Citations

Angiosarcoma of the colon is rare, as is colonic amyloidosis. To our knowledge, there have been no reported cases of angiosarcoma arising in association with amyloid deposition. Herein, we described a case of 77-year-old man who presented with hematochezia, and a sigmoid mass was found on colonoscopy. Histologic examination of the resected specimen showed extensive nodular deposition of AL-lambda amyloid material in the colonic wall, as well as high-grade angiosarcoma which was closely intermingled with the amyloid deposits. While the occurrence of both colonic amyloidosis and angiosarcoma in this patient may represent pure coincidence, given the intimate association of the angiosarcoma and the amyloid deposition and the rarity of both of these lesions, we hypothesize that angiosarcoma could be secondary to amyloid deposition.

Abstract Funding Acknowledgements Mayo Clinic Background Variability in Doppler signals is common in patients with atrial fibrillation (AF) and AF is common in low-gradient AS (LGAS). Presence of high single beat Doppler signals (peak velocity ≥4m/s or mean gradient ≥40mmHg) is not factored into decision-making in low-gradient aortic stenosis (LGAS). Objective Determine prevalence of at least one high Doppler signal in AF LGAS and its relationship to computed tomography aortic valve calcium score (AVCS) versus sinus rhythm (SR) high-gradient aortic stenosis (HGAS). Methods Consecutive patients with aortic valve area ≤1cm2 and left ventricular ejection fraction ≥50% during echo were identified (January 1, 2012-December 31, 2016). At least three consecutive Doppler signals were averaged in sinus rhythm (SR) and five in atrial fibrillation (AF). Results Of 1,854 patients, age 76± 11 years, male 52%, 301/1,854 (16%) were in AF and LGAS was present in 122/301 (41%). At least one high Doppler signal in AF LGAS was present in 43/122 (35%). AVCS within 1 year of echo was available for 36% of patient with SR HGAS and 34% of AS LGAS. Median AVCS was not different in SR HGAS 2424 (IQR 1623, 3445) vs AF LGAS with at least one high Doppler signal 2509 [IQR1547, 3119], p =0.10 AVCS threshold for severe AS (men >2000 women >1200) was met in 80% SR HGAS vs 86% AF LGAS with high signals. Conclusions High Doppler signals in AF LGAS are associated with high AVCS more frequently exceeding thresholds for severe AS. Single-beat high Doppler signals instead of the average correlate better with AVCS and classic HGAS.

Abstract Aims The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS). Methods and results Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50–3.04, P = 0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78–1.58, P = 0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting. Conclusion In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621.

