Langerhans cell histiocytosis sometimes involves the cervical spine
and can be associated with collapse of the vertebral
body1, but
involvement of the atlas is rare. To the best of our knowledge, the cases of
only eight patients with Langerhans cell histiocytosis of the atlas have been
reported2-8.
We report the cases of three patients with Langerhans cell histiocytosis of
the atlas, two of whom appeared to have been successfully treated with
low-dose chemotherapy. The patients and/or their parents were informed that
information concerning the case would be submitted for publication.
Case 1. An eleven-year-old boy had neck pain for two
weeks followed by the development of persistent torticollis. The neck pain
gradually increased, and the symptoms did not improve after the administration
of antipyretic drugs. Two weeks after he began treatment, magnetic resonance
imaging showed a destructive process within the lateral mass of C1, and the
patient was referred to our hospital. The medical history was otherwise
unremarkable.
Four weeks after the onset of symptoms, the boy required walking aids
because of severe neck pain and persistent torticollis; the neck was bent to
the left side and slightly rotated to the right side. Physical examination
revealed stiffness, pain upon motion of the cervical spine, and tenderness of
the left upper cervical spine. There were no neurological deficits. Blood
tests showed a slightly increased C-reactive protein level of 0.5 mg/dL (5
mg/L) (normal, 0.0 to 0.4 mg/dL [0 to 4 mg/L]) and alkaline phosphatase of 414
U/L (normal range for an adult, 90 to 340 U/L), while the white blood-cell
counts were within the normal range.
Cervical radiographs showed torticollis of the cervical spine, and computed
tomography demonstrated an osteolytic lesion in the left lateral mass of the
atlas (Fig. 1). Magnetic
resonance imaging confirmed a mass that was isointensive on the T1-weighted
image and high-intensity on the T2-weighted image
(Fig. 2). The mass was shown to
be expanding to the outside of the atlas on the left side.
With the patient under local anesthesia and in a prone position, a
percutaneous needle biopsy was performed with computed tomography guidance
(Fig. 3, A and
B). The biopsy needle was inserted posterolaterally to
the lesion. There were no complications, and the histologic findings were
diagnostic of Langerhans cell histiocytosis
(Fig. 3, C).
After immobilization of the cervical spine with a collar, the pain and
torticollis gradually improved. Low-dose chemotherapy with oral alternate-day
prednisone (40 mg per square meter of skin per day) and weekly methotrexate
(20 mg per square meter of skin once weekly) was administered for six months,
and a cervical collar was worn for four months. No complications accompanied
the chemotherapy. The symptoms resolved at twelve weeks, and computed
tomography demonstrated partial bone-remodeling. No new symptoms occurred
during the follow-up period of twenty-four months, and computed tomography
scans made at the latest follow-up examination demonstrated excellent
remodeling of the atlas (Fig.
4).
Case 2. A three-year-old boy had neck pain and persistent
torticollis for three days. The initial diagnosis was inflammatory
torticollis, and he was treated with a cervical collar and antipyretic drugs.
Two weeks after he was first seen, a computed tomography scan showed a lytic
lesion in C1 (Fig. 5,
A). Persistent torticollis, pain with motion, and
tenderness of the cervical spine were found. No neurological deficits were
noted on physical examination, and the medical history was unremarkable. Blood
tests showed increased alkaline phosphatase of 655 U/L (normal range for an
adult, 90 to 340 U/L), while the white blood-cell count and C-reactive protein
values were within the normal range.
A computed tomography-guided percutaneous needle biopsy through a
posterolateral approach was performed without any complications. Histological
analysis revealed Langerhans cell histiocytosis. Conservative treatment with
immobilization in a cervical collar for three months and low-dose
chemotherapy, consisting of oral alternate-day prednisone (40 mg per square
meter of skin per day) and weekly methotrexate (20 mg per square meter of skin
once weekly) for a period of six months, was administered. The pain and
torticollis completely resolved without any complications, and a computed
tomography scan at the two-year follow-up showed excellent bone-remodeling
(Fig. 5, B).
