Epithelial and mesenchymal tissues

A malignant neoplasm that contains elements of carcinoma and sarcoma so extensively intermixed as to indicate neoplasia of epithelial and mesenchymal tissue. 

Vainio, S., Karavanova, I., Jowett, A., Thesleff, I. 1993. Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell 75, 45-58. 

Peters, K.G., Werner, S., Chen, G. and Williams, L.T. (1992) Two FGF receptor genes are differentially expressed in epithelial and mesenchymal tissues during limb formation and organogenesis in the mouse. Development 114 233-243. 

Interactions between epithelial and mesenchymal tissues constitute a central mechanism regulating the development of most embryonic organs. Studies on the nature of such interactions require the separation of the interacting tissues from each other and the follow-up of their advancing development in various types of recombined explants. The tissues can be either transplanted and their development followed in vivo or cultured as explants in vitro. 

Mesothelial tumours are pleomorphic. There is much diversity from tumour to tumour, and in different areas of individual tumours and their metas-tases, because both epithelial and connective tissue (mesenchymal) elements are usually present (Suzuki et al. 1976). Four distinct histological patterns are recognised (Table 45). 

Fig. 1. Microenvironmental factors and the invasive process. The primary tumor is a heterogeneous mix of cell populations, further diversified by gradients of blood-borne nutrients, oxygen, and drugs. Hypoxia contributes to treatment resistance, upregulates pro-angiogenic and pro-invasive molecules, and helps to maintain cancer stem-like cell populations. Tumor cells may undergo epithelial-to-mesenchymal transition (EMT), enter blood vessels, and disseminate to distant sites where they extravasate, invade, and colonize the tissues. Once established, the cells may undergo the reverse program (mesen-chymal-to-epithelial transition, MET) and proliferate to form metastases, the major reason for treatment failure.

After epithelialization and the formation of the S-shaped tubule, there is still much that needs to occur in order for the nephron to function. Cells destined to form the podocyte layer of the glomerulus flatten out and lose some of the markers that characterized their earlier transition to epithelium, including c-MYC, HOX-c9, LFB-1 and LFB-3, while keeping a high level of WT1. Expression of more classical mesenchymal markers such as vimentin takes place, but the cells also keep a number of epithelial proteins such as desmosomal components. The result is a tissue that is more organized than most connective tissue but leakier than most epithelium, the optimum design for urine filtration. 

Isolated animal cells in tissue culture, no matter how highly differentiated, tend to revert quickly to one of three basic types known as epitheliocytes, mechanocytes, and amebocytes. Epitheliocytes are closely adherent cells derived from epithelial tissues and thought to be related in their origins to the two surface layers of the embryonic blastula. Mechanocytes, often called fibroblasts or fibrocytes, are derived from muscle, supporting, or connective tissue. Like the amebocytes, they arise from embryonic mesenchymal tissue cells that have migrated inward from the lower side of the blastula (Chapter 32). Neurons, neuroglia, and lymphocytes are additional distinct cell types. 

The enamel of mammalian teeth is much more heavily mineralised than bone, which makes it much harder. In addition, it does not contain collagen, although in its final mature state it does contain small amounts of specialised matrix proteins. Early tooth development is a classical illustration of the interaction between two tissue types (epithelial cells and mesenchymal cells ), whereby a number of signaling molecules are involved in orchestrating reciprocal interactions between the two types of tissue. 

Patterns of mesenchymal differentiation in cutaneous neoplasms are no less diverse than those encountered in deeper soft tissues. Fibroblastic or myofibroblastic, fibrohistiocytic, muscular, neural, epithelial, and vascular lesions may be seen as primary tumors in the dermis and subcutis. As is also true in deep soft tissues, the histologic evaluation of those neoplasms may fail to provide an unequivocal diagnosis. Hence immunophenotyping has proven to be valuable in this context. The diagnostic separation of various spindle-cell, polygonal-cell, epithelioid-cell, and small-cell lesions of the skin is assisted in many settings by immunohistochemical analysis. 

Vimentin, an intermediate filament, is expressed in mesenchymal tissues, normal proliferative endometrial epithelial cells, and in the majority of endometrial carcinomas.jj g coexpression of vimentin and low molecular weight cytokeratin can aid in the differential diagnosis of an endocervical versus an endometrial adenocarcinoma. 

---