Breaking Down Barriers to Treat a Patient With a Germinoma: A Case Study

Susan Bell

Disclosures

J Neurosci Nurs. 2004;36(4) 

In This Article

Abstract and Introduction

Germinomas are the most common type of germ cell tumor occurring commonly before the second decade of life. Because of the radiosensitivity of germinomas, traditional treatment following diagnosis has been conventional radiotherapy. The desire to defer radiotherapy to avoid the delayed neurocognitive effects has led researchers to investigate the use of upfront chemotherapy. A major limitation in using chemotherapy for brain tumors has been the inability to deliver drugs across the blood brain barrier. The blood brain barrier consortium has developed chemotherapy protocols for patients with malignant brain tumors through the use of reversible osmotic opening of the blood brain barrier. While the patient is under general anesthesia, osmotic opening or disruption is achieved by a 30-second intracarotid infusion of mannitol. The mannitol infusion is followed by both intraarterial and intravenous chemotherapy. By administering chemotherapy in conjunction with blood brain barrier disruption, drug delivery to the tumor and the brain around tumor is increased.

A previously healthy 29-year-old married Caucasian female presented with a several year history of amenorrhea after stopping her oral contraceptives. Her endocrine workup was normal except for an elevated serum prolactin level at 151 ng/ml (normal range for nonpregnant females is 2.8-29.2 ng/ml). A magnetic resonance imaging (MRI) scan of the brain was obtained with and without contrast that demonstrated thickening and homogenous enhancement of the infundibular stalk. Differential diagnoses included sarcoidosis, histocytosis, or other granulomatous diseases; Erdheim-Chester disease; and lymphocytic hypophysitis, or most likely, a microscopic prolactinoma. She was treated first with bromocriptine, and after her prolactin levels failed to return to normal, she was placed on cabergoline (Dostinex) 0.25 mg. In an effort to stimulate ovulation, she was placed on conjugated estrogen (Premarin 0.625 mg) and medroxyprogesterone (Provera 5 mg).

At follow-up with her endocrinologist 2 1/2 years later, she was still on the Dostinex, Premarin, and Provera. She never resumed a normal menstrual cycle despite a reduction in her prolactin levels (now 0.3 ng/ml). She complained of some minor dizziness and weight gain. She was gravida 2, para 1 (prior to the amenorrhea), and her last Pap test was reportedly normal. On physical examination she was 66-1/4 inches in height, 146 pounds. Her blood pressure was 96/60 mm Hg with a pulse of 72. Her physical examination otherwise was normal with grossly normal visual fields to confrontation.

The MRI was repeated and now identified a large mass in the sellar and suprasellar regions with other lesions in the subependymal area of the frontal horns of the lateral ventricles without hydrocephalus (Fig 1). A referral was made to a neurosurgeon who believed the tumor was not a typical adenoma but more consistent with either lymphoma or germinoma. She underwent a transsphenoidal biopsy approximately 3 weeks later. The pathology was consistent with a germinoma. Postoperatively, the endocrinologist determined she was panhypopituitary, and she was placed on levothyroxine (Synthroid 88 mcg every day), desmopressin (DDAVP 0.1 mg twice a day), and hydrocortisone (15 mg in the morning and 10 mg in evening). She did well postoperatively and was discharged to her home. A spinal tap was done approximately 3 weeks after surgery for cytology and tumor markers (alpha fetoprotein [AFP] and beta human chorionic gonadotropin [β-HCG]), all of which were negative. She was also seen by the neuro-ophthalmologist. A full ophthalmological workup was completed and revealed that she had excellent vision with normal visual fields. A spine MRI was not done.

Baseline magnetic resonance imaging (MRI) scan with gadolinium. Coronal view showing mass extending out of the pituitary gland up in the hypothalamic area.

Options for treatment were discussed with the patient and family. A decision was made to begin treatment with chemotherapy instead of radiation therapy. Approximately 3 weeks later, she began a high dose chemotherapy regimen with intravenous etoposide phosphate and cytoxan, and intra-arterial carboplatin with osmotic blood brain barrier disruption (BBBD). To prevent chemotherapy-induced high-frequency ototoxicity associated with the intra-arterial injection of carboplatin in conjunction with BBBD, she received intravenous sodium thiosulfate at 4 and 8 hours following her BBBD. By the third month of treatment, she had a complete response; the MRI scan showed no tumor enhancement (Fig 2).

Magnetic resonance imaging (MRI) scan with gadolinium following 3 months of treatment with intra-arterial chemotherapy with blood brain barrier disruption showing no tumor enhancement.

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