Chen Irene, Liu Xiaoqin, Kovar-Peltz Sierra, Conrad Stephanie J, Chen Hannah H, Liao Xiaoyan
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, USA.
Pathology. 2023 Apr;55(3):375-382. doi: 10.1016/j.pathol.2022.08.004. Epub 2022 Oct 13.
Primary appendiceal adenocarcinoma (APCA), goblet cell adenocarcinoma (GCA), and low/high-grade appendiceal mucinous neoplasms (LAMN/HAMN) are distinct entities with overlapping clinical presentation and histomorphology, leading to diagnostic challenges. We retrospectively reviewed our archived cases between 2010 and 2018 for diagnosis reappraisal and comparative analysis using updated terminology and modern parameters. A total of 87 cases (22 APCA, 40 GCA, and 25 LAMN pT≥3) were included. The entire cohort had 49 women and 38 men with a median age of 59.9 (range 26-88) years. There were no statistically significant differences in age and sex among the three groups. Clinically, patients with GCA were more likely to present with acute appendicitis (65%) and more likely to have appendectomy as initial surgery (68%). Both APCA and GCA were more likely to involve the proximal appendix while LAMN was more likely to involve the distal appendix (p<0.05). All APCAs were associated with mucosal precursor lesions, most commonly tubular, tubulovillous, or villous adenoma, flat LAMN/HAMN-pTis mucinous epithelium, or mixed, which correlated with distinct histomorphology, tumour differentiation, and stage. Although polypoid precursor lesions were rare in GCA, a significant proportion of GCA showed crypt atypia associated with neoplastic cells. Immunohistochemically, APCA had more frequent β-catenin nuclear positivity and loss of SATB2 expression (p<0.05). KRAS mutation was more common in APCA than in GCA (8/11 vs 1/7, p<0.01). We further validated the three-tiered grading system (G1, G2, G3) in GCA, which correlated well with tumour stage and patient survival. APCA had worse progression-free and disease-specific survivals than GCA and LAMN (pT≥3) with the latter being relatively indolent even when perforated with peritoneal spread. Our study is the first comprehensive comparison between all three appendiceal neoplasms. We also describe a spectrum of previously under-recognised crypt atypia in GCA, which should trigger a diligent search for GCA if present.
原发性阑尾腺癌（APCA）、杯状细胞腺癌（GCA）以及低/高级别阑尾黏液性肿瘤（LAMN/HAMN）是不同的实体，但临床表现和组织形态学存在重叠，导致诊断存在挑战。我们回顾性分析了2010年至2018年存档病例，采用更新的术语和现代参数进行诊断重新评估和对比分析。共纳入87例病例（22例APCA、40例GCA和25例pT≥3的LAMN）。整个队列中有49名女性和38名男性，中位年龄为59.9岁（范围26 - 88岁）。三组在年龄和性别上无统计学显著差异。临床上，GCA患者更易表现为急性阑尾炎（65%），且更倾向于将阑尾切除术作为初始手术（68%）。APCA和GCA都更易累及阑尾近端，而LAMN更易累及阑尾远端（p<0.05）。所有APCA均与黏膜前体病变相关，最常见的是管状、管绒毛状或绒毛状腺瘤、扁平LAMN/HAMN - pTis黏液上皮或混合型，这与不同的组织形态学、肿瘤分化和分期相关。虽然息肉样前体病变在GCA中罕见，但相当一部分GCA显示与肿瘤细胞相关的隐窝异型性。免疫组化方面，APCA的β - 连环蛋白核阳性更常见，SATB2表达缺失（p<0.05）。KRAS突变在APCA中比在GCA中更常见（8/11 vs 1/7，p<0.01）。我们进一步验证了GCA的三级分级系统（G1、G2、G3），其与肿瘤分期和患者生存率密切相关。APCA 的无进展生存期和疾病特异性生存期比GCA和LAMN（pT≥3）更差，后者即使伴有穿孔和腹膜播散也相对惰性。我们的研究是对所有三种阑尾肿瘤的首次全面比较。我们还描述了GCA中一系列先前未被充分认识的隐窝异型性，如果存在这种情况，应促使对GCA进行仔细排查。
