A 64-year-old male had been complaining of intermittent hemoptysis several times per day for eight months. He had no fever, chest pain, shortness of breath, dizziness or amaurosis. He had no relevant medical history especially no history of cancer. He had no smoking history. The patient was admitted to The First Affiliated Hospital, School of Medicine, Zhejiang University due to symptoms getting worse. Chest computed tomography scan on July 1st, 2018 showed parenchymal infiltration with cystic lesion in the right lower lobe accompanied by enlarged right hilar lymph nodes (Fig. 1). Transbronchial lung biopsy under bronchofibroscopy was free of tumor cells. A primary surgical resection was recommended by surgeons. Lobectomy and systemic lymph node dissection was done on July 4th, 2018. The patient is now well after he recovered from surgery. So far there were no signs of tumor recurrence or metastasis.
Upon grossly pathological examination, the lesion was located in the right lower lobe, 50 mm from the bronchial stump. It was gray-tan to yellow on the section, with foci of hemorrhage. The lesion was a mixture of both cystic and solid components and was 30 mm *20 mm in size with unclear border. The solid component was in the middle of the lesion and was 17 mm*17 mm in size, surrounded by honeycomb cystic components.
Microscopically, the structure of the solid component of the tumor was similar to a typical PSP. It was composed of areas of cuboidal surface cells and stromal round cells. The tumor showed a hemorrhage pattern (Fig. 2). Bronchial adenomatous hyperplasia and cystic dilatation were noticed in surrounding areas. TTF-1 and EMA were positive in both cuboidal surface cells and stromal round cells (Fig. 2) while CKpan and Napsin A were only positive in cuboidal surface cells.
In the case reported, while most of the surface cells being similar to a typical PSP in some areas of the tumor, a few transformed to adenocarcinoma. The nuclei were columnar and containing hyperchromatic nuclear chromatin. In addition, the surface cells replaced the alveolar lining and invaded the fibrous stroma and vascular walls with TTF-1, EMA, Napsin A and CKpan all positive. The Ki-67 proliferation index was 70% (Fig. 3). We also noticed atypical adenomatous hyperplasia (AAH) of cuboidal cells in the transition area (Fig. 3). Cuboidal surface cells proliferated along preexisting alveolar walls with mild to moderate cellular atypia. A typical hobnail appearance was also seen in the atypical cuboidal surface cells. Substantial gaps along the surface of basement membrane in the transition area were also evident of AAH.
A few stromal round cells had small, well-defined borders and central bland nuclei without nucleoli similar to that in a typical PSP. However, mild to moderate atypical stromal round cells proliferation was seen in the transition region (Fig. 4). Binuclearization and intranuclear eosinophilic inclusions were common in the transition area in our case. Furthermore, abundant cytoplasm, nuclear polymorphism, prominent nucleoli and irregular mitosis were observed in malignant stromal round cells, adjoining the transition areas (Fig. 4). Vascular invasion and pulmonary parenchyma involvements were also found in malignant lamellarlike stromal round cells. TTF-1, P63 and EMA were all positive. Only a small amount stromal round cells were positive for CKpan. However, stromal round cells were negative for beta-catenin and E-cadherin. The Ki-67 proliferation index in these areas was 55%, which was significantly increased compared to typical PSP areas (Fig. 4). Both stromal round cells and surface cells were negative for Progesterone receptor, CD20, CD3, S− 100, Melana, HMB45, Myogenin, MyoD1, CgA and Syn. Further molecular investigation using a polymerase chain reaction panel showed that no EGFR, ALK or ROS1 mutation was detected.
In this case, we also found mediastinal lymph nodes involvement. The architecture of lymph nodes was replaced by abnormal proliferated stromal round cells with either vacuolated or eosinophilic cytoplasm (Fig. 5). IHC showed that these cells were positive for TTF-1, partial positive for CKpan and E-cadherin, but negative for beta-catenin. However, the E-cadherin was negative in malignant stromal round cells in the primary tumor (Fig. 4).