A 47-year-old male patient suffered from intermittent cough and fever for over 2 months, these symptoms aggravated for at last 20 days without sputum, shortness of breath, thoracalgia or hemoptysis. Initially, computed tomography (CT) scan of his chest showed a mass lesion in right upper lobe of his lung and partial of right pleural thickening, with diffuse consolidation and ground-glass opacity in bilateral pulmones (Figure 1). The doctors considered about interstitial pneumonia owing to infection. While after several days of antibiotic therapy (including sulbenicillin disodium and etimicin), his symptoms had not improved. So bronchoscopy was carried out. Atypical epithelial cells inclined to denocarcinoma were found in transbronchial smear of cytology, while bronchial brushing and biopsy was negative. Unexpectedly the patient felt swollen of his neck just after bronchoscopy, so he underwent another CT at the same day. The CT scan showed bilateral pneumothorax and emphysema of mediastinum superius. Then he transfered to another hospital for symptomatic treatment 5 days later, positron emission tomography/computed tomography (PET/CT) revealed a nodule of about 2.7 cm of its long diameter with characteristics of lobulation and spiculation in the right lung apex section and diffuse consolidation shadow spreading over rest of lung field. The nodular lesion was deemed to be peripheral lung cancer, which average uptake value of (18)F-FDG was 4.3 and maximal uptake value was 5.7. Remaining consolidation was considered as diffuse lung cancer with mildly elevated uptake value of (18)F-FDG (Figure 2). Furthermore, lymph node metastasis of left hilar was likely to have arised.
The patient came to our hospital for further diagnosis and therapy. After admission, the patient never had a fever again and auscultation of lung was normal. His results of test for complete blood count, erythrocyte sedimentation rate (ESR), C reactive protein(CRP), procalcitonin (PCT) and biochemical parameters (including lactate dehydrogenase, LDH) were normal. The patient's T cell subpopulations were normal and human immunodeficiency virus (HIV) antibody was negative. Serum tumor markers assay showed normal results as carcinoembryonic antigen (CEA): 3.4 ng/ml, section 19 of cytokeratin (CYRFA21-1): 10.9 ng/ml, squamous cell carcinoma antigen (SCC): 0.8 ng/ml, and neuron specific enolase (NSE): 15.9 ng/ml. Blood gas analysis showed hyoxemia with partial pressure of oxygen (PaO2) being 68 mmHg and peripheral blood saturation (SpO2) being 93% on room air,while potential of hydrogen (PH) and partial pressure of carbon dioxide (PaCO2) was normal. Spirometric abnormality is mildly restrictive defect manifested by decreased vital capacity (76.27% of predicted value) and mildly reduced diffusing capacity for carbon monoxide (73.28% of predicted value). Fiberoptic bronchoscopy was applied again for diagnosis. BALF showed a large amount of amorphous red-dyed materials and a few alveolar macrophages scattered in endoalveolar space with PAS positive (Figure 3). Transbronchial lung biopsy (TBLB) found great numbers of unstructured, red-dyed granules with PAS+ and adenocarcinoma with differentiated grade II with immunohistochemical analysis for ALK-D5F3(-), CEA(-), EGFR-E746(-), EGFR-L858(-), Ki-67(5%+), NapsinA(+), TTF-1(+), SPA(+), CD68(+) and CK(+) (Figure 4). Follow-up EGFR detection (ARMS used) showed mutations in exon 19 of the EGFR gene, while mutations were not detected in exon 18, 20 and 21.
We judged clinical stage IIB (cT1cN1M0) according to PET/CT, BALF and lung biopsy. Thoracic surgeons carried out wedge resection in VATS (video-assisted thoracoscopic surgery) with mediastinal lymphnode sampling (group 2,4). Pathological findings (in upper right lung) confirmed adenocarcinoma differentiated grade II~III, mainly presenting as acinar and solid type, rarely papillary type. Amorphous eosinophilic substance can be seen in the alveolar of pulmonary tissue around, which was consistent with PAP (Figure 5). In addition, bilateral lymph nodes of group 2 and 4 proved metastasis and carcinoma did not involve the visceral pleura. Then we revised as stage IIIB(pT1cN3M0) and administered adjuvant chemotherapy (Cisplatin 75 mg/m2 day 1, pemetrexed 500 mg/m2 day 1, every 28 days for 4 cycles). Chest CT after 2 cycles of postoperative chemotherapy (Figure 6) showed no tumor recurrence and no patchy, ground-glass opacities. Chest CT of follow-up visits once every three months in local approved SD (stable disease).However ninth months after therapy, the patient felt pain on the left chest. CT showed multiple, subsolid nodules in both lungs and suspected metastasis in the left sixth rib bone and T8 vertebral bone (Figure 7).SPECT/CT for whole body bone planar imaging showed multiple bone metastasis, considered the recurrence and metastasis of the adenocarcinoma. Then we reassessed as stage IVB (rT4N3M1c) and administered 2cycles of primary chemotherapy (Cisplatin 75 mg/m2 day 1, pemetrexed 500 mg/m2 day 1,every 28 days for 4 cycles) up to now.
Chest CT of ninth months after therapy. (C, D) Multiple subsolid nodules in lower lobe of both lungs.