Mycosis Fungoides with Large-Cell Transformation Metastatic to the Central Nervous System
This paper reports a rare case of a 77-year-old man with long-standing mycosis fungoides who developed large-cell transformation metastatic to the central nervous system, a diagnosis confirmed by stereotactic brain biopsy and molecular analysis of identical T-cell receptor gene rearrangements in both skin and brain lesions despite nondiagnostic cerebrospinal fluid studies.
Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer
Skin is the body's largest organ, a protective barrier that also serves as a home for immune cells. In a condition called mycosis fungoides, a specific type of white blood cell that normally patrols the skin begins to multiply uncontrollably, forming patches and tumors. While this disease often moves slowly over many years, it can sometimes change its nature, becoming more aggressive and spreading to other parts of the body like the lymph nodes or lungs. Even more rarely, these rogue cells can travel to the brain, a place they almost never visit. When they do, the situation becomes critical, yet doctors often struggle to recognize the problem because the symptoms look like many other neurological issues, and standard tests of the fluid surrounding the brain often come back empty.
A team of researchers at the Mayo Clinic and the University of Ottawa recently documented a striking example of this rare event. They followed a 77-year-old man who had lived with mycosis fungoides for thirteen years. For over a decade, his condition was managed with creams and medication, and he had no signs of the disease spreading beyond his skin. Then, in 2025, he began to feel progressively weaker, his walk became unsteady, and he lost weight without trying. These were not typical signs of a skin condition; they pointed to a problem inside the brain. An MRI scan revealed multiple bright spots on both sides of his brain, which initially looked like a primary brain cancer or a different type of lymphoma. To make matters more difficult, when doctors took a sample of the fluid surrounding his brain to look for cancer cells, the test found nothing. The fluid was clear of the disease, even though the brain itself was clearly under attack.
Because the fluid test was inconclusive and the man's condition was worsening, the medical team performed a precise biopsy, taking a tiny sample of one of the brain lesions. Under the microscope, the tissue told a different story. Instead of normal brain cells, the sample was filled with large, abnormal immune cells that had crowded around the blood vessels. These cells were growing rapidly, with a high number of them dividing at any given moment. Crucially, the cells showed a specific pattern of proteins on their surface that matched the cancer cells found in the man's skin biopsy from years earlier. To be absolutely certain, the researchers compared the genetic fingerprint of the cells in the brain with those in the skin. They found that the DNA rearrangements in the immune cells were identical in both places. This confirmed that the disease in the brain was not a new, unrelated cancer, but the original skin cancer that had transformed, changed its appearance, and traveled to the central nervous system.
The case highlights a dangerous shift in the disease. The cells in the brain were much larger and more aggressive than the ones found in the skin years prior. They had acquired new traits, such as a high level of a protein called CD30 and a loss of a protective protein called p16, which likely allowed them to grow unchecked and invade the brain. While the fluid surrounding the brain failed to show the cancer, the tissue biopsy proved the diagnosis beyond doubt. This finding is significant because it shows that even when a patient's skin looks clear or the disease seems controlled, the cancer can still hide and spread to the brain. The researchers emphasize that when a patient with a history of this skin cancer develops new neurological symptoms, doctors must look for brain involvement directly through tissue sampling, rather than relying solely on fluid tests or assuming the skin is the only place the disease exists.
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