Seminoma with Neoplastic Meningitis Treated with Craniospinal Irradiation

This brief communication reports a case of pure seminoma metastatic to the leptomeninges. Details of the successful treatment of this rare event are provided.

Abstract

Pure seminoma is a histological subtype of testicular cancer that accounts for 50% of testicular germ cell tumors. It has a very low rate of metastasis to the central nervous system, with only one previously reported case of neoplastic meningitis (cancer that has spread to the cerebrospinal fluid). Traditionally, neoplastic meningitis has an ominous prognosis when associated with primary tumors that commonly spread to the leptomeninges, like breast and lung. This article highlights a unique case of pure seminoma with neoplastic meningitis and illustrates the effectiveness of craniospinal irradiation as a treatment modality.

Introduction

Testicular cancer is the most common tumor affecting young men aged 15–35 years [1]. Of the testicular cancers in this population, the majority are germ cell tumors (GCTs). Pure seminoma is a histological subtype of GCT that accounts for approximately 50% of all testicular germ cell tumors [1]. Most patients with seminoma are stage I at diagnosis and generally have a good prognosis because of the efficacy of radiation and chemotherapy. Metastatic disease is a known complication of all GCTs, although it is uncommonly metastatic to the central nervous system (CNS), occurring in only about 1%–3% of patients with GCTs [2]. Metastatic lesions to the brain are almost exclusively seen in the nonseminomatous GCTs [2]. The occurrence of metastatic disease to the brain and specifically to the leptomeninges originating from a pure seminoma is extremely rare, with only one previously documented case [3]. We present the case of a patient with a testicular pure seminoma who developed neoplastic meningitis (NM).

A 27‐year‐old man was diagnosed with classical seminoma after noticing a lump in the left testicle. His laboratory studies revealed an elevated Beta‐Human Chorionic Gonadotropin (BHCG) of 22 mIU/mL with normal Alpha Fetoprotein (AFP) and lactate dehydrogenase (LDH). A computed tomography (CT) scan of the chest/abdomen/pelvis (c/a/p) was negative for evidence of metastatic disease at that time. For his stage IS disease he underwent a left orchiectomy and adjuvant radiation to the retroperitoneum. He was in complete remission and monitored with laboratory surveillance and imaging for roughly 2 years when he developed mild dyspnea on exertion.

Given his new symptoms, repeat laboratory work was performed that revealed an increase in his BHCG from <0.06 to 7.3 mIU/mL with normal AFP and LDH. He underwent a CT of the c/a/p that revealed a left perihilar mass as well as precarinal adenopathy. For his metastatic disease, he was treated with three cycles of bleomycin, etoposide, and cisplatin. He tolerated the chemotherapy well, but follow‐up imaging 7 months later revealed new nodular thickening of the left hemidiaphragm, concerning for recurrent diseas. He underwent a biopsy of the affected area, which was positive for metastatic seminoma. He was then treated with a double autologous stem cell transplant. Follow‐up imaging scans showed resolution of all pulmonary lesions, and he remained with no evidence of disease until 1.5 years later, when he developed headache, nausea, and cognitive decline. He underwent magnetic resonance imaging (MRI) of the brain that revealed a 10 cm L posterior temporal‐occipital lobe contrast‐enhancing mass as well as enhancement of the leptomeninges, for which he underwent emergent gross total resection with pathology positive for metastatic seminoma (Fig. 2). He had an MRI of the spine that was negative and positron emission tomography/CT from skull base to thighs was notable only for a 2 mm pulmonary nodule that was too small to characterize. A few months after surgery, a repeat MRI of the brain was performed that showed persistent left‐sided enhancement of the leptomeninges near the posterior temporal lobe, and an MRI of the spine showed nodular foci of abnormal enhancement along the cauda equina nerve roots (Fig. 1A). He then had a lumbar puncture and had cerebrospinal fluid that was notable for a protein of 45, glucose of 49, red blood cell count of 1, and white blood cell count of 10. The cytology was positive for malignant cells with a positive octamer‐binding transcription factor 3/4 immunostain confirming the diagnosis of neoplastic meningitis from his seminoma. Over the next month he developed parasthesias and weakness of the right leg, for which he was treated with craniospinal proton beam radiation (CSI). He had rapid improvement of his symptoms, and MRI showed no evidence of disease after completion of CSI. At follow‐up 4 months after CSI, he continued to have no clinical evidence of disease progression by imaging studies or clinical examination.

