A twenty-four-year-old man began having neck pain in the summer of
2002. He had no history of a fall or trauma. The symptoms progressed, and he
had episodes of paresthesias in both hands and the chest. Later, urinary and
bowel dysfunction occurred. A neurological examination at a local hospital
revealed hyperreflexia of the upper and lower extremities. Computed tomography
scans of the head showed no abnormality. Subsequently, a computed tomography
scan and magnetic resonance imaging study of the cervical spine demonstrated a
large tumor (2.5 × 2 × 4 cm) in the second cervical vertebra as
well as bone destruction and local calcification resulting in severe spinal
stenosis (Figs. 1-A and
1-B). The findings on the
routine laboratory tests were normal. Because of the neurological symptoms,
the patient was managed with intravenous administration of dexamethasone. A
computed tomography-guided needle biopsy of the tumor was performed in
November 2002, but no representative tissue was obtained. A specimen obtained
from a second closed biopsy with use of a trephine needle also showed no signs
of a tumor. An open biopsy from a dorsal approach, including a left-sided
hemi-laminectomy of C1, was performed, and a soft, lobulated, gelatinous, and
gray tumor was found.
Postoperatively, the patient had low grade fevers of up to 37.5°C for
three days, but he had no obvious signs of a local wound infection. The
patient had a leukocyte count of 12,300 cells/mm3 (12.3 ×
109/L) (normal, 4400 to 11,300 cells/mm3 [4.4 to 11.3
× 109/L]) and a serum C-reactive protein of 70.9 mg/dL
(normal, <9 mg/dL). The histological evaluation of the tissue demonstrated
vacuolated cells combined with myxoid masses consistent with the diagnosis of
a chordoma (Fig. 2-A). The
immunohistochemical investigation of the tumor demonstrated positive
immunostaining for cytokeratin, vimentin, epithelial membrane antigen, and
S-100 protein (Fig. 2-B). Two
bone pathologists confirmed the diagnosis of chordoma on review of the
pathology slides. The patient received a daily dose of 40 mg of dexamethasone
for three days, followed by a daily dose of 24 mg for ten weeks, and then the
dose was tapered, with the last dose received twelve weeks after the initial
dose. Two weeks after the open biopsy, the patient was taken to the operating
room for an en bloc resection of the lesion. During the operation, an abscess
was encountered at the location of the previous open biopsy. The operation was
discontinued after lavage and drainage. The microbiological analysis of the
abscess material revealed Escherichia coli. Intravenous antibiotic
therapy with ciprofloxacin (800 mg/day) was initiated and continued for three
weeks. After another two weeks, a magnetic resonance imaging scan revealed the
disappearance of the soft-tissue mass of the tumor at C2
(Fig. 3).
Further and intensive examination of our patient followed. Although the
histological diagnosis of a chordoma had been confirmed by three pathologists,
the possible differential diagnosis included myeloma, lymphoma, and
granulomatosis. A needle biopsy of the bone marrow from the iliac crest and
computed tomography scans of the lungs, abdomen, pelvis, and head showed no
abnormal findings. Bone scintigraphy demonstrated no local increased activity
in the upper cervical spine, but there was a general activation of the bone
marrow. In the fluorescence-activated cell-sorting analysis of leukocytes, no
pathological clonal populations could be found. Because of these findings, a
decision was made to manage the patient nonoperatively with a soft collar and
continued corticosteroid therapy with 24 mg of dexamethasone daily for ten
weeks. The dose was then tapered, with the last dose received twelve weeks
after the initial dose.
At twenty-four months after the original diagnosis, the patient showed no
symptoms at the former tumor location and there was no detectable neurological
deficit. A magnetic resonance imaging scan of the cervical spine demonstrated
no evidence of tumor recurrence, but there was a slight irregularity of C2 and
the adjacent intervertebral disc (Fig.
4).
The histological diagnosis of this chordoma was confirmed by three
independent pathologists. The tumor showed aggressive behavior, including bone
destruction, development of an extraosseous soft-tissue mass, and
calcification, which is typical for a
chordoma2.
Nevertheless, the tumor disappeared without surgical resection or local
radiation, which is atypical for a chordoma.
The differential diagnosis of the lesion includes ecchordosis physaliphora,
a benign tumor that also arises from the notochord but does not show an
invasive behavior and usually is
asymptomatic3,4.
