During the embryonal stage, two types of ossification mechanism are involved. In the endochondral process, ossification starts on the framework of prefabricated chondroid tissue. This type of ossification also forms the basis for bone elongation and callus formation. The osteogenic and chondrogenic processes are so intricately connected that both osteoid and chondroid components are often seen in osteoid forming and chondroid tumors, benign or malignant.

The normal bone homeostasis features constant modeling and remodeling which is a result of concerted efforts of the three key elements (osteogenic progenitors, osteoclasts, and sinusoids) of the hematopoietic microenvironment [1–3]. Benign bone-forming tissue (also chondroid tissue) respects the sinusoid stroma as well as the adjacent benign trabeculae. Malignant osteoid (also chondroid) tissue gains bone matrix absorbing capability which is normally the domain of osteoclasts [4, 5]. This gain of function gives rise to the permeative growth pattern characteristic of malignant osteosarcoma and chondrosarcoma. In permeative growth pattern, the malignant matrix-forming tissue fills the bone marrow cavity and occasionally entraps and destroys preexisting benign trabeculae.

Malignant osteoid is defined as osteoid tissue that is rimmed by stromal cells and/or layers of osteoblasts [6] (Fig. 3.1). When chondroid component is present, the malignant nature of the osteoid can be revealed by the altered interaction pattern. Malignant osteoid is randomly distributed in chondroid lobules (Fig. 3.2). This is in contrast to the peripheral arrangement evidenced in benign tissue. This important feature can be very useful in the differentiation of chondrosarcoma and chondroblastic osteosarcoma. In the former, the reactive (benign) bone formation is in the form of attenuated semicircles which surround the malignant chondroid tissue (Fig. 3.3). In the latter, the chondroid lobules are in direct contact with sheets of spindle cells which produce lacelike osteoid. The lacelike osteoid tissue is scattered throughout the chondroid lobule.