Beydoun Haya Mary, Jeyakumar Julia Edwin, Addo Afua, Olivares Shantel, Zhao Lili, Ma Yangruijue, Ko Jennifer, Bahrami Armita, Florell Scott, Furtado Larissa V, Busam Klaus, Gerami Pedram
Department of Dermatology, Feinberg School of Medicine.
Department of Preventative Medicine, Biostatistics and Informative Division, Northwestern University, Chicago, IL.
Am J Surg Pathol. 2025 Jul 1;49(7):663-673. doi: 10.1097/PAS.0000000000002381. Epub 2025 Apr 24.
Pediatric Spitz melanoma (SM) with bonafide metastatic disease is rare. In this study, we assembled the largest cohort to date of pediatric SM with a verified Spitz-associated genomic driver and clinical follow-up demonstrating bonafide metastasis. We compared the clinical, morphologic, and molecular features of these SMs to a control cohort of 57 pediatric atypical Spitz tumors (ASTs). Pediatric SM patients were significantly older than AST patients (12 vs 8 years of age). While not statistically significant, SMs were more likely to be heavily pigmented (5/7 SMs vs 11/57 ASTs), to have a sheet-like growth pattern (3/7 SMs vs 8/57 ASTs), and have severe nuclear atypia (6/7 SMs vs 20/57 ASTs). SMs had significantly greater mitotic activity (avg of 4.3/mm 2 in SMs and 2.7/mm 2 in ASTs, P =0.008) and more frequent larger cell size ( P =0.006). However, none of these features were specific and could also be seen in ASTs. The presence of homozygous deletions of 9p21 in conjunction with TERT promoter hot spot mutations or PTEN deletions (n=2), as well as MYC overexpression or amplification (n=2) were only seen in the SMs and none of the ASTs. These findings were mutually exclusive in the SM group and mutually exclusive with the presence of complex chromosomal copy number aberrations, which were seen in the remaining 3 pediatric SMs. This study demonstrates that there are multiple pathways to malignancy for pediatric SMs and none of our commonly used biomarkers have a particularly high sensitivity. Hence, the optimal distinction of pediatric SM from ASTs will continue to require the integration of clinical, histologic, and molecular data.
患有真正转移性疾病的儿童斯皮茨黑色素瘤（SM）很罕见。在本研究中，我们汇集了迄今为止最大的一组患有经证实的斯皮茨相关基因组驱动因素且有临床随访证明存在真正转移的儿童SM。我们将这些SM的临床、形态学和分子特征与57例儿童非典型斯皮茨肿瘤（AST）的对照队列进行了比较。儿童SM患者的年龄显著大于AST患者（12岁对8岁）。虽然无统计学意义，但SM更有可能色素沉着严重（5/7例SM对11/57例AST），具有片状生长模式（3/7例SM对8/57例AST），且有严重核异型性（6/7例SM对20/57例AST）。SM的有丝分裂活性显著更高（SM平均为4.3/mm²，AST为2.7/mm²，P = 0.008），且细胞尺寸更大更频繁（P = 0.006）。然而，这些特征均不具有特异性，在AST中也可见。仅在SM中观察到9p21纯合缺失伴TERT启动子热点突变或PTEN缺失（n = 2），以及MYC过表达或扩增（n = 2），而AST中均未观察到。这些发现在SM组中相互排斥，且与其余3例儿童SM中可见的复杂染色体拷贝数畸变的存在相互排斥。本研究表明，儿童SM有多种恶变途径，我们常用的生物标志物均无特别高的敏感性。因此，要将儿童SM与AST进行最佳区分，仍需整合临床、组织学和分子数据。
