Nathan Lane

Distribution of Human Colonic Lymphatics in Normal, Hyperplastic, and Adenomatous Tissue: Its relationship to metastasis from small carcinomas in pedunculated adenomas, with two case reports

Prompted by 2 cases of lymphatic metastasis from focal carcinoma in the head of pedunculated adenomas, lymphatics were studied in the colonic mucosa in normal, hyperplastic, and adenomatous tissue utilizing light and electron microscopic techniques. In all three tissues there is a lymphatic plexus associated with the muscularis mucosae, but there are no lymphatics above this level. This explains why lymphatic metastases from superficial intramucosal foci of carcinoma in adenomas do not occur. In lobules of adenomatous tissue, the total distance between the free surface and the muscularis mucosae may be considerably increased, and a focus of carcinoma in adenomatous tissue must at least reach the muscularis mucosae and its lymphatics in order to metastasize. This lack of lymphatics contrasts with the profusion of blood capillaries at the mucosal surface. This may be an example of a more general biological phenomenon in that other sites also concerned with water and ion transport, such as the renal glomerulus, the gallbladder mucosa, choroid plexus, and ciliary body lack lymphatics but exhibit a rich blood capillary network at their transporting surfaces.

Comparative Electron Microscopic Features of Normal, Hyperplastic, and Adenomatous Human Colonic Epithelium: Variations in cellular structure relative to the process of epithelial differentiation

Abstract Electron microscopic studies of the epithelium of normal human colonic mucosa, hyperplastic polyps, and adenomatous lesions confirm and extend our previous studies of these tissues. In this study the cytology of well defined examples of the three types of epithelium is compared at several crypt levels. The normal epithelium exhibits a regular pattern of differentiation as cells migrate from the base of the crypt to the free surface. Progressive maturation is seen from undifferentiated cells in the base of the crypt to intermediate and immature goblet and absorptive cells in the midcrypt and, finally, to fully mature and even senescent goblet and absorptive cells in the upper one-third of the crypt and at the free surface. The hyperplastic epithelium exhibits a similar progression, the primary difference being that most of the morphological features of maturing and mature cells are found either lower in the crypt or in exaggerated form at the same level of the crypt when compared with normal mucosa of the same colon. The adenomatous epithelium, however, rarely differentiates past the intermediate, partially differentiated cell stage, retaining both the morphological and replicative characteristics of this immature cell type.

Colonic Pericryptal Fibroblast Sheath: Replication, Migration, and Cytodifferentiation of a Mesenchymal Cell System in Adult Tissue: II. Fine structural aspects of normal rabbit and human colon

Summary The colonic pericryptal fibroblast sheath is a self-renewing population of mesenchymal cells which maintains intimate contact with the base of the epithelium as it and the epithelium. migrate synchronously from their germinative zones to the surface of the crypt. The fine structural appearance of the fibroblast changes during the migration from that of an undifferentiated cell at the lower part of the crypt to that of a mature fibrocyte engaged in protein synthesis at the upper part of the crypt. The change in functional appearance is correlated with the appearance of a wide collagen table under the surface epithelium. The shingling of the fibroblasts creates a complete sheath around the lower portion of each crypt. This cellular sheath is fenestrated under the free surface where only delicate, stellate processes of the fibrocytes maintain close contact with the epithelial basal lamina. The fenestrated appearance of the pericryptal fibrocyte processes in the zone of cellular differentiation, which subtends the fully differentiated absorptive epithelium, may shed some light on the nature of the epithelial basal complex and the role of the pericryptal sheath and the collagen table in fluid transport across colonic mucosa. The constant maintenance of intimate fibroblast-epithelial contact throughout the crypt is additional reason to suppose that a well ordered system of epithelial-mesenchymal interaction is involved in normal structure, renewal, and function of colonic mucosa.

The anatomical precursor of colorectal carcinoma

The very common hyperplastic polyp is not a neoplasm and is unrelated to either adenoma or carcinoma. Adenomas, which are only one‐tenth as common, may occur grossly as adenomatous polyps or papillary adenomas. Be they large or small, pedunculated, sessile, or flat, they are true neoplasms—non‐invasive and thought of as benign. Depending on size, and probably related to a sessile mode of growth, in adenomas one may readily observe intramucosal carcinoma and/or „early”︁ invasive cancer. On the other hand, although microscopic examination has been performed on many thousands of minute mucosal lesions (e.g. 5 mm or less), „early”︁ cancer, defined as intramucosal carcinoma with or without microinvasion, does not seem to occur unassociated with adenoma. Since colorectal carcinoma is so common, one should easily find many examples of „early”︁ cancer as defined above if the majority of ordinary adenocarcinomas arose directly from normal crypts of Lieberkühn. (Of course the unusual anaplastic undifferentiated colonic cancers or carcinomas arising in ulcerative colitis remain in an area of unknown morphogenesis). The apparent non‐existence of small foci of intramucosal carcinoma, with or without micro‐invasion, in normal mucosa, and their frequency in adenomas, are two fundamental pathologic facts. They seem to disprove the proposition that cancer cells ordinarily arise de novo from the normal cells of the crypt of Lieberkühn without the interposition of a stage in the neoplastic process that we recognize as adenoma.

