Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review

Abstract

Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy.

Keywords: aggressive pituitary tumor; prolactinoma; radiosurgery; temozolomide.

Figure 1. Coronal Post-Contrast MRI Sequences

Following initial successful treatment with bromocriptine (arrow shows tumor within gland)

Figure 2. Coronal Post-Contrast MRI Sequences

First recurrence despite maximal medical therapy, showing marked enlargement and invasion of both cavernous sinuses

Figure 3. Photomicrographs of Histologic Specimens from First Surgery (400x)

Hematoxylin and eosin stain demonstrating pituitary adenoma with increased nuclear pleomorphism and elevated mitotic activity

Figure 4. Photomicrographs of Histologic Specimens from First Surgery (100x)

Increased immunoreactive Ki-67 labeling index

Figure 5. Photomicrographs of Histologic Specimens from Final Surgery

Hematoxylin and eosin stain with additional nuclear pleomorphism and mitoses

Figure 6. Photomicrographs of Histologic Specimens from Final Surgery (400x)

Markedly increased p53 labeling

Figure 7. Photomicrographs of Histologic Specimens from Final Surgery (100x)

Markedly increased Ki-67 labeling index

Figure 8. Coronal Post-Contrast MRI Sequences

Prior to craniotomy, demonstrating marked expansion with suprasellar extension and compression of optic chiasm (arrow) and intracranial invasion into right middle fossa

Figure 9. Coronal Post-Contrast MRI Sequences

After craniotomy at initiation of TMZ treatment, showing decompression of optic chiasm and debulking of tumor

Figure 10. Coronal Post-Contrast MRI Sequences

After Cyberknife radiosurgery

Figure 11. Coronal Post-Contrast MRI Sequences

Sequential tumor regression over eight cycles of TMZ treatment. Note the prominent reduction in tumor volume and gadolinium enhancement.

Figure 12. Coronal Post-Contrast MRI Sequences

Sequential tumor regression over eight cycles of TMZ treatment. Note the prominent reduction in tumor volume and gadolinium enhancement.