Arrhythmogenic Left Ventricular Mass as the Initial Presentation of Cardiac Sarcoidosis.

Cardiac tumors of the left ventricle are rare, and cardiac magnetic resonance is the preferred imaging tool for evaluation given superior tissue characterization. We present a case of a patient with arrhythmia and left ventricular mass that was ultimately diagnosed with cardiac sarcoidosis, reminding us that tissue is the issue.

Lymphocytic Perimyocarditis Masquerading as Steroid-Dependent Recurrent Pericarditis.

Lymphocytic myocarditis is a pattern of myocardial inflammation typically associated with viral, autoimmune, or idiopathic causes. We present a case of lymphocytic perimyocarditis masquerading as steroid-dependent recurrent pericarditis. This case shows the advantages of using multimodal cardiac imaging and endomyocardial biopsy in clarifying diagnosis in treatment-resistant cases. (Level of Difficulty: Advanced.).

Consensus statement on the processing, interpretation and reporting of temporal artery biopsy for arteritis.

Giant cell arteritis (GCA) is the most common systemic vasculitis in adults in Europe and North America, typically involving the extra-cranial branches of the carotid arteries and the thoracic aorta. Despite advances in noninvasive imaging, temporal artery biopsy (TAB) remains the gold standard for establishing a GCA diagnosis. The processing of TAB depends largely on individual institutional protocol, and the interpretation and reporting practices vary among pathologists. To address this lack of uniformity, the Society for Cardiovascular Pathology formed a committee tasked with establishing consensus guidelines for the processing, interpretation, and reporting of TAB specimens, based on the existing literature. This consensus statement includes a discussion of the differential diagnoses including other forms of arteritis and noninflammatory changes of the temporal artery.

Pearls & Oy-sters: Mitral Annular Calcification as a Cause of Ischemic Stroke: A Case Report.

Evaluation of stroke etiology is an important aspect of stroke care affecting secondary prevention measures. Despite recent advances in diagnostic testing, determining the stroke etiology can remain a challenging task particularly for less common causes of stroke such as mitral annular calcification. This case will review the benefit of histopathologic clot evaluation after thrombectomy to identify uncommon causes of embolic stroke which may change management.

Thoracic Aortic Aneurysm and Dissection: Review and Recommendations for Evaluation.

ABSTRACT: Aortic dissection and rupture (collectively termed "sudden aortic death") are commonly encountered by forensic pathologists, with an estimated incidence at autopsy between 0.6% and 7.7%. Despite this, there is no standard of practice for the evaluation of sudden aortic death at autopsy.Recent studies have shown 20% of patients with thoracic aortic aneurysm or dissection (TAAD) have an identifiable genetic syndrome, and 19% will have an affected first-degree relative. The past 2 decades have seen identification of new culprit genes and syndromes, which can have subtle or nonexistent external phenotypes. A high index of suspicion is warranted to identify possible hereditary TAAD (H-TAAD), allowing family members to obtain screening to avoid catastrophic vascular events. Forensic pathologists need broad knowledge of the spectrum of H-TAAD and awareness of the relative significance of hypertension, pregnancy, substance use, and microscopic changes of aortic architecture.This article reviews the common subtypes of H-TAAD, including Marfan syndrome, vascular Ehlers-Danlos, Loeys-Dietz, and familial thoracic aortic aneurysm and dissection. Recommendations for the evaluation of sudden aortic death at autopsy are presented, including (1) performance of a complete autopsy, (2) documentation of aortic circumference and valve morphology, (3) notifying family of the need for screening, and (4) preservation of a sample for potential genetic testing.

Histologic and Immunohistochemical Features of Antemortem Thrombus Compared to Postmortem Clot: Updating the Definition of Lines of Zahn.

