Moderator:

Gayle L. Winters
Brigham and Women's Hospital
Boston, Massachusetts

Case 1

submitted by:
Allen P. Burke
Armed Forces Institute of Pathology
Washington, D.C.

Clinical Summary:

A 60 year old white male, 5'11", 180 lbs., complained of chest pain one day prior to being found unresponsive on the ground in front of his home. He had a history of thyroid problems, asthma, and recent sinus infection. He was taking anti-allergy medicines [Advair Discus (fluticasone/salmeterol), Allegra-D (fexofenadine & pseudoephedrine), Atrovent (ipratropium bromide), Nasonex (mometasone furoate), and Singulair (montelukast)], an antibiotic [Cefzil (cefprozil)], and Synthroid (levothyroxine). At autopsy, his heart weighed 400 grams; the foramen ovale was probe patent; left ventricular chamber dimensions were normal; there was mild right ventricular hypertrophy (6 mm thick at posterior wall); and there were focal myocardial scarring and hyperemia in the posteroseptal left ventricle and posterior right ventricle. A section of the proximal right coronary artery is available for review.

Slide 1 - Acute myocardial infarct, posterior left ventricle

Slide 2 - Proximal right coronary artery, low magnification (Movat pentachrome stain)

Slide 3 - Higher magnification, demonstrating disruption of thinned fibrous cap, infiltrated by foamy macrophages.

Case 2

submitted by:
Bruce M. McManus
University of British Columbia
Vancouver, British Columbia

Clinical Summary - Case A:

A 54-year-old female dentist had a 5-day history of 'flu-like' symptoms (including cough, fatigue, shortness of breath chills and malaise). On admission to hospital for shortness of breath and an inability to sleep, she was found to have left ventricular failure, cardiogenic shock and marked hypoxemia. She then developed uncontrollable cardiac arrhythmias, became profoundly hypotensive, terminating in ventricular tachycardia and death on the same day.

Slide 4 - Hematoxylin and eosin stained slide from the lateral left ventricular free wall which exemplifies the heavy infiltrates and damage seen throughout the myocardium (X125).

Slide 5 - Higher power of the same area showing myocyte necrosis and a cellular infiltrate (X250).

Slide 6 - Immunohistochemical stain for muscle-specific actin showing widespread myocyte loss (X250).

Clinical Summary - Case B:

A 27-year-old female was admitted to hospital with a 5 day history of exertional chest pain and dyspnea. Her initial ECG demonstrated ST elevation in the anteroseptal leads, ST depression laterally, complete atrioventricular block and frequent premature ventricular complexes. She deteriorated clinically during the first 48 hours, with worsening of hypotension and heart failure requiring inotropic support and intubation. Novel therapies resulted in improvement of the patient's condition by 6 days after initial presentation.

Slide 7 - Hematoxylin and eosin stained slide showing features of a widespread cellular infiltrate with myocyte loss and degeneration (X500).

Slide 8 - Another biopsy fragment from this patient showing features as above (X500).

Case 3

submitted by:
Henry D. Tazelaar
Mayo Clinic
Rochester, Minnesota

Clinical Summary:

A 79 year-old woman with reactive airways disease and systemic hypertension presented with increasing dyspnea, fever and cough. A chest radiograph showed bilateral apical infiltrates and a dilated aorta. Sputum cultures grew H. influenzae. Subsequent transesophageal echo showed a 5.3 cm diameter ascending aortic aneurysm and marked aortic insufficiency. She underwent surgery at which time a large aortic aneurysm involving the aortic root and ascending aorta was identified. The aorta was normal distally. The wall was not obviously thickened, the aneurysm was resected and a graft placed. The specimen received in pathology was an opened portion of aorta measuring 9.4 x 5.1 x 0.1 cm. The endothelial surface was unremarkable.

Slide 9 - The low power image shows a normal thickness advantitia, moderate medial thickening and moderate fibrous intimal thickening.

Slide 10 - The media contains foci of laminar necrosis rimmed with inflammatory cells.

Slide 11 - The inflammatory infiltrate contains numerous lymphocytes, plasma cells, eosinophils and multinucleated giant cells. The wall does not contain significant fibrosis.

Case 4

submitted by:
Richard N. Mitchell
Brigham and Women's Hospital
Boston, Massachusetts

Clinical Summary:

The patient was a 34 year old male with a history of congenital heart disease (D-transposition of the great arteries); a Mustard repair procedure at age 4 was complicated by right phrenic nerve damage and right diaphragmatic paralysis. He subsequently developed progressive failure of his systemic ventricle, and underwent cardiac transplantation in 1990 (at the age of 22); his post-transplant immunosuppression consisted of cyclosporine A, azothioprine, and corticosteroids. His course was notable for two episodes of acute rejection in the first year following transplantation, treated with solumedrol boluses. In addition, within 4 months of transplant, he developed a post-transplant lymphoma in a left submandibular node. This was resected, and he experienced no further recurrence after his immunosuppressive therapy was slightly tapered. Other complications included obesity (eventually developing Pickwickian symptomatology), hypertension, osteoporosis, and hyperlipidemia.

The patient had annual angiographic evaluation of his coronaries; beginning approximately 10 years after transplant, diffuse coronary artery disease was first seen, most apparent in the smaller coronary arteries. Intravascular ultrasound also documented moderate-severe diffuse epicardial vessel disease with up to 85% chronic stenoses. Beginning 11 years after transplant, the patient developed progressive, severe exertional dyspnea and biventricular failure (R>L), although ejection fractions were largely maintained; moderate pulmonary hypertension was documented. PFT's documented profound restrictive and obstructive lung disease; although he was found to be a carrier for cystic fibrosis, his findings were felt overall to be most consistent with central neurogenic hypoventilation.

The patient presented terminally with right lower abdomenal discomfort; CT evaluation showed only mild thickening of the distal ileum and he was discharged to be worked up electively. He subsequently suffered a cardiac arrest at home, and could not be resuscitated. Slides available for review are a representative coronary artery and myocardium from the failed allograft.

Slide 12 - Anterior half of heart sectioned in an echocardiographic 4-chamber view. The lateral free wall and mid-septal walls exhibit focal scarring, as well as depressed glassy-appearing areas indicating granulation tissue.

Slide 13 - Section from mid-left anterior descending coronary artery demonstrating moderate concentric intimal hyperplasia consisting of chronic inflammatory cells, smooth muscle cells, and extracellular matrix. This is representative of the appearance of all the epicardial arteries as well as many of the penetrating intramyocardial arterioles.

Slide 14 - Section of interventricular septum exhibiting diffuse, severe subendocardial myocyte vacuolization indicative of chronic sub-lethal ischemic injury. When seen on routine endomyocardial biopsy in transplant recipients, these changes are highly specific for allograft arteriopathy (See reference: Winters GL and Schoen FJ. J Heart Lung Transplant 1997;16:985-993).

Slide 15 - Section of left ventricular free wall showing well-circumscribed subendocardial microscopic infarction. Such watershed microscopic infarcts are also strongly associated with allograft arteriopathy (See reference: Winters GL and Schoen FJ. J Heart Lung Transplant 1997;16:985-993).