Department of Pathology, University of Texas Southwestern Medical Center, Dallas.
Head & Neck Pathology, Joint Pathology Center, Silver Spring.
Am J Surg Pathol. 2023 Nov 1;47(11):1243-1251. doi: 10.1097/PAS.0000000000002100. Epub 2023 Jul 27.
Adamantinoma-like Ewing sarcoma (ALES) is a rare malignancy currently considered a variant of Ewing sarcoma with most known cases harboring EWSR1 rearrangements. Herein we present a series of 6 cases of EWSR1 -negative ALES. The tumors arose in the sinonasal tract (n=3), major salivary glands (submandibular gland=1; parotid=1), and anterior mediastinum (n=1) in patients ranging from 25 to 79 years of age. Most tumors were basaloid in appearance, growing in large nests separated by interlobular fibrosis without overt squamous pearls. However, 1 case closely resembled a well-differentiated neuroendocrine tumor with uniformly round nuclei, eosinophilic cytoplasm, and trabecular architecture. All cases were diffusely positive for pan-cytokeratin, p40 or p63, and CD99. A subset of cases showed diffuse reactivity for synaptophysin, including 1 sinonasal tumor which also demonstrated sustentacular S100 protein expression. Molecular testing showed FUS rearrangements in all cases. Gene partners included known ETS family members FEV (n=2) and FLI1 (n=1). Our results expand the molecular diagnostic considerations for ALES to include FUS rearrangements. We also show that ALES may harbor FUS :: FLI1 fusion, which has not been previously reported in the Ewing family of tumors. Furthermore, ALES may show unusual histologic and immunophenotypic features that can overlap with olfactory carcinoma including S100-positive sustentacular cells. ALES should be considered in the diagnostic differential of small round cell tumors and tumors with neuroendocrine differentiation with immunohistochemical workup to include p40 and CD99/NKX2.2.
类似于骨外尤文肉瘤的骨瘤（ALES）是一种罕见的恶性肿瘤，目前被认为是尤文肉瘤的一种变体，大多数已知病例都存在 EWSR1 重排。在此，我们报告了 6 例 EWSR1 阴性的 ALES 病例。肿瘤发生于鼻-鼻窦（n=3）、大涎腺（颌下腺=1；腮腺=1）和前纵隔（n=1），患者年龄从 25 岁至 79 岁不等。大多数肿瘤呈基底细胞样外观，呈大巢状生长，巢间有小叶间纤维化分隔，无明显的鳞状珠。然而，有 1 例肿瘤与分化良好的神经内分泌肿瘤非常相似，细胞核均匀圆形，嗜酸性细胞质，呈小梁状结构。所有病例均弥漫性表达细胞角蛋白 pan-cytokeratin、p40 或 p63 以及 CD99。部分病例弥漫性表达突触素，包括 1 例鼻-鼻窦肿瘤，该肿瘤还表达支持细胞 S100 蛋白。分子检测显示所有病例均存在 FUS 重排。基因伙伴包括已知的 ETS 家族成员 FEV（n=2）和 FLI1（n=1）。我们的结果将 ALES 的分子诊断考虑因素扩展到包括 FUS 重排。我们还表明，ALES 可能存在 FUS :: FLI1 融合，这在尤文家族肿瘤中尚未报道过。此外，ALES 可能具有不常见的组织学和免疫表型特征，与嗅神经母细胞瘤重叠，包括 S100 阳性支持细胞。在进行免疫组织化学检查时，应考虑将 ALES 纳入小圆细胞肿瘤和具有神经内分泌分化的肿瘤的鉴别诊断中，包括 p40 和 CD99/NKX2.2。
