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1、外科病理学实践：诊断过程的初学者指南第10章胰第 10 章胰(Pancreas ) Whipple 手术(The Whipple Procedure)The Whipple procedure is, at minimum, a pancreaticoduodenectomy, which may or may not also include pylorus of the stomach and the gallbladder. In the pyloruspreserving Whipple procedure, the simplest version, you receive the
2、segment of duodenum from just past the pylorus to about 20 cm beyond the ampulla of Vater. The head of the pancreas is nestled in the curve of the duodenum near the ampulla; the pancreas is shaped like a J, and the head is the base of the J, with the uncinate process as the hook. The distal common b
3、ile duct runs through the pancreas and enters the ampulla, where it is joined by the main pancreatic duct (Figure 10.1). Usually it is only the head of pancreas that comes out; if the tail is also involved, you may get the total pancreas and spleen.Whipple 手术至少是胰 十二指肠切除术，可能包括或不包括胃幽门和胆囊。在保存幽门的 Whippl
4、e手术中，最简单的术式是从刚过幽门到Vater壶腹外约20厘 米的十二指肠段。胰头位于壶腹附近的十二指肠弯曲处；胰腺呈J形， 胰头为J形的基部，钩突为弯钩处。远端胆总管穿过胰腺进入壶腹，在 壶腹与主胰管相连(图10.1)。通常只有胰头露在外面；如果胰尾也 受累，你可能会得到整个胰腺和脾。Figure 10.1. Diagram of specimen obtain during a Whipple靠近肌性大血管的大导管,几乎总是提示癌(图10.6 )。 Ducts leaving the pancreas to infiltrate the duodenumalways indicate ca
5、ncer.Figure 10.6. Adenocarcinoma next to a vessel. Large duct-like structures (arrow) next to a large-caliber vessel (V) are almost certainly cancer, even if deceptively well differentiated.m 10.6.血 管旁边的腺癌。大口径血管(V )旁边的大导管状结构(箭号)几乎肯 定是癌，即使貌似温良。胰腺中的异型增生(Dysplasia in the Pancreas )The pancreas is not a
6、n organ that can be evaluated with serial biopsies, and thus the natural history and malignant potential of dysplasia are not well understood. However； there are recognized grades of dysplasia within the duct system, called pancreatic intraepithelial neoplasia (PanIN). This ranges from PanIN 1, whic
7、h may overlap with hyperplastic or reactive changes, to PanIN 3, which is carcinoma in situ. A lesion should always be graded bythe highest level of dysplasia seen.胰腺不能通过连续活检来评估, 因此异型增生的自然史和恶性潜能还不清楚。然而，导管系统内存在 公认的异型增生分级，称为胰腺上皮内肿瘤（PanIN ）。其范围从可 能与增生性或反响性改变重叠的PanIN 1到PanIN 3 （原位癌）。始 终按所见的最高异型增生程度进行分级。
8、PanIN 1A has a flat layer of tall columnar cells with basal nuclei and apical mucin and no atypia. The cells are similar to normal endocervical glands （Figure 10.7）. PanIN IB is the same as PanIN 1A but with a papillary or undulating appearance.Panin 1A有一层平坦的高柱状细胞,有基底 核和顶端黏液，无非典型性。这些细胞类似正常的宫颈腺（图10.7
9、 ）。 PanIN IB与PanIN 1A相同，但有乳头状或起伏的结构。Figure 10.7. The grades of pancreatic intraepithelial neoplasia (PanIN). (A) PanIN 1 shows tall mucinous cells resembling endocervix. (B) PanIN 2 shows increasing nuclear crowding, enlargement, and atypia, suggestive of a tubular adenoma of colon. (C) PanIN 3 show
10、s highgrade nuclei with loss of polarity, frequent mitoses, and loss of mucinous differentiation. 图10.7.胰腺上皮内肿瘤(PanIN )的分级。(A ) PanIN 1显示类似 子宫颈内膜的高柱状黏液细胞。(B ) PanIN 2显示核拥挤、核增大和 异型性增加，类似结肠管状腺瘤。(C ) PanIN 3显示高级别细胞核， 极性丧失，核分裂频繁，黏液分化丧失。PanIN 2 is flat or papillarybut with nuclear abnormalities, includin
