Top

Published in:

Open Access 01-06-2020 | Autopsy | REVIEW AND PERSPECTIVES

Autopsy in adults with congenital heart disease (ACHD)

Authors: Annalisa Angelini, Cira di Gioia, Helen Doran, Marny Fedrigo, Rosa Henriques de Gouveia, Siew Yen Ho, Ornella Leone, Mary N Sheppard, Gaetano Thiene, Konstantinos Dimopoulos, Barbara Mulder, Massimo Padalino, Allard C van der Wal, On behalf of Association for European Cardiovascular Pathology (AECVP)

Published in: Virchows Archiv | Issue 6/2020

Abstract

The adult congenital heart diseases (ACHD) population is exceeding the pediatric congenital heart diseases (CHD) population and is progressively expanding each year, representing more than 90% of patients with CHD. Of these, about 75% have undergone surgical and/or percutaneous intervention for palliation or correction. Autopsy can be a very challenging procedure in ACHD patients. The approach and protocol to be used may vary depending on whether the pathologists are facing native disease without surgical or percutaneous interventions, but with various degrees of cardiac remodeling, or previously palliated or corrected CHD. Moreover, interventions for the same condition have evolved over the last decades, as has perioperative myocardial preservations and postoperative care, with different long-term sequelae depending on the era in which patients were operated on. Careful clinicopathological correlation is, thus, required to assist the pathologist in performing the autopsy and reaching a diagnosis regarding the cause of death. Due to the heterogeneity of the structural abnormalities, and the wide variety of surgical and interventional procedures, there are no standard methods for dissecting the heart at autopsy. In this paper, we describe the most common types of CHDs that a pathologist could encounter at autopsy, including the various types of surgical and percutaneous procedures and major pathological manifestations. We also propose a practical systematic approach to the autopsy of ACHD patients.

Available only for authorised users

Gatzoulis M, Webb G (2011) In: Gatzoulis M, Webb G, Daubeney P (eds) Adult with congenital heart Disease: a growing population. in Diagnosis and Management of Adult Congenital Heart Disease. Elsevier, Phyladelphia. https://doi.org/10.1016/C2009-0-54256-0 CrossRef

Perloff JK, Warnes CA (2001) Challenges posed by adults with repaired congenital heart disease. Circulation. https://doi.org/10.1161/01.CIR.103.21.2637

Gilboa SM, Devine OJ, Kucik JE, Oster ME, Riehle-Colarusso T, Nembhard WN et al (2016) Congenital heart defects in the United States: estimating the magnitude of the affected population in 2010. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.115.019307

Mazor Dray E, Marelli AJ (2015) Adult congenital heart Disease: Scope of the Problem. Cardiol Clin. https://doi.org/10.1016/j.ccl.2015.07.001

Webb G, Mulder BJ, Aboulhosn J, Daniels CJ, Elizari MA, Hong G et al (2015) The care of adults with congenital heart disease across the globe: current assessment and future perspective: a position statement from the International Society for Adult Congenital Heart Disease (ISACHD). Int J Cardiol. https://doi.org/10.1016/j.ijcard.2015.04.230

Bhatt AB, Foster E, Kuehl K, Alpert J, Brabeck S, Crumb S et al (2015) Congenital heart disease in the older adult: a scientific statement from the American heart association. Circulation. https://doi.org/10.1161/CIR.0000000000000204

Stout KK, Daniels CJ, Aboulhosn JA, Bozkurt B, Broberg CS, Colman JM et al (2019) 2018 AHA/ACC guideline for the management of adults with congenital heart disease: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation. https://doi.org/10.1161/CIR.0000000000000602

Afilalo J, Therrien J, Pilote L, Ionescu-Ittu R, Martucci G, Marelli AJ (2011) Geriatric congenital heart disease: burden of disease and predictors of mortality. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2011.06.041

Tretter JT, Chikkabyrappa S, Spicer DE, Backer CL, Mosca RS, Anderson RH, Bhatla P (2017) Understanding the spectrum of sinus venosus interatrial communications. Cardiol Young. https://doi.org/10.1017/S1047951116000664

10.

