Wellings S R, Jensen H M, Marcum R G
J Natl Cancer Inst. 1975 Aug;55(2):231-73.
One hundred ninety-six whole human breasts were examined by a subgross sampling technique with histologic confirmation. The method permitted the enumeration and identification of essentially all the focal dysplastic, metaplastic, hyperplastic, anaplastic, and neoplastic lesions. Of the 196, 119 were suitable for complete quantitative morphologic analysis of the focal lesions by type. They consisted of 67 breasts obtained by autopsy, 29 cancerous breasts obtained by mastectomy, and 23 contralateral to those with cancer. All lesions, photographed subgrossly, were subsequently confirmed and correlated histologically. Morphologic evidence supported the hypothesis that most lesions traditionally grouped as mammary dysplasia or fibrocystic disease, including apocrine cysts, sclerosing adenosis, fibroadenomas, various forms of lobules (sclerotic, dilated, hypersecretory, hyperplastic, atypical, or anaplastic), ductal carcinoma in situ (DCIS), and lobular carcinoma in situ (LCIS), arose in terminal ductal-lobular units (TDLU) or in the lobules themselves. A probable exception was papilloma of ducts larger than terminal ones. Isolated foci of DCIS within the TDLU were seen in 40% of cancerous breasts, which indicated that the disease often was multifocal. Of the contralateral breasts, the 60% with clinical cancer contained such lesions, and data were in accord with the clinically known fact that women with previous breast cancer have a high rate of the disease in the remaining one. An atypical lobule (AL) of type A (ALA) had the following characteristics: a) It was more common in cancerous breasts or in those contralateral to cancer than in breasts not so identified; b) it had lobular morphology and was a terminal structure on the mammary tree; c) it tended to persist after the menopause, whereas normal lobules usually atrophied; d) it variable degrees of anaplasia forming an arbitrary continuum from normal lobules to ductal carcinoma in situ; and e) as ALA progressed to DCIS, the unfolded lobule resembled a duct which gave the false impression that DCIS was a ductal lesion. The morphologic evidence supported that hypothesis that the lesions herein called AL were derived from TDLU and were precancerous.
采用亚大体取样技术并经组织学证实，对196个完整的人类乳房进行了检查。该方法能够对基本上所有局灶性发育异常、化生、增生、间变和肿瘤性病变进行计数和识别。在这196个乳房中，119个适合按类型对局灶性病变进行完整的定量形态学分析。它们包括通过尸检获得的67个乳房、通过乳房切除术获得的29个癌性乳房以及与癌性乳房相对的23个对侧乳房。所有病变均在亚大体水平拍照，随后进行组织学证实和关联分析。形态学证据支持这样一种假说，即大多数传统上归类为乳腺发育异常或纤维囊性疾病的病变，包括大汗腺囊肿、硬化性腺病、纤维腺瘤、各种形式的小叶（硬化性、扩张性、分泌过多性、增生性、非典型性或间变性）、导管原位癌（DCIS）和小叶原位癌（LCIS），均起源于终末导管小叶单位（TDLU）或小叶本身。一个可能的例外是大于终末导管的导管内乳头状瘤。在40%的癌性乳房中可见TDLU内孤立的DCIS病灶，这表明该疾病常为多灶性。在对侧乳房中，60%有临床癌症的乳房含有此类病变，数据与临床已知事实相符，即既往有乳腺癌的女性另一侧乳房患该疾病的几率很高。A型非典型小叶（ALA）具有以下特征：a）它在癌性乳房或与癌相对的乳房中比在未发现此类情况的乳房中更常见；b）它具有小叶形态，是乳腺树上的终末结构；c）它在绝经后往往持续存在，而正常小叶通常会萎缩；d）它有不同程度的间变，形成从正常小叶到导管原位癌的任意连续谱；e）当ALA进展为DCIS时，展开的小叶类似导管，给人一种DCIS是导管病变的错误印象。形态学证据支持这样的假说，即此处称为AL的病变起源于TDLU且是癌前病变。