Abstract Abstract 1545 Introduction: The diagnosis of peripheral T-cell lymphoma (PTCL) is difficult and accurate diagnosis and subclassification relies on correlating histologic, immunophenotypic, molecular genetic, and clinical data. Evidence-based guidelines for the appropriate diagnostic work-up of PTCL are lacking. The objective of this study was to evaluate a large series of PTCLs by experienced hematopathologists with a tiered approach to immunohistochemistry (IHC) and molecular genetic characterization to document overall diagnostic accuracy and clinical relevance using this approach. Methods: 7 experienced hematopathologists from 5 institutions reviewed 374 cases of peripheral T and NK cell lymphomas (referred to collectively as PTCL). 6 cases of cutaneous T-cell lymphoma were excluded after final review in addition to 29 non-PTCL cases submitted as control cases to mimic diagnostic practice during the review. Cases received tier 0, 1 and 2 diagnoses by 3 independent pathologists, based on review of hematoxylin and eosin (HE) stain with basic demographic data, panel 1 IHC (CD3, CD5, CD10, CD20, CD21, CD30, CD45, PAX5), and panel 2 IHC (CD2, CD4, CD7, CD8, CD23, PD1, CD56, EBER, ALK, TIA1, TCRg, TCRbF1), respectively. A tier 2b diagnosis was then rendered after gene rearrangement data were available. A final consensus diagnosis was rendered after discussion of each case by the 3 reviewers with all available clinical data. Overall survival (OS) was assessed using Kaplan-Meier (KM) curves and Cox proportional hazards models. Results: 1122 individual diagnoses leading to 339 final consensus PTCL diagnoses were rendered. 341 (91%) cases had complete phenotypic data and 241 had gene rearrangement data. There was no bias of missing data according to final diagnosis subtype. Reviewer diagnoses using specific WHO subclassification were 16.3%, 36.9%, 82.7%, and 85.9% for tier 0, 1, 2, and 2b, demonstrating a significant increase in diagnostic certainty after a complete IHC panel. Gene rearrangement only contributed to a change in diagnosis in 51/650 (8%) individual reviews. Across all 374 cases, a small number of cases (n=28, 7.5%) showed no agreement among the 3 independent reviewers after tier 2b and required debate. These generally represented refinement of the subclassification of a PTCL. The most common disagreements were between PTCL, not otherwise specified (nos) vs. unclassifiable T-cell lymphoma, and PTCL, nos vs. angioimmunoblastic T-cell lymphoma (AITL). Currently, OS data was available in 198 cases and 52% have died (median age follow-up of 15 months for those still alive, range 0–160 mo). Figure 1 shows the KM survival curves for types with more than 10 cases. Of note, unclassifiable PTCL cases had poor OS, comparable to PTCL nos; a trend was seen for CD30+ ALK- ALCL to have a longer OS compared to PTCL nos (HR=0.5, 95% CI: 0.21–1.19, P=.09). EBER positivity in tumor cells was associated with poor OS in the cohort of all PTCL patients (HR=2.32, 95% CI: 1.28–4.23, p=0.006, Figure 2); the association was similar when nasal NK/T-cell lymphoma cases were excluded (HR=2.50, 95% CI: 1.00–6.26, p=0.05). Trends for poor prognosis were also seen for TIA-1 expression in PTCL, nos (HR=1.9, 95% CI 0.91–3.96, P=.09) and PD1 expression in AITL (HR=6.25, 95% CI 0.85–46.09, P=.07). Clinical data collection is still ongoing and will be updated. Conclusions: We demonstrate the diagnostic accuracy among experienced hematopathologists of a defined IHC panel, showing an overall ability to reach consensus diagnosis of 93% in PTCL cases. The resulting consensus diagnostic subtypes showed expected outcomes relative to other large series of PTCLs, and EBER positivity is a poor prognostic marker among T and NK cell lymphomas. A tiered approach to IHC is recommended when a PTCL is under differential diagnostic consideration since the first tier can often resolve the main question of whether a lesion is reactive or lymphoma. This can lead to more efficient use of the expanded tier 2 panel that will enable diagnosis and specific subclassification of PTCL. Gene rearrangement studies are not required in the great majority of cases. This evidence-based approach to the diagnosis of PTCL should inform practicing pathologists, clinical trial design, and policy makers regarding required ancillary studies in this group of diseases. Disclosures: Hsi: Allos: Research Funding. Said:Allos: Research Funding. Macon:Allos: Research Funding. Rodig:Allos: Research Funding. Gascoyne:Seattle Genetics: Research Funding. Ondrejka:Allos: Research Funding. Dorfman:Allos: Research Funding. Maurer:Allos: Research Funding. Dogan:Allos: Research Funding.