Figure 2.

Axial T1 weighted‐contrast enhanced magnetic resonance image demonstrating a large, heterogeneously enhancing left parietal mass found to be pure seminoma.

Figure 1.

Sagittal T1 fat‐saturated postcontrast magnetic resonance images of the lumbar spine. (A): Extensive nodular enhancement of the cauda equina consistent with neoplastic meningitis. (B): Post‐treatment scan 1 year later showing mild smooth enhancement of the cauda equina that has been unchanged over time.

NM occurs when cancer infiltrates into the cerebrospinal fluid and leptomeninges [4]. It is typically a late‐stage complication of various solid tumors with an estimated incidence of about 5% in patients with malignancy [4], [5]. NM is most commonly seen in patients with lung, melanoma, and breast cancer [4]. Without treatment, the prognosis is about 4–6 weeks, and with treatment, survival is extended to 3–6 months [4]. Diagnosing NM involves either detecting malignant cells in the cerebrospinal fluid or identifying abnormal radiographic patterns on MRI [5]. NM typically causes neurological symptoms most often consisting of headaches, back pain, visual disturbances, hearing loss, cranial nerve deficits, and radicular pain [4]. Standard treatments include radiation therapy as well as systemic and intrathecal chemotherapy [5]. Choice of treatment depends on several factors, including tumor histology, patient performance status, and prior treatments [4].

CNS involvement is a very rare event in seminoma with only one previously reported case of NM [3]. Of the patients with GCTs that develop intraparenchymal brain metastasis (BM), only a small minority (less than 5%) have pure seminoma [2]. BM from seminoma and, more broadly, germ cell tumors are a feature of poor prognosis. In a large retrospective study, the overall survival at 3 years in GCTs with BM was 27%–38%, with variability due to subgrouping by BM at relapse or on diagnosis, respectively [2]. Interestingly, despite the overall poor prognosis in these patients, multiple studies have reported a small subset of patients that achieve long‐term survival after aggressive treatment, although these studies did not include individuals with NM. This response has been attributed to the extreme sensitivity of these tumors to chemotherapy and radiation, along with certain prognostic factors such as diagnosis of BM at initial presentation, high Karnofsky Performance Scale (KPS), and solitary brain lesion [2], [6]. Given the prolonged survival of small subsets of patients with GCT and BM, it is possible that neoplastic meningitis may not carry the same ominous prognosis that it does with other solid tumors in certain patients and thus warrants aggressive treatment. Unfortunately, there are extremely limited data regarding prognostic factors and treatment guidelines for NM in patients with GCTs. In the single published case report of NM in seminoma, the patient failed treatment with systemic chemotherapy and intrathecal chemotherapy but had a 2.5‐year‐long disease‐free interval after craniospinal irradiation [3].

In this case, the justification to use CSI was additionally based on data from patients with CNS germinoma. Although CNS germinoma is a distinct entity from CNS seminoma, it was considered the best available analog, particularly regarding its radiosensitivity and predilection to spread through the CSF. Data on CNS germinoma have shown that chemotherapy alone is not as effective as radiotherapy [7]. CSI is the standard of treatment for disseminated germinoma, although this has never specifically been studied. The regimen used in this patient is based on a phase III clinical trial by the Children's Oncology Group investigating postsurgical radiotherapy versus chemotherapy plus response‐based radiotherapy in patients with CNS germinoma. In this trial, patients with disseminated CNS germinoma received either up‐front CSI with involved field radiation for a total of 45 gy of radiation or the same regimen if they achieved only partial response after chemotherapy (NCT00085098). The results of this study have not been published. As the patient had already undergone chemotherapy, his treatment followed the radiotherapy arm of the trial, and he received CSI and involved field boost. The decision to use proton beam radiation was made to minimize the exit dose of radiation past the spinal column, minimizing the amount of cardiac irradiation and reducing the risk of secondary malignancy [8].

Disclosures

Priscilla K. Brastianos: Angiochem, Genentech/Roche, Merck Sharp & Dohme, Eli Lilly & Co. (C/A), Merck (RF). The other authors indicated no financial relationships.

(C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/inventor/patent holder; (SAB) Scientific advisory board