A 66-year-old Japanese woman presented to Kameda Medical Center, a tertiary care and teaching hospital with 925 inpatients beds, due to dyspnea that had started the previous month. She had a past medical history of hypertension, diabetes mellitus, and dyslipidemia. She had no history of smoking or alcohol abuse, and she had no familial history of connective tissue or hematological diseases. She had not come into contact with any animals, including birds. Chest radiography, performed at our hospital four years previously, had revealed no abnormalities.
Upon physical examination, her blood pressure was 136/58 mmHg, and her heart rate was 83 beats/min. Her oxygen saturation level was 90% (room air), her respiratory rate was 20 breaths/min, her body temperature was 36.7  C, and her body mass index was 34. Her mucous membranes were moist, and her nasopharynx and oropharynx had no ulcerations or exudates. Cardiac examination revealed normocardia, with prominent P2 sounds and a regular rhythm without murmurs. Tachypnea was noted. Inspiratory crackles were present in both lungs. No wheezing or rhonchi were present. No clubbing, cyanosis, or edema of the arms, hands, legs, or feet was noted. The abdominal, musculoskeletal, neurologic, and cutaneous examinations were normal. Arterial blood gas quantification showed type 1 respiratory failure (Table 1). Chest radiography revealed diffuse reticular and ground-glass opacities (GGO) in both lungs. Chest computed tomography (CT) demonstrated a bilateral mosaic attenuation pattern, with enlarged pulmonary arteries and patchy GGOs with consolidation (Fig. 1 A). There was no evidence of pulmonary embolism detected via contrast-enhanced CT performed on the following day.
The patient began treatment with a new medication (sitagliptin) for diabetes mellitus two months before presentation; therefore, we initially suspected a drug-induced lung disease, hypersensitivity pneumonia, or nonspecific interstitial pneumonia. On the next day of hospitalization, we stopped all of her medications and advised antigen avoidance. On the 7th day of hospitalization, bronchoalveolar lavage (BAL) was performed. BAL revealed increased numbers of inflammatory cells (Table 1), although the other findings were not specific and the BAL fluid cultures and cytology were negative. Her respiratory failure did not improve with the cessation of medications and antigens; therefore, we initiated the administration of prednisolone (40 mg/day: 0.5 mg/kg ideal body weight) on day 8. However, even after the start of steroid therapy, her respiratory status and CT findings did not improve; in fact, they continued to worsen, despite the subsequent administration of pulse steroid therapy (methylprednisolone: 1000 mg) with tacrolimus treatment (Fig. 1 B). Transthoracic echocardiography on day 10 revealed pulmonary hypertension, with findings that included a transtricuspid pressure gradient of 45 mmHg, flattening of the interventricular septum, right atrial enlargement (57 mm x 45 mm), estimated mean pulmonary artery pressure (PAP) of 27 mmHg, mild tricuspid and pulmonary regurgitation, and preserved ejection fraction of 67%. Therefore, we suspected PTTM and subsequently performed endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB), pulmonary perfusion scintigraphy, positron emission tomography-computed tomography (PET-CT), and right heart catheterization to confirm pulmonary hypertension, identify the primary tumor, and diagnose PTTM. The EBUS-TBLB revealed no malignant cells; however, arteriole stenosis with fibrous intimal thickening was observed (Fig. 3 A-B). Pulmonary perfusion scintigraphy revealed multiple small peripheral perfusion defects in both lungs (Fig. 2 A). PET-CT showed fluorodeoxyglucose (FDG) accumulation in the lungs, with consolidation, as well as in the uterine cervix (Fig. 2 C-D). Right heart catheterization indicated pulmonary hypertension (mean PAP: 28 mmHg) without elevated pulmonary artery wedge pressure (PAWP: 9 mmHg). Cytologic smears of pulmonary wedge arterial blood exhibited only a single atypical cell, characterized by a large, grooved nucleus containing coarsely granular chromatin, dense, round cytoplasm, and high nuclear/cytoplasmic ratio; these findings were compatible with the characteristics of squamous cell carcinoma (Fig. 3 C).
Based on these findings, we suspected that the uterine cervical cancer caused PTTM. We consulted a gynecologist, and uterine cervical cancer was finally diagnosed on the 45th day of hospitalization. Chemotherapy was initiated immediately after diagnosis (1st course: carboplatin [AUC5] + paclitaxel [175 mg/m2], 2nd course onwards: carboplatin [AUC5] + paclitaxel [175 mg/m2] + bevacizumab [15 mg/kg]) under strict informed consent requirements. The patient was discharged on the 60th day of hospitalization. After initiation of chemotherapy, the patient's respiratory status and radiological findings (assessed by chest CT and pulmonary perfusion scintigraphy) improved concomitantly with a reduction in the size of the tumor (Fig. 1 B-C, Fig. 2 A-B). She received chemotherapy every three weeks for a total of 18 weeks (six total courses). Although chemotherapy had to be discontinued due to grade 1 epistaxis, no serious side effects were noted. After six courses of chemotherapy, the patient achieved complete remission from uterine cervical cancer. The patient is still alive and is followed up at our hospital regularly. She has recovered well from respiratory failure, and her condition has improved, even six months after the end of treatment. Currently, the patient only requires oxygen administration upon exertion, at a flow rate of 1 L/min.
PET-CT findings used to diagnose uterine cervical cancer (C-D). PET-CT revealing FDG accumulation with consolidation in both lungs.