Naqvi N, McCarthy KP, Ho SY (2018) Anatomy of the atrial septum and interatrial communications. J Thorac Dis. https://doi.org/10.21037/jtd.2018.02.18

11.

Ellesøe SG, Johansen MM, Bjerre JV, Hjortdal VE, Brunak S, Larsen LA (2016) Familial atrial Septal defect and sudden cardiac death: identification of a novel NKX2-5 mutation and a review of the literature. Congenit Heart Dis. https://doi.org/10.1111/chd.12317

12.

Stoll C, Dott B, Alembik Y, Roth MP (2015) Associated congenital anomalies among cases with down syndrome. Eur J Med Genet. https://doi.org/10.1016/j.ejmg.2015.11.003

13.

Butera G, Romagnoli E, Saliba Z, Chessa M, Sangiorgi G, Giamberti A et al (2010) Percutaneous closure of multiple defects of the atrial septum: procedural results and long-term follow-up. Catheter Cardiovasc Interv. https://doi.org/10.1002/ccd.22435

14.

Vettukattil JJ, Ahmed Z, Salmon AP, Mohun T, Anderson RH (2013) Defects in the oval fossa: morphologic variations and impact on transcatheter closure. J Am Soc Echocardiogr. https://doi.org/10.1016/j.echo.2012.10.019

15.

Ferreira Martins JD, Anderson RH (2000) The anatomy of interatrial communications – what does the interventionist need to know? Cardiol Young. https://doi.org/10.1017/S1047951100008155

16.

Fraisse A, Latchman M, Sharma SR, Bayburt S, Amedro P, di Salvo G, Baruteau AE (2018) Atrial septal defect closure: indications and contra-indications. J Thorac Dis 10:S2874–S2881. https://doi.org/10.21037/jtd.2018.08.111 CrossRefPubMedPubMedCentral

17.

Riahi M, Velasco Forte MN, Byrne N, Hermuzi A, Jones M, Baruteau AE et al (2018) Early experience of transcatheter correction of superior sinus venosus atrial septal defect with partial anomalous pulmonary venous drainage. EuroIntervention. https://doi.org/10.4244/EIJ-D-18-00304

18.

Anderson RH, Mohun TJ, Brown NA (2015) Clarifying the morphology of the ostium primum defect. J Anat. https://doi.org/10.1111/joa.12272

19.

Rao PS, Harris AD (2017) Recent advances in managing septal defects: atrial septal defects. F1000Res. https://doi.org/10.12688/f1000research.11844.1

20.

Vida VL, Tessari C, Castaldi B, Padalino MA, Milanesi O, Gregori D, Stellin G (2016) Early correction of common Atrioventricular Septal defects: a single-center 20-year experience. Ann Thorac Surg. https://doi.org/10.1016/j.athoracsur.2016.09.020

21.

Chau AC, Jones A, Sutherland M, Lilje C, Sernich S, Hagan J, Miller J (2018) Characteristics of isolated ventricular septal defects less likely to close in utero. J Ultrasound Med. https://doi.org/10.1002/jum.14535

22.

Baumgartner H, Bonhoeffer P, De Groot NM, de Haan F, Deanfield JE, Galie N et al (2010) ESC guidelines for the management of grown-up congenital heart disease (new version 2010). Eur Heart J. https://doi.org/10.1093/eurheartj/ehq249

23.

Rajasinghe HA, McElhinney DB, Reddy VM, Mora BN, Hanley FL (1997) Long-term follow-up of truncus arteriosus repaired in infancy: a twenty- year experience. J Thorac Cardiovasc Surg. https://doi.org/10.1016/S0022-5223(97)70259-9

24.

Ferencz C, Rubin JD, McCarter RJ, Brenner JI, Neill CA, Perry LW et al (1985) Congenital heart disease: prevalence at livebirth: the Baltimore-Washington infant study. Am J Epidemiol. https://doi.org/10.1093/oxfordjournals.aje.a113979

25.

