Introduction

Chordomas are unusual tumors with seemingly unconventional traits. Most notably, they are malignant primary bone tumors but not sarcomas. They derive from embryologic cell remnants but predominantly affect late-middle-age adults, and they behave aggressively but grow slowly. Chordomas present with long-standing symptoms related to local mass effect or invasion. At the skull base, they often cause headaches and cranial neuropathies. In the spine, they incite low-grade pain and either weakness, numbness, constipation, or incontinence. Imaging interpreters play an important role in initial diagnosis, treatment response, and surveillance for recurrence.

Evolution: Overview

The majority of malignant bone tumors derive from the cells that compose the building blocks of bone: matrix (osteosarcoma), cartilage (chondrosarcoma), fibrous tissue (fibrosarcoma), neural crest cell (Ewing sarcoma), and hematopoietic marrow (lymphoma). Chordomas, however, arise from vestiges of the primitive notochord, an evolutionarily conserved structure regarded as one of the defining characteristics of the entire chordate phylum. Although several cellular, genetic, and epigenetic markers have been identified, the exact molecular pathogenesis of chordoma remains poorly understood. It is unclear what mutations, environmental insults, molecular signals, or other triggers transform benign notochord rests into malignant tumors later in life. It is also unclear whether malignant cells arise solely from these rests, or whether another pathway to malignancy exists. Regardless, an understanding of the notochord in the embryo can help explain two common attributes of well-differentiated chordoma: T2 high signal and midline location.

The notochord forms a flexible rod-like skeleton before regressing as the spinal column develops. The opposing pressures of its two internal cell layers provide critical mechanical support for the embryo. An outer layer of notochord cells maintains a basement membrane by secreting an extracellular matrix rich in glycogen and mucin. An inner layer of notochord cells contains large, fluid-filled, intra-cytoplasmic vacuoles that inflate the inner cells against the more constrictive basement membrane. While the exact molecular composition and function of these lysosome-related vacuoles remain unclear, they, along with the mucin and glycogen in the extracellular matrix, endow well-differentiated notochord remnants with their characteristic gelatinous T2 bright signal.

The notochord also serves as the principal longitudinal axis of the embryo, signaling the directional positioning (e.g., dorsal—ventral, left—right) and tissue patterning of adjacent cells. In adults, the notochord leaves cellular remnants along its canal, which traverses the nucleus pulposus and vertebral bodies. This central positioning explains why all notochord remnants establish themselves along the midline and why these lesions can emerge anywhere from Rathke pouch to the coccyx. Notochord remnants are never found outside the neural axis in the extremities or ribs.

The role and fate of the notochord in the embryo and later life is depicted in Fig. 28.1 .

This illustration depicts the role and fate of the notochord in the embryo and later life. Shortly after gastrulation the two layers of the notochord provide structural support for the early embryo (A). The notochord also releases signals to induce neurulation and tissue differentiation (B). In the early embryo, the notochord canal extends from the anterior pituitary gland and sella to the coccyx (C). Around 5 weeks, the notochord gradually regresses to segmented levels between developing somites or vertebral body precursors (D). However, if this regression is incomplete or if notochord-derived cells herniate away from their intervertebral levels, then ectopic notochord rests may be found within the developing vertebral bodies or adjacent structures (E). By the late embryonic stage, notochord-derived cells form the nucleus pulposus (F). In most people, these notochord-derived cells remain benign and clinically insignificant throughout life. In about one in one million persons (in the United States), or approximately 300 people annually, unknown factors transform these notochordal cells into chordoma tumors (G). ECM, Extracellular matrix.

Chordomas are closely monitored with imaging after initial therapy because they are locally aggressive tumors located next to many vital structures that frequently recur ( Fig. 28.2 ). Their unique location makes them difficult to completely resect or treat with radiation, and it increases the chance that even a small recurrence will be clinically devastating. Recurrences tend to develop along the margins of the treatment bed or as directly seeded metastases along the surgical tract.

Preoperative appearance of chordoma and postoperative progression of recurrent tumor. Preoperative sagittal T1 (A), axial T2 (B), axial T1 (C), axial T1 postcontrast (D), and sagittal T1 postcontrast (E) images demonstrate a large, T2 hyperintense, heterogeneously enhancing chordoma centered within the clivus. Postoperative axial and coronal T2 images (F and G) show residual unresectable T2 hyperintense chordoma surrounding the cavernous carotid artery, posterior to the clivus, and extending into the nasopharynx (arrows) . Axial and coronal T2 images 1 year (H and I) and 2 years (J and K) after initial resection clearly show gradual enlargement (arrows) .

Spectrum: Overview

Most chordomas display a few characteristic imaging traits: high T2 signal, midline location, aggressive bone changes, and dual bone/soft tissue components. If the imaging interpreter is fortunate enough to encounter the most common appearance of chordoma, recognizing these cardinal clues will lead to a straightforward diagnosis.

In clinical practice, chordomas do not necessarily follow the rules or “read the textbook.” Real-world tumors do not always have high T2 signal; rather, many express intermediate T2 signal. Several factors can explain this signal variability. First, the amount of fluid associated with the vacuoles and proteinaceous extracellular matrix differs with each tumor. Second, tumors grow slowly reaching medium to large sizes before they are discovered, and this allows time to evolve, bleed, or internally degenerate. Third, the pathologic subtype of the tumor can influence its imaging properties.