A 63-year-old Japanese man, a current smoker of more than 45 pack-years, was revealed by routine examination’s chest X-ray to have an abnormal shadow in the left middle lung field. His past medical history was unremarkable. A chest computed tomography (CT) scan showed a 3.6 × 2.8 cm pulmonary lesion in the left upper lobe, with a clear boundary and heterogeneous contrast enhancement (Fig. 1). Positron emission tomography (PET) showed an accumulation of 18F-fluorodexyglucose (FDG) with a maximum standardized uptake value (SUV max) of 4.95 in the early phase and 6.31 in the late phase in the nodule. No accumulation of FDG was noted in the pulmonary hilum, or mediastinal lymph nodes.
A trans-bronchial lung biopsy (TBLB) of the mass in the left upper lobe was performed; it revealed non-small cell carcinoma. Although the serum carcinoembryonic antigen (CEA) level was 52.1 ng/mL (normal range 0–5.0 ng/mL), there were no distant metastases or other cancer lesions. The preoperative clinical diagnosis of primary lung cancer, stage cT2aN0M0 stage IB was considered.
A left upper lobectomy and mediastinal lymph node dissection were performed by video-assisted thoracic surgery. The resected tumor measured 3.8 × 2.8 × 2.8 cm in diameter.
Grossly, the specimen showed a well-established boundary as a grayish lesion with areas of necrosis. The histopathological examination showed a solid proliferation of columnar atypical cells with cell cytoplasm and complex glandular structures with abundant desmoplastic stroma, a morphological resemblance to fetal lung and significant tumor necrosis (Fig. 2a, b). Conventional lung adenocarcinoma, another histological component and morulae were not found. Periodic acid Schiff (PAS) staining demonstrated glycogen in the cytoplasm of the neoplastic cells. Stains for mucin were negative. The immunohistochemical analysis showed positivity for AE1/AE3, CEA, and alpha-fetoprotein (AFP) (focal) (Fig. 2c). Thyroid transcription factor-1 (TTF-1), chromogranin A, synaptophysin, CD56, and p40 were negative. The beta-catenin result was positive, predominantly in the cell membrane (Fig. 2d). The final histopathological diagnosis was H-FLAC.
Both lymphatic and vascular invasion were detected. Microscopically, all margins were free and mediastinal lymph nodes (#5) showed metastasis. The final pathological staging was stage IIIA (pT2aN2M0). Both epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements were negative. The expression of programmed cell death 1 ligand 1 (PD-L1) (Dako, clone 22C3) by resected specimen was negative.
The patient received cisplatin plus vinorelbine as adjuvant chemotherapy, but it was canceled at two courses because of the dehydration and hyperglycemia induced by the chemotherapy. At 25 months after the surgery, the patient had relapsed pleural dissemination. Postoperative serum CEA and AFP was 1.5 and 3.7 ng/mL, respectively. But, serum CEA at the time of relapse was 132.4 ng/mL, and AFP was unfortunately not searched.