Clinical history:
A 57-year-old Asian woman was admitted due to a finding of pulmonary mass in the right lower lobe upon physical examination. The patient, an ex-smoker (10 cigarettes a day × 20 years), had no specific medical history otherwise. The chest computerized tomography (CT) scan (Fig. 1A) revealed a 2.8-cm dorsal segment of the right lower lobe mass. A positron emission tomography scan (PET-CT) showed central hypermetabolic activity only in the right lower lobe, raising suspicions of a neoplastic process (Fig. 1B). Bronchoscopy revealed a dorsal segment of the right lower lobe mass (Fig. 1C), and a biopsy was performed.
Histopathology and ancillary testing:
The hematoxylin and eosin (HE)–stained sections of the biopsy yielded a neoplasm composed of atypical small-to-medium sized epithelioid cells with light eosinophilic to clear cytoplasm and round-to-oval nuclei and inconspicuous nucleoli lacking significant pleomorphism and mitotic activity. The tumour cells were arranged in irregular nests, cords, trabeculae (Fig. 2A) and tubular pattern with a loose myxoid stroma (Fig. 2B). Focally, the tumour cells appeared to connect to the basal layer of the bronchial epithelium and lacked keratinization and in situ carcinoma of the overlying epithelium (Fig. 2C). Immunohistochemistry showed the tumour cells to be positive for CK7 (Fig. 2D); most tumour cells were found to be positive for p40 (Fig. 2E), ck5/6, p63 and negative for PAX8, CD10, RCC, CAIX, TTF1, S100, CDX2, SATB2, CK20, calponin, and SMA. An initial diagnosis of low-grade mucoepidermoid carcinoma with clear cell feathers was rendered. Because mucoepidermoid carcinoma of the lung is rare and involves specific molecular changes [12], molecular testing was performed. Fluorescence in situ hybridization (FISH) was negative for MAML2 gene rearrangement (Fig. 3A). These results prompted a histologic re-review of the case, a literature search, and consultation with an outside expert. A focal hyalinized stroma appreciated by Dr. Zhou prompted the protential diagnoses of HCCC or myoepithelial tumours. Subsequently, additional EWSR1 gene rearrangement and EWSR1-ATF1 gene fusion tested by FISH confirmed the presence of the EWSR1 gene rearrangement (Fig. 3B) and EWSR1-ATF1 gene fusion (Fig. 3C). A final diagnosis of HCCC of the lung was ultimately rendered.
A right lower lobectomy with hilar and mediastinal lymphadenectomy was performed. Grossly, a firm, solitary, well-circumscribed, 2.8-cm tan mass, 1.0 cm from the bronchial margin, was identified (Fig. 4A). H&E-stained sections of the mass showed classical HCCC morphology: tumour cells with light eosinophilic to clear cytoplasm and inconspicuous nucleoli lacking significant pleomorphism and mitotic activity. The tumour cells grew in cords, trabeculae, and nests in a hyalinizing acellular stroma (Fig. 4B). They had infiltrated the periphery alveolar tissue and showed aggregates of chronic inflammation in the periphery of the tumour. No angiolymphatic invasion, perineural invasion, pleural involvement, or necrosis were observed. Immunohistochemistry and FISH results were the same as those of the biopsy. The metastatic foci was found in 1 out of 12 lymph nodes. (Fig. 4C). All surgical margins were negative. At the time of this report, the patient was free of any local recurrence. She was free of metastasis at her 3-month follow-up, despite receiving no additional therapy after surgery.