CONTEXT.­: Distinguishing true antemortem thrombus (AMT) from artifactual postmortem clot (PMC) can occasionally be challenging at autopsy. Lines of Zahn are cited as pathognomonic of AMT, but review of literature reveals heterogeneous definitions of the term. Neutrophil karyorrhexis and CD61 immunohistochemistry can also be used to define AMT, but there has been no systematic study determining the specificity of these features. OBJECTIVE.­: To identify features that distinguish AMT from PMC, and to clarify the definition of lines of Zahn. DESIGN.­: PMC from the heart was collected in 50 hospital autopsies. Fifty arterial and 50 venous surgical thrombectomy specimens were reviewed for comparison. The microscopic features with hematoxylin-eosin staining, phosphotungstic acid-hematoxylin (PTAH) staining, and CD61 immunohistochemistry were documented. RESULTS.­: Thin curvilinear strands of fibrin and clumps of fibrin were frequently observed in both AMT and PMC. Thick bands of nested platelets wrapped in fibrin were nearly exclusive to AMT. Neutrophil karyorrhexis was readily apparent on low power in AMT but was seen in 40 of 50 PMCs (80%) only sparsely on high-power examination. Bone marrow elements were identified in 38 of 50 PMCs (76%). CD61 staining showed a geographic pattern in AMT and a speckled pattern in PMC. PTAH staining confirmed features seen with hematoxylin-eosin. CONCLUSIONS.­: Thin curvilinear strands of fibrin are found in both AMT and PMC and can be misinterpreted as lines of Zahn. We define lines of Zahn as thick bands formed by nested platelets wrapped in fibrin. Diffuse neutrophil karyorrhexis is common in AMT; in contrast, bone marrow elements are often seen in PMC.

Commentary on why implementing and standardizing histologic diagnosis of myocarditis is crucial for the clinical setting and patient care.

Histological examination of endomyocardial biopsy or myocardium at autopsy is key to the diagnosis of myocarditis. Among pathologists there is currently extensive variability in routine practice and criteria used to define, diagnose, and report myocarditis as well as to achieve consensus on cases. Two manuscripts emphasizing the need to standardize and implement histopathological diagnostic criteria for myocarditis are reviewed.

Sudden cardiac death in the young: A consensus statement on recommended practices for cardiac examination by pathologists from the Society for Cardiovascular Pathology.

Sudden cardiac death is, by definition, an unexpected, untimely death caused by a cardiac condition in a person with known or unknown heart disease. This major international public health problem accounts for approximately 15-20% of all deaths. Typically more common in older adults with acquired heart disease, SCD also can occur in the young where the cause is more likely to be a genetically transmitted process. As these inherited disease processes can affect multiple family members, it is critical that these deaths are appropriately and thoroughly investigated. Across the United States, SCD cases in those less than 40 years of age will often fall under medical examiner/coroner jurisdiction resulting in scene investigation, review of available medical records and a complete autopsy including toxicological and histological studies. To date, there have not been consistent or uniform guidelines for cardiac examination in these cases. In addition, many medical examiner/coroner offices are understaffed and/or underfunded, both of which may hamper specialized examinations or studies (e.g., molecular testing). Use of such guidelines by pathologists in cases of SCD in decedents aged 1-39 years of age could result in life-saving medical intervention for other family members. These recommendations also may provide support for underfunded offices to argue for the significance of this specialized testing. As cardiac examinations in the setting of SCD in the young fall under ME/C jurisdiction, this consensus paper has been developed with members of the Society of Cardiovascular Pathology working with cardiovascular pathology-trained, practicing forensic pathologists.

Double Valve Replacement in a Patient With Hunter Syndrome.

Hunter syndrome is a rare disorder in which affected patients have significant airway abnormalities (macroglossia, small mouth opening, and supraglottic narrowing) that complicate their management. Deposition of glycosaminoglycans in the heart leads to cardiomyopathy, and cardiac valve dysplasia that can lead to valvular stenosis or regurgitation or both, necessitating valve replacement. Management of patients with Hunter syndrome is complex and needs a multidisciplinary team approach. Mechanical valve replacement is a suitable treatment option.

