Cancer cells present in skin lesions resulting from mycosis fungoides originate from the blood, disproving previously held hypotheses regarding the disease’s pathogenesis, according to a study published in the American Society of Hematology’s Blood.
Cancer cells present in skin lesions resulting from mycosis fungoides (MF) originate from the blood, disproving previously held hypotheses regarding the disease’s pathogenesis, according to a study published in the American Society of Hematology’s Blood.
In the past, the MF was thought to “develop primarily in the skin by a clonal expansion of a transformed, resident memory T cell.” However, one hallmark of the disease is its widespread skin lesions, which skin-directed therapies have so far failed to cure. Because of this observation, researchers proposed an alternate source.
These findings suggest treating malignant clones in the blood, rather than those present in skin lesions, may be a more effective approach to the disease. An author of the paper, Robert Gniadecki, MD, said in a press release that “even when a patient has a barely noticeable lesion, there is already an abundance of cancer cells in the blood.”
Researchers used a whole-exome sequencing approach to quantify and detect clonotypes in tumor cell clusters that were microdissected from lesions. They analyzed T-cell receptor sequences from 29 patients exhibiting stages 1 through 4 of MF. The analysis “proved the existence of multiple T-cell clones within the tumor cell fraction, with a considerable variation between patients and between lesions from the same patient (median, 11 clones; range 2-80 clones/sample).”
Specifically, the study yielded the following results:
Based on these new findings, one potentially effective treatment could be circulating neoplastic T-cell clones to continually replenish skin lesions, “thus increasing their heterogeneity by a mechanism analogous to the consecutive tumor seeding,” researchers said. This method could also be used as a biomarker in MF.
Because MF is so rare—in the United States, roughly 3.6 cases per 1 million people each year are identified—the disease is often not recognized early. “The diagnostic delay can be up to 5 years until somebody actually makes the diagnosis; it’s not psoriasis, it’s not a bad infection of the skin, it’s actually cancer growing in your skin. It’s progressive, and we have no cure for this. It’s a huge medical need,” Gniadecki said.
Researchers hope the discovery will enable future treatment methods for the rare disease, which was previously targeted by eliminating cancer cells from the skin.
Iyer A, Hennessey D, O’Keefe S, et al. Skin colonization by circulating neoplastic clones in cutaneous T-cell lymphoma. Blood. 2019;124(18):1517-1527. doi: 10.1182/blood.2019002516.