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.