PMC10234330_01
CT images show a lobulated mass in the right lower lobe of the lung (A) non-contrast, (B) contrast-enhanced), enlarged anterior supradiaphragmatic lymph nodes (C), multiple thickening nodules in the right pleura (D), bone destruction in the right fourth rib (E), and CT-guided percutaneous lung biopsy (F).
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Chest CT revealed a lobulated mass with a diameter of approximately 5.3 cm in the right lower lobe of the lung close to the bronchus ( Figure 1A ), which was heterogeneously enhanced ( Figure 1B ). CT also demonstrated multiple enlarged lymph nodes in the right subphrenic and anterior supradiaphragmatic spaces ( Figure 1C ), nodular thickening of the right pleura and the diaphragm around the liver ( Figure 1D ), and bone destruction in the right third, fourth, seventh, and eighth ribs ( Figure 1E ). Subsequently, a CT-guided percutaneous lung biopsy was performed for pathological diagnosis ( Figure 1F ).
Hematoxylin and eosin staining of the core needle biopsy specimen reveals that epithelioid tumor cells with eosinophilic cytoplasm are arranged in nests (A) inset: low-power view of needle biopsy), cords, and trabeculae (B). There are scattered mucocytes among the tumor cell nests (C). Alcian blue staining highlights the mucocytes and loose myxoid stroma (D). Cord-like collagen fibers are seen only in focal areas (E). Immunohistochemical staining shows that the tumor cells are positive for CK5/6 (F), CK7 (G), and p40 (H), the Ki-67 proliferation index of which is about 20% (I).
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Microscopically, the epithelioid tumor cells were arranged in nests ( Figure 2A ), cords, and trabeculae ( Figure 2B ), with moderate cytologic atypia. Loose myxoid stroma and scattered mucus-secreting cells (mucocytes) were observed in focal areas ( Figure 2C ). The mucinous differentiation was demonstrated via Alcian blue staining ( Figure 2D ). Cord-like collagen fibers were observed only in focal areas ( Figure 2E ). TTF1. The Ki-67 proliferation index was approximately 20% ( Figure 2I ).
Fluorescence in situ hybridization is negative for MAML2 gene rearrangement (A) and positive for EWSR1 gene rearrangement (B). Next-generation sequencing with a 425-gene panel reveals the EWSR1::CREM fusion (fusion of EWSR1 exon 11 to CREM exon 7) and IRF2::NTRK3 fusion (fusion of IRF2 intron 6 to NTRK3 intron 14) at DNA level (C, D). RNA sequencing detects the EWSR1::CREM fusion transcript in which exon 10 of EWSR1 is fused to exon 5 and 6 of CREM (E, F), respectively.
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Although the morphology and the immunophenotype suggested the diagnosis of mucoepidermoid carcinoma (MEC), fluorescence in situ hybridization (FISH) failed to disclose the rearrangement of MAML2 gene ( Figure 3A ), a typical genetic alteration in MEC, which casted doubt on the initial diagnosis of MEC. Interestingly, we found the rearrangement of EWSR1 gene ( Figure 3B ), implying the nature of HCCC or myoepithelial carcinoma. Subsequently, next-generation sequencing (NGS) with a 425-gene panel was conducted, which revealed EWSR1::CREM fusion ( Figure 3C ) and IRF2::NTRK3 fusion ( Figure 3D ) at the DNA level. Unexpectedly, only EWSR1::CREM fusion was found at the RNA level ( Figures 3E, F ).