Differences in Aortic Histopathology in Patients Undergoing Valve Reimplantation Surgery for Various Clinical Syndromes.

OBJECTIVES: The study aims to investigate aortic histopathologic differences among patients undergoing aortic valve reimplantation, suggest different mechanisms of aortic root aneurysm pathogenesis, and identify factors associated with long-term success of reimplantation. METHODS: From 2006 to 2017, 568 adults who underwent reimplantation for repair of aortic root aneurysm, including patients with tricuspid aortic valves with no connective tissue disease (TAV/NoCTD, n = 314/568; 55.3%), bicuspid aortic valves (BAVs, n = 86/568; 15.1%), or connective tissue disease (CTD, n = 177/568; 31.2%), were compiled into three comparison groups. Patients with both BAV and CTD (n = 9/568; 1.6%) were omitted to increase study power. Patient records were analyzed retrospectively, focusing on pathology reports, which were available for 98.42% of patients, and were classified based on their descriptions of aortic tissue samples, primarily from the noncoronary sinus. Mean follow-up time available for patients was 2.97 years. RESULTS: Aortitis, medial fibrosis, and smooth muscle loss were more common histopathologic findings in patients with TAV/NoCTD than in patients with BAV and CTD (p < 0.05). Cystic medial degeneration was most often found in patients with CTD, then TAV/NoCTD, and least in BAV (p < 0.01). Increases in mucopolysaccharides were found more often in the BAV group than in the TAV/NoCTD and CTD groups (p < 0.01). There were no differences in the frequency of elastic laminae fragmentation/loss across these three groups. Among all patients, 1.97% (n = 11/559) had an unplanned reintervention on the aortic valve after reimplantation, but no significant demographic or histopathologic differences were identified. CONCLUSION: Despite some common histopathologic features among patients undergoing aortic valve reimplantation, there were enough distinguishing features among aortic tissue samples of TAV/NoCTD, BAV, and CTD patients to suggest that these groups develop root aneurysms by different mechanisms. No histopathologic features were able to predict the need for late reintervention on the aortic valve.

Multimodality imaging evaluation of incidentally discovered intracardiac mass.

Incidentally discovered intracardiac masses often represent diagnostic dilemmas. No guideline-directed algorithm exists for evaluation and management in these cases. Understanding the utility and limitations of different imaging modalities expedites evaluation of differential diagnoses and management, particularly when there are discordant imaging findings. This case further demonstrates that benign cardiac tumors may grow rapidly, and that new and rapid emergence of an intracardiac mass does not necessarily correlate with a diagnosis of thrombus or malignancy. It also highlights the importance of a broad differential diagnosis and a systematic management approach in patients with intracardiac masses.

