Malignant Prolactinoma: Prolactin Surge with Minimal Growth Masks Widespread Metastases

Abstract

Malignant prolactinomas are an exceptionally rare condition with metastatic spread and resistance to conventional treatments. Here is a report of a case of a 40-year-old male presenting initially responsive to dopamine agonist treatment who eventually demonstrated an exponential increase in his prolactin levels without much tumor progression wherein eventual investigations showed metastases over the abdominal and thoracic and vertebral regions. The patient in question had continued deterioration despite surgical debulking, radiotherapy, and systemic chemotherapy, and still had persisting high levels of prolactin. This case report points to the special challenge of clinical management presented by malignant prolactinomas with discordant patterns of hormonal and tumor growth, requiring careful follow-up and innovative therapies.

Introduction

Prolactinomas are the most common type of hormone-secreting pituitary tumors; they are typically benign and responsive to dopamine agonists such as cabergoline or bromocriptine. However, malignant prolactinomas are exceedingly rare, characterized by aggressive behavior and the capacity to metastasize. Rapid tumor growth is often the hallmark of these malignancies; however, there are cases in which the tumor shows minimal growth with disproportionate hormonal escalation.

The case study now describes a very rare occurrence of malignant prolactinoma in which a symptomatic increase of prolactin levels has occurred without perceived growth of the tumor on imaging. She eventually progressed under multiple therapeutic approaches to metastasize to the abdomen, thoracic region, and vertebral bones, thus pointing out the aggressive nature of the condition.

Case Presentation

This is a 40-year-old man who comes in complaining of continuous headaches and disturbances in vision that have worsened gradually over six months. The symptoms also reported have included fatigue, low libido, and erectile dysfunction. Preliminary laboratory investigations showed a prolactin level of 6,000 ng/mL (Normal range: 5-20 ng/mL). The MRI study of the brain demonstrated a 1.2 cm pituitary tumor without evidence of cavernous sinus invasion or compression of the optic chiasm.

Cabergoline was started as the first line of treatment for this patient. After starting, the levels of serum prolactin were reduced to 2,500 ng/mL, and the symptoms also disappeared. Six months into treatment, though she remained compliant with the treatment, her prolactin level began to rise exponentially, and her level was now 15,000 ng/mL. In follow-up imaging, minimal alteration in tumor size was seen at around 1.3 cm. Due to poor response to cabergoline, the patient was changed over to bromocriptine, but her prolactin levels continued to climb.

He was thus referred to an endocrinologist and neurosurgeon for further follow-up. The case at this point was considered a potential carcinoma of the pituitary if there was a discordance between tumor size and prolactin levels; however, this patient had none of the signs of local invasion or metastases at this time. Over the following months, his prolactin levels rose to over 50,000 ng/mL, accompanied by exacerbating pain in the back and abdominal discomfort.

Diagnostic Workup and Discovery of Metastases

Given the unusual clinical course, a full-body MRI and PET-CT scan were performed to assess for metastatic spread. Imaging revealed multiple lesions in the thoracic and lumbar vertebrae, suggestive of bony metastases, as well as metastatic deposits in the abdominal cavity. A biopsy of the vertebral lesions confirmed the presence of metastatic pituitary carcinoma.

The diagnosis of malignant prolactinoma was made based on the presence of distant metastases and the exponentially increasing prolactin levels despite minimal tumor growth. This finding was striking, as malignant prolactinomas typically exhibit more pronounced tumor enlargement before metastasizing. The patient’s prolactin levels at the time of metastatic discovery were over 100,000 ng/mL.

Treatment and Disease Progression

The patient underwent surgical debulking of the primary tumor followed by stereotactic radiotherapy to the pituitary gland. Despite this, prolactin levels remained elevated, and symptoms of metastasis, including persistent back pain and abdominal discomfort, worsened. Systemic chemotherapy with temozolomide, an alkylating agent commonly used in treating pituitary carcinomas, was initiated.

After six cycles of chemotherapy, imaging revealed stabilization of the vertebral metastases, but new lesions were detected in the thoracic cavity. The patient continued to experience profound fatigue, and prolactin levels remained above 80,000 ng/mL, indicating poor response to treatment.

Given the aggressive nature of the disease and the patient’s worsening quality of life, palliative care measures were initiated. The patient continued to receive pain management, and his case was discussed at a multidisciplinary tumor board for potential experimental therapies or enrollment in clinical trials.

Discussion

Malignant prolactinoma is a very rare occurrence, comprising less than 1% of all prolactin-secreting pituitary adenomas. The diagnosis is taken based on the presence of distant metastases, since in most cases, histopathological differentiation between benign and malignant prolactinomas can be hard to establish. Bones, liver, lungs, and lymph nodes were most commonly affected in this case.

Malignant prolactinomas have variable clinical presentations. In this case, the salient feature was an exponential rise in prolactin levels without the coupled growth of the tumor, a situation that many would expect from a growing malignant process. Typically, malignant prolactinomas are growing rapidly and invade surrounding structures with neurological deficits from compression. The problem in this case is that the size of the tumor remained relatively small despite the skyrocketing elevation in prolactin levels and the development of metastases.

The mechanisms responsible for the disproportionate hormonal output in malignant prolactinomas are not well understood. It is also hypothesized that mutations in the DRD2 gene or changes in the signaling of the prolactin receptor could also confer resistance to treatment and excessive, unregulated secretion of prolactin. Additionally, systemic alterations induced by metastatic disease may also promote hormone secretion independent of the primary tumor.

Therapeutic Challenges

Malignant prolactinomas pose therapeutic challenges. Dopamine agonists are very effective in the treatment of benign prolactinomas but usually fail to be effective in malignant cases, such as this patient. The failure to respond to cabergoline and bromocriptine is consistent with previously noted resistance to dopamine agonists in aggressive prolactin-secreting carcinomas.

The major local control treatment modalities have been surgical resection and radiotherapy, but these treatments do not very often achieve sustained remission, especially in those with metastatic disease. Chemotherapy with temozolomide has been effective in treating pituitary carcinomas, especially in patients whose MGMT promoter is methylated, though the response rates remain low overall.

Although the poor prognosis of malignant prolactinomas underscores the need for novel therapeutic approaches, promising methods in development include immunotherapy-targeted therapies and tumor-specific molecular profiling. It is obvious that aggressive disease patients would benefit from agents targeting the prolactin receptor or the tumor microenvironment-based approaches under clinical investigation.

Conclusion

This case is meant to illustrate unusual presentations of malignant prolactinoma with an exponential rise in prolactin levels, minimal tumor growth, and resistance to conventional therapies. Widespread metastases formation underscores the aggressive nature of this rare condition. Early recognition of malignant prolactinoma, particularly in patients with discordant hormonal and imaging findings, is critical to the initiation of appropriate treatment.

The existing therapeutic backbone includes dopamine agonists, surgery, radiotherapy, and chemotherapy, but the prognosis for malignant prolactinomas remains poor. Ultimately, further research into the molecular mechanisms that govern prolactin secretion and tumor metastasis is needed to facilitate improved treatment options for this difficult disease.

References

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