Anderson RH, Allwork SP, Ho SY, Lenox CC, Zuberbuhler JR (1981) Surgical anatomy of tetralogy of Fallot. J Thorac Cardiovasc Surg 81(6):887–896CrossRef

26.

Mart CR, Zachary CH, Kupferschmid JP, Weber HS (2001) Tetralogy of Fallot with right aortic arch and isolation of the left innominate artery from a left-sided patent ductus arteriosus. Pediatr Cardiol 22:58–59. https://doi.org/10.1007/s002460010154 CrossRefPubMed

27.

O’Brien P, Marshall AC (2014) Tetralogy of Fallot. Circulation. https://doi.org/10.1161/CIR.113.005547

28.

Hofferberth SC, Nathan M, Marx GR, Lu M, Sleeper LA, Marshall AC et al (2018) Valve-sparing repair with intraoperative balloon dilation in tetralogy of Fallot: Midterm results and therapeutic implications. J Thorac Cardiovasc Surg. https://doi.org/10.1016/j.jtcvs.2017.08.147

29.

Bacha E (2017) Valve-sparing or valve reconstruction options in tetralogy of Fallot surgery. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. https://doi.org/10.1053/j.pcsu.2016.09.001

30.

Vida VL, Guariento A, Zucchetta F, Padalino M, Castaldi B, Milanesi O, Stellin G (2016) Preservation of the pulmonary valve during early repair of tetralogy of Fallot: surgical techniques. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 19:75–81. https://doi.org/10.1053/j.pcsu.2015.12.008 CrossRefPubMed

31.

Khairy P, Ionescu-Ittu R, Mackie AS, Abrahamowicz M, Pilote L, Marelli AJ (2010) Changing mortality in congenital heart disease. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2010.03.085

32.

Arya S, Kovach J, Singh H, Karpawich PP (2014) Arrhythmias and sudden death among older children and young adults following tetralogy of Fallot repair in the current era: are previously reported risk factors still applicable? Congenit Heart Dis. https://doi.org/10.1111/chd.12153

33.

Valente AM, Gauvreau K, Assenza GE, Babu-Narayan SV, Schreier J, Gatzoulis MA, Groenink M, Inuzuka R, Kilner PJ, Koyak Z, Landzberg MJ, Mulder B, Powell AJ, Wald R, Geva T (2014) Contemporary predictors of death and sustained ventricular tachycardia in patients with repaired tetralogy of Fallot enrolled in the INDICATOR cohort. Heart 100:247–253. https://doi.org/10.1136/heartjnl-2013-304958 CrossRefPubMed

34.

Villafañe J, Feinstein JA, Jenkins KJ, Vincent RN, Walsh EP, Dubin AM et al (2013) Hot topics in tetralogy of Fallot. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2013.07.100

35.

Ferraz Cavalcanti PE, Sá MPBO, Santos CA, Esmeraldo IM, Escobar RR, Menezes AM et al (2013) Pulmonary valve replacement after operative repair of tetralogy of Fallot: meta-analysis and meta-regression of 3,118 patients from 48 studies. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2013.04.107

36.

Phillips ABM, Nevin P, Shah A, Olshove V, Garg R, Zahn EM (2016) Development of a novel hybrid strategy for transcatheter pulmonary valve placement in patients following transannular patch repair of tetralogy of fallot. Catheter Cardiovasc Interv. https://doi.org/10.1002/ccd.26315

37.

Fedak PWM, Verma S, David TE, Leask RL, Weisel RD, Butany J (2002) Clinical and pathophysiological implications of a bicuspid aortic valve. Circulation. https://doi.org/10.1161/01.CIR.0000027905.26586.E8

38.

Fricke TA, d'Udekem Y, Brizard CP, Wheaton G, Weintraub RG, Konstantinov IE (2015) Surgical repair of supravalvular aortic stenosis in children with Williams syndrome: a 30-year experience. Ann Thorac Surg. https://doi.org/10.1016/j.athoracsur.2014.11.044

39.

