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Published on: January 17, 2018
Case Report: Temozolomide Treatment of Refractory Prolactinoma Resistant to Dopamine Agonists
Hao Tang1, Yijun Cheng1, Jinyan Huang2
1Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Abstract:
Therapeutic agents for refractory prolactinomas that are resistant to dopamine agonists (DAs) are troublesome, and surgery often only removes a large part of the tumor without complete remission. Among the various second-line treatment regimens, the treatment effect of the alkylating agent temozolomide (TMZ) is only effective for approximately half of patients; however, complete remission is rare. Here we report a patient with prolactinoma who was resistant to high-dose cabergoline (CAB) treatment, demonstrating a continuous increase in both the tumor volume and the prolactin (PRL) level. Given that this case is a refractory prolactinoma, the patient underwent two transsphenoidal approach (TSA) surgeries. The pathological analysis indicated that the Ki-67 index increased significantly from 3% to 30%, and the expression levels of DRD2 and MGMT were low. Finally, TMZ treatment was recommended. A total of six cycles of TMZ standard chemotherapy shrank the tumor volume and the tumor disappeared completely. During the 6-month follow-up period, the tumor did not relapse again, and the PRL level was also normal. RNA sequencing and DNA whole genome sequencing were performed on this prolactinoma specimen, revealing 16 possible gene mutations, including a missense mutation of the PABPC1 gene. Additionally, the copy number variation analysis results showed that several chromosomes had copy number gains compared to the matched peripheral blood sample. In this case, low expression of DRD2 and high proliferation led to resistance to CAB, whereas low MGMT expression contributed to sensitivity to TMZ treatment. The results of genome sequencing still need further investigation at the molecular level to explain the tumor aggressiveness and high sensitivity to TMZ.
Insights
This case study highlights a patient with refractory prolactinoma resistant to dopamine agonists. Temozolomide (TMZ) chemotherapy achieved complete tumor remission, suggesting its potential for aggressive pituitary tumors.
Area of Science:
- Neuroendocrinology
- Oncology
- Genetics
Background:
- Refractory prolactinomas pose significant treatment challenges, often showing resistance to dopamine agonists (DAs) and incomplete surgical remission.
- Second-line treatments like temozolomide (TMZ) have shown limited efficacy, with complete remission being rare in prolactinoma cases.
Observation:
- A patient with prolactinoma exhibited resistance to high-dose cabergoline (CAB), with progressive tumor growth and elevated prolactin (PRL) levels.
- Despite two transsphenoidal surgeries, pathological analysis revealed a significant increase in the Ki-67 index (3% to 30%) and low expression of DRD2 and MGMT.
- The patient's prolactinoma showed resistance to CAB due to low DRD2 expression and high proliferation, but sensitivity to TMZ due to low MGMT expression.
Findings:
- Six cycles of temozolomide (TMZ) chemotherapy resulted in complete tumor shrinkage and disappearance, with no relapse during a 6-month follow-up.
- Genetic analysis identified 16 potential gene mutations, including a PABPC1 missense mutation, and copy number gains in several chromosomes.
- Low DRD2 expression and high proliferation contributed to CAB resistance, while low MGMT expression correlated with TMZ sensitivity.
Implications:
- This case demonstrates the potential of temozolomide (TMZ) as an effective treatment for refractory prolactinomas, even those resistant to dopamine agonists.
- Genetic profiling, including mutation and copy number variation analysis, may offer insights into tumor aggressiveness and predict treatment response.
- Further molecular investigation is warranted to elucidate the mechanisms underlying tumor aggressiveness and high sensitivity to TMZ in this patient.
