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The lesions that appear during hepatocarcinogenesis can be separated into morphologically distinct entities, which have been arranged into sequences believed to represent stages in carcinogenesis. Similarly, the primary and transplantable hepato-cellular carcinomas (HCC) can be arranged into a sequence of stages believed to represent the progression toward the ultimate cancer cell. Separation of morphological entities has been most successful in rat liver. Ultrastructural studies differentiate between lesions derived from hepatocytes and those originating in other cellular components of the liver. They show that there is variability and divergence in the structure of cellular organelles in the early stages of carcinogenesis, that there is simplification of cellular structure and of organelles during the progression of HCC, and that qualitative changes specific for cancer cells do not exist. Toxic changes associated with the process of carcinogenesis are loss of stacks; wrapping of cisternae around mitochondria; dilation, denudation, and vesiculation of cisternae; increase of autophagy; depletion of glycogen, and enlargement of nuclei and nucleoli. Early changes are storage of glycogen and hyperplasia of smooth endoplasmic reticulum. Subsequent alterations are increased variability in the size, shape, and structure of mitochondria and in the structure of endoplasmic reticulum, including the appearance of fingerprints. A transient stage recognizable by storage of lipid may represent a degenerative process. Ultrastructural characteristics of basophilic cells such as abundance of free ribosomes and absence of glycogen and of smooth endoplasmic reticulum suggest that they may be a stage in the formation of HCC. Progression of HCC is associated with a decrease in the number and size of mitochondria, reduction of mitochondrial cristae, decrease in the number and complexity of microbodies, reduction of the tubulovesicular form of smooth reticulum, accumulation of free ribosomes, and increase of the granular component and condensation of the fibrillar component of nucleoli. Various types of nuclear inclusions reflect the increased mitotic rate of the neoplastic tissue. Changes of the cellular surface are believed to be associated with the ability of the cells to invade and metastasize. Future investigations will require the use of single doses of potent carcinogens, application of morphometric methods at the ultrastructural level, and acceptance of primates as models for human hepatocarcinogenesis.

The opossum prostate is highly complex cytologically, containing six different secretory cell types, each possessing a recognizably different secretory product. Secretory granules in cells of the first segment contain numerous particles 60 A in diameter of high electron density. They are transferred to the lumen by apocrine secretion. Both granules and lumina contain iron (Turnbull blue reaction). Segment two possesses three cell types. Type A cells have spherical secretory granules containing acid mucopolysaccharides. In type B cells, secretory granules are elongate and possess densely packed protein filaments, 80 A in diameter. Secretory granules in type C cells contain crystalloids of hexagonally packed cylinders with a spacing of 600 A. Third segment cells contain few organelles and have a broad irregular microvillar border. Most of the cytoplasm is filled with glycogen particles. The secretion is apocrine. The lumen contains lipoprotein lamellae, probably derived from shed microvilli, and also membrane bound glycogen globules originating from the cytoplasm. The contents are positive for acid, di- and tri-phosphatases and peroxidase. Catalase activity in the third segment is unusually high.

Ductuli efferentes in four examined genera of family Didelphidae are organized into highly convoluted tubules, located within a conical body adjacent to the vascular plexus supplying the testis. They have yellowish-green color in the adult Didelphis virginiana and grey pink color in other genera. The ductuli efferentes in all examined animals are lined by very low columnar cells, covered by microvilli or booth cilia and microvilli. Histochemical analysis reveals several types of cytoplasmic granules in the genera examined. A single sperical body about 1.5 μ in diameter is found in epithelial cells of the four eyed opossum (genus Philander); this body stains positively for RNA and non-histone protein, and appears granular under the electron microscope, without a limiting membrane. Abundant cytoplasmic bodies in the Virginia opossum show strong reactions for SH groups; these granules may be responsible for the green color of the ductuli in this species. Ultrastructural studies show that the morphology of membrane limited granules in the ductuli of the examined genera is characteristic for each genus. Abundant pinocytotic vacuoles in the apices of these cells and a strongly positive alkaline phosphatase reaction suggest a marked absorptive activity of epithelial cells.

The external prostate of male hedgehogs (Erinaceus europeus, Hemiechinus sp.) was studied at the beginning and at the end of the breeding seasons. Its tubular secretory units contain two types of epithelia, columnar and stratified. The columnar epithelium has abundant rough endoplasmic reticulum and forms secretory granules. The stratified epithelium undergoes cellular changes culminating in appearance of nuclear and cytoplasmic inclusions, nuclear pyknosis and desquamation of cells and nuclei into lumen. The nuclear inclusions contain protein and abundant silver-reducing substances. These inclusions may be derived from the residual protein of the nucleus.