Systematic disorders can be depicted as oral changes, which can be their first signs and symptoms. These alterations can alert an oral health professional, and they can be the first to start investigating the beginning of the evolution of some of these systematic diseases. It has been proven that many immunosuppressive conditions often show oral changes, and these changes can be their first clinical manifestation.[1,2]
Leukemia is a component of oncohematological diseases. Oncohematology includes iron deficiency anemia, hemophilia, sickle cell disease, thalassemia, leukemia/lymphoma, and cancer of other organs. It affects the bone marrow and peripheral blood and is secondary to the malignant proliferation of the white blood cell precursors.[3,4] The failure of maturation of precursor/blast cells results in the accumulation of blasts in the marrow and suppression of normal hematopoietic stem cells leading to deficiency of mature leukocytes, platelets, and erythrocytes in the peripheral circulation. Such a scenario will cause immunodeficiency, anemia, and thrombocytopenia. Leukemic cells also tend to infiltrate various body tissues, such as the gingiva, spleen, skin, lymph nodes, and central nervous system. Frequently recurrent and severe bleeding episodes and infections are life-threatening complications of leukemia.[6–9] Acute leukemia is the most common form of neoplasm in pediatric patients younger than 15 years.[9,10] It has shown a worldwide incidence of close to 3.7/100,000 persons and age-dependent mortality in the range of 2.7–18/100,000 persons; further, it accounts for about 4% of all deaths from malignancies. Based on clinical behavior, leukemia has been distinguished into acute and chronic.[6,7] Acute leukemia has an acute onset, and they are more aggressive with primitive blast cells released into the peripheral circulation. A recent study has suggested that the age-standardized incidence rate of acute myeloid leukemia (AML) increased from 1.35/100,000 to 1.54/100,000 with an estimated average percentage change of 0.56 (95% confidence interval 0.49,0.62). AML is commonly classified under eight subgroups according to the French–American–British (FAB) classification system. The World Health Organization 2017 has proposed six main categories in AML. Symptoms with which the patients of AML present are mostly related to thrombocytopenia, anemia, fatigue associated with easy fatiguability, neutropenia, infections of variable severity, and hemorrhagic findings in the form of gingival bleeding, ecchymosis, or epistaxis.
Gingival overgrowth has multiple etiological factors, including poor oral hygiene, use of certain medications, hematological disorders, and genetic conditions to name a few. Gingival infiltration represents 5% frequency in the initial presenting complication of AML. Gingival infiltration of leukemic cells is most commonly seen in acute myelomonocytic leukemia (M4) and acute monocytic leukemia (M5). All subtypes of AML, chronic myeloid leukemia, acute lymphocytic leukemia, and chronic lymphocytic leukemia present with oral manifestations. Many a time, the oral symptoms in AML precede the systemic manifestations, the knowledge of the whole spectrum of presentation of systemic disease is of utmost importance to the oral health-care professionals as their knowledge and wisdom might help in early and prompt diagnosis, which can make a significant difference in the long-term survival of the patient.
This report highlights the extreme level of gingival enlargement secondary to the infiltration of blast cells in AML. Various advanced tools were used to diagnose the underlying etiology, which has helped the health-care providers to customize the treatment plan.
An 11-year-old female attended the department of dentistry with a chief complaint of generalized gingival enlargement [Figure 1]. The gingival enlargement started 1 month ago in the maxillary left posterior region, and over 3 weeks, there was a gradual generalized gingival enlargement in the maxillary and mandibular arches. The patient gave a history of mild fever, sore throat, fatigue, and weight loss at the time of initial gingival enlargement. She visited local health-care centers, but only symptomatic treatment was provided to the patient, which delayed appropriate therapy. Two weeks after the observation for the first gingival enlargement, the patient-reported mild, spontaneous gingival bleeding from the maxillary arch that lasted for 3 days and subsided on its own. The clinical examination revealed gingiva with a pale and bulbous appearance, with loss of stripling and focal hemorrhagic areas. Lymph nodes of the orofacial region, i.e., submandibular and submental, were tender and enlarged on palpation, with no involvement of the cervical group of lymph nodes. The patient was on antibiotics and analgesics prescribed at the local healt-care center before visiting the department of Dentistry. Bone loss was not evident in the panoramic radiograph.
Further, she was advised for a complete blood count (CBC) test and peripheral blood smear. Initial reports revealed a marked increase in white blood count suggestive of leukocytosis with 70% blasts, decreased red blood count with lowered hematocrit and hemoglobin levels, and a low platelet count [Tables 1 and 2 and Figure 2]. Peripheral blood smear displayed mostly immature monocytes. The patient was referred to the department of hematoncology, with the preliminary diagnosis of leukemia. A subsequent bone marrow aspirate smear from the right posterior superior iliac spine revealed 90% hypercellularity and near-total replacement of the bone marrow by sheets of intermediate-to-large size myeloid blasts/promonocytes with moderate, pale basophilic finely granular cytoplasm, round nuclei, open chromatin, and few prominent nucleoli [Figure 3a]. Further, it showed evidence of erythrophagocytosis and the presence of cytoplasmic granules in scattered leukemic blasts [Figure 3b].
