Citations

Abstract Objectives Given the increased complexity of molecular and cytogenetic testing (MOL-CG), the Society for Hematopathology Education Committee (SH-EC) was interested in determining what the current expectations are for MOL-CG education in hematopathology (HP) fellowship training. Methods The SH-EC sent a questionnaire to HP fellowship program directors (HP-PDs) covering MOL-CG training curricula, test menus, faculty background, teaching, and sign-out roles. These findings were explored via a panel-based discussion at the 2018 SH-EC meeting for HP-PDs. Results HP fellows are expected to understand basic principles, nomenclature, and indications for and limitations of testing. Interpretation of common assays is within that scope, but not necessarily proficiency in technical troubleshooting of testing or analysis of complex raw data. Conclusions The consensus was that HP fellows should understand the components of MOL-CG testing necessary to incorporate those results into an accurate, clinically relevant, and integrated HP report.

536 Background: The management of malignant mesothelioma of the tunica vaginalis of the testes (MMTVT) is not clearly defined, though retroperitoneal lymph node dissection has been reported as a diagnostic and potentially therapeutic option. Herein we present our experience with robot assisted retroperitoneal lymph node dissection (RARPLND) in a series of patients with MMTVT. Methods: The Mayo Clinic cancer registry was queried from 1972-present for all patients who had a diagnosis of MMTVT. Six patients were identified, five of whom were treated with RPLND, where four underwent RARPLND. Data was collected on pertinent demographic, preoperative, perioperative, postoperative outcomes and follow-up oncological data. Results: In five patients who underwent RPLND, the median age was 50 years (IQR 34-51), median BMI was 26.9 (IQR 26.4-30.6). Four patients originally presented with right sided symptomatic hydroceles, while one presented with right sided chronic epididymitis. Orchiectomy (one simple, two inguinal radical) was performed in three patients and hydrocelectomy in the other two patients prior to presentation. Preoperative cross-sectional imaging, including PET-CT scan in three patients, was negative for lymphadenopathy or metastasis. RARPLND was performed in 4/5 (80%) cases and concomitant hemiscrotectomy in 4/5 (80%) cases. Full bilateral template was performed in three patients and right modified template was performed in the remaining two. Median lymph node yield was 29 (IQR 22-32) and median blood loss was 275 cc (IQR 200-300). Positive retroperitoneal lymph nodes were found in 3/5 (60%) cases. Final margins of hemiscrotectomy were negative in all four cases. All patients who underwent RARPLND were discharged home on postoperative day one. One patient received four cycles of adjuvant Cisplatin and Pemetrexed. Mean follow-up was 27 months (range 2-47). No patients recurred. Conclusions: MMTVT is a very rare malignancy with high potential for retroperitoneal lymph node dissemination. Regardless of the approach, RPLND may provide both a diagnostic and therapeutic benefit, with the robotic approach affording a potentially expedited recovery.

492 Background: There is scant information about intermediate and long-term comparative outcomes between RARC and ORC, with the exception of a recent, small randomized-trial. We present our experience with RARC and ORC in managing bladder cancer patients who require cystectomy. Methods: A query of all patients who underwent radical cystectomy for a primary bladder tumor between 01/2007 and 6/2017 at our institution yield 469 patients. Data was collected on patient demographics, pre-operative information, operative details, pathology, and follow-up. Most RARCs were performed by a high-volume robotic surgeon who preferentially used the robotic approach at the start of all cases. Statistical analyses were generated using SPSS 22.0. Any open conversions were analyzed in the RARC cohort. Results: In 469 total patients, 197 (42.0%) and 272 (58.0%) underwent RARC and ORC, respectively. There were 163 (82.7%) and 224 (82.4%) males in each group and the mean ages (SD) were 71.5 (8.6) and 70.2 (10.5) years. Mean follow-up (SD) was 75 (37.7) and 61 (35.7) months, respectively. There were 130 (66.0%) and 172 (63.2%) patients who presented with T2 or greater disease (p=0.605). Soft-tissue margin rates were 4.1% for RARC and 6.7% for ORC patients (p=0.232). Neoadjuvant chemotherapy was used in 56.9% of RARC and 45.9% of ORC patients with ≥ cT2 disease (p=0.058). The 5-year overall survival was 60.0% vs 57.0% and the 10-year overall survival was 40.3% vs 44.8% for RARC vs. ORC patients, respectively (p=0.283). The 5-year recurrence-free survival was survival (RFS) was 71.7% vs 65.7% and the 10-year RFS was 70.5% vs 62.3% for the RARC vs. open groups, respectively (p=0.078). Aggressive histological variants, which were associated with greater likelihood for recurrence, were more common in the ORC group (13.7 vs. 22.4% p=0.013). Atypical recurrences (i.e. peritoneal, extrapelvic nodes) occurred in 6 (3.0%) and 14 (5.1%) RARC and ORC patients, respectively (p=0.266). Conclusions: In experienced hands, intermediate and long-term outcomes of RARC appear equivalent to ORC with regards to recurrence free survival, overall survival, and risk of atypical recurrences.

