INTRODUCTION: ACCP guidelines do not routinely recommend lung biopsy for evaluation of pulmonary artery hypertension (PAH). We report a case of PAH in whom lung biopsy provided an unexpected diagnosis.
CASE PRESENTATION: A 66-year-old female presented with exertional dyspnea, dry cough, orthopnea and leg swelling for six weeks. Her past medical history was significant for sarcoidosis, quiescent for thirty years. Physical examination revealed hypoxia on room air, bilateral crackles, jugular venous distension and pedal edema. Echocardiogram showed normal left ventricular function and pulmonary artery systolic pressure of 80 mmHg, and on cardiac catheterization, the mean pulmonary artery pressure was 42 mmHg, with normal capillary wedge pressure and cardiac output. CT chest revealed mild, bibasilar interstial lung disease (ILD) without evidence of pulmonary embolism. V/Q and gallium scans of the lung, and 4-channel sleep study were non-diagnostic. Pulmonary function study showed a moderate restrictive ventilatory defect. Extensive rheumatological work up was negative, except for an elevated ESR (60 mm/hr) and a positive ANA (1:320) with nucleolar pattern. Patient continued to detoriate with worsening respiratory failure, necessitating an open lung biopsy, which showed histopathologic features of tumor embolism (figures1, 2) and PAH. Immunohistochemical staining was suggestive of a primary site in pancreas, kidney or upper gastrointestinal tract. Despite further work-up, the primary tumor was not found. Her post-op course was complicated by progressive cor pulmonale and respiratory failure. She died 2 weeks later despite maximal supportive therapy.
DISCUSSIONS: Pulmonary tumor embolism is a rare, but recognized, cause of PAH. However, this possibility is often not entertained. Pulmonary tumor embolism is characterized by occlusion of small pulmonary arteries, arterioles and alveolar septal capillaries by aggregates of tumor cells and platelet-fibrin thrombosis. Autopsy series of cancer patients has demonstrated pulmonary tumor embolism in up to 26% of patients, but the diagnosis is made ante-mortem in only 6% of autopsy-proven cases. Intravascular tumor emboli cause serious pulmonary disease in <1% of all cancer patients. PAH ensues when tumor emboli occlude >65% of pulmonary vasculature. Pulmonary tumor emboli are mostly associated with adenocarcinomas of breast, lung, stomach and colon, hepatoma, choriocarcinoma and renal cell carcinoma. Tumor cells enter the systemic circulation by invading small veins or releasing fragments into the tumor neovasculature. Pulmonary angiography is not sensitive for tumor emboli as they are <1 mm in diameter. Cytological examination of blood aspirated from a wedged pulmonary artery catheter has high sensitivity for diagnosis. Therapy is directed at the primary tumor and occasionally, this may result in resolution of the tumor emboli. Although, the official ACCP guidelines do not recommend lung biopsy as part of the evaluation of PAH due to increased morbidity and mortality, our case illustrates the possible role for early lung biopsy in cases of PAH of uncertain etiology. In our patient, the lung biopsy was done to evaluate ILD, because the degree of PAH was disproportionate to the pulmonary infiltrates. Early diagnosis of pulmonary tumor embolism would minimize the inadvertent use of unhelpful therapies, and may potentially improve survival if the primary tumor is treatable. Given the increasing popularity of costly designer treatments such as anti-endothelin antibodies, there exists an economic imperative to avoid use of these drugs in patients with little hope of response, such as those with tumor emboli. An alternative to lung biopsy may be to mandate cytological sampling from the pulmonary artery in idiopathic PAH. A right heart catheterization is commonly performed in the evaluation of PAH, and the cytology yield for tumor emboli is high.
CONCLUSION: Pulmonary tumor embolism should be included in the differential diagnosis of PAH. Lung biopsy may have a potential role in the evaluation of PAH of unknown etiology.
DISCLOSURE: Aditya Dubey, None.