Lasota Jerzy, Krupińska Martyna, Kaczorowski Maciej, Chłopek Małgorzata, Kinkor Zdenek, Švajdler Marian, Perret Raul, Charville Gregory W, Bradová Martina, Ylaya Kris, Wesołowska Małgorzata, Rozmus-Piętoń Magdalena, Ryś Janusz, Michal Michael, Michal Michal, Miettinen Markku
Laboratory of Pathology, National Cancer Institute, Bethesda, MD.
Department of Pathology, University Hospital of the Canary Islands, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.
Am J Surg Pathol. 2025 Apr 15;49(8):800-806. doi: 10.1097/PAS.0000000000002400.
The diagnosis of Ewing sarcoma can be challenging, particularly when the tumor is present in an atypical location and resembles histologic mimics. The hallmark feature of Ewing sarcoma is chromosomal translocation, t(11;22)(q24;q12), involving EWSR1 and ETS gene family members. For decades, fluorescence in situ hybridization with a break-apart EWSR1 probe has been the diagnostic gold standard. However, EWSR1 rearrangements have been identified in other malignancies; thus, the detection of chimeric EWSR1 transcripts has become a preferable approach. Occasionally, insufficient tissue, severe RNA degradation, or economic constraints hamper molecular testing. This study evaluated Protein Kinase C Beta II (PKC β II) expression in >1000 tumors and assessed the utility of PKC β II immunohistochemistry in the differential diagnosis of Ewing sarcoma. Tumors harboring EWSR1 :: FLI1 (n=26), EWSR1 :: ERG , EWSR1 :: ETV4 (n=1), and FUS :: ERG (n=6) fusions were evaluated, revealing strong diffuse immunoreactivity, although a patchy pattern was seen in 3 cases. Undifferentiated round cell sarcomas (n=46), including BCOR -, CIC -, NFATC2 -, NUTM1 -, and PATZ1 rearranged/fusion-sarcomas were negative. Two of the 130 synovial sarcomas, including 1 with a poorly differentiated morphology, showed diffuse, moderate-to-strong positivity. One of the 26 poorly differentiated carcinomas from the head and neck region, probably small cell lung carcinoma metastasis, showed strong PKC β II expression. Neuroblastomas (>50%) expressed PKC β II, although none showed a strong diffuse pattern. Diffuse moderate-to-strong immunoreactivity was observed in 2 sarcomatoid mesotheliomas and 2 metastatic melanomas. Diffuse but weak staining was observed in 73% (11/15) of the T-cell lymphoblastic lymphomas, including 10 CD99-positive cases. Similarly, weak predominantly patchy staining was seen in half (40/80) of other non-Hodgkin lymphomas and sporadically in embryonal rhabdomyosarcoma, Merkel cell carcinoma, small cell lung carcinoma, and Wilms tumor. Thus, diffuse and strong PKC β II immunoreactivity appears to be a reliable diagnostic marker for distinguishing classic Ewing sarcoma from histologic mimics.
尤因肉瘤的诊断可能具有挑战性，特别是当肿瘤位于非典型部位且类似于组织学上的模仿物时。尤因肉瘤的标志性特征是染色体易位，t(11;22)(q24;q12)，涉及EWSR1和ETS基因家族成员。几十年来，使用断裂分离的EWSR1探针进行荧光原位杂交一直是诊断金标准。然而，在其他恶性肿瘤中也发现了EWSR1重排；因此，检测嵌合EWSR1转录本已成为一种更可取的方法。偶尔，组织不足、严重的RNA降解或经济限制会妨碍分子检测。本研究评估了蛋白激酶CβII（PKCβII）在1000多个肿瘤中的表达，并评估了PKCβII免疫组织化学在尤因肉瘤鉴别诊断中的效用。对携带EWSR1::FLI1（n=26）、EWSR1::ERG、EWSR1::ETV4（n=1）和FUS::ERG（n=6）融合的肿瘤进行了评估，结果显示为强弥漫性免疫反应，尽管3例可见斑片状模式。未分化圆形细胞肉瘤（n=46），包括BCOR-、CIC-、NFATC2-、NUTM1-和PATZ1重排/融合肉瘤均为阴性。130例滑膜肉瘤中有2例，包括1例形态学分化差的病例，显示弥漫性、中度至强阳性。26例头颈部低分化癌中有1例，可能是小细胞肺癌转移，显示PKCβII强表达。神经母细胞瘤（>50%）表达PKCβII，尽管无一例显示强弥漫性模式。在2例肉瘤样间皮瘤和2例转移性黑色素瘤中观察到弥漫性中度至强免疫反应。在73%（11/15）的T细胞淋巴母细胞淋巴瘤中观察到弥漫性但弱阳性染色，包括10例CD99阳性病例。同样，在一半（40/80）的其他非霍奇金淋巴瘤中可见弱阳性且主要为斑片状染色，在胚胎性横纹肌肉瘤、默克尔细胞癌、小细胞肺癌和肾母细胞瘤中偶见。因此，弥漫性和强PKCβII免疫反应似乎是区分经典尤因肉瘤与组织学模仿物的可靠诊断标志物。