Abstract Abstract 3992 Little is known about the rare entities of heavy and light chain amyloidosis (AHL) and heavy chain amyloidosis (AH). In this study, we report the renal and hematologic characteristics, pathology, and outcome of 17 patients with renal AH/AHL including 5 with AH (4 IgG and 1 IgA) and 12 with AHL (7 IgGλ, 3 IgAκ, 1 IgAλ, and 1 IgMλ), and compare them with 202 patients with renal AL amyloidosis (AL) diagnosed during the same time period. All cases were diagnosed by kidney biopsy that showed Congo red-positive deposits. Amyloid typing was done by laser microdissection and mass spectrometry (LMD/MS) (12 patients) or by immunofluorescence (5 patients). All patients with renal AH/AHL were Caucasians, with a M:F ratio of 2.4 and a median age at biopsy of 63 years. Compared with patients with renal AL, those with renal AH/AHL had less frequent concurrent cardiac involvement, higher likelihood of having circulating complete monoclonal Ig, lower sensitivity of fat pad biopsy and bone marrow biopsy for detecting amyloid, higher incidence of hematuria, and better patient survival. The hematologic and renal responses to chemotherapy were comparable to renal AL. In 42% of patients, AH/AHL could not have been diagnosed without LMD/MS. In conclusion, renal AH/AHL is an uncommon but under-recognized form of amyloidosis, and its diagnosis is greatly enhanced by the use of LMD/MS for amyloid typing. The accurate histological diagnosis of renal AH/AHL and distinction from AL may have important clinical and prognostic implications. Table 1. Demographics and hematologic characteristics AH/AHL AL p value No. of patients 17 202 Gender: Male/female 12/5 (71%/29%) 126/76 (62%/38%) 0.61 Age, median (range) 63 (50–77) 62 (36–86) 0.73 Additional organ involvement 8 (47%) 126 (62%) 0.3 Cardiac involvement 3 (18%) 100 (50%) 0.01* % of plasma cells in bone marrow, median (IQR) 8 (5–15) 6 (5–10) 0.82 ≥30 plasma cells 4 (24%) 11/198 (6%) 0.02* Positive SPEP/SIF for paraprotein 15 (88%) 158/200 (79%) 0.53 Presence of whole monoclonal protein on SPEP 14 (82%) 108/200 (54%) 0.04* Positive UPEP/UIF for paraprotein 13/16 (81%) 158/189 (84%) 0.73 Presence of whole monoclonal protein on UPEP 10/16 (63%) 61/189 (32%) 0.03* Abnormal serum FLC ratio (<0.26 or >1.65) 9/12 (75%) 150/188 (80%) 0.71 Markedly abnormal FLC ratio (< 0.125 or > 8) 5/12 (42%) 100/188 (53%) 0.55 Positive bone marrow for amyloid 6/16 (38%) 135/183 (74%) 0.004* Positive fat pad biopsy for amyloid 2/14 (14%) 105/145 (72%) <0.001* IQR, interquartile range. Table 2. Renal characteristics at kidney biopsy AH/AHL AL p value No. of patients 17 202 24h urine protein in g, median (IQR) 5.1 (3.2–9.0) 6.0 (3.2–10.0) 0.9 Full nephrotic syndrome 9/16 (56%) 132/197 (67%) 0.42 Serum albumin in g/dl, median (IQR) 2.7 (2.2–3.3) 2.5 (1.9–2.9) 0.29 % albuminuria on UPEP, median (IQR) 68 (61–72) 70 (60–76) 0.47 Serum creatinine in mg/dl, median (IQR) 1.4 (1.1–2.1) 1.2 (0.9–1.8) 0.25 Serum creatinine >1.2 mg/dl 10/16 (63%) 92/201 (46%) 0.3 eGFR, median (IQR) 47 (27–67) 58 (36–75) 0.29 Decreased eGFR 10/16 (63%) 103/201 (51%) 0.44 Microscopic hematuria 9/16 (56%) 44/169 (26%) 0.02* IQR, interquartile range. Disclosures: No relevant conflicts of interest to declare.

Hypoplastic left heart syndrome is one of the most complex congenital heart diseases and requires several cardiac surgeries for survival. The diagnosis is usually established prenatally or shortly after birth. Each stage of surgery poses a unique hemodynamic situation that requires deeper understanding to manage common pediatric problems such as dehydration and respiratory infections. Careful multidisciplinary involvement in the care of these complex patients is improving their outcome; however, morbidity and mortality are still substantial. In this review, we focus on the hemodynamic aspects of various surgical stages that a primary care provider should know to manage these challenging patients.

AbstractWe describe a case of a mass‐like echocardiographic density on a mechanical prosthetic aortic valve. We initially suspected a thrombus vs vegetation on transthoracic echocardiography, but after transesophageal echocardiography, the density was subsequently determined to be cavitation by reviewing the initial images in slow motion.

Abstract Aims We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS). Methods and results We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P &lt; 0.001) and 5-year mortality (68.9% vs. 16.7%, P &lt; 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission. Conclusions Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.