Abstract
Aims: The observation of peritumoral granulomatous reactions (PGRs) in two endometrial carcinomas (ECs) with a PMS2-deficient/MLH1-intact expression pattern led us to investigate whether PGRs in EC were specifically associated with DNA mismatch repair (MMR) protein deficiency, particularly PMS2 loss. Methods and results: Hysterectomy specimens from 22 MMR protein-intact and 54 MMR protein-deficient ECs were reviewed with specific attention to the presence of a PGR and a tumour-associated lymphoid reaction [including tumour-infiltrating lymphocytes (TILs) and stromal lymphoid infiltrates]. The MMR protein-deficient ECs included 22 cases with combined MLH1/PMS2 loss, 11 with combined MSH2/MSH6 loss, 11 with isolated MSH6 loss, and 10 with PMS2 loss but intact MLH1 staining (including the two ‘index’ cases). Overall, PGRs were identified in seven of 54 (13%) MMR protein-deficient ECs, five of which showed a PMS2-deficient/MLH1-intact immunophenotype; three of these patients had germline PMS2 mutations and one additional patient had a germline MSH6 mutation. None of the MMR protein-intact tumours showed a PGR. Although five of the seven PGR-positive ECs had a high-grade histological component, six were stage I. Most ECs with PGRs also showed TILs and stromal lymphoid reactions, similarly to MMR protein-deficient ECs in general. Conclusions: MMR protein-deficient ECs, particularly those with PMS2 loss, occasionally show PGRs in addition to stromal lymphoid infiltrates and TILs. Therefore, PGRs could be considered to constitute a histological prompt for consideration of Lynch syndrome. The potential prognostic significance of PGRs in EC requires further study.
Original language | English |
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Pages (from-to) | 428-437 |
Number of pages | 10 |
Journal | Histopathology |
Volume | 73 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Sept 2018 |