After 25 years, “Ackerman’s conundrum”, namely, the distinction of benign from malignant Spitz neoplasms, remains challenging. Genomic studies have shown that most Spitz tumors harbor tyrosine and serine/threonine kinase fusions, includingALK,ROS1,NTRK1,NTRK2,NTRK3,BRAFandMAP3K8, or some mutations, such asHRASandMAP3K8. These chromosomal abnormalities act as drivers, initiating the oncogenetic process and conferring basic bio-morphological features. Most Spitz tumors show no additional genomic alterations or few ones; others harbor a variable number of mutations, capable of conferring characteristics related to clinical behavior, includingCDKN2Adeletion andTERT-p mutation. Since the accumulation of mutations is gradual and progressive, tumors appear to form a bio-morphologic spectrum, in which they show a progressive increase of clinical risk and histological atypia. In this context, a binary classification Spitz nevus-melanoma appears as no longer adequate, not corresponding to the real genomic substrate of lesions. A ternary classification Spitz nevus-Spitz melanocytoma-Spitz melanoma is more adherent to the real neoplastic pathway, but some cases with intermediate ambiguous features remain difficult to diagnose. A prognostic stratification of Spitz tumors, based on the morphologic and genomic characteristics, as a complement to the diagnosis, may contribute to better treatment plans for patients.
25年过去了，"阿克曼难题"，即区分良性斯皮茨肿瘤与恶性斯皮茨肿瘤，仍然具有挑战性。基因组研究表明，大多数斯皮茨肿瘤携带酪氨酸和丝氨酸/苏氨酸激酶融合，包括ALK、ROS1、NTRK1、NTRK2、NTRK3、BRAF和MAP3K8，或某些突变，如HRAS和MAP3K8。这些染色体异常作为驱动因素，启动肿瘤发生过程并赋予基本的生物形态学特征。大多数斯皮茨肿瘤没有额外的基因组改变或仅有少数改变；其他肿瘤则携带数量不等的突变，这些突变能够赋予与临床行为相关的特征，包括CDKN2A缺失和TERT-p突变。由于突变的积累是渐进式的，肿瘤似乎形成了一个生物形态学谱系，其中临床风险和组织学异型性逐渐增加。在此背景下，斯皮茨痣-黑色素瘤的二元分类法显得不再适用，与病变的实际基因组基础不符。斯皮茨痣-斯皮茨黑色素细胞瘤-斯皮茨黑色素瘤的三元分类法更符合实际的肿瘤发展路径，但一些具有中间模糊特征的病例仍然难以诊断。基于形态学和基因组特征的斯皮茨肿瘤预后分层，作为诊断的补充，可能有助于为患者制定更好的治疗计划。
Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman’s Conundrum
肿瘤(癌症)患者之家