Fox Chase Cancer Center Researchers Propose a New Type of Sarcoma, PHF1::TFE3-Positive Fibromyxoid Sarcoma

Wei
Shuanzeng “Sam” Wei, MD, PhD, has published research that showed that a rare soft-tissue tumor that is usually benign can in some cases be a malignant sarcoma, an aggressive cancer.

PHILADELPHIA (October 9, 2024) — Ossifying fibromyxoid tumor, or OFMT, is a rare soft-tissue tumor that is usually benign. But a new study from researchers at Fox Chase Cancer Center has found that some of these growths are malignant sarcomas, an aggressive cancer.  

Understanding the difference and making a correct diagnosis is crucial to getting patients potentially life-saving treatment, said first and corresponding author Shuanzeng “Sam” Wei, MD, PhD, an Associate Professor in the Department of Pathology and Medical Director of the Clinical Genomics Laboratory at Fox Chase.

While it was previously known that most OFMTs are benign, a small number of cases have been classified as malignant. This study is the first time scientists have concluded that many of these malignant cases represent a different kind of tumor altogether.  

“We don’t think it’s the same thing,” said Wei, who conducted the study with colleagues from Fox Chase and researchers from other institutions. “The molecular alteration is different, the morphology is different, and the clinical behavior is different. It’s a different tumor.”

The study was sparked by two cases of malignant OFMT from consultation files at Fox Chase. “I dug into the literature and found that there have been a lot of OFMT cases with PHF1::TFE3 fusion that have malignant behavior,” Wei said.

The research team found that the behavior and morphology of the malignant tumors had more in common with sarcoma than OFMT. They also identified a key genetic difference between the two types of tumors.  

Fusion genes involving the gene PHF1 were previously known to be present in OFMT. However, when Wei took a closer look, he found that many sarcoma-like OFMT had PHF1 upstream in the fusion gene (PHF1::TFE3), compared to positioning downstream in all other fusion genes (EP400::PHF1, MEAF6::PHF1, and EPC1::PHF1). This different placement can be used as a genetic marker to correctly identify which tumor is which, he said.

“Molecular testing is very important to get the right diagnosis,” Wei said. “The tumor with PHF1::TFE3 should be treated more aggressively.” Therefore, using the name PHF1::TFE3-positive fibromyxoid sarcoma may be appropriate, he added.

The researchers plan to continue studying the tumors to better understand their differences and how to treat them. “This tumor is rare, so we’re collecting more cases — not only to confirm our findings but also to investigate the treatment options,” Wei said.  

The study, “PHF1::TFE3-Positive Fibromyxoid Sarcoma? Report of 2 Cases and Review of 13 Cases of PHF1::TFE3-Positive Ossifying Fibromyxoid Tumor in the Literature,” was published in the American Journal of Clinical Pathology.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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