Sternberg A, Amar M, Alfici R, Groisman G
Department of Surgery, Hillel Yaffe Medical Center, Hadera, Israel.
J Clin Pathol. 2002 Jan;55(1):17-21. doi: 10.1136/jcp.55.1.17.
Venous invasion is an established predictor of prognosis in colorectal cancer (CRC). The reported incidence of venous invasion in CRC specimens varies between 10% and 89.5%, mainly as a result of interobserver variability and differences in specimen processing (for example, staining with haematoxylin and eosin (H+E) alone versus the addition of an elastic fibre stain). This study was performed with three purposes in mind, namely: (1) To assess and compare the incidence of venous invasion diagnosed on H+E stained tissue versus tissue stained with both H+E and an elastic fibre stain. (2) To estimate the inherent false negative rate associated with the diagnosis of venous invasion by histopathological evaluation of resected CRC specimens. (3) To compare the resulting data regarding incidence, quantity, site, and type of venous invasion to the pertinent literature.
Venous invasion was assessed on sections from 81 CRCs resected from patients with synchronous distant metastases (hepatic and non-hepatic). Only stage IV tumours were studied for the following reasons: (1) it can be assumed that in all patients with distant haematogenous metastases venous invasion had occurred, thus enabling the false negative rate to be calculated; (2) there can be no dispute about the clinical relevance of the various characteristics of venous invasion identified in the tumours of patients with synchronous distant haematogenous metastases; and (3) to eliminate the effect of variance in tumour stage on the incidence of venous invasion. Initially, H+E stained sections were studied for venous invasion. Sections that were negative or questionable with regard to venous invasion were then stained with an elastic fibre stain, and a second search for venous invasion was carried out. Venous invasion was characterised by incidence, quantity, type, and site. The chi(2) test for independence was used to compare the incidence of venous invasion in colonic versus rectal and rectosigmoid primary tumours, and in patients with hepatic versus non-hepatic metastases.
Venous invasion was identified in 42 (51.9%) (of the 81 specimens on H+E stained sections. The addition of the elastic fibre stain enabled the diagnosis of venous invasion in 15 (38.5%) of the remaining 39 specimens, increasing the overall incidence to 57 of 81 cases (70.4%). Of the 57 positive specimens, venous invasion was minimal in 27 (47.4%), intermediate in five, (8.8%) and massive in 25 (43.9%). Only intramural veins were involved in 18 (31.6%), only extramural veins in 26 (45.6%), and both intramural and extramural veins in 13 (22.8%) of the 57 positive specimens. The filling type of venous invasion was found in 41 (71.9%), the floating type in 28 (49.1%), and the infiltrating type in six (10.5%) of the 57 positive specimens. There was no significant difference between the incidence of venous invasion in the colon (42 of 60; 70%) versus rectal and rectosigmoid tumours (15 of 21; 71.4%; p = 0.8539), nor in the incidence of venous invasion in patients with hepatic (49 of 70; 70%) versus non-hepatic (eight of 11; 72.7%) metastases (p = 0.9018).
The addition of an elastic fibre stain enables the identification of venous invasion in a considerable proportion of sections from CRC tumours that are falsely negative for venous invasion on H+E stain alone. The inherent chance of missing venous invasion on histopathological evaluation of CRC tumours stained with H+E and elastic fibre stains is at least 10.5%, and may be as high as 29.6%. In a large proportion of stage IV CRCs, despite the presence of synchronous distant metastases, only a minimal extent of venous invasion (that is, one to two involved veins) is demonstrable in the primary tumour. This suggests that only minimal venous invasion is required for the seeding of clinically relevant haematogenous metastases, and emphasises the careful, dedicated search for venous invasion that is required from the pathologist. Although extramural venous invasion was predominant in stage IV CRCs, in a considerable proportion of tumours (about a third) only intramural venous invasion was found. This suggests that intramural venous invasion may also seed clinically relevant haematogenous metastases, and should therefore also be considered as an indicator of poor prognosis.
静脉侵犯是结直肠癌（CRC）预后的既定预测指标。报道的CRC标本中静脉侵犯的发生率在10%至89.5%之间，主要是由于观察者间的差异以及标本处理方式的不同（例如，仅苏木精和伊红（H+E）染色与添加弹性纤维染色）。本研究旨在实现三个目的，即：（1）评估并比较仅用H+E染色的组织与同时用H+E和弹性纤维染色的组织中诊断出的静脉侵犯发生率。（2）通过对切除的CRC标本进行组织病理学评估，估计与静脉侵犯诊断相关的固有假阴性率。（3）将有关静脉侵犯的发生率、数量、部位和类型的所得数据与相关文献进行比较。
对81例患有同步远处转移（肝转移和非肝转移）患者切除的CRC标本切片进行静脉侵犯评估。仅对IV期肿瘤进行研究，原因如下：（1）可以假定，在所有有远处血行转移的患者中均已发生静脉侵犯，从而能够计算假阴性率；（2）对于同步远处血行转移患者肿瘤中所确定的静脉侵犯的各种特征的临床相关性不存在争议；（3）消除肿瘤分期差异对静脉侵犯发生率的影响。最初，对H+E染色切片进行静脉侵犯研究。对于静脉侵犯为阴性或有疑问的切片，随后用弹性纤维染色，并再次进行静脉侵犯检查。静脉侵犯通过发生率、数量、类型和部位进行特征描述。采用独立性卡方检验比较结肠与直肠及直肠乙状结肠原发性肿瘤中静脉侵犯的发生率，以及肝转移与非肝转移患者中静脉侵犯的发生率。
在81个标本的H+E染色切片中，有42个（51.9%）发现有静脉侵犯。在其余39个标本中，添加弹性纤维染色后使15个（38.5%）标本诊断出静脉侵犯，使81例中的总体发生率增至57例（70.4%）。在57个阳性标本中，27个（47.4%）静脉侵犯轻微，5个（8.8%）为中度，25个（43.9%）为重度。在57个阳性标本中，仅壁内静脉受累的有18个（31.6%），仅壁外静脉受累的有26个（45.6%），壁内和壁外静脉均受累的有13个（22.8%）。在57个阳性标本中，静脉侵犯的填充型有41个（71.9%），漂浮型有28个（49.1%），浸润型有6个（10.5%）。结肠（60个中的42个；70%）与直肠及直肠乙状结肠肿瘤（2个中的15个；71.4%；p = 0.8539）中静脉侵犯的发生率之间无显著差异，肝转移（70个中的49个；70%）与非肝转移（11个中的8个；72.7%）患者中静脉侵犯的发生率之间也无显著差异（p = 0.9018）。
添加弹性纤维染色能够在相当比例的CRC肿瘤切片中识别出仅用H+E染色时静脉侵犯呈假阴性的情况。对用H+E和弹性纤维染色的CRC肿瘤进行组织病理学评估时，漏诊静脉侵犯的固有几率至少为10.5%，可能高达29.6%。在很大一部分IV期CRC中，尽管存在同步远处转移，但在原发性肿瘤中仅可显示出极小范围的静脉侵犯（即一至两条受累静脉）。这表明临床相关血行转移的播散仅需要极小范围的静脉侵犯，并强调病理学家需要仔细、专注地查找静脉侵犯。尽管壁外静脉侵犯在IV期CRC中占主导，但在相当比例的肿瘤（约三分之一）中仅发现壁内静脉侵犯。这表明壁内静脉侵犯也可能播散临床相关的血行转移，因此也应被视为预后不良的指标。