Association Between Atrial Uptake on Cardiac Scintigraphy With Technetium-99m-Pyrophosphate Labeled Bone-Seeking Tracers and Atrial Fibrillation.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disease, in which atrial fibrillation (AF) has been shown to be prevalent. Cardiac scintigraphy with technetium-99m-pyrophosphate (99mTc-PyP) labeled bone-seeking tracers is used to noninvasively make the diagnosis of ATTR-CA, based on ventricular myocardial uptake. Assessment of atrial wall uptake (AU) on 99mTc-PyP is currently not used in the clinical setting Methods: We analyzed a cohort of patients referred for 99mTc-PyP scan at a tertiary center to explore AU and associations between any and incident AF, ATTR-CA, and all-cause mortality. RESULTS: Among 580 patients included, 296 patients (51%) had a diagnosis of AF; 164 patients (28%) had scans consistent with ATTR-CA while 117 patients (20%) had AU. Of 117 patients with AU, 107 (91%) had any AF. In contrast, of 463 patients without AU 191(41%) had any AF. Of those with AU, 59/117(50%) patients had a 99mTc-PyP diagnosis of ATTR-CA while 58/117(50%) patients did not have such a diagnosis (P=1.00). Patients with AU had significantly more any AF (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04]; P<0.001), independent of ATTR-CA diagnosis and sex. On multivariable Cox proportional hazards analyses adjusting for age, AU, ATTR-CA diagnosis, sex, smoking, hypertension, diabetes, left ventricular ejection fraction, and coronary artery disease, both age (HR, 1.03 [95% CI, 1.02-1.04]; P<0.0001) and AU (HR, 2.68 [95% CI, 2.11-3.41]; P<0.0001) were independently associated with the development of any AF. Freedom from incident AF at 1-year was significantly lower in patients with AU, both in patients with and without ATTR-CA respectively (HR, 2.27 [95% CI, 1.37-3.78]; P<0.0001 versus HR, 2.21 [95% CI, 1.46-3.34]; P<0.0001). CONCLUSIONS: In a consecutive cohort of patients undergoing 99mTc-PyP scans, 20% had AU, which was statistically associated with any AF, independently of ATTR-CA diagnosis and sex. AU was associated with significantly lower freedom from incident AF at 1-year. Overlooking AU on 99mTc-PyP scans could potentially miss an earlier disease manifestation, or an additional risk factor for any/incident AF.

Histoplasma capsulatum Pacemaker-related Endocarditis Presenting as Endogenous Endophthalmitis.

PURPOSE: To report a unique case of pacemaker-related infective endocarditis manifesting as endogenous endophthalmitis with chorioretinitis secondary to Histoplasma capsulatum. METHOD: Case Report. RESULTS: A 75-year-old man was diagnosed with blood culture-negative infective endocarditis and was admitted with deteriorating vision and ocular inflammation. Examination of the eye indicated significant vitreous inflammation and retinitis. Vitreous cultures were negative, but universal fungal PCR of the vitreous fluid was positive for Histoplasma capsulatum. Histopathology of the fibrous cuff around the extracted right atrial lead demonstrated hyphal and yeast forms and PCR of this material identified Histoplasma capsulatum. Despite aggressive antifungal and surgical treatment, the eye became phthisical. CONCLUSION: We highlight the importance of considering Histoplasma capsulatum in the differential diagnosis of endogenous endophthalmitis, particularly among patients from endemic areas who present with possible endovascular infection.

Mitral annular calcification and valvular dysfunction: multimodality imaging evaluation, grading, and management.

Mitral annular calcification (MAC) refers to calcium deposition in the fibrous skeleton of the mitral valve. It has many cardiovascular associations, including mitral valve dysfunction, elevated cardiovascular risk, arrhythmias, and endocarditis. Echocardiography conventionally is the first-line imaging modality for anatomic assessment, and evaluation of mitral valve function. Cardiac computed tomography (CT) has demonstrated importance as an imaging modality for the evaluation and planning of related procedures. It also holds promise in quantitative grading of MAC. Currently, there is no universally accepted definition or classification system of MAC severity. We review the multimodality imaging evaluation of MAC and associated valvular dysfunction and propose a novel classification system based on qualitative and quantitative measurements derived from echocardiography and cardiac CT.

Invasive Aortic Valve Endocarditis: Clinical and Tissue Findings From a Prospective Investigation.