11、g nuclear crowding and enlargement stratification, hyperchromasia, and sometimes basal mitoses. This epithelium should remind you of a tubular adenoma or what would be called low-grade dysplasia in the gastrointestinal tract (see Figure 10.7).PanIN 2 呈平坦或乳头状， 但有核异常，包括核拥挤和增大、复层化、深染，有时有基底部核分 裂。这种上皮让你想
12、起管状腺瘤或胃肠道的低度异型增生(见图 10.7 )。 PanIN 3 is carcinoma in situ. You may see a cribiforming, papillary, or micropapillary architecture or necrosis. Cytologic features include large ugly nuclei with prominent nucleoli, total loss of polarity, atypical mitoses, maloriented goblet cells (upside down)一essentia
13、lly the same criteria you would use for highgrade dysplasia in other gastrointestinal epithelia (see Figure 10.7).PANIN3是原位癌。可能会看到筛状、乳头状或微乳头状结构或 坏死。细胞学特征包括丑陋的大核，核仁显著，极性完全丧失，非典 型核分裂象，方向错乱的杯状细胞(倒置)一基本上与其他胃肠道上 皮高度异型增生的标准相同(见图10.7 )。Invasive carcinoma arising out of PanIN 3 is well documented. However;
14、remember that PanIN is a common incidental finding in a pancreas. It is not visible radiologically, it does not make a mass, and it does not cause obstruction. If you have a clinical mass, you should be thinking instead of an invasive carcinoma or intraductal papillary mucinous neoplasm (IPMN; see n
15、ext section). Also, do not worry too much about the PanINs. With the exception of PanIN 3, they are of no proven clinical significance; margins with PanIN 1 or PanIN 2 lesions can safely be called negative起源于 PanIN 3 的浸 润性癌已有大量的文献报道。然而，请记住，PanIN是胰腺中常见的 偶然发现。放射学上看不见，不形成肿块，也不造成阻塞。如果有临 床肿块，应该考虑的浸润性癌或导管
16、内乳头状黏液性肿瘤(IPMN ;见 下一节)o另外，不要太担忧PanIN。除PanIN 3外，它们没有已证 实的临床意义；PanIN 1或PanIN 2病变的切缘可以平安地称为阴性。 导管内乳头状黏液性肿瘤(Intraductal Papillary Mucinous Neoplasm ) An IPMN is defined as a mucin-producing neoplasm arising in either the main pancreatic duct or a secondary (sidebranch) duct. The ducts are usually dilate
17、d because they are full of a papillary proliferation and abundant mucin. The main lesion to consider in the differential diagnosis is the mucinous cystic neoplasm (discussed later). If you have a mucin-producing cystic neoplasm in the pancreas, always probe the main duct to see if the cysts are conn
18、ected to it (an IPMN) or not (a mucinous cystic neoplasm). Essentially it is a gross diagnosis and may even be an endoscopic one; if mucin was seen coming out of the ampulla, the cysts must be connected to the pancreatic ducts and the lesion is more I汰ely to be an IPMN. However, once you have identi
19、fied an IPMN grossly, you must look microscopically to evaluate the level of atypia and rule out an invasive carcinoma. Intraductal papillary mucinous neoplasms are divided into three categories:IPMN的定义是一种产生黏液的肿瘤，发生在主胰管或副 胰管(侧支)。导管通常扩张，因为充满乳头状增殖和丰富的黏液。 主要鉴别诊断是黏液性囊性肿瘤(稍后讨论)。如果在胰腺发现分泌 黏液的囊性肿瘤，一定要探测主导管
