Solid endobronchial tumor with EWSR1‐FLI1 fusion gene – A diagnostically challenging case of the Ewing sarcoma

Abstract

To the Editor, Recently, we have encountered a diagnostically challenging, unusual case of the Ewing sarcoma (ES), presenting as an endobronchial tumor, and causing atelectasis in the peripheral lobe. This tumor displayed a solid growth pattern of variable size of nests with a hyalinized fibrous stroma. Since the tumor cells were arranged in a sheet‐like pattern, with seemingly epithelial adhesion, we considered a wide range of differential diagnoses including basaloid squamous carcinoma, myoepithelial carcinoma, and adamantinoma‐like ES (ALES). However, only a minimal degree of epithelial differentiation was confirmed immunohistochemically. By contrast, diffuse immunoreactivities to CD99 and NKX2.2 and the molecular detection of the EWSR1‐FLI1 fusion gene in this case affirmed a tumor belonging to the tumor family of ES. ALES of the lung is extremely rare, and only one case of pulmonary ALES has been documented as PNET with neuroendocrine differentiation. The present case did not show neuroendocrine differentiation in contrast to the previously reported case. Moreover, the present case seemed to show less epithelial differentiation than ALES cases described in other organs. We report herein the case of an endobronchial tumor arranged in a solid growth pattern, most probably displaying an unusual phenotype of ES, which is potentially located in their morphologic spectrum of ES between typical primitive small round‐cell tumors and that with overt epithelial differentiation. A 39‐year‐old woman having persistent productive cough was admitted to our hospital. Despite a treatment with antibiotics for 2 months, chest radiography on admission indicated persistent atelectasis in the right lower lobe. Computed tomography (CT) and subsequent bronchoscopy confirmed the presence of an endobronchial tumor in the right inferior lobar bronchus. 18‐Fluorodeoxyglucose positron emission tomography CT (FDG‐PET/CT) showed a mild uptake in the tumor, and no other lesion other than the endobrochial tumor was detected. A transbronchial biopsy showed solid tumor nests of varying shape and size, arranged in a sheet‐like growth pattern, with seemingly epithelial adhesion, and accompanied by a hyalinized fibrous stroma. Squamous differentiation, keratinization, ductal proliferation or mucin production was not observed. The tumor cells were round or spindle‐shaped and had scant‐ to‐moderate amounts of eosinophilic or clear cytoplasm and vesicular nuclei containing prominent nucleoli. Differential diagnoses included basaloid squamous carcinoma, myoepithelial carcinoma, neuroendocrine tumors and synovial sarcoma. However, tumor cells were diffusely positive for vimentin and only focally positive for cytokeratins such as AE1/AE3 and EMA, and p63, but negative for other cytokeratins (CAM5.2, CK5/6), TTF‐1, p40, α‐SMA, desmin, calponin, S‐100 proteins, CD68, synaptophysin, chromogranin A and CD56. No SS18‐ SSX fusion gene was detected by reverse transcription‐ polymerase chain reaction (RT‐PCR). Despite the histological findings suggesting subtle epithelial differentiation, no apparent squamous, basaloid, myoepithelial or neuroendocrine differentiation was identified. Ki‐67 labeling index was approximately 10%. Since the atelectasis was not improved, combined middle and lower lobectomy was performed. Gross examination of the resected lobe revealed a whitish polypoid tumor (18 × 16 × 12mm in size) (Figure 1a), protruding into the right inferior lobar bronchus and causing atelectasis in the peripheral lung. Microscopically, an invasive growth of the tumor cells into the surrounding bronchial smooth muscle and cartilage was observed. The lesion was covered with a flattened bronchial epithelium and composed of a compact sheet‐like proliferation of the tumor cells, with a hyalinized fibrous stroma (Figure 1b,c). Although a continuity between the tumor cells and bronchial glands was noted, it was uncertain whether the tumor might have originated from the bronchial glands or it represented tumor cell invasion into the bronchial glands. No perineural, vascular, or lymphatic invasion was observed. In our thorough examination of the resected specimen, no apparent squamous differentiation such as keratinization, basaloid features, ductal proliferation or mucous production was seen in the tumor. The histological and immunohistochemical features of the tumor were equivalent to those of the biopsy specimen. However, additional immunohistochemistry revealed diffuse and strong immunoreactivity towards CD99 and NKX2.2 (Figure 1d). Fluorescence in situ hybridization