Distinguishing benign notochordal cell tumors from vertebral chordoma

Six lesions consistent with BNCT have been documented previously by others [1, 2, 9‐11]. Darby and coauthors [1] first described a case in 1999, which was surgically excised. A 39-year-old man who complained of a 7-week history of persistent low back pain was found to have an intraosseous lesion replacing almost the entire fifth lumbar vertebra. Radiographs and scintigraphy appeared normal. The lesion was well visualized by MRI, but showed only mild sclerosis on a CT scan. Histological findings were identical to those of our cases presented here. They were not typical for chordoma; however, the authors suspected that the lesion might be an intraosseous chordoma rather than a giant notochordal rest. Mirra and Brien [2] reported 2 cases under the name of giant notochordal hamartoma of intraosseous origin. A 42-year-old woman complained of low back pain after falling down the stairs and was found to have an intraosseous lesion involving almost the entire sixth thoracic vertebral body on MRI. The other case was a 41-year-old man who had suffered from intermittent stiffness and mild pain in the neck. MR images demonstrated an intraosseous lesion involving about 98% of the fifth cervical vertebral body. Neither of the lesions was visible on radiographs. CT scans revealed osteosclerosis in the center of the affected vertebral bodies. The lesions showed low signal intensity on T1-weighted MR images and intermediate to high signal intensity on T2-weighted images and no extraosseous disease. No abnormal uptake was detected on bone scintigrams in either case. The patients did not undergo a surgical procedure after the biopsies. The follow-up examinations after 10 years and 38 months respectively demonstrated no progressive disease and indicated their benign nature. Kyriakos et al. [9] reported a case that involved the fourth lumbar vertebra. An 11-year-old boy with Tourette’s syndrome had a 2.5-year history of repeated low back pain after a playground injury. Radiographs, CT scan, and single photon emission computed tomographic bone scan (SPECT) were normal. MRI revealed an intraosseous lesion with low T1- and high T2-weighted signal intensities within the fourth lumbar vertebral body. Cell block material obtained by a fine needle aspiration biopsy led to the diagnosis of chordoma, and the patient underwent L4 vertebrectomy. On subsequent evaluation, they concluded that the lesion was likely a giant notochordal rest rather than chordoma. The most recently documented case reported by Chauvel et al. [10] was an intraosseous lesion in the fifth lumbar vertebral body. The patient was a 45-year-old woman who had complained of low back pain for 2 years. Radiographs and bone scan were normal; however, CT scan revealed fine sclerosis in the L5 vertebra. MRI demonstrated an intraosseous lesion with homogenous low signal on T1-weighted image and high on T2-weighted image. The patient underwent L5 vertebrectomy because the lesion was histologically diagnosed as a chordoma on biopsy. The histological features from the L5 vertebra were similar to those of previously documented cases reported by Darby et al. [1], Mirra and Brien [2], and Kyriakos et al. [9]. A further case was illustrated in the textbook by Dorfman and Czerniak [11]. The lesion entirely occupied the third lumbar vertebra.

Recent studies have discovered unique benign notochordal cell lesions within axial bone that may be precursors of chordoma [3‐6, 12]. The new term “benign notochordal cell tumor” was proposed for these lesions [4, 5]. Careful autopsy examination can identify the lesions in approximately 20% of adult cadavers [4, 5]. They are usually tiny or small and found most frequently in both ends of the axial skeleton followed by the mobile spine. Their histological features are different from those of classic chordoma or notochordal vestiges in fetal intervertebral disks (Table 3). BNCTs are characterized histologically by intraosseous sheets of adipocyte-like vacuolated chordoid cells intermingled with less vacuolated eosinophilic cells of various degrees. The lesions were not lobulated. Some colloid-like material containing cystic spaces are seen in the lesions; however, the lesions lack any myxoid background. The nuclei are usually bland, but sometimes appear mildly atypical. No mitotic figures are recognized. The affected bone trabeculae are sclerotic because of appositional or reactive new bone formation. These histological features are completely identical to those of the lesions reported by Darby et al. [1], Mirra and Brien [2], Kyriakos et al. [9], Chauvel et al. [10], and Dorfman and Czerniak [11]. These reported cases are considered by us to represent BNCTs that grew and replaced almost the entire vertebrae.

Benign notochordal cell tumors are usually asymptomatic or indolent. Most lesions are overlooked, even at autopsy, because of their anatomical location or size. Only one such lesion had been documented with a name of ecchordosis physaliphora vertebralis in 1982 [13]. Enlarged BNCTs may be detected on CT or MR images, or rarely by conventional radiography. The imaging findings of our cases are somewhat variable, but distinctive in the absence of trabecular destruction on CT or of a soft tissue mass on either CT or MR images (Table 3). Gadolinium enhancement was absent in the 3 patients in whom it was administered. Radiographs may reveal ill-defined, vague sclerosis in the vertebral body and occasionally show diffuse sclerosis presenting as an ivory vertebra (Fig. 3). Often the lesions are invisible on radiographs. CT scans may reveal unequivocal sclerosis, which is much more obvious than on radiographs. No bone destruction or cortical disruption is recognized. T1-weighted MR images reveal relatively well-demarcated intraosseous lesions with homogeneous low signal intensity. T2-weighted MR images show homogeneous high signal intensity. Gadolinium-DTPA enhanced T1-weighted MR images do not show enhancement. Bone scintigraphy did not show any abnormal uptake.