The Colonic Pericryptal Fibroblast Sheath: Replication, Migration, and Cytodifferentiation of a Mesenchymal Cell System in Adult Tissue: III. Replication and differentiation in human hyperplastic and adenomatous polyps

Electron microscopic and autoradiographic studies of the pericryptal fibroblast sheath of human hyperplastic and adenomatous colonic polyps confirm the suggestion of Lane et al. (Lane N, Kaplan H, Pascal RR: Minute adenomatous and hyperplastic polyps of the colon: divergent patterns of epithelial growth with specific associated mesenchymal changes. Contrasting roles in the pathogenesis of carcinoma. Gastroenterology 60:537–551, 1971) that these two lesions may represent divergent extremes of the normal differentiation of the colonic mucosa. The sheath of the hyperplastic mucosa is fully differentiated and excessively developed, paralleling precisely the differentiation and development of the overlying epithelium. Conversely, the immaturity of the sheath of the adenomatous epithelium, demonstrated by continued fibroblast division at all levels, failure of morphological maturation of the fibroblasts, and failure of the fibroblasts to secrete their normal extracellular products, collagen and mucopolysaccharides, parallels the degree of immaturity of the overlying adenomatous epithelium. The clinical significance of these findings is discussed.

Defining the Precursor Tissue of Ordinary Large Bowel Carcinoma: Implications for Cancer Prevention

To accomplish the purpose indicated in the title of this chapter, i.e., to define the precursor tissue of ordinary large bowel carcinoma, particular attention has been given to terminology. We have attempted to use simple and accurate terms, with the help of diagrams and illustrations, so that internists, surgeons, radiologists, and pathologists will have the same mental image and hence the ease of communication so needed for proper diagnosis and treatment in this field.

Coexisting lobular neoplasia and carcinoma of the breast

In a review of 3040 cases of carcinoma of the breast of all types in the files of the Laboratory of Surgical Pathology at Columbia for the years 1960 to 1980, 267 cases were found in which the lobular neoplasia lesion coexisted with one of the usual forms of breast carcinoma. These patients had a separate and distinct, and of course malignant, clinicopathologic entity which is distinguished from benign lobular neoplasia occurring alone. Comparing these findings in lobular neoplasia coexisting with one of the usual forms of carcinoma with our findings in lobular neoplasia occurring alone, it was found that the patients with the latter lesion were younger. Three of the nine microscopic features studied in both forms of lobular proliferation were considerably more frequent in lobular neoplasia coexisting with carcinoma: (1) loss of cohesion of the cells filling up the lobules; (2) macroacini; and (3) a maximal amount of lobular neoplasia. The great majority of the forms of carcinoma that were found coexisting with lobular, neoplasia were well differentiated, small cell, intraductal, and tubular, and metastasized less often than carcinomas usually do. Carcinoma developed in the second breast three times more frequently in patients with lobular neoplasia preceding or coexisting with unilateral carcinoma than it did in patients without lobular neoplasia.

Observations on the Adenoma as precursor to ordinary large bowel carcinoma

The very common hyperplastic polyp is not a neoplasm and is unrelated to either adenoma or carcinoma. Adenomas, which are only one-tenth as common, are true neoplams. Depending on size, and probably related to a sessile mode of growth, in adenomas one may readily observe intramucosal carcinoma and/or early invasive cancer. Although microscopic examination has been performed on many thousands of minute mucosal lesions (e.g., 5 mm or less), “early” cancer, defined as intramucosal carcinoma with or without microinvasion, does not seem to occur unassociated with adenoma. The apparent nonexistence of small foci of intramucosal carcinoma, with or without microinvasion, in normal mucosa, and their frequency in adenomas, are two fundamental pathologic facts. They seem to disprove the proposition that cancer calls ordinarily arise de novo from the normal cells of the crypt of Lieberkühn without the interposition of a stage in the neoplastic process that we recognize as adenoma.

Lysozyme content of granulation tissue.

The highest lysozyme concentrations in the mammalian body occur in tears and in the mucosa of the antrum, pllorus, and duodenu1n. 1 The origin of these high local concentrations presumably is epithelium, i.e., the tear glands and as yet undetermined cell types in the gastrointestinal mucosa. In contrast, the Iysozyme titer in mesodermal tissue is low; for example, serum averages 1 unit/ccl, and human leucocytes (from the buffy coat of normal blood) contain only 1.8 units per 5,000,000 cells2 However, human cartilage averages about 40 units/g, although this value is without doubt too low because of the difficulty in extracting this tissue. Normal human skin (including a considerable quantity of fibrous tissue) was found to have less than 1 unit/g. The finding of high lysozyme titres in granulation tissue was)therefore unexpected. The lysozyme assays on granulation tissue of man and dog are shown in the accompanying table. The assays were done by a viscosimetric method 4 on extracts prepared as previously described. 3 As a result of these observations it is now apparent that high lysozyme concentrations are associated with some mesodermal cell types as well as with epithelium. Therefore, further study is warranted with regard to the role of this tissue in the production of lysozyme in ulcerative alimentary disease. The deleterious effect of egg white lysozyme on the gastrointestinal mucosa 1 3 has been confirmed in our own 5 as well as other laboratories. 6 7 Furthermore, high stool titres in the absence of occult blood in the feces and with sigmoidoscopically non-ulcerated mucosa are frequently observed in chronic ulcerative colitis. These two considerations render less likely the possibility that granulation tissue is the source of the major fraction of the lysozyme titre in ulcerative alimentary disease.