Researchers at Children’s Hospital of Philadelphia’s (CHOP) Cancer Center evaluated two infants with rapidly growing soft-tissue tumors that were difficult to interpret microscopically but driven by a targetable gene alteration. Both case reports, published in the Journal of Hand Surgery and JCO Precision Oncology, make a compelling case that selecting the appropriate genetic tests is critical because distinct types of gene alterations require different detection methods, and using the wrong assay can miss actionable targets that could change the treatment approach and potential outcomes.
In the JCO Precision Oncology case report, a newborn had a large, purple mass on his lip and nose that blocked one nostril and threatened breathing; a microscopic exam was inconclusive. RNA testing plus long‑read DNA sequencing revealed a complex PDGFRB rearrangement that left the protein permanently active – a change that can drive cancer growth.
“Long‑read sequencing was crucial because it revealed a complex genomic alteration with two deletions flanking an inversion that altered splicing, important details missed by short‑read testing. This information allowed us to rule out a germline mutation,” said Marilyn M. Li, MD, MS, a corresponding author on the JCO paper, Vice Chief of the Division of Genomic Diagnostics and Director of Cancer Genomic Diagnostics at CHOP.
That clear result allowed doctors to identify the drug imatinib as a potential solution because it targets proteins in cancer cells and stops them from growing. At about one month old, the baby started imatinib; the tumor shrank quickly and was clinically gone by four months. After approximately a year of treatment, imatinib use was discontinued. The child has remained recurrence-free more than three years after treatment was completed.
In the case reported in the Journal of Hand Surgery, a premature infant had an infantile fibrosarcoma-like tumor, a locally aggressive tumor that traditionally requires chemotherapy and radical excision or amputation. Recently, targeted therapies have been used to reduce similar tumors and make them small enough to require less invasive surgery. However, in this case, the tumor did not have the typical genetic alteration seen in infantile fibrosarcoma (an NTRK gene fusion).
Instead, testing revealed an anaplastic lymphoma kinase (ALK) fusion, when part of the ALK gene gets stuck to another gene, making a permanently “on” protein that can cause cancer cells to grow. The team treated the infant with oral lorlatinib, an ALK inhibitor, before surgery to shrink the tumor, then performed staged conservative resections and grafting to preserve tendons and nerves.
Because portions of the tissue remained positive for cancer cells, doctors continued the lorlatinib after surgery. Two years later the child is still on lorlatinib with no recurrence or metastasis, good hand function, only manageable side effects and limited scaring that required additional surgery and therapy to support mobility.
“Precision testing and targeted therapy can spare infants harsh treatments and preserve function. In these cases, multidisciplinary collaboration is vital, since distinct genetic drivers require specific tests and individualized treatments,” said Theodore W. Laetsch, MD, a co-senior author of the Journal of Hand Surgery paper and a pediatric oncologist who leads CHOP’s Developmental Therapeutics Program and Very Rare Malignant Tumors Program.
The authors acknowledge that these are single-case reports and that the best duration of targeted therapy is unknown. The researchers continue to study long-term outcomes.
The PDGRFB research was supported by NIH grant (HG013359), (1R50CA305079), Alex’s Lemonade Stand Foundation and CHOP’s Frontier Program, CHOP Omics.
Valle et al. “Infantile Fibrosarcoma of the Hand: Limb-Sparing Treatment with Modern Targeted Oral Chemotherapy and Conservative Surgical Resection.” J Hand Surg. Online December 5, 2025. DOI: 10.1016/j.jhsg.2025.100887.
Bastianelli et al. “Molecular Characterization of a Complex PDGFRB Structural Variation in Infantile Myofibroma with Complete Response to Imatinib.” JCO Precis Oncol. Online January 14, 2026. DOI: 10.1200/PO-25-00943.
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Researchers at Children’s Hospital of Philadelphia’s (CHOP) Cancer Center evaluated two infants with rapidly growing soft-tissue tumors that were difficult to interpret microscopically but driven by a targetable gene alteration. Both case reports, published in the Journal of Hand Surgery and JCO Precision Oncology, make a compelling case that selecting the appropriate genetic tests is critical because distinct types of gene alterations require different detection methods, and using the wrong assay can miss actionable targets that could change the treatment approach and potential outcomes.
In the JCO Precision Oncology case report, a newborn had a large, purple mass on his lip and nose that blocked one nostril and threatened breathing; a microscopic exam was inconclusive. RNA testing plus long‑read DNA sequencing revealed a complex PDGFRB rearrangement that left the protein permanently active – a change that can drive cancer growth.
“Long‑read sequencing was crucial because it revealed a complex genomic alteration with two deletions flanking an inversion that altered splicing, important details missed by short‑read testing. This information allowed us to rule out a germline mutation,” said Marilyn M. Li, MD, MS, a corresponding author on the JCO paper, Vice Chief of the Division of Genomic Diagnostics and Director of Cancer Genomic Diagnostics at CHOP.
That clear result allowed doctors to identify the drug imatinib as a potential solution because it targets proteins in cancer cells and stops them from growing. At about one month old, the baby started imatinib; the tumor shrank quickly and was clinically gone by four months. After approximately a year of treatment, imatinib use was discontinued. The child has remained recurrence-free more than three years after treatment was completed.
In the case reported in the Journal of Hand Surgery, a premature infant had an infantile fibrosarcoma-like tumor, a locally aggressive tumor that traditionally requires chemotherapy and radical excision or amputation. Recently, targeted therapies have been used to reduce similar tumors and make them small enough to require less invasive surgery. However, in this case, the tumor did not have the typical genetic alteration seen in infantile fibrosarcoma (an NTRK gene fusion).
Instead, testing revealed an anaplastic lymphoma kinase (ALK) fusion, when part of the ALK gene gets stuck to another gene, making a permanently “on” protein that can cause cancer cells to grow. The team treated the infant with oral lorlatinib, an ALK inhibitor, before surgery to shrink the tumor, then performed staged conservative resections and grafting to preserve tendons and nerves.
Because portions of the tissue remained positive for cancer cells, doctors continued the lorlatinib after surgery. Two years later the child is still on lorlatinib with no recurrence or metastasis, good hand function, only manageable side effects and limited scaring that required additional surgery and therapy to support mobility.
“Precision testing and targeted therapy can spare infants harsh treatments and preserve function. In these cases, multidisciplinary collaboration is vital, since distinct genetic drivers require specific tests and individualized treatments,” said Theodore W. Laetsch, MD, a co-senior author of the Journal of Hand Surgery paper and a pediatric oncologist who leads CHOP’s Developmental Therapeutics Program and Very Rare Malignant Tumors Program.
The authors acknowledge that these are single-case reports and that the best duration of targeted therapy is unknown. The researchers continue to study long-term outcomes.
The PDGRFB research was supported by NIH grant (HG013359), (1R50CA305079), Alex’s Lemonade Stand Foundation and CHOP’s Frontier Program, CHOP Omics.
Valle et al. “Infantile Fibrosarcoma of the Hand: Limb-Sparing Treatment with Modern Targeted Oral Chemotherapy and Conservative Surgical Resection.” J Hand Surg. Online December 5, 2025. DOI: 10.1016/j.jhsg.2025.100887.
Bastianelli et al. “Molecular Characterization of a Complex PDGFRB Structural Variation in Infantile Myofibroma with Complete Response to Imatinib.” JCO Precis Oncol. Online January 14, 2026. DOI: 10.1200/PO-25-00943.
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