Clinical Report: Novel PTRH2::ALK Fusion in ALK-positive Histiocytosis

Overview

This report details a rare case of ALK-positive histiocytosis in an infant, initially misdiagnosed as a liver abscess. The identification of a novel PTRH2::ALK fusion gene expands the molecular understanding of this condition and underscores the importance of accurate diagnosis.

Background

ALK-positive histiocytosis is a rare pediatric neoplasm characterized by ALK gene rearrangements. Its clinical presentation can mimic infectious diseases, leading to potential misdiagnosis. Understanding its molecular basis and clinical features is crucial for timely and appropriate management.

Data Highlights

Case data includes:
- Patient: 8-month-old male
- Hemoglobin level: 63 g/L
- Serum S-100 protein level: 9.11 ug/L
- Largest liver lesion: approximately 7 × 8 mm
- Treatment: ALK inhibitor crizotinib

Key Findings

• ALK-positive histiocytosis is a novel histiocytic neoplasm recognized in recent classification systems.
• The case presented involved an infant with symptoms misattributed to a liver abscess.
• Histopathological examination confirmed the diagnosis through the presence of ALK rearrangement.
• A novel PTRH2::ALK fusion was identified, expanding the known molecular landscape of this disease.
• Crizotinib was effective in managing the patient's condition post-diagnosis.

Clinical Implications

Healthcare providers should consider ALK-positive histiocytosis in pediatric patients presenting with atypical fever and hepatic masses. Early molecular testing for ALK rearrangements can prevent misdiagnosis and facilitate appropriate treatment with ALK inhibitors.

Conclusion

This case highlights the importance of recognizing ALK-positive histiocytosis in infants and the role of molecular diagnostics in guiding treatment. The identification of a novel fusion gene contributes to the understanding of this rare neoplasm.

References

1. Acta Neuropathologica, 2021 -- Activation of NTRK2 and ALK Receptor Tyrosine Kinase Fusions Broadens the Molecular Profile of Early Childhood Pleomorphic Xanthoastrocytomas: Implications for Differential Diagnosis with Infant-Type Hemispheric Glioma
2. Acta Neuropathologica, 2022 -- Identification of a Targetable ROS1::GIT2 Fusion in Non-Langerhans Cell Histiocytosis Affecting the Central Nervous System
3. Blood Cancer Journal, 2016 -- Crizotinib Efficacy in Treating Refractory Pediatric Acute Myeloid Leukemia Associated with RAN-Binding Protein 2-ALK Fusion Gene
4. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms | Leukemia, 2022
5. ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition | Blood, 2022
6. Open Forum Infectious Diseases — Utilization of Gastrointestinal Multiplex PCR Panel for Diagnosing Amoebic Liver Abscess: A Report on Three Pediatric Cases
7. ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition
8. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms | Leukemia
9. ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition | Blood | American Society of Hematology