Evaluating mismatch repair deficiency in colorectal cancer biopsy specimens.

Mismatch repair (MMR) testing on all new cases of colorectal cancer (CRC) has customarily been preferably performed on surgical specimens, as more tissue is available; however, new clinical trials for the use of immune checkpoint inhibitors in the neoadjuvant setting require MMR testing on biopsy samples. This study aims at identifying advantages, disadvantages and any potential pitfalls in MMR evaluation on biopsy tissue and how to cope with them. The study is prospective-retrospective, recruiting 141 biopsies (86 proficient (p)MMR and 55 deficient (d)MMR) and 97 paired surgical specimens (48 pMMR; 49 dMMR). In biopsy specimens, a high number of indeterminate stains was observed, in particular for MLH1 (31 cases, 56.4%). The main reasons were a punctate nuclear expression of MLH1, relatively weak MLH1 nuclear expression compared to internal controls, or both (making MLH1 loss difficult to interpret), which was solved by reducing primary incubation times for MLH1. A mean of  ≥ 5 biopsies had adequate immunostains, compared to ≤ 3 biopsies in inadequate cases. Conversely, surgical specimens rarely suffered from indeterminate reactions, while weaker staining intensity (p < 0.007) for MLH1 and PMS2 and increased patchiness grade (p < 0.0001) were seen. Central artefacts were almost exclusive to surgical specimens. MMR status classification was possible in 92/97 matched biopsy/resection specimen cases, and all of these were concordant (47 pMMR and 45 dMMR). Evaluation of MMR status on CRC biopsy samples is feasible, if pitfalls in interpretation are known, making laboratory-specific appropriate staining protocols fundamental for high-quality diagnoses.

Clinical and ultrasonographic characteristics of pregnancy-related enhanced myometrial vascularity: prospective cohort study.

OBJECTIVES: To assess the ultrasonographic, epidemiological, clinical and evolutive characteristics of enhanced myometrial vascularity (EMV) following a first-trimester termination of pregnancy (TOP) or management of non-viable pregnancy. METHODS: This prospective study included women who underwent follow-up ultrasound examination 5-6 weeks after a first-trimester TOP or after management of a first-trimester non-viable pregnancy at the University Hospital Polyclinic San Martino of Genoa between March 2021 and March 2022. EMV was characterized using two- and three-dimensional ultrasound and Virtual Organ Computer-aided Analysis. Ultrasonographic diagnosis of EMV was made when an unusual, tortuous myometrial vessel structure, with high-velocity blood flow, protruding towards the endometrium was observed, while an abnormal junctional zone, absent endometrial midline and heterogeneous endometrium supported the diagnosis. Patients with EMV underwent expectant management with planned ultrasonographic follow-up every 2 weeks until resolution. RESULTS: During the study period, 305 women underwent TOP, of whom 132 attended the initial follow-up 5-6 weeks later, at which 52 were diagnosed with EMV. Ninety-six women were managed for a non-viable pregnancy, of whom 32 presented for follow-up, at which six had a diagnosis of EMV. Thus, overall, 164 of 401 women were included in the study and EMV was identified in 58 (35%) of these. The prevalence of EMV 5-6 weeks after a TOP was therefore between 52/305 (17%) and 52/132 (39%), and that after management of a non-viable pregnancy was between 6/96 (6%) and 6/32 (19%). Bleeding/pelvic pain was present in half (29/58) of the women with EMV, and serum human chorionic gonadotropin was detectable in 29% (17/58) at the first follow-up examination. At ultrasound assessment, all cases with EMV presented abundant tortuous myometrial vessels with high-velocity flow projecting from the myometrium towards the endometrium, along with non-uniform heterogeneous endometrium in 97% of cases, which often (67% of these) contained cystic areas, absence of the endometrial midline in 98% of cases and an abnormal junctional zone in 97% of cases (64% interrupted, 33% irregular). Most (67%) women with EMV were parous and 90% of them had undergone TOP rather than management for a non-viable pregnancy. Medical management of the TOP or non-viable pregnancy was more frequent in women with than those without EMV (93% vs 77%, P = 0.023). Multiple regression analysis showed the risk of EMV to be increased following TOP vs non-viable pregnancy (odds ratio (OR), 3.67 (95% CI, 1.16-11.56), P = 0.026) and in parous compared with nulliparous women (OR, 2.95 (95% CI, 1.45-6.01), P = 0.002). All women with EMV underwent expectant management. Eleven women did not return for subsequent follow-up examinations and did not present to our outpatient or emergency facilities, so were lost to further follow-up. Spontaneous resolution of the lesion was observed within 7-16 weeks after the procedure in 96% (45/47) of the remaining cases. Two women chose to undergo surgery for pelvic discomfort, and histology showed the presence of neovessels mixed with retained chorionic villi. CONCLUSION: EMV is a transient and common finding 5-6 weeks following first-trimester TOP or management of non-viable pregnancy. TOP and being parous are risk factors for EMV. Expectant management of EMV is appropriate, because, in almost all cases, this resolves spontaneously, without complications, within 2-4 months. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.