Departments of *Dermatology ‡Preventive Medicine §Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL †Department of Dermatopathology, Memorial Sloan-Kettering Cancer Center, New York, NY.
Am J Surg Pathol. 2014 May;38(5):638-45. doi: 10.1097/PAS.0000000000000160.
Studies have shown that atypical Spitz tumors (ASTs) with homozygous deletions in 9p21 have worse prognosis than those without this finding. Conversely, numerous studies have shown that a range of other copy number aberrations including isolated 6q23 or 3p21 loss may be seen in ASTs without conferring higher risk for aggressive behavior. We studied 31 cases of ASTs with heterozygous 9p21 loss and hypothesize that heterozygous 9p21 loss in ASTs does not confer an increased risk for aggressive behavior. We compared clinical, histopathologic, and immunohistochemical features of 31 ASTs with heterozygous 9p21 deletions with 30 ASTs with homozygous 9p21 deletions. No ASTs with heterozygous 9p21 deletions resulted in distant metastasis. Severe cytologic atypia, a predominance of epithelioid cytomorphology and increased dermal mitotic activity were more frequent in ASTs with homozygous deletions versus ASTs with heterozygous deletions (P=0.0003, 0.0004, and 0.042, respectively). Expression of p16 and mutated BRAF proteins was also evaluated in 17 conventional (nonspitzoid) melanomas with homozygous 9p21 loss and the 2 groups of ASTs. Expression of p16 was retained in 67% of ASTs with heterozygous loss, whereas among ASTs with homozygous loss, 100% of cases had areas with complete loss of staining. Mutated BRAF protein expression was detected in 53% of conventional melanomas, in none of the ASTs with heterozygous loss, and in 1 AST with homozygous loss (P=0.0007 between homozygous ASTs and the conventional melanomas). Coexisting BRAF mutation and 9p21 deletion was more common in conventional melanomas than in ASTs with heterozygous or homozygous 9p21 deletion. BRAF mutation was highly uncommon among the ASTs.
研究表明，与没有这种发现的肿瘤相比，存在同源性 9p21 缺失的非典型 Spitz 肿瘤（AST）具有更差的预后。相反，大量研究表明，在 AST 中可能会出现一系列其他拷贝数异常，包括孤立的 6q23 或 3p21 缺失，但不会增加侵袭性行为的风险。我们研究了 31 例存在杂合性 9p21 缺失的 AST，并假设 AST 中的杂合性 9p21 缺失不会增加侵袭性行为的风险。我们比较了 31 例存在杂合性 9p21 缺失的 AST 和 30 例存在纯合性 9p21 缺失的 AST 的临床、组织病理学和免疫组织化学特征。没有 AST 出现杂合性 9p21 缺失导致远处转移。与存在杂合性 9p21 缺失的 AST 相比，存在纯合性 9p21 缺失的 AST 具有更严重的细胞学异型性、上皮样细胞形态学占优势和真皮有丝分裂活动增加（P=0.0003、0.0004 和 0.042）。我们还在 17 例存在纯合性 9p21 缺失的常规（非 Spitz 样）黑色素瘤和两组 AST 中评估了 p16 和突变型 BRAF 蛋白的表达。在存在杂合性 9p21 缺失的 AST 中，有 67%的病例保留了 p16 的表达，而在存在纯合性 9p21 缺失的 AST 中，100%的病例有完全缺失染色的区域。在 53%的常规黑色素瘤中检测到突变型 BRAF 蛋白表达，在存在杂合性 9p21 缺失的 AST 中均未检测到，在 1 例存在纯合性 9p21 缺失的 AST 中检测到 1 例（纯合性 AST 与常规黑色素瘤之间的 P=0.0007）。在常规黑色素瘤中，BRAF 突变和 9p21 缺失共存比在存在杂合性或纯合性 9p21 缺失的 AST 中更为常见。AST 中 BRAF 突变非常罕见。
