Can leukemia present with a swollen tongue (macroglossia)?

Can Leukemia Present with a Swollen Tongue?

Yes, leukemia can present with tongue swelling (macroglossia), though this is an uncommon manifestation that occurs through several distinct mechanisms including direct leukemic infiltration (myeloid sarcoma), neutrophilic infiltration in Sweet's syndrome, or secondary effects from gingival/oral involvement.

Mechanisms of Tongue Swelling in Leukemia

Direct Leukemic Infiltration (Myeloid Sarcoma)

• Myeloid sarcoma (MS) can occur in the tongue as an extramedullary manifestation of acute myeloid leukemia (AML), particularly acute promyelocytic leukemia (APL). 1
• This represents direct infiltration of leukemic cells into the tongue tissue and may precede bone marrow involvement, making it a potential first manifestation of the disease. 1
• MS of the tongue is extremely rare but has been documented with presenting symptoms including tongue pain, irregular tumor masses on the lateral tongue edge, and systemic symptoms like fever and bleeding. 1

Sweet's Syndrome-Associated Macroglossia

• Sudden massive tongue swelling can occur in patients with acute myelogenous leukemia through Sweet's syndrome (acute febrile neutrophilic dermatosis). 2
• This mechanism involves infiltration of mature neutrophils into the tongue tissue, similar to the neutrophilic infiltrates seen in cutaneous lesions of Sweet's syndrome. 2
• Approximately 10-20% of Sweet's syndrome cases occur in patients with malignancy, with acute myelogenous leukemia being the most commonly associated neoplasm. 2

Common Oral Manifestations of Leukemia

Primary Oral Lesions

• Oral manifestations occur in up to 90% of acute myeloid leukemia cases and may be the presenting feature of the disease. 3
• The most frequent oral findings include gingival enlargement and bleeding, oral ulceration, petechiae, mucosal pallor, hemorrhagic bullae on the tongue, and cracked lips. 4, 3
• Acute myeloid leukemia (72.72%) and acute lymphoblastic leukemia (18.18%) most commonly present with oral manifestations as first clinical signs. 5

Tissue Distribution

• The principal oral tissues affected are gingival tissue, buccal mucosa, and hard/soft palate. 5
• When hard tissues (maxilla or mandible) are involved, dental mobility becomes the principal clinical sign. 5
• Tongue involvement specifically can manifest as hemorrhagic bullae, color changes, or mass lesions depending on the underlying mechanism. 4, 1, 3

Clinical Implications and Diagnostic Approach

Recognition as Initial Presentation

• Oral lesions can present as initial evidence of leukemia or its relapse, making early recognition critical for diagnosis and improved patient outcomes. 4
• These manifestations arise from either direct infiltration of leukemic cells (primary) or secondary to thrombocytopenia, neutropenia, or impaired granulocyte function. 4

Diagnostic Workup

• When tongue swelling or other oral lesions suggest leukemia, diagnosis requires anatomopathological and immunohistochemical study of the lesion, along with molecular testing for definitive leukemia subtype confirmation. 1
• Complete blood count with differential, peripheral blood smear, and bone marrow examination are essential for establishing the diagnosis of leukemia. 6, 7

Critical Pitfalls to Avoid

• Do not dismiss isolated tongue swelling or oral lesions as benign without considering hematologic malignancy, especially when accompanied by systemic symptoms like fever, fatigue, or bleeding. 1, 5
• Failure to recognize acute promyelocytic leukemia immediately is particularly dangerous, as it requires immediate ATRA therapy upon clinical suspicion due to high mortality risk. 7
• The rarity of tongue involvement should not delay appropriate hematologic evaluation when clinical suspicion exists. 1