Diagnosis of the cases presented was based upon biopsy or preoperative imaging; the diagnosis was chordoma in 5 cases and osteonecrosis in 2. Hence, 5 patients underwent vertebrectomy, wide resection, or curettage. All patients but 1 are well without recurrent or metastatic disease. Two patients who underwent only biopsy had no progressive disease, as judged by radiography, CT, or MR images, for 13 months and 44 months respectively. As described by Mirra and Brien, the follow-up information was consistent with the benign nature of the tumors.

The terminology of the lesions is controversial. Dorfman and Czerniak [11], Kyriakos et al. [9] and Chauvel and coauthors [10] used the term giant notochordal rest. Mirra and Brien [2] proposed the term giant notochordal hamartoma of intraosseous origin. In addition, the International Skeletal Society has used the term benign chordoma on the brochure of the Pathology Refresher Course since 2003. However, we prefer the term “BNCT” to the others. BNCTs show histological and immunohistochemical features that are different from those of notochordal vestiges in fetal intervertebral disks. BNCTs lack any myxoid background and show positive immunoreactivity for cytokeratin 18 although notochordal vestiges in the fetal intervertebral disks are associated with myxoid matrix and are negative for cytokeratin 18. Notochordal vestiges are often found in the intervertebral disks of neonates and finally disappear by the age of 1 to 3 years. In our personal autopsy experience, we have never seen any notochordal tissue in the vertebral bodies in fetuses and babies who had notochordal vestiges in their intervertebral disks. In contrast, BNCTs are found in 20% of the axial skeleton dissected from adult cadavers. Therefore, BNCTs are considered to develop after birth. The term of hamartoma is not proper for the lesions, as mentioned by Kyriakos et al. [9] and one of the present authors [3]. The term of benign chordoma is oxymoronic because “chordoma” has been used to describe a malignant notochordal cell tumor [14].

In 15 clinically identified BNCTs, including our cases and those reported by others, 6 tumors were found in the lumbar spine, 5 in the cervical spine, 2 in the sacrum, and 1 each in the thoracic spine and coccyx. This anatomical distribution is different from that found at autopsy [2]. We believe the reason for this discrepancy is that the cervical and lumbar regions often are examined with MRI for neck pain and low back pain. Lesions in the sacrum and coccyx may be overlooked because they are less frequently imaged.

The most important disease that should be distinguished from BNCT is chordoma. Microscopically, chordoma is composed of cords or strands of atypical chordoid cells with a myxoid matrix of various degrees [11, 15, 16]. Chordomas are associated with a large soft tissue component. However, differential diagnosis may be difficult because cellular atypia of BNCT and chordoma may overlap. They also share the same immunohistochemical profile [3]. Imaging is critical in separating the benign lesion from the chordoma. Chordomas are osteolytic tumors. In contrast, BNCTs may show osteosclerotic reaction and do not exhibit osteolytic change. Chordomas are not intracompartmental lesions and are associated with a soft tissue mass. In those cases with histological overlap, with our present understanding of these diseases, we would suggest that the absence of a soft tissue mass should favor a BNCT and the presence of a soft tissue mass should indicate a chordoma.

Biopsy specimens of BNCTs may be easily mistaken for fatty marrow because of their morphological similarity to that tissue. Indeed, 2 lesions among our cases were overlooked as normal fat marrow on biopsy sections. Careful observation can distinguish BNCTs from fatty marrow. Furthermore, immunohistochemical study can help to distinguish BNCTs from fatty marrow. BNCTs stain positive for epithelial markers whereas fat cells do not (Fig. 5). Differential diagnosis also includes metastatic carcinoma, particularly originating from clear cell carcinoma of the kidney. Metastatic clear cell carcinoma usually is osteolytic on radiographs and CT scans. Gadolinium-DTPA enhanced T1-weighted MR images have increased signal intensity. Histologically, clear cell carcinoma has an alveolar pattern and vascular fibrous septa. Clear cell carcinoma rarely exhibits positive immunoreaction for S-100 protein [17].

Large BNCTs may be found during routine clinical examination. They may have the potential of malignant transformation to chordoma; however, the transformation, as we know from the collected cases, is a rare happening [6]. We, however, are not aware of any cases of what we term BNCT growing beyond the confines of bone and displaying features of chordoma, and therefore they should be managed as benign lesions and carefully followed by thin section CT and MRI for signs of extraosseous disease. More extensive follow-up by cross-sectional imaging over a long period of time would be required before firmly determining the biological behavior of BNCTs. BNCTs do not require any surgical management until they undergo malignant transformation. BNCTs should be recognized by radiologists, pathologists, and orthopedic surgeons to prevent unnecessary radical surgery and carefully followed by advanced imaging.