20、，看看囊肿与之相连(IPMN ), 或不相连(黏液性囊性肿瘤)。本质上，这是一个大体诊断，甚至可 能是一个内窥镜诊断；如果看到壶腹流出黏液，囊肿必然与胰管相连, 病变更可能是IPMN。然而，一旦你大体上确定了 IPMN，你必须在显 微镜下观察以评估非典型性水平并排除浸润性癌。导管内乳头状黏液 性肿瘤分为三类： With low-grade dysplasia: These neoplasms are cytologically bland and have the same criteria as PanIN 1.伴低度异型增生：这些肿瘤的细胞形态学温和，其标准与PanIN 1相同。 With
21、 moderate dysplasia (formerly known as borderline): These neoplasms cytologically show increasing nuclear abnormalities and have the same criteria as PanIN 2. 中度异型增生(以前称为交界性)：这些肿瘤细胞学显示核异常 增加，其标准与PanIN 2相同。 With high-grade dysplasia: These neoplasms are cytologically malignant (see PanIN 3 criteria,
22、discussed earlier). Any IPMN with high-grade dysplasia must be carefully scrutinized for invasive carcinoma slipping out of the duct. 伴高度异型增生：这些肿瘤细胞学呈恶性(参见前面讨论的 PanIN 3标准)。任何伴有高度异型增生的IPMN都必须仔细检查是 否有浸润性癌超出导管范围。 A common question is, how can I tell PanIN in a largish duct from IPMN in a smallish sideb
23、ranch duct? Features that favor an IPMN include the following: 一个常见的问题是，如何区分大导管中的PanIN和较小侧支管 管道中的IPMN ?倾向IPMN的特点包括： Long papillae, or finger-like projections with fibrovascular cores (Figure 10.8) 长乳头，或指状突起，有纤维血管轴心(图10.8 )Figure 10.8. Papillary projections, intraductal papillary mucinous neoplasm wi
24、th moderate dysplasia. These tall papillary fronds are covered with mucinous cells showing moderate dysplasia, similar to PanIN 2.图10.8.乳头状突起，导管内乳头状黏 液性肿瘤伴中度异型增生。这些高高的乳头结构被覆黏液细胞，显示 中度异型增生，类似于PanIN 2e Blue mucin in the lumen of the duct 导管腔中的蓝色黏液 Continuity with one of the main pancreatic ducts 与其中一条
25、主胰管相连 Grossly or radiologically visible 肉眼可见或放射学上可见When it comes right down to it, identifying the grade of dysplasia correctly right is much more important than distinguishing between an IPMN and a PanIN.归根结底，正确识别 异型增生的等级比区分IPMN和PanIN更重要。浸润性导管腺癌 (Invasive Adenocarcinoma (Ductal) The most common for
26、m of infiltrating adenocarcinoma in the pancreas is ductal. It usually arises in the head and often invades adjacent structures before coming to clinical attention. The histologic features of ductal adenocarcinoma have been described earlier. Once you have established carcinoma, look carefully at al
27、l sections of duodenum and extrapancreatic bile duct to see if the carcinoma invades those structures (in increase in stage). The bile duct and ampullary region have numerous benign glands branching off of them, but remember that the benign glands will have a lobular and symmetric look at low power.
28、 Variants of ductal adenocarcinoma include adenosquamous, colloid (mucinous), hepatoid, medullary, signet ring cell, undifferentiated (anaplastic), and undifferentiated carcinoma with osteoclast-like giant cells.胰 腺中最常见的浸润性腺癌是导管腺癌。它通常发生在胰头，并在引起 临床注意之前侵入邻近结构。导管腺癌的组织学特征已在前面描述过。 一旦确定了癌，仔细观察十二指肠和胰外胆管的所有
29、局部，看看癌是 否侵入这些结构(分期升级)。胆管和壶腹区有许多良性腺体从中分 支出来，但要记住，良性腺体在低倍镜下呈小叶状和对称外观。导管 腺癌的变异型包括腺鳞癌、胶样癌(黏液癌)、肝样癌、髓样癌、印 戒细胞癌、未分化癌(间变性癌)，和具有破骨细胞样巨细胞的未分 化癌。胰腺其他囊性病变(Other Cystic Lesions of the Pancreas)黏液 囊性肿瘤(Mucinous Cystic Neoplasm)The mucinous cystic neoplasm occurs almost always in middle-aged women, usually in the