Abstract Aims To investigate valve sizing and the haemodynamic relevance of the predicted left ventricular outflow tract (LVOT) in patients with mitral annular calcification (MAC) undergoing transatrial transcatheter valve implantation (THV). Methods and results In total, 21 patients undergoing transatrial THV, multiplanar reconstruction (MPR), maximum intensity projection (MIP), and cubic spline interpolation (CSI) were compared for MA sizing during diastole. In addition, predicted neo-LVOT areas were measured in 18 patients and correlated with the post-procedural haemodynamic dimensions. The procedure was successful in all patients (100%). Concomitant aortic valve replacement was performed in eight patients (43%) (AVR group). Sizing using MPR and MIP yielded comparable results in terms of area, perimeter, and diameter, whereas the dimensions obtained with CSI were systematically smaller. The simulated mean systolic neo-LVOT area was 133.4 ± 64.2 mm2 with an anticipated relative LVOT area reduction (neo-LVOT area/LVOT area × 100) of 59.3 ± 14.7%. The systolic relative LVOT area reduction, but not the absolute neo-LVOT area, was found to predict the peak (r = 0.69; P = 0.002) and mean (r = 0.65; P = 0.004) post-operative aortic gradient in the overall population as well as separately in the AVR (peak: r = 0.91; P = 0.002/mean: r = 0.85; P = 0.002) and no-AVR (peak: r = 0.89; P = 0.003/mean: r = 0.72; P = 0.008) groups. Conclusion In patients with severe MAC undergoing transatrial transcatheter valve implantation, MPR, and MIP yielded comparable annular dimensions, while values obtained with CSI tended to be systematically smaller. Mitral annular area and the average annular diameter appear to be reliable parameters for valve selection. Simulated relative LVOT reduction was found to predict the post-procedural aortic gradients.

SummaryThis study evaluated the differences in clinical features of 1077 newly diagnosed AL amyloidosis patients with renal involvement (n = 229, 21%), both cardiac and renal involvement (n = 443, 41%) and cardiac involvement (n = 405, 38%). Significant differences in dFLC (difference in involved and uninvolved light chains) were noted (renal, both, cardiac median: 83, 234 and 349 mg/l, P < 0.001). The proportion of patients with ≥ 10% bone marrow plasma cells (BMPCs) was lowest in renal only patients: 44%, 57%, 64%, respectively, P < 0.001. In a multivariate linear regression model incorporating organ involvement type and BMPCs ≥10%, organ involvement was a significant predictor of dFLC (P < 0.001). Median overall survival (OS) across the three groups was 83 vs. 19 vs. 16 months (P < 0.001) in patients not undergoing transplant and 5‐year OS in patients undergoing transplant was 90% vs. 75% vs. 64% (P = 0.007), respectively. In conclusion, renal involvement alone or renal + cardiac involvement in AL amyloidosis is associated with lower circulating light chain burden, which cannot be fully explained by BMPC burden alone. Increased sensitivity of the kidney to light chains, given significant interactions with the renal tubular system and secretion of modified light chain products may play a role in pathogenesis of renal AL amyloidosis and warrants further investigation.

Abstract We evaluated the impact of achieving a rapid response in 840 newly diagnosed multiple myeloma patients from 2004 to 2015. Rates of very good partial response (VGPR) or better were 29% (240/840) after 2 cycles of treatment, 42% (350/840) after 4 cycles of treatment, and 66% (552/840) as best response. Early responders after 2 cycles of treatment had higher rates of light chain disease, anemia, renal failure, International Staging System (ISS) stage III disease, and high-risk cytogenetics, especially t(4;14), and were more likely to have received triplet therapy and undergo transplant. Median progression-free survival (PFS) and overall survival (OS) were not different among patients with ≥VGPR and &lt;VGPR after 2 cycles (PFS, 28 vs 30 months, P = .6; OS, 78 vs 96 months, P = .1) and 4 cycles (PFS, 31 vs 29 months; OS, 89 vs 91 months, P = .9), although both were improved, with ≥VGPR as best response (PFS, 33 vs 22 months, P &lt; .001; OS, 102 vs 77 months, P = .003). On multivariate analysis stratified by transplant status, achievement of ≥VGPR after 2 cycles was not associated with improved PFS (hazard ratio [95% confidence interval]; transplant cohort, 1.1 [0.7-1.6]; nontransplant cohort, 1.2 [0.8-1.7]) or OS (transplant cohort, 1.6 [0.9-2.9]; nontransplant cohort, 1.5 [1.0-2.4]). Covariates in the model included high-risk cytogenetics, ISS stage III, triplet therapy, creatinine ≥2 mg/dL, light chain disease, and age. Although patients with high-risk disease are more likely to achieve early response, a rapid achievement of a deep response by itself does not affect long-term outcomes.

SummaryDespite the absence of high‐risk cytogenetics and lower International Staging System (ISS) stages, a subset of patients with multiple myeloma (MM) experience poor overall survival (OS). We studied 1461 patients with newly diagnosed MM to identify patient and disease characteristics that predict a high‐risk phenotype among standard‐risk patients. Fifty‐six percent of all patients presented with standard‐risk disease. Among them, advanced age, extremes of body mass index, non‐hyperdiploid karyotype and abnormal lymphocyte counts were associated with worse OS. Standard‐risk patients with 0–1 of these adverse factors (hazard ratio [HR] 0·32, 95% confidence interval [CI] 0·24–0·43, P < 0·001) and 2 adverse factors (HR 0·54, 95% CI 0·41–0·72, P < 0·001) experienced better OS than high‐risk patients. Two or more adverse factors were present in 17% of standard‐risk patients and were associated with OS comparable to high‐risk patients (HR 0·91, 95% CI 0·67–1·24, P = 0·548). Predictive power among standard‐risk patients was improved using score groups compared to ISS stages. Patients with standard‐risk MM are a heterogeneous group with one in six patients experiencing OS comparable to high‐risk disease. Patients at risk can be identified using readily available patient and disease characteristics. These findings emphasize the importance of accurate risk stratification and help explain part of the heterogeneity observed in clinical practice.