Cushing’s patients’ pituitary tumors become aggressive cancers
Case report highlights rare development in 2 middle-aged women
The noncancerous pituitary gland tumors that cause Cushing’s disease can rarely become cancerous, leading to rapidly progressing disease, a recent case report highlighted.
Scientists reported on two middle-aged women with Cushing’s who underwent surgery and radiation therapy for their pituitary tumors. The tumors eventually recurred and spread, showing signs that they had become cancer.
While it is possible that the radiation therapy itself drove this cancerous process, the exact cause of the rare phenomenon remains unclear.
The study, “Emergence of NEC features in corticotroph PitNETs: primary tumor, radiation-induced transformation, or metastasis?” was published in Brain Tumor Pathology.
Patients showed evidence of aggressive malignant transformation
In Cushing’s disease, a tumor in the brain’s pituitary gland produces abnormally high amounts of adrenocorticotropic hormone (ACTH), which signals the adrenal glands above the kidneys to make too much of the stress hormone cortisol. This cortisol excess drives the various symptoms of Cushing’s disease.
First-line treatment involves surgery to remove the tumor. Radiation therapy, where focused high-energy beams are used to shrink the tumor, may be used in cases where the tumor persists or recurs.
Cushing’s-related tumors belong to a class called pituitary neuroendocrine tumors (PitNETs), previously referred to as pituitary adenomas. They are usually benign, or noncancerous.
However, in rare cases, they can become cancerous — spreading to other tissues and resisting treatment — in a process called malignant transformation.
Between 2005 and 2022, researchers in Japan surgically removed more than 4,000 PitNETs. Of the affected patients, two showed evidence of rapid and aggressive malignant transformation, at which point the cancer is called a neuroendocrine carcinoma. The scientists discussed these two cases in more detail in the recent report.
Exactly how these cancerous tumors arise is unclear
The first patient was a woman in her 60s who underwent surgery to remove the pituitary tumor that was causing her Cushing’s disease. Her symptoms initially improved, but ACTH and cortisol levels rose again the following year, and she was treated with radiation therapy.
After six years in disease remission, the tumor suddenly and aggressively started to grow again, leading to progressive neurological symptoms for which she required additional surgery.
Tissue analyses revealed that the previously benign tumor had undergone a malignant transformation, showing cellular features consistent with cancer.
Following surgery, the woman received additional radiation and hormone-modulating medications. Still, the cancer continued to spread, and she died of progressive disease seven months later.
The absolute risk remains low and must be weighed against the therapeutic benefit.
The second patient, a woman in her 50s, underwent three surgeries and radiation for her Cushing’s disease over a period of a few years. A tissue analysis after the third surgery suggested a standard, benign pituitary tumor.
However, two years later, the woman experienced sudden vision loss, and an MRI showed a new mass that was compressing her optic nerve, which sends signals between the brain and eyes.
The scientists performed a fourth tumor removal surgery, at which point the tissue showed signs of malignant transformation. Despite hormone-modulating and chemotherapy treatment, the cancer grew, and she died five months later.
The researchers noted that exactly how these cancerous tumors arise is not clear. Some research has suggested that radiation therapy for the original tumor could rarely cause genetic changes in the tumor that drive malignant transformation.
Still, the researchers indicated that “the absolute risk remains low and must be weighed against the therapeutic benefit.”
It’s also possible that the cancerous tumors did not develop secondarily to the initial Cushing’s tumor, and either spread from elsewhere or occurred spontaneously on their own. However, the scientists don’t think that’s as likely.
“Further research is warranted to elucidate the mechanisms and risk factors underlying this malignant transformation process,” the team concluded.
About the Author
