Discussion and Conclusions
Compared to adults, children have a higher proportion of leukemias such
as ALL and acute myeloid leukemia, followed by brain tumors, lymphomas,
neuroblastomas, and other malignant tumors.11, 12
Among all malignant tumors in children, leukemia accounts for 38.4%,
ALL for 70%, and BCP-ALL for 80–85% of cases.
In general, fever, hemorrhage, and anemia are the three major initial
signs of acute leukemia. Other findings include enlarged lymph nodes,
skin symptoms, hepatosplenomegaly, and neurological symptoms, which vary
according to the type of disease.
Takagi et al. and Marukawa et al. reported that approximately 20–35%
of patients with leukemia had oral symptoms as the initial
manifestation, indicating that leukemia with an oral origin is
relatively common. Therefore, it is important to accurately understand
the oral symptoms of leukemia in patients and to always include it in
the differential diagnosis of oral diseases.13, 14
The main oral symptoms that occur in patients with leukemia include
gingival hemorrhage, gingival swelling, hypersensitivity, jawbone
abnormalities, and tooth movement,3-8, 13, 14 pointing
to the importance of oral lesions in the diagnosis of acute lymphocytic
leukemia.15
The patient in the present case was seen by a previous dentist because
of marked swelling and pain of the gingiva, tooth movement, and alveolar
bone resorption. However, when the patient returned to the dentist’s
office four weeks later, the inflammatory lesions, which were thought to
be periodontitis, had spread further and worsened over the entire jaw,
and thus the patient was referred to our department. At first
presentation at our department, the patient’s general condition was
characterized by mild fever and malaise, and the periodontal tissue
showed inflammatory findings that had no improvement.
Confirmation of bone marrow blasts by tests is effective in the
diagnosis of leukemia.16 However, Okamoto et al.
reported a case in which the patient did not show typical oral symptoms
and was in poor general condition; therefore, the diagnosis of
periodontal disease, including the possibility of leukemia, should be
made with more careful consideration.5
When leukemia is severe, oral symptoms become more severe and oral
intake becomes difficult, which results in the deterioration of
nutritional status and the general condition. Therefore, it is important
to provide adequate oral care during the treatment of leukemia in
affected patients to prevent secondary oral infections and deterioration
of their general condition.
To identify the cause of the jawbone abnormalities associated with ALL,
Takada et al.17 performed site-specific autopsies of
the mandible in 21 patients with leukemia and evaluated the presence of
leukemia cell infiltration, which was confirmed in the mandibular bone
marrow and gingiva (n=21), alveolar bone marrow (n=19), periodontal
ligament (n=19), and dental pulp (n=20). These results showed that
leukemic cell infiltration into the mandible begins in the jaw bone
marrow and subsequently invades the alveolar bone and then the
supporting tissue of the teeth. It is thought that leukemia cells
infiltrate the mandible, starting from the jaw bone marrow, then invade
the alveolar bone, which is the supporting tissue of the tooth, and
subsequently invade and proliferate into the periodontal ligament and
pulp. Therefore, it is highly likely that patients with leukemia first
develop symptoms in the jawbone, which is infiltrated by leukemia cells,
followed by tooth movement and gingival abnormalities due to the
infiltration of leukemia cells into the surrounding tissues of the
teeth, and finally by the infiltration of leukemia cells into the dental
pulp, resulting in symptoms in the teeth.
However, in the present case, the clinical symptoms showed a clear
systemic abnormality rather than local disease in the oral cavity, so a
gingival biopsy was not performed to avoid the risk of spreading the
disease.18 Additionally, the panoramic radiographic
examination in this case showed a high degree of jaw bone resorption,
and we considered it highly likely that the tooth movement and alveolar
bone resorption were caused by infiltration of leukemia cells into the
jaw bone, as previously reported.
Leukemia is a malignant hematologic tumor that develops mainly in the
bone marrow, resulting first in bone destruction. In children with ALL,
bone mineral loss is sometimes observed from the time of diagnosis, and
this is due to a decrease in bone formation markers such as type I
procollagen, C-terminal propeptide, and bone alkaline phosphatase, as
well as an increase in bone resorption by parathyroid hormone-related
peptide secreted by the leukemia cells, a decrease in 1,25(OH)2D3, and
hypercalciuria, and the destruction of the sea-level chamber by leukemic
cell infiltration.19, 20
There have been many reports of bone destruction due to leukemia cell
infiltration in leukemia patients, even in organs other than the
jawbone, and when the leukemia cell infiltration was cured by remission
therapy, the destroyed bones recovered in correlation with the remission
of the leukemia.9, 21
In the present case, the patient also complained of symptoms related to
the shoulder joint at the time of the initial examination and was
diagnosed with a fracture of the shoulder joint after a visit to an
orthopedic surgeon. The shoulder joint fracture was also considered to
have recovered because the infiltrating leukemia cells disappeared along
with the remission of ALL.
It is generally known that jawbone resorbed by chronic marginal
periodontitis does not recover.22 However, in the case
of jaw bone resorption associated with leukemia, there is a high
possibility that the jaw bone will recover, as has been reported for the
hands and feet.23, 24
Even in cases of severe bone resorption, as in the present case, there
is a high likelihood of recovery with the remission of leukemia.
Although there are a few reports of extraction procedures performed on
patients with ALL and tooth movement immediately after the onset of
leukemia, there are cases in which the alveolar bone completely
recovers, as seen in the present case.
In Japan, there are many case reports of patients with oral symptoms
caused by leukemia, especially jaw bone resorption resulting in tooth
movement, but there are no reports of cases in which highly resorbed jaw
bone and tooth movement recovered with successful chemotherapy.
We report a case of a pediatric patient with ALL who had marked tooth
movement and jaw bone resorption, whose jaw bone alveolar bone opacities
on X-ray image increased with chemotherapy and remission of ALL. The
tooth movement also resolved and occlusal function was restored.