BACKGROUND: Advanced aortic valve infective endocarditis (IE) with progression and destruction beyond the valve cusps-invasive IE-is incompletely characterized. This study aimed to characterize further the invasive disease extent, location, and stage and correlate macroscopic operative findings with microscopic disease patterns and progression. METHODS: A total of 43 patients with invasive aortic valve IE were prospectively enrolled from August 2017 to July 2018. Of these patients, 23 (53%) had prosthetic valve IE, 2 (5%) had allograft IE, and 18 (42%) had native aortic valve IE. Surgical findings and intraoperative photography were analyzed for invasion location, extent, and stage. Surgical samples were formalin fixed and analyzed histologically. The time course of disease and management were evaluated. RESULTS: Pathogens included Staphylococcus aureus in 17 patients (40%). Invasion predominantly affected the non-left coronary commissure (76%) and was circumferential in 15 patients (35%) (14 had prosthetic valves). Extraaortic cellulitis was present in 29 patients (67%), abscess in 13 (30%), abscess cavity in 29 (67%), and pseudoaneurysm in 8 (19%); 7 (16%) had fistulas. Histopathologic examination revealed acute inflammation, abscess formation, and lysis of connective tissue but not of myocardium or elastic tissue. Median time from onset of symptoms to antibiotics was 5 days, invasion confirmation 15 days, and surgery 37 days. Patients with S aureus had a 21-day shorter time course than patients non-S aureus. New or worsening heart block developed in 8 patients. CONCLUSIONS: Advanced invasive aortic valve IE demonstrates consistent gross patterns and stages correlating with histopathologic findings. Invasion results from a confluence of factors, including pathogen, time, and host immune response, and primarily affects the fibrous skeleton of the heart and expands to low-pressure regions.

A Clinico-Pathologic Approach to the Differential Diagnosis of Pericardial Tumors.

PURPOSE OF REVIEW: Tumors of the pericardium are rare, but a wide variety of congenital, infectious, inflammatory, and neoplastic processes have been reported. Pericardial tumors can be categorized as non-neoplastic or neoplastic. Neoplastic lesions can be further divided into benign or malignant, with malignancies being either primary or secondary (metastatic). Clinical, radiographic, and pathologic features of the most common entities are discussed. RECENT FINDINGS: Metastatic neoplasms involving the heart and pericardium are far more common than primary pericardial neoplasms. Of primary pericardial malignancies, mesothelioma is the most common; notably, cytology of effusion fluid is relatively insensitive to the diagnosis. The prognosis for most malignancies of the pericardium, primary or secondary, is poor. Increasingly, clinically recognized diseases that involve the pericardium include Erdheim-Chester and IgG4-related disease. This article provides a comprehensive review of the most recent literature to develop a structured framework to the differential diagnosis of pericardial tumors.

Case report of isolated cardiac sarcoidosis presenting as hypertrophic obstructive cardiomyopathy-a clinical picture printed on lenticular paper.

BACKGROUND: Cardiac sarcoidosis (CS) is an inflammatory granulomatous process of the myocardium that can be asymptomatic or have several different clinical phenotypes. One of its rarely described presentations consists of hypertrophy of the septal myocardium, similar to hypertrophic cardiomyopathy (HCM). Isolated cardiac sarcoidosis that haemodynamically mimics hypertrophic obstructive cardiomyopathy (HOCM) has been rarely described in the literature. CASE SUMMARY: A 64-year-old Caucasian female previously diagnosed with non-critical aortic stenosis presented with pre-syncope, and echocardiography showed significant obstruction based on left ventricular outflow tract gradients, confirmed by cardiac magnetic resonance (CMR), concerning for a phenocopy of HCM. Septal myectomy was performed and pathology specimen revealed non-caseating granulomata consistent with cardiac sarcoidosis. She was started on oral corticosteroids and initial cardiac fluorodeoxyglucose positron emission tomography (FDG-PET) done after 1 month of treatment was negative. Repeat FDG-PET 15 months later, in the setting of haemodynamic decompensation, demonstrated diffuse FDG uptake in the myocardium without extra-cardiac involvement. DISCUSSION: Our case brings together two entities: isolated cardiac sarcoidosis and its presentation mimicking HOCM, which has been very rarely described in the literature. And it also shows the scenario of surgical pathology diagnosis of sarcoidosis that was not suspected by initial CMR or FDG-PET, despite adequate preparation, only appearing on repeat FDG-PET done 15 months later. Isolated cardiac sarcoidosis should remain a differential diagnosis for any non-ischaemic cardiomyopathy without a clear cause, despite imaging evidence of HCM.