[Footnote 48: _Untersuchungen über Lymphdrüsen-Tuberkulose_, 1871.] Although the typical tubercle is thus constituted, the structural features depend somewhat upon its age. It is generally admitted that the freshest tubercles, as found in the external coat of the smaller arteries of the pia mater, are composed of little else than a circumscribed accumulation of small, round cells, without a distinct reticulum. The giant-cells, the epithelioid cells, and the well-characterized reticulum appear as the tubercle increases in age. It is thought probable that the giant-cells represent the agglomeration of the small, round cells in pre-existing cavities, lymphatics, blood-vessels, or secretory canals. The epithelioid cells in like {96} manner are considered to result from the enlargement or fusion of the smaller cells, while the reticulum represents either a secretion from, or a transformation of, the cellular elements of which the tubercle is composed. The subsequent history of the tubercle is dependent upon its metamorphoses. These are known as cheesy degeneration, calcification, and fibrous transformation. The absence of blood-vessels, already stated, and the abundantly cellular nature of the growth, with the possible action of micro-organisms, result in a tendency to the early death of the cells and a necrosis of the tubercle. This is the cheesy degeneration, and is regarded as a form of coagulative necrosis, which begins at the centre, advances toward the periphery, and results in the transformation of the gray into a yellow tubercle. This termination in cheesy degeneration likewise affects inflammatory products surrounding the tubercle, and even relatively normal tissues in which numerous tubercles may lie. This cheesy material either softens or becomes infiltrated with lime salts, calcified. The softening of the tubercle results in the formation of a material capable of removal as a discharge from the surfaces of the body or by absorption through the lymphatics and blood-vessels. In the former event ulcers arise upon, and cavities communicate with, the surfaces of the body opening externally. The cheesy material frequently becomes calcified, thus remaining as a comparatively inert mass. The earthy salts may be diffused throughout a uniformly cheesy basis, or they may be deposited in a partially softened, cheesy menstruum, when a mortar-like material results. The tubercle becomes fibrous with the diminution in the number of its cells and the increase in the thickness of the reticulum, with the transformation of the latter into a homogeneous hyaline substance. The cornified, horn-like tubercle is one whose size is diminished from the shrinkage of its cells into glistening flakes, without an evident associated cheesy or fatty degeneration.