Fig. 46.1
Physaliferous cells with multivacuolation swimming in mucin-rich matrix
The cells contain relatively uniform, small, oval, eccentric nuclei with smooth nuclear contours and evenly distributed chromatin. Although rare, nuclear pleomorphism characterized by anisonucleosis and hyperchomasia might be associated with infrequent mitoses [1, 5, 6, 10–12]. In addition, typical chordomas contain areas of coagulation necrosis, recent and old hemorrhage, and entrapped bone trabeculae [1, 12]. Likewise, vascular invasion is rare and tumor matrix varies in appearance [12].
Chondroid chordoma is a variant of chordoma first identified by Heffelfinger et al. that demonstrates better diagnosis than the conventional chordomas [3, 5, 6, 10, 11]. This variant is more commonly seen in the skull base [1, 10, 11]. In chondroid chordomas, although varying in percentage, hyaline or myxoid cartilage resembling stroma wraps neoplastic cells in lacunae unlike classic chordomas (Fig. 46.2). It is widely accepted that chondroid chordomas may be histologically indistinguishable from well-differentiated chondrosarcoma when a classic chordomatous component is not present [5, 7, 10, 11].
Fig. 46.2
Physaliferous cells floating in mucin-rich chondroid matrix
Chordoma associated with a high-grade sarcoma is called “dedifferentiated” chordoma or sarcomatoid chordoma [3, 5]. Therefore, they are biphasic tumors composed of both typical chordoma and a pleomorphic sarcomatous component [5, 10]. Dedifferentiated chordoma is a high-grade subtype of chordoma, often results in distant metastasis, and most patients have a poorer prognosis. They account for less than 5 % of all chordomas.
Histologically, the mucoid matrix in nonskull base chordomas was more abundant than in skull base chordomas. Conversely, skull base chordomas presented with phagocytosis (hemosiderin deposits) more frequently compared with nonskull base chordomas [3].
Increased patient age, clinical status, and nuclear pleomorphism are found to be closely related to the proliferative ability of conventional chordoma particularly those of originating from skull base [3, 12].
46.3 Immunohistochemical Findings
Chordoma (Fig. 46.3a) and chondroid chordoma (Fig. 46.3b) are immunopositive for epithelial markers including cytokeratin AE1/AE3 and epithelial membrane antigen (EMA) (Fig. 46.4a, b). The majority of conventional (Fig. 46.5a) and chondroid chordomas (Fig. 46.5b) are positive for S-100 protein [5, 7, 10, 11, 13]. On the contrary, dedifferentiated chordomas lack reactivity for epithelial markers [10].
Fig. 46.3
(a) Multivacuolated “physaliferous” cells of chordoma with strong cytoplasmic reactivity for cytokeratin (cytokeratin). (b) “Physaliferous” cells with strong cytoplasmic reactivity for cytokeratin (cytokeratin)
Fig. 46.4
(a) Chordoma cell membranes reacting with EMA (EMA). (b) Bubbles bearing tumor cell membranes reacting with EMA in chondroid chordoma (EMA)
Fig. 46.5
(a) Multivacuolated “physaliferous” cells of chordoma with strong nuclear and cytoplasmic reactivity for S-100 (S-100). (b) Multivacuolated “physaliferous” cells with strong nuclear and cytoplasmic reactivity for S-100 (S-100)
Genuine notochordal origin is supported by their expression of brachyury and CD 24, which may prove to be useful diagnostic markers [6, 13]. Brachyury is the transcription factor protein product of a T-box gene whose function is to regulate formation of the mesoderm and notochord in humans. Specifically, immunohistochemical expression of brachyury is highly sensitive and specific for chordomas. Interestingly, brachyury is apt be lost in histologically and clinically more aggressive chordomas. As another example, less than 60 % chordomas are positive for CD24, polyclonal CEA, and GFAP [13].
MIB-1 labeling and E-cadherin were correlated with disease-free survival and recurrence in pediatric skull base chordomas [9, 14]. MIB-1 labeling index (LI) of nonskull base chordomas was higher than that of skull base chordomas (Fig. 46.6a, b). Being an independent factor, increased patient age is directly proportional with MIB-1 LI [3, 15]. In the same way, immunohistochemical staining of p53 protein is associated with a worse prognosis and decreased survival in patients with chordoma [9, 16] (Fig. 46.7).