30、 tail of the pancreas. This mucinous neoplasm produces multilocular cysts that do not communicate with the main duct system. They have, by definition, a rim of ovarian stroma (Figure 10.9), so think of them as mucinous ovarian tumors heterotopic into the pancreas. As in the ovary, they have three gr
31、ades, and these grades conveniently parallel the three grades of the IPMN: 黏液囊性肿瘤几乎总是发生在中年女性，通常发生在胰尾。该肿瘤产Figure 10.9. Mucinous cystic neoplasm. The cyst lining isFigure 10.9. Mucinous cystic neoplasm. The cyst lining is生多房囊肿，与主导管系统不相连。根据定义，它们有一圈卵巢型间 质（图10.9 ）,因此可以视为异位进入胰腺的黏液性卵巢肿瘤。与卵 巢一样分三级，与IPMN的三个等
32、级平行：composed of mucinous cells, benign in this example, and underlying blue spindly ovarian-type stroma (arrow).图 10.9.黏液 囊性肿瘤。囊肿被覆黏液细胞，本例为良性，下面为蓝色梭形卵巢型 间质(箭号)。 With low-grade dysplasia: no atypia, like PanIN 1 低伴度异型增生：无非典型性，如PanIN 1 With moderate dysplasia: increasing nuclear atypia and/or architec
33、tural complexity, like PanIN 2 伴中度异型增生：核异型性和/或结构复杂性增加，如PanIN 2 With high-grade dysplasia: carcinoma in situ, like PanIN 3 伴高度异型增生：原位癌，如PanIN 3Approximately one third of mucinous cystic neoplasms have an associated invasive carcinoma, which would be called infiltrating moderately differentiated adeno
34、carcinoma arising in association with a mucinous neoplasm with high-grade dysplasia.大约1/3黏液囊性肿瘤伴有浸润性癌，称为浸润性中分化腺癌起 源于并发的黏液性肿瘤伴高度异型增生。浆液性囊腺瘤(Serous Cystadenoma)Serous cystadenomas of the pancreas, unlike the serous cystadenomas of the ovary, are almost always microcystic. Grossly, they have a central
35、scar and radiating small clear-fluid-filled cysts, like the cross section of a lime. Microscopically, the cysts are lined by cuboidal cells with clear cytoplasm (glycogen) and small, uniform, round nuclei (Figure 10.10). Areas of more solid or trabecular growth may look much like metastatic renal ce
36、ll carcinoma, which is in fact in the differential. Serous cystadenocarcinomas exist but are extremely rare.与卵巢浆液性囊腺瘤不同，胰腺浆液性囊腺瘤几乎都是微囊。大 体上，有一个中心瘢痕和放射状分布的充满透明液体的小囊肿，像酸 橙的横截面。显微镜下，囊肿被覆立方形细胞，胞质透明(糖原)， 核小、圆而均匀(图10.10 ) o更加实性或小梁生长的区域可能貌似转 移性肾细胞癌，确实需要鉴别。也存在浆液性囊腺癌，但极为罕见。Figure 10.10. Serous cystadenoma, h
37、igh power. The cells lining the multilocular cyst are small, with dense round nuclei and clear cytoplasm (arrow).图10.10.浆液性囊腺瘤，高倍。多房囊肿的 被覆细胞小，有致密的圆核和透明胞质(箭头)。实性假乳头状肿瘤 (Solid-Pseudopapillary Neoplasm)Solid-pseudopapillary neoplasms are unusual and distinctive tumors in the differential diagnosis of c
38、ystic lesions in young women. They are malignant but extremely indolent. The cell of origin is not known； and so the neoplasm is named based on its appearance. These neoplasms start out solid but undergo cystic degeneration and therefore may present as a cyst (despite the name). The cells are charac
39、teristically noncohesive, and so the remaining solid areas show a pseudopapillary growth pattern (meaning there is solid growth along fibrovascular septa, with a dropout of the loosely cohesive cells in between septa and a resulting papillary look). The nuclei are small, oval, bland, and procedure.