Flow cytometric immunophenotypic analysis has suggested that cell population gated on CD45/SSC (Blasts) was positive for CD34, HLA-DR, CD117, CD33 (bright), CD13 (variable), CD 64 (bright), CD14 (subset) CD11c, and CD15 (subset) along with increased monocytes [Figure 4]. In correlation with flow cytometric immunophenotypic analysis, bone marrow cytomorphological features were characteristic of AML. Further, cytogenetic analysis was carried out, and the chromosome karyotype was 46, XX with translocation (6:11) (q27:Q23) (20). Further, it was diagnostically interpreted as all metaphases analyzed were abnormal and showed the t (6;11) results in the fusion of the AFDN gene (also known as MLLT4) at 6q27 with the MLL gene at 11q23, was a recurrent, nonrandom abnormally observed in AML [Figure 5]. The t (6;11) fusion is generally associated with an unfavorable prognostic outcome in AML.[17,18] A confirmatory diagnosis was made of acute monocytic leukemia (FAB classification M5)/AML with recurrent genetic abnormalities (WHO classification).
The patient was admitted to the hematoncology ward for treatment. She was started on induction chemotherapy as per the United Kingdom Medical Research Council AML protocol, including cytarabine, daunorubicin, etoposide, and triple intrathecal therapy (methotrexate, cytarabine, and hydrocortisone). Hematological and laboratory tests were repeated at regular intervals and are shown in Table 3. She received multiple units of packed red blood cell and platelet transfusions for anemia and thrombocytopenia. Postinduction, she developed febrile neutropenia (FN), which was managed successfully with intravenous antibiotics, blood products, and granulocyte colony-stimulating factors.
Bone marrow examination was done on day 28 of induction, and she was found to be in the stage of incomplete remission. Then, she was administered second induction chemo, and postchemo FN was managed conservatively without any adverse events. Gingival enlargement of the maxillary and mandibular arches showed a remarkable improvement and exhibited a near-normal appearance [Figure 6].
There are several etiologies for gingival overgrowth, and the differential diagnosis for such a condition would include drug-induced hyperplasia, hyperplastic gingivitis, neoplastic disorders, and gingival fibromatosis. Gingival overgrowth may manifest as a localized metastatic deposit or hematological diseases such as lymphoma or a leukemic infiltration.
The case discussed here raised several diagnostic challenges as to the approach in establishing a confirmatory diagnosis. It begins with a CBC and the comment on the peripheral smear in situations where the clinician suspects leukemia. Further, a full hematological profile assessment is always desired to diagnose leukemia more efficiently. Bone marrow examination, in this case, resulted in the appropriate diagnosis.
Studies have suggested that 65% of leukemic patients presented with some oral manifestation, which leads them to seek help from the oral health-care professional. Oral presentations have been seen in 15%–80% with leukemia and are more commonly seen in acute (65%) rather than chronic leukemia (30%). These oral manifestations can be in the form of gingival hyperplasia, bleeding, or mucosal ulceration.[1,2,6,10] Gingival hyperplasia is most commonly seen with acute monocytic leukemia (AML-M5) (66.7%) and acute myelomonocytic leukemia (AML-M4) (18.5%). In this case, a rapid gingival enlargement with associated bleeding was the main reason for seeking the oral health professional’s help. The absence of microbial plaque or calculus accumulation, duration of gingival overgrowth, and spontaneous bleeding from gingiva has alerted the oral health-care professional to consider a systemic disease such as probably one of the hematological diseases, i.e., leukemia. In these patients, any dental intervention without hematological consultation could be fatal. Through this case report, we have tried to highlight that patients can seek initial consultation for conditions related to the oral cavity, which can be the only manifestation of a systemic disorder (AML in this case). A well-planned and interdisciplinary diagnosis and treatment approach is a must for optimal delivery of the desired care. In this case report, we used all the recommended diagnostic tools to diagnose the case, which helped us to deliver the standard therapy without delay for a better outcome. The patient is asymptomatic and hemodynamically stable with a near-normal oral condition. Now she is receiving consolidation chemotherapy (high-dose cytarabine) without any untoward events.
This case reminds health-care professionals of the importance of recognizing the oral manifestations of systemic diseases. Often, such patients first seek the help of oral health-care professionals due to oral signs and symptoms that can be the only presentation of systemic diseases. The oral health-care professionals should diagnose and go for the preliminary diagnostic investigation to confirm the conditions, which helps them refer the case for interdisciplinary care. This case report highlights that the chemotherapy protocols can best manage gingival enlargement secondary to leukemia.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her names and initials will not be published, and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
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Conflicts of interest
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