Faculty Bibliography

Atherosclerosis is a systemic disease that involves multiple vascular beds. The pathological characteristics and clinical presentation, however, vary among the different vascular territories. Acute coronary syndrome is a relatively common manifestation of coronary atherosclerotic disease, wherein the thrombosis occurs secondary to disruption (65%-75%) and erosion (25%-35%) of the fibrous caps of atheromatous plaques. The plaques associated with plaque rupture have large necrotic cores and thin and inflamed fibrous caps. However, the pathological manifestations of peripheral artery disease result from thrombosis regardless of the extent of atherosclerosis. Approximately 75% of peripheral arteries with significant stenosis demonstrate presence of thrombi, of which two-thirds have thrombi associated with insignificant atherosclerosis. The presence of obliterative thrombi in peripheral arteries of patients with critical limb ischemia in the absence of coronary artery-like lesions suggests a locally thrombogenic or remotely embolic basis of disease. Extensive calcification of the medial vascular layer is commonly observed. In this review, we have described and compared the pathological basis of coronary and peripheral artery disease in patients with acute coronary syndrome and critical limb ischemia. It is expected that pathogenetic characterization would allow for definition of strategic targets for superior management of peripheral artery disease.

Immunoglobulin G4-related disease is a systemic fibroinflammatory disease; pericardial involvement has occasionally been reported in publications. A 79-year-old man with biopsy-proven immunoglobulin G4-related disease with pleural involvement was admitted in acute heart failure, with imaging and hemodynamic studies consistent with constrictive pericarditis. He was treated with corticosteroids for 2 months with partial response manifest by decreases in pericardial thickening and immunoglobulin G4 levels. However, persistent constriction required pericardiectomy, leading to significant symptomatic improvement. (Level of Difficulty: Intermediate.).

PURPOSE: Passive transmission of hepatitis C (HCV) viremia from actively infected donors to uninfected recipients at the time of heart transplantation may modulate response to alloantigens and risk of allograft rejection. We evaluated the one-year incidence of acute cellular rejection (ACR) in patients transplanted from nucleic amplification testing positive (NAT+) HCV donors compared to those from NAT negative (NAT-) donors.
METHOD(S): Since January 2018, 25 patients completed one-year follow-up. All recipients underwent right ventricular endomyocardial biopsy (EMB) per our institution protocol. ACR was graded according to both the 1990 and the revised 2004 International Society for Heart and Lung Transplantation (ISHLT) criteria. All NAT+ donor recipients developed viremia detected by RT-PCR. Mixed models were used to assess the association between donor HCV NAT status, recipient viremia, tacrolimus levels and ACR in the first year post-transplant.
RESULT(S): Twelve NAT+ recipients (mean age 60, 67% male) and 13 NAT- recipients (mean age 54, 77% male) completed one-year follow-up; 182 and 191 EMB were performed, respectively. NAT+ recipients were associated with higher grade rejection compared with NAT- recipients (p=0.041). At least one episode of high grade rejection (2R/3A) occurred in 4 NAT+ recipients (33%) compared with 2 NAT- recipients (15%). At least one episode of low grade rejection (1R/1B or 1R/2) occurred in 11 NAT+ recipients (92%) compared with 7 NAT- recipients (54%). These findings were independent of the presence and magnitude of viremia and tacrolimus levels. No episodes of ACR 3R or antibody mediated rejection were detected during one-year follow-up in either group. There was no allograft dysfunction or mortality related to ACR in either group.
CONCLUSION(S): One year data from our institution demonstrate increased ACR in heart transplant recipients from NAT+ donors. Most of the rejection episodes in the NAT+ group were low grade and did not translate into any adverse outcomes through one-year follow-up.
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Background Arrhythmogenic cardiomyopathy (ACM) can mimic inflammatory processes. We present a complex patient with scleroderma (Sc)-dermatomyositis overlap syndrome (Sc-DM) and cardiac disease. Case A 57-year-old woman with family history of Sc presented with progressive weakness, dyspnea, edema, and Raynaud's (1A). Troponin was 1.6 ng/mL and CRP was 13.2 mg/L. EKGs revealed sinus rhythm with RBBB and AV sequential pacing with multifocal PVCs (1B-C). CT chest showed bibasilar fibrosis (1D). Echocardiography revealed biventricular dysfunction. Cardiac catheterization showed non-obstructive coronaries and a cardiac index of 1.8 L/min/m2. Cardiac MRI had diffuse biventricular subendocardial late gadolinium enhancement (1E). Electromyography revealed proximal myopathy. Rheumatologic workup was consistent with seronegative Sc-DM. Decision-making She was treated with steroids, mycophenolate, IV immunoglobulins, diuretics, and inotropes. Her course was complicated by recurrent VT cardiac arrests, prompting escalation to VA-ECMO. She underwent cardiac transplant on day 9 of ECMO. Pathology revealed biventricular fibrofatty replacement consistent with ACM (1F-G), patchy fibrosis of the pericardium, and mitral valve with thickened and fused chordae suggestive of inflammatory changes from Sc (1H-I). Conclusion This case highlights an atypical presentation of ACM in a patient with Sc-DM and the multidisciplinary approach necessary for proper diagnosis and management. [Figure presented]
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Cardiac amyloid A (AA) amyloidosis is rare. We present the case of a 72-year-old woman with obstructive hypertrophic cardiomyopathy (HCM) and biopsy-proven renal AA amyloidosis whose dyspnea and exercise intolerance had worsened over the previous year. Her AA amyloidosis was suspected to be secondary to chronic diverticulitis for which she had undergone hemicolectomy and sigmoidectomy 3 years prior. Echocardiographic findings were consistent with worsening left ventricular outflow tract obstruction at rest. Cardiac magnetic resonance imaging revealed patchy areas of midwall late gadolinium enhancement. Right ventricular endomyocardial biopsy did not reveal amyloid deposition, and cardiac technetium-99m pyrophosphate scintigraphy did not suggest transthyretin amyloidosis. The patient underwent septal myectomy with resection of an accessory papillary muscle. Pathological examination of the myectomy specimen was consistent with HCM. In addition, there was a thick layer of diffuse endocardial and vascular amyloid deposition that was identified as AA type by laser-microdissection with liquid chromatography-coupled tandem-mass spectrometry. This case report highlights the presence of 2 distinct disease processes occurring simultaneously and the importance of tissue diagnosis of AA amyloidosis, a condition that is not commonly associated with HCM.