Avendaño-Pérez L, Soto ME, Ávila-Vanzzini N, Bracamontes-Castelo G, Ruán-Díaz JC, Alexanderson-Rosas E, Espinola-Zavaleta N (2018) Mechanical deformation in adult patients with unrepaired aortic coarctation. Int J Cardiovasc Imaging 34:735–741. https://doi.org/10.1007/s10554-017-1286-9 CrossRefPubMed

40.

Warnes CA, Williams RG, Bashore TM, Child J, Connolly HM, Dearani JA et al (2008) ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2008.10.001

41.

Beckmann E, Jassar AS (2018) Coarctation repair—redo challenges in the adults: what to do? J Vis Surg. https://doi.org/10.21037/jovs.2018.04.07

42.

Forbes TJ, Moore P, Pedra CA, Zahn EM, Nykanen D, Amin Z et al (2007) Intermediate follow-up following intravascular stenting for treatment of coarctation of the aorta. Catheter Cardiovasc Interv. https://doi.org/10.1002/ccd.21191

43.

Hijazi ZM, Kenny DP (2014) Covered stents for coarctation of the aorta: treating the interventionalist or the patient? J Am Coll Cardiol Intv. https://doi.org/10.1016/j.jcin.2013.12.200

44.

Galiñanes E, Krajcer Z (2016) Most coarctations, recoarctations, and coarctation-related aneurysms should be treated endovascularly. AORTA. https://doi.org/10.12945/j.aorta.2015.14.049

45.

Stone JR, Bruneval P, Angelini A, Bartoloni G, Basso C, Batoroeva L et al (2015) Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology: I. Inflammatory diseases. Cardiovasc Pathol. https://doi.org/10.1016/j.carpath.2015.05.001

46.

Hornung TS, Derrick GP, Deanfield JE, Redington AN (2002) Transposition complexes in the adult: a changing perspective. Cardiol Clin. https://doi.org/10.1016/S0733-8651(02)00012-7

47.

Rashkind WJ, Miller WW (1966) Creation of an Atrial Septal Defect Without Thoracotomy: A Palliative Approach to Complete Transposition of the Great Arteries. JAMA. https://doi.org/10.1001/jama.1966.03100240125026

48.

Baker F, Baker L, Zoltun R, Zuberbuhler JR (1971) Effectiveness of the Rashkind procedure in transposition of the great arteries in infants. Circulation 43: I-1–I-6 https://doi.org/10.1161/01.CIR.43.5S1.I-1

49.

Cuypers JAAE, Eindhoven JA, Slager MA, Opić P, Utens EM, Helbing WA et al (2014) The natural and unnatural history of the mustard procedure: long-term outcome up to 40 years. Eur Heart J. https://doi.org/10.1093/eurheartj/ehu102

50.

Moons P, Gewillig M, Sluysmans T, Verhaaren H, Viart P, Massin M et al (2004) Long term outcome up to 30 years after the mustard or Senning operation: a nationwide multicentre study in Belgium. Heart. https://doi.org/10.1136/hrt.2002.007138

51.

Tobler D, Williams WG, Jegatheeswaran A, Van Arsdell GS, McCrindle BW, Greutmann M et al (2010) Cardiac outcomes in young adult survivors of the arterial switch operation for transposition of the great arteries. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2010.03.031

52.

Connelly MS, Liu PP, Williams WG, Webb GD, Robertson P, McLaughlin PR (1996) Congenitally corrected transposition of the great arteries in the adult: functional status and complications. J Am Coll Cardiol. https://doi.org/10.1016/0735-1097(95)00567-6

53.

Filippov AA, Del Nido PJ, Vasilyev NV (2016) Management of systemic right ventricular failure in patients with congenitally corrected transposition of the great arteries. Circulation. https://doi.org/10.1161/CIR.116.022106

54.

