Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, 03766, USA.
Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, 03766, USA; Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA.
Hum Pathol. 2021 Jun;112:35-47. doi: 10.1016/j.humpath.2021.02.001. Epub 2021 Feb 24.
The most recent World Health Organization classification for skin tumors (2018) categorizes melanomas and their precursor lesions, benign or intermediate, into nine pathways based not only on their clinical and histomorphologic characteristics but also on their molecular profile and genetic fingerprint. In an index case of a partially sampled atypical spitzoid lesion, which proved to be an 11p-amplified Spitz nevus with HRASQ61R mutation, we observed cross-reactivity with the NRASQ61R antibody (clone SP174). Overall, we assessed the status of HRAS and NRAS genes and their immunoreaction to NRASQ61R antibody in 16 cases of 11p-amplified Spitz nevi/atypical Spitz tumors. We also assessed the immunoexpression of NRASQ61R antibody in various malignancies with proven BRAFV600E, NRASQ61R, L or K, KRASQ61R and HRASQ61R, and HRASQ61R mutations and ALK+ Spitz lesions. Finally, we assessed the expression of PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry in our 11p Spitz cohort. Three of 16 cases (3/16) harbored the HRASQ61R mutation and exhibited diffuse immunoreaction with the NRASQ61R antibody. All the cases in our cohort were negative for the NRASQ61R mutation. All NRASQ61R-, KRASQ61R-, and HRASQ61R-mutated neoplasms were positive for the antibody, further supporting the cross-reactivity between the RAS proteins. All the cases of our cohort were essentially negative for PRAME immunohistochemistry. In the era of pathway-based approach in the diagnosis of melanocytic neoplasms, the cross-reactivity between the NRASQ61R- and HRASQ61R-mutated proteins can lead to a diagnostic pitfall in the assessment of lesions with spitzoid characteristics.
最新的世界卫生组织皮肤肿瘤分类（2018 年）不仅根据临床和组织形态学特征，还根据分子特征和遗传指纹，将黑素瘤及其前体病变（良性或中间型）分为九种途径。在一个部分取样的非典型 Spitz 样病变的索引病例中，该病变被证明是一个 11p 扩增的 Spitz 痣，具有 HRASQ61R 突变，我们观察到与 NRASQ61R 抗体（克隆 SP174）的交叉反应。总的来说，我们评估了 16 例 11p 扩增 Spitz 痣/非典型 Spitz 肿瘤中 HRAS 和 NRAS 基因的状态及其对 NRASQ61R 抗体的免疫反应。我们还评估了具有已知 BRAFV600E、NRASQ61R、L 或 K、KRASQ61R 和 HRASQ61R 以及 HRASQ61R 突变和 ALK+Spitz 病变的各种恶性肿瘤中 NRASQ61R 抗体的免疫表达。最后，我们评估了我们的 11p Spitz 队列中 PReferentially expressed Antigen in MElanoma（PRAME）免疫组化的表达。我们的 16 例中有 3 例（3/16）携带 HRASQ61R 突变，对 NRASQ61R 抗体呈弥漫性免疫反应。我们队列中的所有病例均为 NRASQ61R 突变阴性。所有 NRASQ61R、KRASQ61R 和 HRASQ61R 突变的肿瘤均对抗体呈阳性，进一步支持 RAS 蛋白之间的交叉反应。我们队列中的所有病例基本上对 PRAME 免疫组化呈阴性。在黑素瘤诊断的基于途径的方法时代，NRASQ61R-和 HRASQ61R-突变蛋白之间的交叉反应可能导致评估具有 Spitz 样特征的病变时出现诊断陷阱。
