Acute Non-Lymphoblastic Leukemias Presenting with Gingival Hyperplasia: Diagnosis and Management Updates

Background: Leukemias represent a heterogeneous group of hematological malignancies, which are characterized by the disordered proliferation of neoplastic hematopoietic cells, with the diffuse bone marrow involvement. Most frequent oral findings in leukemias are cyanotic or erythematous gingival hyperplasia with or without necrosis, petechiae, ecchymoses, mucosal ulcers and hemorrhage. Gingival hyperplasia is reported as a consistent symptom, which forwards patients for a dentistry consultation, that may lead to an early diagnosis of acute leukemias. The recognition of gingival enlargement as an initial oral manifestation of leukemic involvement assumes major practical significance, especially for the early diagnosis of non-lymphoblastic leukemias.

Objectives: The aims of researches were the evaluation of diagnosis and management of hyperplastic gingivitis in acute leukemias.

Material and Methods: The patients' follow-up and treatment were realized at the comprehensive cancer center. Our observational, analytical and descriptive study enrolled 8 patients with acute leukemias, who were treated at the Institute of Oncology from Moldova between 2012-2023. The diagnosis was asserted by the bone marrow aspiration with cytochemical reactions, tissue biopsy, buccal swab, or fine needle aspiration cytology. The immunophenotyping was performed in selected cases. The types of acute leukemias were assessed and distinguished according to the 2017 Revision of WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. This prospective study was related to the hospitalized and outpatient care.

Results: Hyperplastic gingivitis developed in cases with myelomonocytic and monocytic acute leukemias. The leukemia patients were admitted to the Institute of Oncology with a history of fatigue, fever, bone pain, gingival bleeding and enlargement detected by dentistry and family doctors from the consulting centers. ECOG-WHO performance score was 2-3. The intra-oral examination revealed generalized gingival hyperplasia. There were the amounts of plaque and calculus, which did not justify the enlargement degree. The gingiva was spongy and painless on palpation, with solitary sectors of necrosis and mucosal bleeding. Multiple soft and tender lymph nodes ranging from 0.8-1.5 cm in diameter were palpable bilaterally in the cervical and axillary regions. Splenomegaly of various degree was revealed by ultrasound scan in all patients. Complete blood count values ranged between: Hb 66-104 g/l, RBC 2.3-3.7 x 10 ¹²/l, WBC 11.3-47.2 x 10 ⁹/l, PLT 17.0-115.0 x 10 ⁹/l, blast cells 17-65%. The bone marrow aspiration detected hypercellularity, myeloid and monocytic blast cells (31.0-58.0%), as well as monocytes (9.0-14.0%). The studied cases were not suggestive of presence of FLT3 mutations. Hyperplastic gingivitis regressed in 5 (62.5%) cases after the achievement of complete (4 patients) and partial (1 patient) hematological responses under the first-line combined chemotherapy with conventional doses of cytarabine, anthracyclines and etoposide (2 patients). Local treatment included daily administration of oral steroids, antiseptic and hemostatic drugs. The narrative review of the recent references revealed that 37-53% of patients with monocytic and myelomonocytic leukemias were reported to develop gingival hyperplasia.

Conclusions: Hyperplastic gingivitis emerges in acute leukemias mostly due to the gingival infiltration with neoplastic blast cells. Gingival hyperplasia may regress under the combined chemotherapy and local treatment in patients with complete or partial hematological responses. Early diagnosis and treatment, thus, can increase the leukemia patients' prospects for complete hematological and local responses.