Cardiac Sarcoidosis: the Chal- Lenge of Radiologic-Pathologic Correlation1

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Cardiac Sarcoidosis: the Chal- Lenge of Radiologic-Pathologic Correlation1 Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at www.rsna.org/rsnarights. CARDIAC IMAGING 657 Cardiac Sarcoidosis: The Chal- lenge of Radiologic-Pathologic Correlation1 | FROM THE RADIOLOGIC PATHOLOGY ARCHIVES FROM THE RADIOLOGIC PATHOLOGY Jean Jeudy, MD Allen P. Burke, MD Cardiac sarcoidosis is a rare but potentially fatal disorder with a Charles S. White, MD nonspecific spectrum of clinical manifestations, including conduc- Gerdien B. G. Kramer, MD tion disorders, congestive heart failure, ventricular arrhythmias, and Aletta Ann Frazier, MD sudden cardiac death. Although early treatment to improve morbid- ity and mortality is desirable, sensitive and accurate detection of Abbreviations: ARVC = arrhythmogenic right cardiac sarcoidosis remains a challenge. Except for the histopatho- ventricular cardiomyopathy, CS = cardiac sar- logic finding of noncaseating granulomas in an endomyocardial bi- coidosis, ECG = electrocardiography, FDG = fluorine 18 fluorodyoxyglucose, JMHW = Japa- opsy specimen, most diagnostic tests are limited and nonspecific at nese Ministry of Health and Welfare, LGE = best. Therefore, the decision to initiate treatment is based largely on late gadolinium-induced enhancement, PSIR = phase-sensitive inversion recovery, SSFP = the patient’s clinical symptoms and the course of the disease, rather steady-state free precession than histologic confirmation. Successful recognition of cardiac RadioGraphics 2015; 35:657–679 sarcoidosis ultimately requires rigorous collaboration among a cli- nician, radiologist, and pathologist. Advanced imaging modalities, Published online 10.1148/rg.2015140247 such as cardiac magnetic resonance imaging and positron emission Content Codes: tomography with fluorodeoxyglucose, have become increasingly 1From the Department of Diagnostic Radiology useful in facilitating diagnosis and therapeutic monitoring, although and Nuclear Medicine (J.J., C.S.W., A.A.F.) and limited prospective studies exist. This article describes the clinical Department of Pathology (A.P.B.), University of Maryland Medical Center, 22 S Greene St, Bal- parameters and pathologic findings of cardiac sarcoidosis and the timore, MD 21201; the Joint Pathology Center, advanced imaging features and differential diagnostic challenges Silver Spring, Md (A.P.B.); Department of Med- ical Imaging, Vrije Universiteit Medical Center, that must be considered for a successful diagnostic approach. In Amsterdam, the Netherlands (G.B.G.K.); and addition, to improve the understanding of abnormalities detected Department of Cardiovascular Imaging, Ameri- can Institute for Radiologic Pathology, Silver with different imaging modalities, we suggest a unified terminology Spring, Md (A.A.F.). Received September 12, in describing radiologic findings related to cardiac sarcoidosis. 2014; revision requested October 27 and re- ceived January 11, 2015; accepted January 16. ©RSNA, 2015 • radiographics.rsna.org For this journal-based SA-CME activity, the au- thors, editor, and reviewers have disclosed no rel- evant relationships. Address correspondence to J.J. (e-mail: [email protected]). The work was supported by the American Insti- Introduction tute for Radiologic Pathology, the Joint Pathol- Sarcoidosis is a multisystem disorder with unknown etiology that is ogy Center, and Uniformed Services University of the Health Sciences. The views expressed in characterized by the presence of noncaseating, nonnecrotic granulo- this article are those of the authors and do not mas in the involved organs. Sarcoidosis typically manifests as bilateral necessarily reflect the official policy or posi- tion of the Department of Defense or the U.S. hilar lymphadenopathy, pulmonary infiltration, and ocular and/or skin Government. lesions, although other locations, including the heart, central nervous system, bone, and gastrointestinal tract, may be affected. Prevalence, SA-CME LEARNING OBJECTIVES clinical expression, and disease severity vary widely by patient age, sex, After completing this journal-based SA-CME race, and genetic and environmental factors (1,2). activity, participants will be able to: ■■Describe the clinical manifestations and histologic features of cardiac sar- coidosis. ■■Recognize the indications for imaging, select optimal modalities, and interpret imaging appearances for differential di- agnosis of cardiac sarcoidosis. ■■Discuss the relevance of collaborative diagnosis when considering cardiac sar- coidosis. See www.rsna.org/education/search/RG. 658 May-June 2015 radiographics.rsna.org mas is the criterion standard, but this procedure is TEACHING POINTS rarely performed and has a limited diagnostic