Case 3. A six-year-old girl had been treated with chemotherapy
and radiation therapy for multifocal Langerhans cell histiocytosis of the
thoracic spine, right femur, and skull for four years. She had neck pain and
torticollis for three months. A computed tomography study revealed severe
torticollis, a lesion involving C1, and severe atlantoaxial subluxation
(Fig. 6, A). Physical
examination revealed pain with motion and tenderness of the cervical spine but
no neurological deficits.
A halo vest was worn for two weeks, and then an operation that included
curettage of the lesion and posterior fixation with instrumentation and
bone-grafting was performed (Fig. 6,
B). Histological analysis revealed Langerhans cell
histiocytosis. A cervical collar was worn for three months, and the pain and
torticollis completely resolved without any complications. A follow-up
radiograph made eight years later demonstrated excellent bone-remodeling and
fusion with no recurrence of the Langerhans cell histiocytosis.
Langerhans cell histiocytosis is a benign condition of localized or
multifocal proliferation of histiocytes. Its prevalence is approximately
1:1,500,000 people9.
Schajowicz reported that 81% of all patients with Langerhans cell
histiocytosis have a solitary eosinophilic granuloma, 7% have multiple
eosinophilic granulomas, and 11% have widely disseminated lesions of
Hand-Schüller-Christian disease syndrome or Letterer-Siwe
syndrome10. This
group of diseases was introduced as histiocytosis X and was later renamed
Langerhans cell histiocytosis on the basis of the pathologic
findings11,12.
Langerhans cell histiocytosis in the spine is relatively rare, with a
frequency that has been reported to range between 6.5% and
25%10,13,14.
Clinical symptoms are often severe, and the diagnosis is sometimes difficult.
Bertram et al.15
reported that the cervical spine at C3-C5 is involved in 60% of children with
Langerhans cell histiocytosis, but it is quite rare for the disease to affect
the atlas.
The most common symptoms of Langerhans cell histiocytosis involving the
cervical spine are neck pain and restricted range of motion, or torticollis.
The three patients described in the present report demonstrated all of these
symptoms without neurological deficits. Although lytic lesions of the atlas
were found on radiographs, vertebral plana, which is a typical radiographic
finding in pediatric patients, was not found. Because the magnetic resonance
imaging and computed tomography studies suggested diseases such as
osteosarcoma, Ewing sarcoma, and spinal infection, biopsy specimens for
histologic diagnosis were required. Computed tomography-guided percutaneous
needle biopsies were performed without complications. In our institution, the
radiologist does the procedure and frozen sections are made to confirm that
the biopsy had obtained lesional tissue. Computed tomography-guided needle
biopsy has been reported to be a safe and effective technique for histologic
diagnosis, with an accuracy in achieving a diagnosis of 70% to
100%16-18.
As for the treatment of Langerhans cell histiocytosis of the cervical
spine, many authors have reported that immobilization is adequate for most
patients11,19-22.
While an operative procedure may not be needed for a solitary osseous lesion,
one of our current patients who had severe torticollis and persistent
atlantoaxial subluxation required posterior arthrodesis. On the other hand,
Womer et al.23
described using alternate-day prednisone and weekly methotrexate for the
treatment of low-risk Langerhans cell histiocytosis in thirteen patients who
were more than one year old and had no bone marrow involvement or organ
dysfunction. Twelve of these patients were treated successfully, with limited
toxicity manifested by slight and transient elevations in hepatic enzymes in
three patients. Those authors concluded that low-dose chemotherapy was safe
and effective for patients with low-risk Langerhans cell histiocytosis. The
use of chemotherapy to treat Langerhans cell histiocytosis is controversial,
but it seems to have been safe and effective in the two patients in the
present report who did not have atlantoaxial subluxation.
In conclusion, three patients with Langerhans cell histiocytosis of the
atlas were treated and all had a full recovery and complete resolution of the
symptoms. Imaging studies and computed tomography-guided percutaneous needle
biopsies were useful for diagnosing Langerhans cell histiocytosis at an early
stage. It is important for surgeons to recognize that Langerhans cell
histiocytosis may involve the atlas. ?