Acral lentiginous melanoma (ALM) is a rare subtype of melanoma with aggressive behavior. IMPDH enzyme, involved in de novo GTP biosynthesis, has been reported to assemble into large filamentary structures called rods/rings (RR) or cytoophidium (cellular snakes). RR assembly induces a hyperactive state in IMPDH, usually to supply a high demand for GTP nucleotides, such as in highly proliferative cells. We investigate whether aggressive melanoma tumor cells present IMPDH-based RR structures. Forty-five ALM paraffin-embedded tissue samples and 59 melanocytic nevi were probed with anti-IMPDH2 antibody. Both the rod- and ring-shaped RR could be observed, with higher frequency in ALM. ROC curve analyzing the proportions of RR-positive cells in ALM versus nevi yielded a 0.88 AUC. Using the cutoff of 5.5% RR-positive cells, there was a sensitivity of 80% and specificity of 85% for ALM diagnosis. In ALM, 36 (80%) showed RR frequency above the cutoff, being classified as RR-positive, compared with only 9 (15%) of the nevi (p < .001). Histopathology showed that 71% of the RR-positive specimens presented Breslow thickness > 4.0mm, compared with only 29% in the RR-low/negative (p = .039). We propose that screening for RR structures in biopsy specimens may be a valuable tool helping differentiate ALM from nevi and accessing tumor malignancy.

中文翻译：

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肢端黑色素瘤中的IMP脱氢酶棒/环结构。

肢端慢性黑色素瘤（ALM）是一种黑色素瘤，具有侵略性行为，是罕见的亚型。据报道，参与从头合成GTP生物合成的IMPDH酶可组装成大的丝状结构，称为杆/环（RR）或细胞丝（细胞蛇）。RR装配在IMPDH中诱导过度活跃状态，通常例如在高度增殖的细胞中提供对GTP核苷酸的高需求。我们调查侵略性黑色素瘤肿瘤细胞是否存在基于IMPDH的RR结构。用抗IMPDH2抗体探测了45个ALM石蜡包埋的组织样品和59个黑素细胞痣。可以观察到杆状和环状RR，在ALM中具有较高的频率。通过ROC曲线分析ALM与痣中RR阳性细胞的比例，得出0.88 AUC。使用5.5％RR阳性细胞的临界值，诊断ALM的敏感性为80％，特异性为85％。在ALM中，36个（80％）的RR频率高于临界值，被归为RR阳性，而痣中只有9个（15％）（p <.001）。组织病理学表明，RR阳性样本中有71％的Breslow厚度> 4.0mm，而RR低/阴性的样本中只有29％（p = .039）。我们建议筛选活检标本中的RR结构可能是一种有价值的工具，可帮助区分ALM和痣样以及进入肿瘤恶性肿瘤。相比之下，RR低/负值仅为29％（p = .039）。我们建议筛选活检标本中的RR结构可能是一种有价值的工具，可帮助区分ALM和痣样以及进入肿瘤恶性肿瘤。相比之下，RR低/负值仅为29％（p = .039）。我们建议筛选活检标本中的RR结构可能是一种有价值的工具，可帮助区分ALM和痣样以及进入肿瘤恶性肿瘤。