yield ■ Histologic examination of an endomyocardial biopsy speci- of 20%–50% (4–6). The most widely adopted men that demonstrates noncaseating granulomas is the criterion standard, but this procedure is rarely performed set of clinical criteria for guiding diagnosis were and has a limited diagnostic yield of 20%–50%. The most established by the Japanese Ministry of Health widely adopted set of clinical criteria guiding diagnosis were and Welfare (JMHW) (Table 1) (7). Treatment of established by the Japanese Ministry of Health and Welfare CS is initiated largely on the basis of a measured (JMHW). Treatment of CS is initiated largely on the basis of consideration of symptoms, ECG and advanced a measured consideration of symptoms, electrocardiography and advanced imaging findings, and disease course, rather imaging findings, and disease course, rather than than histologic confirmation. histologic confirmation. ■ The rate of left ventricular dilatation was similar (25%) in pa- This article presents the pathologic findings, tients who died of incidental sarcoidosis and those who died clinical parameters, and advanced imaging fea- of CS with extensive involvement of the heart. Subepicardial tures of CS. We review the differential diagnoses scars were most common, followed by midmyocardial and considered in the imaging interpretation of pos- subendocardial disease. Often, the scars are randomly distrib- sible CS. Finally, we address some of the current uted and may even involve the myocardium diffusely, without clear separation from uninvolved myocardium. pathologic and diagnostic dilemmas, to facilitate ■ According to the JMHW criteria, the diagnosis of CS is assigned radiologic description of CS. to either of two scenarios. In the first scenario, CS is confirmed by the presence of epithelioid noncaseating granulomas at his- Pathologic Considerations tologic examination of an endomyocardial biopsy specimen. The second scenario requires one or more of the following find- Background ings: conduction system abnormalities at ECG, functional and structural abnormalities at echocardiography, abnormal find- CS is an inflammatory myocardial process that ings at nuclear medicine or cardiac magnetic resonance imag- varies greatly in extent, distribution, and histologic ing, and interstitial fibrosis without granulomas identified at features among affected patients. The pathologic histologic examination of an endomyocardial biopsy specimen. features of CS are known primarily on the basis ■ Clinical experts agree that the following patients merit as- of autopsy studies (8–10). Endomyocardial biopsy sessment for CS: (a) patients who have already received a provides only a small tissue sample from the right- diagnosis of extracardiac sarcoidosis and have cardiac symp- side endocardium and yields no data on distribu- toms and/or signs (including chest pain and 12-lead ECG or echocardiographic abnormalities); (b) patients younger than tion of disease. Autopsy studies have generally 55 years who have not received a diagnosis of sarcoidosis and shown that a high proportion of deaths from CS who have unexplained conduction abnormalities, ventricu- are sudden and occur in patients without previously lar dysrhythmias, syncope, or nonischemic heart failure; and identified cardiac involvement (8–10). Sudden car- (c) patients with known CS (to document the severity of in- diac death almost invariably corresponds to grossly flammation or the effect of immunosuppressive therapy). evident extensive involvement of the heart, whereas ■ Accurate diagnosis of CS is difficult because of the overlap of both clinical and imaging findings with other inflammatory incidental cardiac involvement in patients who die and infiltrative conditions affecting the heart. Myocarditis, of pulmonary disease or other causes is typically dilated cardiomyopathy, hypertrophic cardiomyopathy, microscopic. The seminal autopsy series published amyloidosis, and ARVC are often considered in the radiologic in 1974 (4) showed a substantial overlap in clinical differential diagnosis. Appropriate clinical context is essential history of arrhythmias and conduction disorders when considering CS, because of its broad and nonspecific spectrum of appearances at imaging. in patients with sarcoidosis who had no, minimal, or extensive cardiac involvement; this finding em- phasized the lack of specificity of ECG and clinical symptoms and underscored the need for better im- Cardiac involvement in sarcoidosis was first aging capabilities in facilitating the diagnosis of CS. described in 1929 during a postmortem examina- tion that unexpectedly revealed epicardial granulo- Distribution of Lesions in CS mas similar to those identified in the patient’s skin Early autopsy series stressed the presence of (3). At present,
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