Challenges in Differential Diagnosis of Diffuse Gingival Enlargement: Report of Two Representative Cases and Literature Review

<b>Background/Objectives:</b> The etiology of diffuse gingival enlargement is multifactorial, and the definitive diagnosis may be challenging. To highlight the nuances of the differential diagnosis, we present two cases of generalized gingival overgrowth and discuss the diagnostic dilemmas. <b>Case description:</b> In the first case, an 82-year-old male with a medical history of hypertension and prostatitis had a chief complaint of symptomatic oral lesions of a 20-day duration, accompanied by fever and loss of appetite. The clinical examination revealed diffusely enlarged, hemorrhagic, and focally ulcerative upper and lower gingiva, ecchymoses on the buccal mucosa, as well as bilateral cervical lymphadenitis. The histopathologic and immunohistochemical findings combined with the hematologic examination led to a final diagnosis of acute myeloid leukemia, and the patient was referred to a specialized hematology/oncology unit for further management. The second case was a 74-year-old female with a medical history of breast cancer (successfully managed in the past), type II diabetes mellitus, and cardiovascular disease, taking various medications. An intraoral examination revealed diffusely enlarged, erythematous, and hemorrhagic upper and lower gingiva. An incisional biopsy showed hyperplastic granulation and fibrous connective tissue with a predominantly chronic inflammatory infiltrate. Considering the patient's medical history and current medications, the clinical and microscopic findings were in support of the diagnosis of drug-induced gingival overgrowth associated with calcium channel blocker (amlodipine), partially controlled diabetes serving as an additional predisposing factor. Gingivectomy and periodontal scaling, along with substitution of the offending medication, were curative, and better diabetic control was recommended. <b>Conclusions:</b> Diffuse gingival overgrowth may be caused by a variety of diverse conditions, ranging from an exuberant response to local factors, potentially exacerbated by hormonal influences (e.g., puberty or pregnancy), to drug side effects to genetic, systemic, or even neoplastic diseases. A careful evaluation of the medical and drug history and clinicopathologic correlation is essential for accurate diagnosis and appropriate management.