An undiagnosed case of acute myeloid leukemia.

Leukemia is a neoplastic disease characterized by an excessive proliferation of immature white blood cells and their precursors. Oral lesions may be the presenting feature of acute leukemia, which can be rapidly fatal if left untreated. Although many cases of gingival enlargement in patients with acute myeloid leukemia's have been reported in the literature, cases diagnosed by the oral manifestations in India are very few. This report describes the case of a 43-year-old female who presented with gingival bleeding and gingival enlargement. Within a month she developed signs and symptoms of systemic disease such as, and splenomegaly, and upon further investigation, she was diagnosed with acute myeloid leukemia to which she succumbed within 10 days after diagnosis. The need for early diagnosis and referral of this fatal disease are also underline.

INTRODUCTION

Leukemia results from the proliferation of a clone of abnormal hematopoietic (HP) cells with impaired differentiation, regulation, and programmed cell death (apoptosis). Leukemic cell multiplication at the expense of normal HP cell lines causes marrow failure, depressed blood cell count (cytopenia), and death as a result of infection, bleeding, or both.[1]

Oral lesions may be the presenting feature of acute leukemia and are therefore important diagnostic indicators of the disease. Lesions in oral cavity may occur due to direct leukemic infiltration of tissues, or be secondary to immunodeficiency, anemia, and thrombocytopenia. Typical oral manifestations of acute leukemia include gingival swelling, oral ulceration, spontaneous gingival bleeding, petechiae, mucosal pallor, herpetic infections, and candidacies.[2] Acute myeloid leukemia (AML) is a clonal proliferation of immature myeloid cells. It presents with marrow failure and cytopenia. Symptoms include fever, fatigue, pallor, mucosal bleeding, petechiae, and local infections.[1]

The causes of leukemia are poorly defined. However, radiation exposure, chromosomal abnormalities, chemical injuries and viral infections have been implicated. With worldwide incidence of 3.7 per 100 000 persons, and age-dependent mortality of 2.7 to nearly 18 per 100 000 persons; leukemia accounts for about 4% of all deaths from malignant disease.[3] The annual incidence rate of childhood leukemia varies worldwide between 20 and 60 cases per million.[4] The rate of progression varies considerably in different types of leukemia but death is the usual outcome in untreated disease as a result of compromised production of mature blood cells.[56]

CASE REPORT

A 43-year-old female patient reported to the Department of Periodontology, with the chief complaint of generalized bleeding gums, and gingival swelling from last 2 months. Patient gave no history of fever, malaise, weight loss in the recent past. Patient was not under any medication for chronic illness. Extra oral examination reveals bilateral submandibular and deep cervical lymphadenopathy; lymph nodes were indurated and tender on palpation. Systemic examination reveals mild hepatomegaly and splenomegaly.

Intraoral examination revealed generalized enlargement of the maxillary and mandibular gingiva involving the buccal, lingual, and palatal aspects [Figure 1a–c]. The gingiva was swollen, inflamed, erythematous, and devoid of stippling. On palpation gingiva was firm and edematous, tender and bleeding on slight provocation. There was a fair amount of plaque and calculus, but did not justify the amount of enlargement. Orthopantomogram did not reveal any significant findings.

Figure 1

(a) Gingival enlargement involving labial aspects of upper and lower anteriors. (b) Gingival enlargement involving palatal aspect of maxillary arch. (c) Gingival enlargement involving lingual aspect of Mandibular arch

The following differential diagnoses were considered: Inflammatory enlargement, conditioned enlargement, systemic enlargement, and neoplastic enlargement.

Complete blood count [Table 1] revealed marked increase in white blood cells, decrease in red blood cells with decrease in hemoglobin levels, and low platelets count; indicative of leukocytosis, anemia, and thrombocytopenia.

Table 1

Complete blood count

Peripheral smear depicted numerous blast cells, mainly immature leukocytes with few erythrocytes and thrombocytes [Figure 2].