Baruteau A, Abrams DJ, Ho SY, Thambo JB, McLeod CJ, Shah MJ (2017) Cardiac conduction system in congenitally corrected transposition of the great arteries and its clinical relevance. J Am Heart Assoc. https://doi.org/10.1161/jaha.117.007759

55.

Barbara DW, Edwards WD, Connolly HM, Dearani JA (2008) Surgical pathology of 104 tricuspid valves (2000-2005) with classic right-sided Ebstein’s malformation. Cardiovasc Pathol. https://doi.org/10.1016/j.carpath.2007.07.005

56.

Luu Q, Choudhary P, Jackson D, Canniffe C, McGuire M, Chard R, Celermajer DS (2015) Ebstein’s anomaly in those surviving to adult life - a single Centre experience. Hear Lung Circ. https://doi.org/10.1016/j.hlc.2015.03.016

57.

da Silva JP, da Silva Lda F (2012) Ebstein’s anomaly of the tricuspid Valve: The cone repair. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. https://doi.org/10.1053/j.pcsu.2012.01.008

58.

Dearani JA, Bacha E, da Silva JP (2008) Cone reconstruction of the tricuspid valve for Ebstein’s Anomaly: Anatomic Repair. Oper Tech Thorac Cardiovasc Surg. https://doi.org/10.1053/j.optechstcvs.2008.03.003

59.

Jacobs ML, Anderson RH (2006) Nomenclature of the functionally univentricular heart. Cardiol Young. https://doi.org/10.1017/S104795110500226X

60.

Khairy P, Fernandes SM, Mayer JE Jr, Triedman JK, Walsh EP, Lock JE, Landzberg MJ (2008) Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.107.738559

61.

Pérez-Pomares JM, de la Pompa JL, Franco D, Henderson D, Ho SY, Houyel L et al (2016) Congenital coronary artery anomalies: a bridge from embryology to anatomy and pathophysiology-a position statement of the development, anatomy, and pathology ESC working group. Cardiovasc Res. https://doi.org/10.1093/cvr/cvv251

62.

Basso C, Maron BJ, Corrado D, Thiene G (2000) Clinical profile of congenital coronary artery anomalies with origin from the wrong aortic sinus leading to sudden death in young competitive athletes. J Am Coll Cardiol. https://doi.org/10.1016/S0735-1097(00)00566-0

63.

Muriago M, Sheppard MN, Ho SY, Anderson RH (1997) Location of the coronary arterial orifices in the normal heart. Clin Anat. https://doi.org/10.1002/(SICI)1098-2353(1997)10:5<297::AID-CA1>3.0.CO;2-O

64.

Basso C, Corrado D, Rossi L, Thiene G (2001) Ventricular preexcitation in children and young adults: atrial myocarditis as a possible trigger of sudden death. Circulation. https://doi.org/10.1161/01.CIR.103.2.269

65.

Diller GP, Kempny A, Alonso-Gonzalez R, Swan L, Uebing A, Li W et al (2015) Survival prospects and circumstances of death in contemporary adult congenital heart disease patients under follow-up at a large tertiary Centre. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.115.017202

66.

Alshawabkeh LI, Hu N, Carter KD, Opotowsky AR, Light-McGroary K, Cavanaugh JE, Bartlett HL (2016) Wait-list outcomes for adults with congenital heart disease listed for heart transplantation in the U.S. J. Am. Coll. Cardiol. https://doi.org/10.1016/j.jacc.2016.05.082

67.

Ross HJ, Law Y, Book WM, Broberg CS, Burchill L, Cecchin F et al (2016) Transplantation and mechanical circulatory support in congenital heart Disease: A Scientific Statement from the American Heart Association. Circulation. https://doi.org/10.1161/CIR.0000000000000353

68.

Alshawabkeh LI, Opotowsky AR (2016) Burden of heart failure in adults with congenital heart disease. Curr Heart Fail Rep 13:247–254. https://doi.org/10.1007/s11897-016-0301-0 CrossRefPubMed

69.

