Chordomas: A Personal Perspective

Chordoma, an oddity for years, remains a baffling and defiant tumor. Despite the surge in studies and the advancements of imaging and techniques, chordoma is still plagued by unpredictability and misconceptions. The opinions and methods regarding treatment today are still diversified, conflicting, and subject to advocacy and promotion. Unfortunately, this leaves the patient anxious, confused, torn, and stricken not only with their grave disease but also with the outcome of their presumed “choice.” Owing to their rarity, studies and experience in chordoma are very limited. The landmark article of Heffelfinger et al lists only 55 patients of clival chordomas over a 60-year period drawn to their world-referral center. ² It became clear to me (O. A.) 30 years ago that long-term follow-up is the key to determine patient outcome and the effectiveness of a proposed treatment. I have been privileged over the last 30 years of managing nearly 300 patients with chordoma with perseverance in obtaining follow-up. I kept abreast with the literature and the new studies and thoughtfully analyzed and reported this experience, with an aim of defining the disease, chordoma, that is enveloped by old and new myths. Although this volume contains an encyclopedic coverage of chordoma, we appreciate the opportunity to encapsulate our study and experience in this chapter.

24.2 Only Chordoma Is Chordoma

Because of the clinical and radiologic features, location, means of treatment, and sometimes even the histologically masquerading appearance, skull base chordoma is confused with a low-grade chondrosarcoma and to date the two are frequently lumped together. However, they are totally different disease entities with disparate outcome. I am happy that this book is dedicated solely to chordomas. Hence, I believe that chordoma diagnosis should only be accepted with positive immunohistochemical markers demonstrating its epithelial origin (cytokeratin, EMA, and brachyury). ³ Once there is positive immunohistochemical staining, the histologic subtype of chondroid chordoma does not have any better prognosis ⁴ ( ▶ Fig. 24.1).

Fig. 24.1 The variant chondroid chordoma (a) can masquerade histologically chondrosarcoma (b) and only immunohistochemical stain for epithelial origin confirms the diagnosis: (c) positive cytokeratin in chordoma and (d) negative in chondrosarcoma.

24.3 Chordoma Is Not a Benign Disease

Chordoma is frequently described as a benign, slow-growing disease, totally contradicting its natural history and outcome. This deceptive impression might lead to a course of observation in small, incidental, asymptomatic lesions that I believe should be radically excised like any other malignancy at the time of their detection ( ▶ Fig. 24.2). Chordoma metastasizes, ⁵^,⁶ spreads through the cerebrospinal fluid (CSF), and surgically implants ⁷ ( ▶ Fig. 24.3, ▶ Fig. 24.4), mandating early treatment to limit the time for metastasis, extradural approaches to avoid CSF spread, and a surgical field precaution to prevent implantation. In other words, it should be handled as a malignant disease.

Fig. 24.2 A small, incidental lesion at the upper clivus because of the suspicion of chordoma due to the erosion of the posterior cortex treatment and resection is indicated without a period of observation. Preoperative sagittal CT (a) and MRI (b) and postoperative (c) sagittal CT scan following anterior clivectomy showing the lesion and its complete resection.

Fig. 24.3 Advanced case of chordoma with neighboring invasion, distal metastasis in the calvarium and ribs, and surgical implantation in the nasal cavity. (a) Sagittal and (b) axial MRI showing neighboring invasion; (c) axial MRI showing surgical implantation in the nasal cavity; (d) axial CT scan of the chest showing metastasis to the ribs; and (e) axial MRI showing calvarial metastasis.

Fig. 24.4 Coronal MRI showing CSF spread of tumor into the fourth ventricle and upper cervical spinal canal.

24.4 Tumor Progression in Chordoma

It has always been postulated that chordoma originates from remnants of the notochord ⁸ ( ▶ Fig. 24.5). However, chordoma is frequently observed to take a different growth pattern. Tumor biology and genetic studies have been scarce, but there has been a surge in interest in the subject. However, the simple question of what makes a benign remnant of the notochord accelerate in aggressiveness is easily answered: Chordoma is a fine example of the oncologic doctrine of tumor progression that tumors become more aggressive as they accumulate added genetic aberrations. ⁹ It has been demonstrated that chordoma that has a normal karyotype has a better prognosis and disease-free survival. ¹⁰ It has further been demonstrated that chordoma is exposed to ever-changing genetic aberrations that involve many chromosomes and this chaotic instability is associated with increased clinical recurrence within a shorter period of time with a faster growth ( ▶ Fig. 24.6). Furthermore, the end destiny of this progression can be dedifferentiation to the highly malignant sarcoma. These findings lead again to designing initial management that eliminates the original tumor cells so that they will not be allowed to go through the progression with recurrences of a more aggressive tumor. Like other highly malignant tumors with continuous added mutations, finding an effective targeted medical therapy may be elusive.

Fig. 24.5 Sagittal (a) CT and (b) MRI showing the origin of the chordoma from the spheno-occipital synchondrosis and (c) histology slide showing transition from the normal synchondrosis to tumor cells.

Fig. 24.6 A case example where chordoma demonstrates the oncologic “tumor progression” where accumulated genetic aberrations on recurrences lead to more malignant histology and aggressive course. (a) Recurrent chordoma. Pathology-chondroid chordoma. (b) Chondroid chordoma. Moderately immunoreactive for EMA and strongly immunoreactive for cytokeratin. Ki-67 -8%. (c) Chordoma with prominent cytologic atypia and scattered mitotic figures. Ki67- 25%.

24.5 Once It Recurs, It Never Leaves

Chordoma remains with a very high recurrence rate despite the best management options. Hence, it refutes much of the suggested management ¹¹^,¹²^,¹³^,¹⁴ ( ▶ Fig. 24.7). The management of chordoma, once it occurs, is palliative and doomed to repeated interventions and continuous progression associated with additional deficits, risks, and complications, both from the tumor and the repeated interventions. Hence, chordoma should be treated at the onset with the most radical approach to aim for longer disease-free survival.

Fig. 24.7 A patient treated for his original tumor (a) with partial resection and radiation; he recurred in 2 years (b) where he was treated again surgically. He then recurred another 2 years later (c) when he was treated with radiosurgery (d). He recurred again in 2 years (e) and was retreated with a cranial approach only to have an uncontrolled recurrence 2 years later (f, g) leading to fatality.