Background: When the first diagnosis of a well-differentiated neuroendocrine neoplasm (WDNEN) is made on a biopsy, crush artifact may impede mitotic counting, and the Ki-67 proliferative index (KPI) plays a more important role in grading. Few studies have examined the reliability of KPI in the grading of metastatic (met) WDNEN.
Design(s): Cases were retrieved from 2008-19. For each primary (1degree) and met, a 40x hotspot image of a Ki-67 stained slide was taken. KPI was analyzed by the ImmunoRatio Plugin using ImageJ software. All were validated by independent manual counting. In 1 case, crush artifact precluded use of ImageJ. If multiple mets were present, the largest was selected. Cytology and cases with fewer than 100 cells were omitted. Tumors were graded as G1(KPI<3%), G2(KPI 3-20%), or G3(KPI>20%). Grade and KPI were compared between each 1degree and met.
Result(s): 67 cases, including 38 mets from 29 1degree WDNEN, were evaluated. There were 12, 2, 2, 1, 17, and 4 mets from lung, thymus, middle ear, pancreas, small bowel, & colon respectively. The greatest variations in KPI from 1degree to met were seen in lung compared to all other sites. In 24/38(63%) of all mets, the grade was the same as 1degree. In 14/38(37%) of all mets, the grade was different: 4/14(29%) were lower while 10/14(71%) were higher than 1degree. In mets from lung, 2 had lower, 6 had the same, & 4 had higher grade. In mets from middle ear, the grades increased. In mets from small bowel 2 had lower, 12 had the same, and 3 had higher grade. In mets from colon 3 had the same and 1 had higher grade. And in mets from thymus & pancreas, the grades remained the same. See Fig 1. 3 mets were diagnosed before 1degree (2 days to 2 months). Mets with higher grade than 1degree tended to have longer time interval between 1degree and met, but this was not significant at the 95% confidence level (Kruskal-Wallis test, p=0.08). 28 mets were regional and 10 were distant. There was no correlation between met site and grade change (Person Chi-square, p=0.33). Also see Table 1. (Table presented)
Conclusion(s): Our study showed that in most met WDNEN (63%), the grade remained the same as the 1degree. The grade was higher in 10/38(26%) and lower in 4/38(11%). There was a trend toward higher grade in mets that occurred at a longer time interval after the 1degree. Fig 2 shows a potential diagnostic pitfall when the met shows much higher KPI than 1degree. In conclusion, if a met WDNEN is suspected as a firsttime diagnosis, KPI must be used cautiously for classification of WDNEN since over/under-grading may occur

Background: Spread through air spaces (STAS) has been reported to be associated with a worse prognosis in adenocarcinoma of lung. Recently it has been proposed that STAS be reported on frozen sections (FS) as an indication for more aggressive surgery (lobectomy vs sublobar resection). We undertook this study to evaluate the reliability of STAS assessment on FS compared to FS controls (FSC) and non-frozen remaining tumor (RT).
Design(s): Cases of adenocarcinoma that had FS of the tumor were identified retrospectively from two institutions. For each case, the following was recorded: Presence(+)/absence(-) of STAS on FS, FSC, and RT; and % of tumor patterns: Lepidic(L), acinar(A), papillary(P), micropapillary(M), solid(S). Grades were defined as follows: G1=L predominant with A/P G2=A/P predominant with <20% M/S G3=M/S predominant or >=20% M/S Cross-tabulations and Spearman's correlations (rs) were performed in SPSS (see Table). rs 0.3-<0.5 = low correlation.
Result(s): 165 cases were found. In 2 cases the tumor was only present on FS/FSC slides. STAS+ was present on FS in 47/165(28%), of which 28/47(60%) had STAS+ on FSC (rs=0.39) and 22/46(48%) had STAS+ on RT (rs=0.34) (1 tumor was only present on FS/FSC). Of the 40 STAS+ cases on RT, 18/40(45%) did not have STAS (STAS-) on FS (rs=0.34). 118/165 of cases were STAS- on FS; of these, 18/117(15%) were STAS+ on RT (rs=0.34) (1 tumor was only present on FS/FSC). Fig 1. Of the 47 cases with STAS+ on FS, 4(15%) were G1, 15(32%) were G2, and 28(60%) were G3 (rs =0.30). Of the 15 G2 cases with STAS+ on FS, 7 had 10% to <20% high grade pattern (M/S). Of the 28 G3 cases with STAS+ on FS, 13 had >= 30% high grade pattern. Of the 40 cases with STAS+ on RT, 1(2.5%) case was G1, 7(18%) cases were G2, and 32(80%) cases were G3 (rs=0.46). Fig 2. (Table presented)
Conclusion(s): The correlations among FS, FSC, and RT are low. FS STAS+ cases remain STAS+ only in 60% of FSC and 48% of RT. STAS shows higher correlation with grade on RT than it does on FS. These results show a lack of reliability in the assessment of STAS on FS, and do not support the proposal of reporting STAS in FS to make intraoperative clinical decisions, as doing so may subject patients to unnecessarily aggressive surgery