40、The head of the pancreas comes out attached to a segment of duodenum. The main pancreatic duct is visible at the pancreatic neck margin (a surgical margin). The common bile duct enters the pancreas to join the pancreatic duct (also a surgical margin). The uncinate process is the tip of the pancreas,
41、 and its edge abuts major vessels (a soft tissue margin).图 手术标本示意图。露在外面的胰头与一段十二指肠相连。 主胰管在胰颈切缘(手术切缘)可见。胆总管(也是一个外科切缘) 进入胰腺与胰管相连。钩突在胰腺的一端，其切缘邻接大血管(软组 织切缘)o图中文字：proximal margin ,近端切缘ampulla ,壶腹 distal margin ,远端切缘 duodenum ,十二指肠 pancreatic neck and duct,胰颈和胰管 common bile duct，胆总管 uncinate ,钩突 inked edge
42、 ,墨染切缘 There are five principal margins that are usually sampled on frozen section (see Figure 10.1). The first is the pancreatic margin, or the pancreatic neck (where the J is transected). This is usually taken as a shave margin, sampling the entire cross section of pancreas, and cancer anywhere on
43、 the slide is a positive margin. There is no neck margin on a total pancreatectomy.冰冻切片通常要取5个主要切缘(见图10.1)。第一个是胰腺切 缘或胰颈切缘(J形被切断的地方)。这里通常削取切缘，取胰腺的整 个横截面，切片上任何位置有癌都视为阳性切缘。全胰腺切除术没有 胰颈切缘。The second margin is the common bile duct margin, which is a shave of the bile duct stump. This ensures that cancer is
44、 not tracking up the bile duct toward the liver.第二个切缘是胆总 管切缘，这是胆管残端，也是幻灯片。这确保癌不会沿着胆管向肝转 移。The third is the uncinate margin. This is the tip of the short end of the J, and it represents the place where the pancreas sits against the major vessels. For the uncinate, you should take one representative p
45、erpendicular margin, and the edge of the tissue grooved （Figure 10.11）.在年轻女性囊性病变的鉴别诊断中，实性假 乳头状肿瘤是一种少见的独特肿瘤。它们是恶性的，但极其惰性。起 源细胞未知，因此根据其形态学命名。这些肿瘤开始是实性，但会发 生囊性变，因此可能表现为囊性（尽管名称不同）。细胞的特征是无 黏附性，因此其余的实性区域显示假乳头状生长模式（意思是沿着纤 维血管间隔呈实性生长，间隔之间的细胞呈松散黏附并脱落，因此看Figure 10.11. Solid pseudopapillary tumor. The small pl
46、asmacytoid cells with neuroendocrine-type chromatin could be mistaken for islet cell tumor or acinar cell carcinoma. However,this growth pattern, with rosette-like growth around fibrovascular cores （arrows） and dropout of the intervening cells, is typical of the solid pseudopapillary tumor.图 10.11.实
47、性假乳头 状肿瘤。浆细胞样小细胞伴神经内分泌型染色质，可能误诊为胰岛细 胞瘤或腺泡细胞癌。然而，这种生长模式（围绕纤维血管轴心（箭号） 的菊形团样生长，介于其间的细胞脱落）是实性假乳头状肿瘤的典型 表现。The differential diagnosis for this neoplasm includes well- differentiated pancreatic endocrine neoplasm and acinar cell carcinoma, both of which are discussed later. Immunohistochemical labeling is
48、 very helpful, as solid- pseudopapillary neoplasms are CD10 positive and show nuclear labeling for p-catenin.该肿瘤的鉴别诊断包括高分化胰腺内分泌肿瘤和腺泡细胞癌(下 文讨论)。免疫组化非常有用，因为该肿瘤呈CD10阳性，并且核表 达 p-catenino 假囊肿(Pseudocyst)The definition of a pseudocyst is lacking an epithelial lining/ This is a walled-off area of fat necro
49、sis and granulation tissue containing high levels of pancreatic enzymes that is not usually mistaken for a malignancy, clinically or microscopically. Remember that most pseudocysts are actually extrapancreatic.假囊肿的定义是“缺乏被覆上皮。这 是由脂肪坏死和肉芽组织构成的封闭区域，含有高水平的胰酶，在临 床或显微镜下通常不会被误认为恶性肿瘤。记住，大多数假囊肿实际 上是胰腺外的。胰腺其他实性肿瘤(Other Solid Tumors in the Pancreas)There are only two pancreatic cell types not yet discussed (not counting soft tissue elements such as vessels and nerves): the acinar ce