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UNUSUAL PULMONARY VASCULAR PATHOLOGY IN A YOUNG DYSPNOEIC WOMAN PART 2

EXPLANATION AND DIAGNOSIS: PULMONARY TUMOUR THROMBOTIC MICROANGIOPATHY (PTTM) RESULTING FROM DIFFUSE-TYPE ADENOCARCINOMA OF THE STOMACH Histological examination of the lungs revealed prominent and tortuous pulmonary arteries (Fig. 1). Striking eccentric or concentric fibrocellular intimal proliferation was present, causing luminal narrowing or occlusion (Fig. 2). There were also thrombi, associated with variable degrees of recanlisation (Fig. 3). In some blood vessels, carcinoma cells were attached to the endothelium or admixed with fibrin thrombi (Fig. 3). The carcinoma cells were remarkably highlighted by immunostaining for cytokeratin (Fig. 4). No parenchymal tumour nodules were found in the lungs. The pathological features of the pulmonary vasculature are typical of pulmonary tumour thrombotic microangiopathy (PTTM), also known as carcinomatous arteriopathy. PTTM can be distinguished from idiopathic pulmonary hypertension by the lack of thickening of the media, and from thromboembolic type pulmonary hypertension by a looser fibromyxoid proliferation and presence of carcinoma cells in some vessels. The stomach ulcer showed involvement by diffuse-type adenocarcinoma (Fig. 5), and all the other tumour nodules and the enlarged lymph nodes were composed of similar tumour. The lung is a frequent site of tumour metastasis, and a variety of distinctive patterns of metastasis has been recognised, such as multiple or solitary nodules, lymphangitic metastasis, endobronchial metastasis and tumour embolisation. PTTM is an uncommon complication of disseminated carcinoma first described by von Herbay et al. in 1990, with less than 50 cases having been reported in the literature. 10,11 This condition is not well recognised – it is not mentioned in a major textbook of lung pathology.12 PTTM is distinct from conventional tumour emboli in that the intraluminal tumour thrombi do not cause mechanical obstruction of the affected vessels as true emboli. Instead, the intraluminal tumour cells cause damage to the endothelium, leading to activation of coagulation cascade and release of inflammatory mediators, resulting in deposition of platelet and fibrin thrombi, fibrocellular subintimal proliferation, and smooth muscle cell colonisation of the affected vessels. This proliferative process leads to diffuse narrowing of the pulmonary arterial system and increased vascular resistance, which may be followed by fatal pulmonary hypertension and acute or subacute cor pulmonale. In a prospective study of 222 autopsies of patients with solid malignancies, arterial tumour embolism (including some cases of PTTM) was observed in 20% of cases, among whom right ventricular hypertrophy and right ventricular dilatation were demonstrated in 42.1 and 26.3%, respectively. Right ventricular hypertrophy and dilatation was not evident in the current case, but it has been estimated that about 2 months of increased pulmonary vascular pressure would be required to produce myocardial hypertrophy. PTTM is distinguishable from malignant inflammatory vasculitis, which represents a paraneoplastic genuine vasculitis, and from the recently described vasculitis carcinomatosa, which features transmural infiltration of tumour cells without intraluminal tumour emboli. Clinically, patients with PTTM often present with progressive dyspnoea and pulmonary hypertension; there may or may not be known malignancy. Because there is diffuse involvement of the vasculature without forming a discrete embolus, ventilation-perfusion scan is usually unrewarding. Activation of the coagulation system and release of inflammatory cytokines may also lead to a consumptive coagulopathy and sepsis-like symptoms, as seen in this case. In a study of 630 consecutive autopsies on patients with carcinoma, PTTM was observed in 19 cases (3.3%), most commonly associated with adenocarcinoma, particularly gastric adenocarcinoma, pancreatic carcinoma, breast carcinoma, hepatocellular carcinoma and choriocarcinoma. Uncommonly, the primary tumour is occult.2,7,16,17 As most cases are diagnosed only at postmortem examination and there is no effective treatment, the prognosis is invariably poor.