2.1 Background
A 48-year old woman succumbed to heart failure due to an inoperable heart tumour, which was diagnosed four years earlier.
Initially she was admitted due to oedema and a weight gain of 5 kg over the previous 10 days, combined with fever, headache and abdominal pain. She had no significant medical history prior to this. A CT scan revealed pericardial effusion, widespread inflammation in the retroperitoneum, and sclerotic lesions in the spine and pelvis. Diagnostic workup (including cytologic investigation) did not suggest malignancy or infection. During the subsequent six months, she was admitted several times due to recurrent idiopathic pericardial effusion.
Eventually, a MR-scan of the heart disclosed a mass involving the right ventricle, the right atrium, and partially the left atrium, highly suspicious of neoplasia.
The patient was operated to obtain a biopsy for histologic diagnosis, and to resect the tumour if possible.
At surgery, the pericardium had multiple soft adherences and appeared inflamed and in some areas covered by fibrin. Pericardial fluid was abundant. Dense tumour-tissue was found incorporated as a band located at the lateral side of the right atrium stretching from the superior to the inferior caval vein, approximately 2 cm thick, and protruding somewhat into the atrial cavity. Tumour tissue was also found to be incorporated in the anterior wall of the right ventricle as an approximately 4 cm wide band arching along the atrio-ventricular groove, encroaching the right coronary artery, and following the acute margin to the apex of the heart. The rest of the anterior wall of the right ventricle had no evidence of tumour invasion. The tumour was pale and sparsely vascularised. Biopsies were obtained for histology. The tumour was technically impossible to resect.
Histology revealed a mass of mainly fibrous tissue, mixed with chronic inflammatory cells, oedema and abundant minor vessels. Solitary fibrous tumour was considered a plausible diagnosis, as well as some kind of reactive fibrous condition. But no unambiguous diagnosis was concluded.
The possibility of heart transplantation was discussed, but initially rejected because the patient suffered few symptoms at this stage. When she finally was considered sick enough (!), a transplant was deemed impossible as the tumour seemed to involve the large vessels.
One year after the first biopsy, and approximately 2.5 years before death, a trans-venous myocardial biopsy was performed. Histopathology showed the same changes as earlier. Neoplasm, including malignancy, was considered. A solitary fibrous tumour was re-considered, but the diagnosis was decided to be: “Unspecific chronic inflammation and fibrosis.” The sections were seen by several pathologists.
She was treated symptomatically as a heart failure patient and over the next couple of years her symptoms, (dyspnoea, fatigue, oedema) worsened dramatically, and she was no longer able to work nor perform daily life activities. She was admitted several times, acutely as well as electively. Finally she was transferred to a hospice where she eventually died (4 years after initial consultation).
2.2 Autopsy findings
External examination revealed no abnormal pathology beside a 30 cm long sternotomy scar. Internal examination of the thoracic cavity revealed a massive fibrous pale tumour growth, measuring 27 cm, surrounding the heart, involving the pericardium as well as the cavities of both atria and ventricles (Fig. 1a-b). Focally the mass was seen infiltrating the myocardium. All three lobes of the right lung were infiltrated by the mass. The left lung was compact and displaced cranially, but seemed uninvolved by the tumour mass. The mass was adherent to the thoracic wall and the thoracic spine.
An identical pale mass, measuring up to 4.5 cm in diameter, was surrounding the thoracic and abdominal aorta, as well as the renal arteries and the inferior caval vein. The mass also involved the retroperitoneum, infiltrating the renal fat patch and the small intestinal mesentery, as well as the peripancreatic and periadrenal tissue bilaterally, and a small area of the liver capsule. There seemed to be no involvement of the organs.
The histopathologic changes were identical in all samples (Fig. 1c, 2–3), showing a fibrous proliferation with a mixture of small lymphocytes without atypia, plasma cells, and abundant histiocytes, including a few histiocytic giant cells. The histiocytes stained positively for CD68 and negatively for CD1a. Only a few IgG4 positive plasma cells were seen. No microorganisms were shown. The lung tissue showed a distinct distribution with involvement of pleura, interlobular septa and bronchovascular bundles while the intervening alveolar parenchyma was spared. The bone marrow revealed no myeloid dysplasia or accumulation of histiocytes
BRAFV600E mutation was found in histiocytes in sections from the pericardium, lungs and retroperitoneum.
Based on the characteristic anatomic distribution of disease combined with histopathology and BRAFV600E mutation, ECD was finally diagnosed.