In a population-based study in the United States, the age-adjusted incidence
of chordoma was 0.08 per
100,0005, whereas a
recent study including a literature review demonstrated that the cases of only
eight patients with symptomatic ecchordosis physaliphora have been described
in the medical literature to
date4. Usually, an
ecchordosis physaliphora is located at the base of the skull; however, the
cases of two patients who had ecchordosis physaliphora at C2 and one who had
it at T8-T9 have been
reported3,4,6.
The differentiation between an ecchordosis physaliphora and a chordoma on the
basis of clinical, radiographic, and histopathological evidence is
difficult4. The less
aggressive behavior of an ecchordosis physaliphora results in only a minimal
osseous defect, without calcification of the tumor, and there is no contrast
enhancement on magnetic resonance
imaging3,4.
Histopathologically, both the ecchordosis physaliphora and chordoma have
physaliferous
cells7,8.
Hypocellularity, sparse pleomorphism, and the absence of mitoses are more
typical for ecchordosis physaliphora but are not
pathognomonic4,7,8.
In a study on an ecchordosis physaliphora of the thoracic spine, Rengachary
et al. concluded that the only method of differentiating these two lesions is
long-term clinical
follow-up9. As the
behavior of an ecchordosis physaliphora is much less aggressive than that of a
chordoma and the lesion is usually asymptomatic, less aggressive intervention
is
required3,4.
A giant notochordal hamartoma is a possible diagnosis, but this lesion is
usually confined to the bone and is without a soft-tissue
mass10. An
additional differential diagnosis is an os
odontoideum11,12.
Because this condition is associated with atlantoaxial instability, the
development of either hypertrophy of a soft-tissue mass or a synovial cyst,
which can mimic a tumor in the periodontoid region, is
possible11,12.
The generally accepted treatment of choice for a patient with a chordoma is
wide en bloc resection of the
lesion2. Modern
techniques for preoperative diagnosis and surgical treatment of tumors have
resulted in substantially improved local tumor control and an increased rate
of survival13.
However, in two series of thirty-nine and 100 patients with chordoma of the
sacrum and the mobile spine who were managed surgically, the estimated
survival rates ranged from 78% to 84% at five years and from 36% to 64% at ten
years13,14.
Corticosteroids are known to be effective in the induction chemotherapy of
leukemia and therefore are considered as very important therapeutic agents,
although toxic side effects, including severe infections, have been observed
during therapy15.
Dexamethasone is an anti-inflammatory glucocorticoid and often is used after
injury to reduce edema in neurologic tissue and to otherwise mitigate the
consequences of neural
inflammation16,17.
The administration of dexamethasone in our patient was performed to reduce
edema, and it was administered for a longer time-period since three invasive
procedures had to be performed until the diagnosis was secured. Additionally,
the patient received intravenous administration of high-dose ciprofloxacin for
three weeks. This antibiotic is known to have a cytotoxic effect on tumor
cells18. The
influence of corticosteroids and ciprofloxacin on notochordal tumors has not
been studied, to our knowledge.
Spontaneous tumor regression has been reported for some malignant
tumors19,20.
In a review of the literature on the spontaneous regression of hepatocellular
carcinoma, Takeda et al. estimated that spontaneous regression of this cancer
occurred once in 60,000 to 100,000
cases19. In some
cases, the regression was attributed to the accompanying production of
cytokines, such as tumor necrosis factor and interleukin, and to the presence
of fever in the case of a bacterial
infection19. In the
case of our patient, the local bacterial infection might have led to the
production of cytokines. The intravesical administration of bacille
Calmette-Guérin has been shown to be the most effective way to prevent
the recurrence of superficial bladder
cancer21,22.
A recent study on immunotherapy with bacille Calmette-Guérin clearly
demonstrated the activation of tumor cytotoxic natural killer
cells21. These
findings led to the assumption that the local infection with Escherichia
coli in our patient also might have had an influence on the course of the
tumor, either immunologically or as a direct result of the necrosis of tumor
tissue.
Because the disappearance of this tumor may have been the result of the
systemic administration of corticosteroids and/or ciprofloxacin, a prospective
study to evaluate the influence of these two drugs on notochordal tumors may
be warranted. ?