Till the discovery of Villemin, the recognition of the tubercle was {95} essentially based upon its anatomical characteristics. Previous to the studies of Reinhardt and Virchow these related to appearances, which were attributed to a deposition of material, scrofulous or tuberculous, from the blood or lymph. The idea was eventually maintained that this material formed the basis of a growth or new formation, and Virchow showed that the tubercle was composed of a tissue, of cells and intercellular substance, growing within and from pre-existing tissues. He classified the tubercles among the tumors as circumscribed new formations whose structure resembled that of granulation-tissue. The specific tubercle was, at the outset, minute, smaller than a millet-seed, submiliary, although indefinite numbers of these minute tubercles might be grouped together and form closely massed aggregations. From this agglomeration of single tubercles, and their frequent association with inflammatory products, both of which were prone to early death and transformation into a cheese-like mass, the extensive tubercular infiltrations of organs arose. The latter were regarded as a frequent cause of the wasting disease phthisis, which was either pulmonary, intestinal, or renal according as the lungs, intestine and mesenteric glands, or kidneys were the predominant seat of the tubercular growth. The histological features of the tubercle were further investigated by Wagner,[47] who described the resemblances and differences of the structure of the tubercle and the lymphatic gland. Schüppel[48] soon after published his monograph, essentially confirming the statements of Wagner. According to these observers, the typical tubercle, as found in lymphatic glands, presents essentially the same peculiarities of structure when seen elsewhere in the body. This structure consists of a non-vascularized network of fibres, in the meshes of which cells are imbedded. The fibrous network resembles the reticulum of a lymphatic gland, and nuclei are often found at those points where the fibres are united. This appearance has suggested that the network is formed of branching and anastomosing cells. Within the meshes are three sorts of cells--viz. giant-cells, epithelioid (endothelioid) cells, and small, round, indifferent cells. One or several giant-cells, each with its abundant nuclei, lie near the centre of the tubercle or are diffused throughout the same. These are usually immediately surrounded by the large epithelioid cells, with one or more nuclei, which are often so numerous as to compose the greater part of the tubercle. The indifferent cells, resembling lymph-corpuscles, occur singly or in groups, distributed throughout the tubercle more abundantly at the periphery, between the cells previously described, and with them completely fill the spaces of the fibrous network. [Footnote 47: "Das tuberkelähnliche Lymphadenom," _Archiv der Heilkunde_, 1870, xi. 6; xii. 1.]