Figure 2

Peripheral smear depicting numerous blast cells, mainly immature leukocytes with few erythrocytes and thrombocytes (×25)

These results confirmed the final diagnosis of acute myeloid leukemia. Oral hygiene instruction was given to the patient. Patient was instructed to use soft bristle toothbrush, as gingiva was inflamed, friable and edematous use of hard or regular brush is not recommended. Thrice a day Chlorhexidine (0.2%) was prescribed as oral rinse.[7] Scaling and root planning was postponed since the treatment needs a minimum platelet count of 60 000 in this condition. Patient was immediately referred to the oncology centre for further management, where bone marrow biopsy confirms acute myeloid leukemia M5 and chemotherapy started. Patient did not respond well to chemotherapy and succumbed to the disease within 10 days of admission.

DISCUSSION

Gingival enlargement is one of the commonest manifestations of the periodontal disease. Gingival enlargement can be caused by a wide variety of etiologies and is classified according to these etiologic factors: Inflammatory enlargement, drug-induced enlargement, enlargement associated with systemic diseases or conditions; conditioned enlargement (pregnancy, puberty, vitamin C deficiency, plasma cell gingivitis, nonspecific conditioned enlargement), systemic diseases causing gingival enlargement (Leukemia, Granulomatous diseases), neoplastic enlargement, and each enlargement has its own characteristic growth pattern.[8]

Leukemia is a hematological disorder, arises from a hematopoietic stem cell caused by disordered differentiation and proliferation of neoplastic cells, and leads to marked increase in circulating immature or abnormal white blood cells.[9]

According to the lineage of white blood cells (WBC) involved, leukemia is classified as lymphocytic or myelocytic; a subgroup of the myelocytic leukemia is monocytic leukemia. According to their evolution, leukemia can be acute, which is rapidly fatal, subacute, or chronic.[6] AML has many types (FAB: French, American, British classification) including M0 (undifferentiated leukemia), M1 (acute myeloblastic leukemia), M2 (acute myeloblastic leukemia with maturation), M3 (acute promyelocytic leukemia), M4 (acute myelomonocytic leukemia), M5 (acute monocytic leukemia), M6 (acute erythroblastic leukemia), and M7 (acute megakaryoblastic leukemia).[10]

Neoplastic proliferation in bone marrow results in decreased production of normal erythrocytes, causing anemia, weakness, fatigue, pallor; granulocytes causing granulocytopenia, fever, and infection; and platelets causing thrombocytopenia, bleeding, and petechiae. Leukemic cells may also infiltrate spleen, lymph nodes, skin, gingiva, and central system.[6] Oral manifestation have been observed in 15-80% of leukemic cases and more commonly seen in (65%) acute rather than in chronic leukemia (30%).[11] A study of 1076 adult patients with leukemia showed 3.6% of the patients with teeth had leukemic gingival proliferative lesions, with the highest incidence in patients with M5 (66.7%), followed by M4 (18.7%) and M1, M2 (3.7%).[9]

Lynch and Ship found that petechiae or bleeding (56%), ulceration (53%), and gingival enlargement (36%) were the most common initial diagnosis manifestation of leukemia in a 10-year retrospective study of 155 patients.[12]

Gingival hyperplasia is characterized by progressive enlargement of the interdental papillae as well as the marginal and attached gingiva. In severe conditions, the crowns of the teeth may be covered. Gingiva appears swollen, devoid of stippling and pale red to deep purple in color. Mucosal hemorrhages, ulcerative gingivitis, and infectious gingivitis may be observed. Pallor, spontaneous hemorrhage, petechiae, and ulceration have been described.[101213]

Infections and anemia are the major causes of death in leukemic patients. Untreated, acute leukemia has an aggressive course, with death occurring within 6 months or less.[1] The patient died in spite of our immediate referral because valuable time had been lost until the patient visited our department.

CONCLUSION

The fact that gingival alterations are sometimes the first manifestations of the disease implies that dental professionals must be sufficiently familiarized with the clinical manifestations of systemic diseases to ensure prompt detection and referral. Since oral manifestations in all types of leukemia occur early in the course of the disease, it must be emphasized that unnecessary dental procedures may aggravate the situation and give rise to exacerbation of acute symptoms. The suspicion of oral lesions, which may be the presentations of leukemia, should be observed by general dental practitioner. The early observation may be of immense help to the patient when the general dental practitioner refers the patient to the higher centre for management that can prolong his life span.