University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Boston Children's Hospital, Boston, Massachusetts.
Oregon Health & Science University, Portland, Oregon; Indiana University, Indianapolis, Indiana.
Mod Pathol. 2023 Dec;36(12):100334. doi: 10.1016/j.modpat.2023.100334. Epub 2023 Sep 17.
The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and fusions involving this gene have been reported in a variety of mesenchymal neoplasms. ALK-altered tumors with epithelioid morphology have been described in epithelioid inflammatory myofibroblastic sarcoma and epithelioid fibrous histiocytoma. Herein, we describe the clinicopathologic features of 7 ALK-rearranged mesenchymal tumors with epithelioid morphology occurring predominately in the pediatric population. Tumors occurred in 4 females and 3 males with an age ranging from 1 month to 28 years. Five tumors were superficial and solitary, while 1 presented with multiple peritoneal/omental nodules, and 1 presented as a large mediastinal mass. Morphologically, all tumors comprised epithelioid cells arranged in sheets, anastomosing cords, or small clusters embedded in a myxohyaline stroma. The cells had slightly variably sized ovoid nuclei with moderately prominent nucleoli and abundant eosinophilic cytoplasm. Four cases had sparse mitotic figures without necrosis. The remaining 3 tumors (2 deep and 1 superficial) had more than 10 mitoses per 10 high-power fields as well as foci of necrosis. ALK fusions were identified in all cases. The fusion partners included HMBOX1 (n = 1), VCL (n = 1), PRRC2B (n = 1), MYH10 (n = 1), STRN (n = 1), and EML4 (n = 2). One tumor recurred locally 2 years after initial resection; 1 patient had widely metastatic disease (mediastinal tumor). At the time of last follow-up (n = 6), 4 patients were alive without evidence of disease, 1 died due to complications of therapy (peritoneal tumor), and 1 was alive with disease. Our findings expand the spectrum of ALK-rearranged mesenchymal tumors. Our cases predominately occurred in older children and mainly exhibited epithelioid to round cell morphology, as opposed to spindle cell morphology. We also show that tumors in a deep location with higher-grade features follow a more aggressive clinical course.
间变性淋巴瘤激酶 (ALK) 基因编码一种受体酪氨酸激酶，该基因的融合已在多种间充质肿瘤中报道。具有上皮样形态的 ALK 改变的肿瘤已在上皮样炎症性肌纤维母细胞瘤和上皮样纤维组织细胞瘤中描述过。在此，我们描述了 7 例主要发生在儿童人群中具有上皮样形态的 ALK 重排间充质肿瘤的临床病理特征。肿瘤发生于 4 名女性和 3 名男性，年龄范围为 1 个月至 28 岁。5 个肿瘤为表浅性和孤立性，1 个表现为多个腹膜/网膜结节，1 个表现为巨大纵隔肿块。形态上，所有肿瘤均由上皮样细胞组成，呈片状、吻合索状或小簇状，嵌入黏液样基质中。细胞具有稍呈卵圆形、大小不等的核，中度明显的核仁，丰富的嗜酸性细胞质。4 例有稀疏的有丝分裂象，无坏死。其余 3 例（2 例深部和 1 例表浅）每 10 个高倍视野有超过 10 个有丝分裂和局灶性坏死。所有病例均发现 ALK 融合。融合伙伴包括 HMBOX1（n=1）、VCL（n=1）、PRRC2B（n=1）、MYH10（n=1）、STRN（n=1）和 EML4（n=2）。1 例肿瘤在初次切除后 2 年内局部复发；1 例患者有广泛的转移疾病（纵隔肿瘤）。在最后一次随访时（n=6），4 例患者无疾病存活，1 例死于治疗并发症（腹膜肿瘤），1 例有疾病存活。我们的发现扩展了 ALK 重排间充质肿瘤的范围。我们的病例主要发生在年龄较大的儿童中，主要表现为上皮样到圆形细胞形态，而不是梭形细胞形态。我们还表明，位置较深、具有高级别特征的肿瘤具有更具侵袭性的临床病程。