Stout KK, Broberg CS, Book WM, Cecchin F, Chen JM, Dimopoulos K et al (2016) Chronic heart failure in congenital heart Disease: A Scientific Statement from the American Heart Association. Circulation. https://doi.org/10.1161/CIR.0000000000000352

70.

Warnes CA (2009) Adult congenital heart disease. Importance of the right ventricle. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2009.06.048

71.

Khairy P (2016) Ventricular arrhythmias and sudden cardiac death in adults with congenital heart disease. Heart. https://doi.org/10.1136/heartjnl-2015-309069

72.

Dimopoulos K, Wort SJ, Gatzoulis MA (2014) Pulmonary hypertension related to congenital heart disease: a call for action. Eur Heart J. https://doi.org/10.1093/eurheartj/eht437

73.

Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A et al (2016) 2015 ESC/EAS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. https://doi.org/10.1093/eurheartj/ehv317

74.

Rosenzweig EB, Abman SH, Adatia I, Beghetti M, Bonnet D, Haworth S et al (2019) Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management. Eur Respir J. https://doi.org/10.1183/13993003.01916-2018

75.

Thiene G (2017) Eisenmenger syndrome revisited world J. Pediatr Congenit Hear Surg. https://doi.org/10.1177/2150135117727259

76.

Engelfriet PM, Duffels MG, Möller T, Boersma E, Tijssen JG, Thaulow E et al (2007) Pulmonary arterial hypertension in adults born with a heart septal defect: the euro heart survey on adult congenital heart disease. Heart. https://doi.org/10.1136/hrt.2006.098848

77.

Simonneau G, Montani D, Celermajer DS, Denton CP, Gatzoulis MA et al (2019) Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. https://doi.org/10.1183/13993003.01913-2018

78.

Daliento L, Rebellato L, Angelini A, Frescura C, Mazzotti E, Rotundo M, Thiene G (2002) Fatal outcome in Eisenmenger syndrome. Cardiovasc Pathol. https://doi.org/10.1016/S1054-8807(02)00105-9

79.

Pietra GG, Capron F, Stewart S, Leone O, Humbert M, Robbins IM et al (2004) Pathologic assessment of vasculopathies in pulmonary hypertension. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2004.02.033

80.

Basso C, Aguilera B, Banner J, Cohle S, d'Amati G, de Gouveia RH et al (2017) Guidelines for autopsy investigation of sudden cardiac death: 2017 update from the Association for European Cardiovascular Pathology. Virchows Arch. https://doi.org/10.1007/s00428-017-2221-0

81.

Thiene G, Corrado D, Basso C (2016) Sudden Cardiac Death in the Young and Athletes https://doi.org/10.1007/978-88-470-5776-0

Title: Autopsy in adults with congenital heart disease (ACHD)
Authors: Annalisa Angelini
Cira di Gioia
Helen Doran
Marny Fedrigo
Rosa Henriques de Gouveia
Siew Yen Ho
Ornella Leone
Mary N Sheppard
Gaetano Thiene
Konstantinos Dimopoulos
Barbara Mulder
Massimo Padalino
Allard C van der Wal
On behalf of Association for European Cardiovascular Pathology (AECVP)
Publication date: 01-06-2020
Publisher: Springer Berlin Heidelberg
Keywords: Autopsy
Pathology
Published in: Virchows Archiv / Issue 6/2020
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-020-02779-8

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Autopsy in adults with congenital heart disease (ACHD)

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2020

The autopsy debate during the COVID-19 emergency: the Italian experience

Atypical goblet cell hyperplasia occurs in CPAM 1, 2, and 3, and is a probable precursor lesion for childhood adenocarcinoma

HER2 gene (ERBB2) amplification is a low-frequency driver with potential predictive value in gallbladder carcinoma

ALK-rearranged renal cell carcinoma with a novel PLEKHA7-ALK translocation and metanephric adenoma-like morphology

Primary bone sarcoma with BCOR internal tandem duplication

Higher density of stromal M2 macrophages in breast ductal carcinoma in situ predicts recurrence