P2.224: A Masquerading Presentation of ALCL in a Young Child

Introduction: Anaplastic Lymphoma Kinase (ALK)-positive Anaplastic Large Cell Lymphoma (ALCL) is a rare, CD30-positive mature T-cell lymphoma. Though the median age for ALK-positive ALCL is 35 years, it accounts for 10–15% of pediatric non-Hodgkin lymphoma cases[1, 2] . Diagnosis often occurs at advanced stages (III/IV)[3]. Clinical presentation frequently includes B symptoms (55%), and the disease most frequently involves peripheral lymph nodes (90%), mediastinum (45%), and skin (25%)[3]. Involvement of the oral cavity is particularly rare and can mimic benign conditions, leading to delays in diagnosis and treatment[3, 4].

Case Description: A previously healthy 3-year-old male presented to urgent care with fevers, jaw pain, and fatigue, initially raising suspicion for an infectious etiology. As symptoms persisted, he was evaluated at a children’s hospital emergency department (ED) three weeks later, where friable white plaques were visualized on the floor of his mouth, and he was treated for thrush. With worsening jaw pain, he presented to the ED two weeks later, and was thought to have an abscess. At this time, he was transferred to a tertiary care center, where biopsy revealed fibrinopurulent necroinflammatory debris, consistent with an ulcer, but with no evidence of malignancy. The patient was discharged for outpatient evaluation.
Another two weeks later, he re-presented with progressive jaw swelling that was warm to the touch. A second biopsy was performed, and further workup, including immunohistochemistry (IHC), revealed ALK positivity. Fluorescence in situ hybridization (FISH) confirmed an ALK rearrangement in 49% of cells, identifying an NPM1::ALK fusion; and comprehensive disease evaluation revealed stage III ALCL. Tumor sequencing revealed pathogenic changes, including a TP53 mutation and copy number alterations in 17p (loss) and 17q (gain). The patient was treated with chemotherapy per ANHL12P1, brentuximab arm.

Discussion: ALK-positive ALCL is rare in pediatric patients, typically presenting with lymphadenopathy or extranodal masses. Oral involvement is exceedingly uncommon, and its occurrence in a 3-year-old patient makes this case particularly noteworthy. Delayed diagnosis of ALK-positive ALCL is associated with poorer outcomes, and in this case, initial misdiagnosis led to a delay in appropriate treatment[3]. This underscores the importance of considering malignancy in pediatric oral lesions refractory to typical therapies and maintaining a broad differential early in evaluation[4].
Molecular testing with proper IHC and FISH were crucial to confirming the diagnosis and identifying the NPM1::ALK fusion as the oncogenic driver within the biopsy specimen. Additionally, ALK-positive ALCL in pediatric patients demonstrates molecular heterogeneity, and further genetic analysis can enhance our understanding of its molecular pathology while guiding treatment strategies[5].

Conclusion: This case highlights the diagnostic challenges and unique presentation of ALK-positive ALCL in a pediatric patient with oral involvement. Increased awareness of atypical presentations and prompt recognition of malignancy in unusual sites may improve early diagnosis and outcomes in patients.