Adamantinoma-like Ewing Sarcoma of the Salivary Glands: A Newly Recognized Mimicker of Basaloid Salivary Carcinomas

Abstract

Adamantinoma-like Ewing sarcoma (ALES) is a rare tumor that demonstrates the EWSR1-FLI1 translocation characteristic of Ewing sarcoma despite overt epithelial differentiation including diffuse expression of cytokeratins and p40. Most cases of ALES described to date have occurred in the head and neck where they can mimic a wide range of small round blue cell tumors. Because distinguishing ALES from basaloid salivary gland carcinomas can be particularly difficult, we analyzed a series of 10 ALESs that occurred in the salivary glands with the aim of identifying features that allow for better recognition of this entity. The salivary ALESs included 8 parotid gland and 2 submandibular gland tumors in patients ranging from 32 to 77 years (mean: 52 y). Nine were initially misclassified as various epithelial neoplasms. Although these tumors displayed the basaloid cytology, rosette formation, infiltrative growth, and nuclear monotony characteristic of ALES, peripheral palisading and overt keratinization were relatively rare in this site. Salivary ALESs not only displayed positivity for AE1/AE3, p40, and CD99, but also demonstrated a higher proportion of synaptophysin reactivity than has been reported for nonsalivary ALESs. These morphologic and immunohistochemical findings make ALES susceptible to misclassification as various other tumors including basal cell adenocarcinoma, adenoid cystic carcinoma, squamous cell carcinoma, NUT carcinoma, large cell neuroendocrine carcinoma and myoepithelial carcinoma. Nevertheless, monotonous cytology despite highly infiltrative growth and concomitant positivity for p40 and synaptophysin can provide important clues for consideration of ALES, and identification of the defining EWSR1-FLI1 translocations can confirm the diagnosis.

Figure 1:

ALES demonstrated a lobulated appearance at low power (A; 2x) but were highly infiltrative into salivary parenchyma and surrounding fibroadipose tissue (B; 4x) with prominent fibrous stroma (C; 4x) that showed occasional prominent myxoid change (D; 10x) or deposition of basement-membrane like material (E; 4x) with a mix of nested, trabecular, and lobular growth (F; 10x).

Figure 2:

ALES showed well-developed rosettes (A; 20x) with occasional peripheral palisading (B; 20x) and only rare overt keratinization with squamous pearl formation (C; 20x). Despite high mitotic activity (D; 20x) and scattered foci of necrosis (E; 20x), tumor cells were monotonous with minimal clear to basaloid cytoplasm, round nuclei, vesicular chromatin, and single prominent nucleoli (F; 40x).

Figure 3:

All ALES were strongly and diffusely positive for cytokeratin AE1/AE3 (A; 40x), membranous CD99 (B; 40x), and p40 (C; 40x), with frequent positivity for synaptophysin (D; 40x). The ALES also demonstrated rearrangements of EWSR1 (A) and FLI1 (B), with separated red (centromeric) and green (telomeric) signals (arrows) on break-apart fluorescent in-situ hybridization.