Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Department of Medicine, Icahn Medical Center at Mount Sinai, New York, NY, USA.
Histopathology. 2020 Feb;76(3):461-469. doi: 10.1111/his.13986. Epub 2019 Dec 23.
High-grade appendiceal mucinous neoplasm (HAMN) was recently proposed as a disease entity histologically analogous to low-grade appendiceal mucinous neoplasm (LAMN), but characterised by high-grade cytological atypia. The pathogenesis and clinical features of HAMN have not been fully elucidated.
Nine cases of HAMN, eight LAMN, 10 appendiceal mucinous adenocarcinomas (MACA) and five appendiceal serrated polyps resected between 2008 and 2017 contributed by three medical centres underwent targeted next-generation sequencing of 50 cancer-related genes. The patients in each category had similar profiles with respect to gender, age, tumour stage and follow-up intervals. Both LAMN and HAMN harboured mutations of KRAS [nine of nine and eight of eight (100%), respectively] and GNAS [five of eight (63%) and five of nine (56%), respectively] in significantly higher proportions than MACA [KRAS, seven of 10 (70%, P = 0.04); GNAS: one of 10 (10%, P = 0.02)] and serrated polyps [KRAS, one of five (20%, P = 0.0007); GNAS: none of five (0%, P = 0.04)]. Four cases of HAMN, but none of LAMN, harboured mutations of TP53 [four of nine (44%)] and/or ATM [two of nine (22%)]. Three cases of HAMN (33%) showed extra-appendiceal spread with retention of the same mutational profiles in the intra- and extra-appendiceal components. The 10 cases of MACA harboured a similar prevalence of TP53 mutations (n = 5, 50%) as HAMN but, unlike LAMN and HAMN, some harboured mutations in PIK3CA, APC, FBXW7, PTEN and SMAD4.
HAMN and LAMN share high rates of KRAS and GNAS co-mutations supporting a common histogenesis and distinguishing them from MACA. Acquisition of TP53 or ATM mutations by HAMN may drive its progression to a more advanced phenotype.
高级阑尾黏液性肿瘤 (HAMN) 最近被提议为一种组织学上类似于低级别阑尾黏液性肿瘤 (LAMN) 的疾病实体，但具有高级别的细胞学异型性。HAMN 的发病机制和临床特征尚未完全阐明。
本研究纳入了 2008 年至 2017 年间由三个医学中心切除的 9 例 HAMN、8 例 LAMN、10 例阑尾黏液性腺癌 (MACA) 和 5 例阑尾锯齿状息肉，对 50 个与癌症相关的基因进行了靶向下一代测序。每个类别中的患者在性别、年龄、肿瘤分期和随访时间方面具有相似的特征。LAMN 和 HAMN 均以更高的比例（分别为 100%[9/9 和 8/8]和 56%[5/9 和 5/8]）携带 KRAS [9/9 和 8/8（100%）]和 GNAS [5/8（63%）和 5/9（56%）]突变，明显高于 MACA [KRAS，7/10（70%，P=0.04）；GNAS：1/10（10%，P=0.02)]和锯齿状息肉[KRAS，1/5（20%，P=0.0007）；GNAS：无 5/5（0%，P=0.04）]。4 例 HAMN，但无 LAMN，携带 TP53 [9/9（44%）]和/或 ATM [9/9（22%）]突变。3 例 HAMN（33%）表现出阑尾外扩散，在阑尾内和阑尾外成分中保留相同的突变谱。10 例 MACA 同样具有 TP53 突变（n=5，50%）的高发生率，与 HAMN 不同，但与 LAMN 和 HAMN 不同，一些病例存在 PIK3CA、APC、FBXW7、PTEN 和 SMAD4 突变。
HAMN 和 LAMN 具有较高的 KRAS 和 GNAS 共突变率，支持共同的组织发生，并将其与 MACA 区分开来。TP53 或 ATM 突变的获得可能导致 HAMN 向更高级别的表型进展。
