases were further subdivided into @entity4309 and LL groups on the basis of the presence or absence of a confirmatory mutation by germline testing, and the clinicopathologic features of these cases were compared. A deficiency of >= 1 MMR protein was observed in 31.4% (66/210) of @entity1204 , including 26 @entity4309 cases, 15 of which had germline testing. Directed germline sequencing confirmed @entity4309 in 46.7% (7/15); the remaining cases were classified as LL. High-grade and/or biphasic morphology was seen in 42.9% (3/7) of @entity4309 and 62.5% (5/8) of LL cases; the remaining cases showed low-grade, conventional endometrioid morphology. High level microsatellite instability was observed in 71.4% (5/7) of LL cases. The majority of cases from both groups ( @entity4309 : 85.7% [6/7]; LL: 87.5% [7/8]) were low-stage (T1a/T1b). @entity1204 was the presenting @entity5 in 85.7% (6/7) of @entity4309 @entity1 and 87.5% (7/8) of LL @entity1 . Family history was suggestive of @entity4309 in 28.5% (2/7) of @entity4309 @entity1 and 12.5% (1/8) of LL @entity1 . Screening algorithms based on age and @entity5 history would have failed to identify @entity4309 @entity1 in 57.1% (4/7) of cases. Although universal MMR-IHC identifies @entity1204 @entity1 with @entity4309 who would have been missed using targeted screening algorithms, it also identifies @entity5 with discordant IHC and germline results for which the somatic versus germline origin of the MMR defect is unclear. Further study of this LL group is required before drawing definitive conclusions about their @entity5 risk.
