A macroprolactinoma becoming resistant to cabergoline and developing atypical pathology

Area of Science:

• Endocrinology
• Neurosurgery
• Pathology

Background:

• Pituitary adenomas are common intracranial neoplasms, with prolactinomas being the most frequent type.
• Dopamine agonists (DAs) are the primary treatment for prolactinomas, while surgery and radiotherapy are reserved for specific complications or resistance.
• Tumor behavior can range from typical and non-invasive to aggressive and malignant.

Purpose of the Study:

• To present a case of a prolactin-secreting macroadenoma that developed secondary resistance to dopamine agonists.
• To highlight the potential for tumor de-differentiation and aggressive transformation in response to treatment resistance.
• To emphasize the importance of a multidisciplinary approach in managing complex pituitary adenomas.

Main Methods:

• Case report of a 62-year-old male with a prolactin-secreting macroadenoma.
• Initial management with partial resection and cabergoline therapy.
• Subsequent treatment involved dose escalation of cabergoline, further surgical resections, and eventual radiotherapy referral due to tumor progression and resistance.

Main Results:

• The patient's prolactinoma initially responded to cabergoline but later became resistant, exhibiting rapid growth and vision worsening.
• Histological examination of the recurrent tumor revealed features of aggressive behavior (atypical adenoma with high proliferation index), not present initially.
• Despite multiple interventions, the tumor continued to enlarge, and prolactin levels remained significantly elevated.

Conclusions:

• Secondary resistance to dopamine agonists in prolactinomas may indicate de-differentiation and potential malignant transformation.
• Consecutive histological findings of significant de-differentiation suggest a possible transition towards malignancy.
• Histological 'alarm' features, persistent growth, and DA treatment escape in recurrent adenomas necessitate vigilant clinical suspicion and close follow-up.