An 80-year-old woman was admitted to our hospital because of progressive dyspnea on exertion for the previous two months. She had been treated for hypertension and dyslipidemia. She had no known history of cancer. On admission, her oxygen saturation (SpO2) was 94%, which decreased to 74% with exertion. Her body temperature was 37C, heart rate was 82 beats per minute (regular), and blood pressure was 161/77 mmHg. Physical examination of her heart and chest showed no abnormality at that time. Several submental lymph nodes were palpable as rubbery, non-tender masses, and they measured less than 2 cm in size.
Arterial blood gas (ABG) on ambient air showed arterial oxygen tension (PaO2) of 64 mmHg and alveolar-arterial oxygen tension difference (AaDO2) of 43 mmHg (Table). Chest X-rays, electrocardiography (ECG), and ultrasound cardiography (UCG) showed no abnormality. Pulmonary function tests showed a decreased diffusing capacity (%DLCO; 74%). A high-resolution computed tomography (HRCT) scan showed almost no abnormalities in the lung fields and a contrast-enhanced CT scan showed no findings of pulmonary embolism. Transbronchial lung biopsy (TBLB) and bronchoalveolar lavage revealed no evidence of disease, including malignancy.
As this patient showed a decreased diffusing capacity without any parenchymal lung abnormalities, we suspected that she had problems in her pulmonary circulation. We could exclude pulmonary thromboembolism by contrast-enhanced CT. These findings indicated that this patient had peripheral pulmonary vascular disease. A lung perfusion scan was performed and revealed multiple wedge-shaped subsegmental defects (Fig. 1A). From these findings, we considered PTTM to be a possible cause of her illness.
Her serum tumor markers and immunological tests were normal (Table). Upper gastrointestinal endoscopy and mammography revealed no evidence of malignancy. Positron emission tomography (PET)-CT showed an abnormal uptake in her right deep neck with a maximal standardized uptake value (SUVmax) of 3.8. There were no remarkable uptakes in the lung fields.
MRI of the head and neck showed a right parotid mass that had invaded the parapharyngeal space, medial pterygoid muscle, and mandibular bone. A biopsy of the submandibular lymph nodes revealed metastatic adenocarcinoma, and an immunohistochemical examination showed cytokeratin 7 (CK7) and gross cystic disease fluid protein 15 (GCDFP15) to both be positive. These findings were compatible with salivary duct carcinoma. We diagnosed her to have PTTM caused by adenocarcinoma of the parotid gland according to these radiological and pathological findings. We could not perform a biopsy directly from the parotid gland because its location was deep and difficult to approach.
The patient complained of increasing exertional dyspnea, and a further decrease of SpO2 at rest was noted within a month after admission. A split of the second heart sound (S2) at the apex, a clinical sign of pulmonary hypertension, had become apparent by this time. ECG showed new-onset T-wave inversion in leads II, III, aVf, and V1-5. UCG at this time revealed tricuspid regurgitation with a pressure gradient (TRPG) of 57 mmHg, right ventricular dilatation, and flattening of the interventricular septum. These findings suggested that the patient had significant pulmonary hypertension. HRCT showed dilatation of the peripheral pulmonary arteries and a diffuse patchy distribution of ground-glass opacity (GGO) in the bilateral lung fields (Fig. 2). Enhanced CT revealed no findings of pulmonary emboli or deep vein thrombosis of the lower extremities. Based on these findings we considered the cause of pulmonary hypertension to be diffuse pulmonary embolization at the peripheral pulmonary arteries, which was compatible with the findings of PTTM.
Although the diagnosis of PTTM was not pathologically definitive, we started chemotherapy with paclitaxel (PTX; 170 mg/m2)/carboplatin (CBDCA; AUC 4.5). Dyspnea and the physical signs of PAH improved gradually during the first two weeks after starting chemotherapy, and a decrease of TRPG was found after another two weeks. The defects in the lung perfusion scan also showed some improvement (Fig. 1B). Two months after the first course of chemotherapy, her symptoms deteriorated again with the increase of TRPG. We treated her with five courses of PTX/CBDCA and a course of docetaxel (DOC). Her symptoms and the findings of PAH first improved, but then deteriorated repeatedly (Fig. 3). Eleven months after her initial visit, severe dyspnea, hypoxia and pulmonary hypertension developed and she died suddenly on her way to the restroom.
Autopsy findings of her lung showed multiple tumor embolisms, thrombus formation, recanalization, and intimal fibrocellular proliferation in the muscular pulmonary arteries measuring from 100 to 200 mum in diameter (Fig. 4). The diagnosis of PTTM was made pathologically. Salivary duct carcinoma with lymphovascular invasion was found in her right parotid gland and it was considered to be the primary lesion of PTTM. Her heart showed significant dilation and thickening of the right ventricle, and her other organs were congestive, which suggested that significant PAH and right-sided heart failure were the causes of death. Slight alveolar wall thickening and inflammatory cell infiltration with hyaline membrane formation was observed focally. There were almost no tumor cells in these alveoli.