Gordon I. Kaye

Malignant soft tissue tumors of probable histiocytic origin (malignant fibrous histiocytomas): General considerations and electron microscopic and tissue culture studies

Correlated light and electron microscopic study of four fibrous histiocytomas of proven malignancy has confirmed the presence of histiocyte‐like and fibroblast‐like cells in this tumor. In addition, an undifferentiated cell type, giant cells, xanthomatous cells, and rare cells with morphological characteristics intermediate between those of histiocytes and fibroblasts were seen. “Nuclear body” type inclusions were commonly present in both principal cell types in all four cases, as were the somewhat less common cytoplasmic inclusion bodies. Electron microscopic study of a tissue culture of one of these tumors demonstrated only fibroblast‐like, histiocyte‐like, and xanthomatous cells. The possibility is suggested that both principal cell types in this tumor may derive from the same undifferentiated stem cell.

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.

Synovial sarcoma Electron microscopic study of a typical case

A case of histologically typical synovial sarcoma has been studied by means of electron microscopy. The more important findings are: 1. the confirmation at the ultrastructural level of the biphasic pattern of the tumor; 2. the presence of a basal lamina between the “epithelial” and the “stromal” part of the tumor; 3. the presence of specialized junctions in the form of desmosomes or maculae adhaerentes between neoplastic cells; these are mostly seen in the epithelial part of the tumor but are not infrequent among stromal cells, and 4. the existence in the extracellular component of the neoplasm of mostly amorphous material, microfibrils, and thin fibrils without periodicity. Only a few mature collagen fibers are seen.

Recent studies on the nature and function of the corneal endothelial barrier

Abstract The development of new perfusion procedures, the development of new colloidal tracer techniques and the application of the concept of pump-leak to the corneal endothelium has led us to reinvestigate several aspects of the barrier function of the corneal endothelium. A barrier to free diffusion of fluids across the endothelium can be demonstrated in corneas perfused in vitro under a variety of conditions. This barrier can be reduced or abolished by perfusion with a Ca 2+ -free medium, eye-bank type storage, and perfusion at increased perfusion (intraocular) pressures. In the first instance a clear morphological basis for the loss of barrier function, the disintegration of the endothelial junctional complex, is easily demonstrable. Both the physiological and morphological effects of Ca 2+ -free perfusion are reversible within limits. In the other two instances of reduced barrier function no clear morphological correlate has yet been demonstrated. In fact, the apical membrane, apical junction and apical microfilament network appear to be particularly resistant to the damage caused by storage of corneas at 4°C. The application of new colloidal tracer techniques involving horseradish peroxidase and lanthanum nitrate to the study of the endothelial junction have shown that this is not a tight junction and that particles as larga as 3 nm can penetrate the apical junctional zone in rabbit and monkey. The present report reviews and summarizes the work of our laboratory during the past several years and indicates some of the still unanswered questions concerning the endothelial barrier. In addition, we suggest some pathways of investigation which we believe would be particularly fruitful at this time.

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.

Primary malignant melanocytic tumors of the sympathetic ganglia, with an ultrastructural study of one

Three cases of melanocytic tumors arising in the sympathetic chain were studied. A metastasis from one of them was studied with electron microscopy. Both light and electron microscopy demonstrated the presence in these tumors of true melanogenesis and autophagic activity in melanocytes as well as phagocytosis of mature melanin by associated histiocytes. Review of the embryology, biochemistry and in vitro culture of sympathetic nervous tissue showed a close relationship between it and pigmented cells in other parts of the body which are also derived from neural crest. These findings support the clinical and morphological conclusion that these rare pigmented tumors are true melanocytic tumors originating from the sympathetic chain. The malignant potential of these tumors is emphasized by the fact that the two patients who survived initial surgery later died of metastatic disease.

Electron Microscopy: Sodium Localization in Normal and Ouabain-Treated Transporting Cells

When rabbit corneas are fixed in an osmic acid fixativeto which potassium pyroantimonate has been added, an electron-opaque precipitate of sodiium pyroantimonate is localized along the cellular side of the lateral plasmla membrane of the endothelial cells. This heavy precipitate represents areas of high Na+ concentration and may represent the site of a saturated, high-affinity Na+ carrier. Significantly heavier precipitate occurs at the same site when ouabain is injected into the aqueous humor prior to fixation of the cornea.

Epithelioid sarcoma. A light and electron microscopic study suggesting a synovial origin

Two cases of “epithelioid sarcoma” were studied by light and electron microscopy. In both cases, the tumor consisted of a collagen‐rich fibrous stroma with nests of large epithelial‐like cells with acidophilic cytoplasm, giving the neoplastic tissue a biphasic pattern. The ultrastructural study showed that the tumor cells were of three types: “clear” and “dark” cells (recalling those of the synovium and synovial sarcoma) with distorted nuclei and abundant cytoplasm, and a less common, more immature cell. The histologic and ultrastructural features of the neoplastic cells, as well as those of the ground substance, indicate that the tumor is neither of chrondroid nor of histiocytic origin. The cells of the epithelioid islands are similar to the stromal component of synovial sarcoma. It is suggested that epithelioid sarcoma may be a variant of this tumor.