Department of Pathology, Emory University Hospital, Atlanta, GA, USA.
Am J Surg Pathol. 2010 Dec;34(12):1731-48. doi: 10.1097/PAS.0b013e3181f8ff05.
There has been no uniform terminology for systematic analysis of mass-forming preinvasive neoplasms (which we term tumoral intraepithelial neoplasia) that occur specifically within the ampulla. Here, we provide a detailed analysis of these neoplasms, which we propose to refer to as intra-ampullary papillary-tubular neoplasm (IAPN).
Three hundred and seventeen glandular neoplasms involving the ampulla were identified through a review of 1469 pancreatoduodenectomies and 11 ampullectomies. Eighty-two neoplasms characterized by substantial preinvasive exophytic component that grew almost exclusively (>75%) within the ampulla (in the ampullary channel or intra-ampullary portions of the very distal segments of the common bile duct or pancreatic duct) were analyzed.
(1) Clinical: The mean age was 64 years, male/female ratio was 2.4, and mean tumor size was 2.7 cm. (2) Pathology: The tumors had a mixture of both papillary and tubular growth (each constituting at least 25% of the lesion) in 57%; predominantly (>75%) papillary in 23%, and predominantly (>75%) tubular in 20%. High-grade dysplasia was present in 94% of cases, of which 39% showed focal (<25% of the lesion), 28% showed substantial (25% to 75%), and 27% showed extensive (>75%) high-grade dysplasia. In terms of cell-lineage morphology, 45% had a mixture of patterns. However, when evaluated with a forced-binary approach as intestinal (INT) versus gastric/pancreatobiliary (GPB) based on the predominant pattern, 74% were classified as INT and 26% as GPB. (3) Immunohistochemistry: Percent sensitivity/specificity of cell-lineage markers were, for INT phenotype: MUC2 85/78 and CDX2 94/61; and for GBP: MUC1 89/79, MUC5AC 95/69, and MUC6 83/76, respectively. Cytokeratin 7 and 20 were coexpressed in more than half. (4) Invasive carcinoma: In 64 cases (78%), there was an associated invasive carcinoma. Size of the tumor and amount of dysplasia correlated with the incidence of invasion. Invasive carcinoma was of INT-type in 58% and of pancreatobiliary-type in 42%. Cell lineage in the invasive component was the same as that of the preinvasive component in 84%. All discrepant cases were pancreatobiliary-type invasions, which occurred in INT-type preinvasive lesions. (5) OUTCOME: The overall survival of invasive cases were significantly worse than that of noninvasive ones (57% vs. 93%; P=0.01); and 3 years, 69% versus 100% (P=0.08); and 5 years, 45% versus 100% (P=0.07), respectively. When compared with 166 conventional invasive carcinomas of the ampullary region, invasive IAPNs had significantly better prognosis with a mean survival of 51 versus 31 months (P<0.001) and the 3-year survival of 69% versus 44% (P<0.01).
Tumoral intraepithelial neoplasia occurring within the ampulla are highly analogous to pancreatic or biliary intraductal papillary and tubular neoplasms as evidenced by their papillary and/or tubular growth, variable cell lineage, and spectrum of dysplastic change (adenoma-carcinoma sequence), and thus we propose to refer to these as IAPN. IAPNs are biologically indolent; noninvasive examples show an excellent prognosis, whereas those with invasion exhibit a malignant but nevertheless significantly better prognosis than typical invasive ampullary carcinomas unaccompanied by IAPNs. Twenty eight percent (64 of 230) of invasive carcinomas within the ampulla arise in association with IAPNs.
目前对于特定发生在壶腹内的肿块形成性癌前病变（我们称之为肿瘤上皮内瘤变），尚无统一的术语来进行系统分析。在此，我们详细分析了这些肿瘤，我们建议将其称为壶腹内乳头状-管状肿瘤（IAPN）。
通过对 1469 例胰十二指肠切除术和 11 例壶腹切除术的回顾，我们发现了 317 例涉及壶腹的腺性肿瘤。我们分析了 82 例具有显著的外生性肿瘤前成分的肿瘤，这些肿瘤几乎完全（>75%）生长在壶腹内（在壶腹通道或胆总管或胰管的远段的壶腹内部分）。
（1）临床：平均年龄为 64 岁，男女比例为 2.4，平均肿瘤大小为 2.7cm。（2）病理学：肿瘤具有混合的乳头和管状生长（每种成分至少占病变的 25%），占 57%；以乳头状为主（>75%），占 23%，以管状为主（>75%），占 20%。94%的病例存在高级别异型增生，其中 39%表现为局灶性（<病变的 25%），28%表现为广泛（25%至 75%），27%表现为广泛（>75%）高级别异型增生。在细胞谱系形态方面，45%的病例存在混合模式。然而，当根据主要模式以肠型（INT）与胃/胰胆管型（GPB）进行强制二元分类时，74%的病例被归类为 INT，26%的病例被归类为 GPB。（3）免疫组织化学：肠型（INT）表型的细胞谱系标志物的敏感性/特异性分别为：MUC2 85/78 和 CDX2 94/61；而胃/胰胆管型（GPB）分别为：MUC1 89/79、MUC5AC 95/69 和 MUC6 83/76。超过一半的病例同时表达细胞角蛋白 7 和 20。（4）浸润性癌：在 64 例（78%）病例中，存在相关的浸润性癌。肿瘤大小和异型增生程度与浸润的发生率相关。58%的浸润性癌为 INT 型，42%为胰胆管型。在 84%的病例中，浸润性成分的细胞谱系与肿瘤前病变的细胞谱系相同。所有不一致的病例均为浸润性的 GPB 型，发生在 INT 型肿瘤前病变中。（5）预后：浸润性病例的总生存率明显差于非浸润性病例（57%比 93%；P=0.01）；3 年生存率分别为 69%比 100%（P=0.08）；5 年生存率分别为 45%比 100%（P=0.07）。与 166 例常规壶腹浸润性癌相比，浸润性 IAPN 的预后明显更好，平均生存时间分别为 51 个月和 31 个月（P<0.001），3 年生存率分别为 69%和 44%（P<0.01）。
发生在壶腹内的肿瘤上皮内瘤变与胰腺或胆管内乳头状和管状肿瘤高度相似，证据是其具有乳头状和/或管状生长、可变的细胞谱系和异型增生（腺瘤-癌序列）的特征，因此我们建议将其称为 IAPN。IAPN 具有生物学惰性；非浸润性病例预后良好，而浸润性病例表现出恶性，但与不伴有 IAPN 的典型浸润性壶腹癌相比，预后仍然显著更好。28%（230 例浸润性癌中的 64 例）的壶腹内浸润性癌与 IAPN 相关。
