Tumor cells left behind in surgery can cause Cushing’s recurrence, per report
Woman, 30, needed second procedure when disease returned after 4 years
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Although rare, researchers say that recurrent Cushing’s disease can be caused by tumor cells accidentally left in the sphenoid sinus — an air-filled space behind the nose — during surgery to remove a tumor from the brain’s pituitary gland through the nasal passages.
That’s what happened to a young woman in Japan who underwent the procedure, called a transsphenoidal adenomectomy, to treat her Cushing’s disease, according to a new case report.
Initially, the woman was successfully treated, with her Cushing’s going into remission. However, when the disease returned several years later despite normal brain scans, doctors performed a second surgery where they removed a small tumor behind the nose, suggesting that tumor cell seeding along the surgical path should be considered. In other words, dislodged tumors inadvertently left behind in the first surgery were the cause of the recurrence.
According to the researchers, this area should be carefully examined when symptoms return. Additionally, to prevent this complication, “thorough irrigation of the operative field with normal saline before closure is a simple maneuver that may help reduce the risk of tumor cell seeding,” the team wrote.
The study, “Recurrent Cushing’s disease due to postoperative seeding of tumor cells in the sphenoid sinus: a case report with review of the literature,” was published in the Endocrine Journal.
Cushing’s disease occurs when a tumor in the pituitary gland produces and releases an excess of adrenocorticotropic hormone (ACTH), which signals the production of cortisol by the adrenal glands located on top of the kidneys. An excess of cortisol can result in a wide range of symptoms, such as high blood pressure.
A transsphenoidal adenomectomy is a minimally invasive surgery used to remove tumors from the pituitary gland. Surgeons access the tumor through the nasal passages and the sphenoid sinus, which allows direct access to the base of the brain. Although rare, dislodged tumor cells can be left along the path of a surgical instrument as it is withdrawn, the researchers noted.
First surgery had appeared to remove entire tumor
In this case, a 30-year-old woman was first referred to the hospital after high blood pressure was detected during a visit for a respiratory infection. Blood tests showed high cortisol and ACTH, which raised suspicion of Cushing’s disease. She also had signs of Cushing’s disease, including a buildup of fat around the abdomen and neck, purple stretch marks, and thin, bruised skin.
Magnetic resonance imaging (MRI) with contrast dye showed a tumor in the pituitary gland, which was found to produce excess ACTH. The woman underwent transsphenoidal adenomectomy, and the entire visible tumor was removed. The tumor had a very low Ki-67 index, a marker of how quickly tumor cells divide, suggesting slow growth, per the report.
One week after surgery, cortisol and ACTH had returned to normal, indicating remission. She temporarily received hydrocortisone to replace cortisol because her body needed time to restart its own cortisol production. Her blood pressure was well controlled, and her medication was stopped.
About four years later, the woman began gradually developing muscle weakness and gaining excess weight. Blood tests confirmed that Cushing’s disease had returned. She was treated with cabergoline, which reduces the production of ACTH, metyrapone, which reduces the production of cortisol, and pasireotide, which acts on tumor cells.
However, these medications could not fully control the excess cortisol. Over the next several years, repeated MRI scans failed to identify any recurrent tumor.
Finally, her doctors decided to perform a second transsphenoidal adenomectomy. During the second surgery, they found a small, soft, white tumor attached to the back of the front wall of the sphenoid sinus.
After removal of the tumor, cortisol and ACTH quickly returned to normal, showing that the disease was once again in remission. When the doctors reviewed the earlier exams, they found that the small tumor had actually been visible but had been overlooked because it was located outside the pituitary gland.
The doctors concluded that recurrence was probably caused by tumor cells that had accidentally been dislodged into the sphenoid sinus during the first surgery and later grew into a new tumor.
As such, the researchers noted that “awareness of this mechanism is crucial for evaluating MRI-negative recurrences.”
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