胰腺黏液性囊腺瘤中多数黏液性上皮衬里存在多个 KRAS 突变。

Multiple KRAS mutations in the non-mucinous epithelial lining in the majority of mucinous cystic neoplasms of the pancreas.

机构信息

Department of Pathology, Incheon St Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Seoul, Republic of Korea.

Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

出版信息

Histopathology. 2019 Oct;75(4):559-567. doi: 10.1111/his.13897. Epub 2019 Jul 26.

DOI:10.1111/his.13897

PMID:31077597

Abstract

AIMS

Mucinous cystic neoplasms (MCNs) of the pancreas are cystic neoplasms lined by mucinous lining epithelium (MLE) with associated ovarian-type stroma. Although a non-MLE (NMLE) can be observed in some MCNs, whether cystic neoplasms with ovarian-type stroma and NMLE should be classified as MCNs or separately designated is debated.

METHODS AND RESULTS

To test this, NMLEs were defined as flat or cuboidal epithelial cells without intracytoplasmic mucin. A total of 112 MCNs were reviewed, and the epithelium was classified as NMLE or MLE. A total of 110 females and two males with a mean age of 46.5 ± 12.3 years were included in this study. At least focal NMLE was noted in 76.8% (86/112) of MCNs. The mean percentage of the neoplastic epithelium that was NMLE in these 86 cases was 46%. NMLE was predominant (>50%) in 38.4% (43/112) of cases. MCNs with NMLE were smaller (42 ± 21 mm) than those with MLE (60 ± 36 mm, P < 0.001), and all NMLEs had low-grade dysplasia. Twelve MCNs with NMLE or MLE were selected for KRAS mutation analysis with droplet digital polymerase chain reaction after laser capture microdissection. All 12 MCNs showed multiple types of KRAS mutation, which were detected in 92% (11/12) of NMLE foci and 89% (8/9) of MLE foci. Predominant NMLE was common in small MCNs with low-grade dysplasia.

CONCLUSIONS

Clonal KRAS mutations were observed in both NMLE and MLE, supporting the hypothesis that MCNs with NMLE should be classified as MCNs.

摘要

目的

胰腺黏液性囊性肿瘤（MCN）是由黏液性衬里上皮（MLE）和相关的卵巢型基质组成的囊性肿瘤。虽然在一些 MCN 中可以观察到非 MLE（NMLE），但具有卵巢型基质和 NMLE 的囊性肿瘤是否应归类为 MCN 或单独指定仍存在争议。

方法和结果

为了验证这一点，NMLE 被定义为无细胞内黏液的扁平或立方上皮细胞。共回顾了 112 例 MCN，将上皮细胞分为 NMLE 或 MLE。共纳入 110 名女性和 2 名男性，平均年龄为 46.5±12.3 岁。在 112 例 MCN 中，至少有 76.8%（86/112）存在局灶性 NMLE。在这 86 例中，NMLE 占肿瘤上皮的平均百分比为 46%。38.4%（43/112）的病例中 NMLE 占优势（>50%）。NMLE 的 MCN 较小（42±21mm），而 MLE 的 MCN 较大（60±36mm，P<0.001），且所有 NMLE 均为低级别异型增生。选择 12 例具有 NMLE 或 MLE 的 MCN 进行 KRAS 突变分析，采用激光捕获微切割后进行液滴数字聚合酶链反应。12 例 MCN 均显示多种 KRAS 突变类型，在 92%（11/12）的 NMLE 焦点和 89%（8/9）的 MLE 焦点中均有检测到。在具有低级别异型增生的小 MCN 中，常见主导 NMLE。