METHODOLOGY OF THE SUBGROSS STUDY

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slide1.jpg 374.44 Kb Slide 1. The mouse MAMMARY FAT PADS are a few millimeters thick so a whole mount of one, as displayed here stained with hematoxylin, will disclose all diseased areas. Note the delicately branching DUCT TREE arising from the NIPPLE (N). The arrows point to HYPERPLASTIC ALVEOLAR NODULES, the precursor lesions to mammary cancer. Photographed at 2x magnification.	slide2.jpg 401.31 Kb Slide 2. "Whole Mounts" of human BREASTS were produced by slicing whole breasts parasagitally into 2-3mm thick slices on a butcher's meat slicer after the whole breast had been fixed for several months in 10% formalin.	slide3.jpg 699.07 Kb Slide 3. The slices were placed sequentially on a tray.	slide4.jpg 675.06 Kb Slide 4. Thereafter, they were placed on grids to be stained with hematoxylin, dehydrated in graded alcohols and xylene and immersed in methylsalicylate before they were placed in plastic bags.
slide5.jpg 219.45 Kb Slide 5. One slice through the nipple is seen here. The section is a full thickness of the breast with the pectoralis muscle at the bottom and the mammary fat pad between the nipple (upper) and the muscle.	slide6.jpg 556.46 Kb Slide 6. Each slice was viewed at low power in a dissection microscope and screened for abnormal structures.	slide7.jpg 503.58 Kb Slide 7. Abnormal structures were delineated with a marking pen on the plastic bag.	slide8.jpg 481.23 Kb Slide 8. Two breast slices are seen. All lesions within a given breast were delineated. Photographs were taken of all lesions in the slices. They were cut out of the slices and processed for light microscopy.
slide9.jpg 450.04 Kb Slide 9. The slice is 2-3 mm thick and stained with hematoxylin staining the nuclei blue, allowing the microarchitecture of entire lesions to be visualized. Thus 3-dimensional interpretation is possible. In this image, the branching DUCT TREE (D) is distended with secretion. Arrows point to a blue, i.e., cellular lesion arising from the distal end of the duct tree. It is composed of convoluted coarse DUCTULES. Photographed at 6x magnification.	slide10.jpg 566.28 Kb Slide 10. The corresponding histologic slide shows the ducts (D) and a cluster of coarse cellular ductules, in the lower center. Notice that you cannot discern on this 7 micron thick section that all these structures are connected. However, the structures are easily visualized in the subgross (slide 9). Photographed at 6x magnification.	slide11.jpg 596.70 Kb Slide 11. Some of the ductules are distended. Photographed at 25x magnification.	slide12.jpg 538.55 Kb Slide 12. These distended coarse ductules have a lining with more than 2, less than 4 layers of cells. Photographed at 63x magnification. Comparing the lesion in 3 dimensions in its totality in the slice with the histopathology was done for all lesions and thus each breast was quantitated and qualitated for lesions. The microarchitecture of this lesion called BLUNT DUCT ADENOSIS by pathologists showed that it arises at the terminal end of the duct tree and that it is a variant of the normal LOBULE as seen later.

 Science 1976 Jan 23;191(4224):295-7
 Jensen HM, Rice JR, Wellings SR   Preneoplastic lesions in the human breast.

A subgross sampling technique with histological confirmation was used to study the pathology of 119 whole human breasts, either cancer-associated (that is, containing cancer or contralateral to a cancer) or taken from random routine autopsies. Atypical lobules were observed much more frequently in the cancer-associated group than in the group of routine autopsy breasts. Atypical lobules showed varying degrees of anaplasia that formed a continuum between normal epithelium and carcinoma in situ, usually of the common ductal type. As apprarent markers for increased cancer risk, atypical lobules in the human breast may be homologous to hyperplastic alveolar nodules that are abundant in high mammary cancer strains of mice. This indirect evidence supports the hypothesis that atypical lesions are common preneoplastic lesions in the human mammary gland.

J Natl Cancer Inst 1975 Aug;55(2):231-73
Wellings SR, Jensen HM, Marcum RG  An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions.

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.

J Natl Cancer Inst 1973 May;50(5):1111-8
Wellings SR, Jensen HM  On the origin and progression of ductal carcinoma in the human breast.

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