Foamy gland pattern of pancreatic ductal adenocarcinoma - A deceptively benign-appearing variant

Foamy gland pattern of pancreatic ductal adenocarcinoma - A deceptively benign-appearing variant
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DOI:
10.1097/00000478-200004000-00003
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发表时间:
2000-04-01
影响因子:
5.6
通讯作者:
Vaitkevicius, V
Vaitkevicius, V
中科院分区:
医学1区
文献类型:
--
作者:
Adsay, V;Logani, S;Vaitkevicius, V

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胰腺癌的病理诊断通常是一个挑战,特别是在小活检,冷冻切片,并在转移灶。我们在此报道了一种具有明显微泡胞浆的导管腺癌,其形态学特征与前列腺相似,但表面上看上去是良性的。这种变异,我们称之为泡沫腺型(FGP),在冰冻切片或活检中经常被误诊,在手术标本中其病理分期被低估。组织学上,诊断特征为:(1)白色且脆泡沫状的“微泡”细胞质;(2)通常位于基底且被压缩的深染核,让人想起颈内腺体(和所谓的“腺瘤”)或胃小凹腺;(3)不规则的核轮廓形成皱纹(葡萄干样)核在某些地区;和(4)一个独特的嗜色凝聚的细胞质物质在管腔方面的细胞形成刷状边界样区(BLZ)。组织化学上,该BLZ为粘蛋白胺、阿辛蓝和高铁二胺阳性,但PAS不阳性。其余细胞质对所有这些染色均呈阴性。相反,良性粘液导管,构成了主要的鉴别诊断,有更均匀的嗜酸性细胞质,缺乏BLZ,并显示PAS染色的细胞质。免疫组化显示肿瘤细胞呈弥漫性CEA和细胞角蛋白8强阳性,而B72.3染色呈局灶性弱阳性。MUC 1染色主要局限于BLZ。MUC 2呈阴性。在研究的20例病例中,有16例检测到P53染色,其中5例呈强阳性和弥漫性。8例中有6例K-ras基因突变。在这项研究中的20例患者(4例纯和16例混合与普通导管癌)的临床表现似乎没有显着不同的普通导管腺癌的胰腺。11例患者为男性,9例为女性;平均年龄为62岁,平均肿瘤大小为4.4 cm。17例患者的随访信息可用,其中7例在平均随访23个月(范围,7-104个月)时存活,10例在中位随访15个月(范围,4-42个月)时死于疾病。4例单纯FGP患者的中位生存期为18个月。在作者的经验中,中位生存期似乎并不明显长于可切除的普通导管腺癌患者(109例患者,中位生存期为12个月,p = 0.48)。总之,浸润性胰腺导管癌的泡沫腺型在形态学上是独特的,容易误诊为良性过程。病理分期往往被低估,由于缺乏认识和误解为粘液导管。仔细观察其显微特征足以准确诊断。组织化学和免疫组化染色是有用的,以确认恶性肿瘤的诊断,在挑战性的情况下。
Pathologic diagnosis of pancreatic adenocarcinoma is frequently a challenge, particularly in small biopsies, frozen sections, and in metastatic foci. Here we report a deceptively benign-appearing and morphologically distinctive pattern of ductal adenocarcinoma with prominent microvesicular cytoplasm, giving the cells a foamy appearance similar to that described in the prostate (Am J Surg Pathol 1996;20:419). This variant, which we refer to as foamy gland pattern (FGP), was frequently misdiagnosed in frozen sections or biopsies and its pathologic stage underestimated in surgical specimens. Histologically, the diagnostic features were: (1) white and crisply foamy, "microvesicular" cytoplasm; (2) often basally located and compressed, hyperchromatic nuclei reminiscent of endocervical glands (and so-called "adenoma malignum") or gastric foveolar glands; (3) irregular nuclear contours forming wrinkled (raisinoid) nuclei in some areas; and (4) a distinctive chromophilic condensation of the cytoplasmic material in the luminal aspect of the cells forming a brush border-like zone (BLZ). Histochemically, this BLZ was positive for mucicarmine, alcian blue, and high iron diamine, but not PAS. The remainder of the cytoplasm was negative for all these stains. In contrast, benign mucinous ducts, which constitute the major differential diagnosis, had more homogeneous acidophilic cytoplasm, lacked BLZ, and showed cytoplasmic staining with PAS. Immunohistochemically, the tumor cells were diffusely and strongly positive for CEA and cytokeratin 8 whereas B72.3 staining was focal and weak. MUC1 staining was largely confined to the BLZ. MUC2 was negative. P53 staining was detected in 16 of the 20 cases studied and was strong and diffuse in five. K-ras mutation was detected in 6 of 8 cases studied. The clinical findings in the 20 patients in this study (4 pure and 16 mixed with usual ductal carcinoma) did not appear to differ significantly from those of ordinary ductal adenocarcinoma of the pancreas. Eleven patients were men and nine were women; the mean age was 62 years and the mean tumor size was 4.4 cm. Follow-up information was available in 17 patients of whom 7 were alive at an average follow up of 23 months (range, 7-104 mos), and 10 were dead of disease at a median follow up of 15 months (range, 4-42 mos). The median survival of the four patients with pure FGP was 18 months. The median survival did not appear to be significantly longer than that of the patients with resectable ordinary ductal adenocarcinoma in the authors' experience (109 patients, median survival of 12 mos, p = 0.48). In conclusion, foamy gland pattern of invasive pancreatic ductal carcinoma is morphologically distinctive and is prone to misdiagnosis as a benign process. The pathologic stage is often underestimated as a result of the lack of its recognition and misinterpretation as mucinous ducts. Careful attention to its microscopic features is adequate for accurate diagnosis. Histochemical and immunohistochemical stains are useful in confirming the diagnosis of malignancy in challenging cases.