Germinomas arising from the optic nerve or chiasm are extremely rare. According to our literature search, there are only 7 reported germinomas, all nonexophytic. Our patient appears unique as she had a primary exophytic optic chiasm germinoma.
A 25-year-old woman was referred for progressive visual loss for over 1 year associated with diabetes insipidus (DI). Visual acuity was 20/70 right eye, nasal letters only and 20/25 left eye, nasal letters only. Color vision was reduced in the right eye and intact in the left eye. There was a right relative afferent pupillary defect. Confrontation fields revealed that she could count fingers in all quadrants except the superotemporal quadrants bilaterally. Funduscopic examination was unremarkable. Her medications were prednisone and desmopressin.
Hematologic studies revealed an elevated prolactin of 199 ng/mL (normal: 4.8–23.3 ng/mL). Lumbar puncture, chest radiograph, and abdominal ultrasound were normal. Magnetic resonance imaging (MRI) of the brain revealed a 1.8 × 1.2 cm enhancing mass of the optic chiasm, suggestive of a glioma (Fig. 1).
A right frontal craniotomy was performed with a subfrontal approach. Gross inspection of the optic chiasm revealed an exophytic abnormal grayish mass bulging from within the chiasm. The chiasm itself was swollen, and the tumor was completely within the confines of the optic chiasm. The mass was not well circumscribed; rather, it was infiltrative making it difficult to distinguish between normal optic nerve fibers and abnormal tissue at the periphery of the lesion. Beginning with an incision at the center of the mass, the resection was limited only to the very abnormal grayish-appearing portion without breaching any myelinated fibers. A conservative partial resection was achieved. The tumor did not extend into the optic nerves or below the chiasm but rather was expanding the chiasm. The operation was without complications, and the patient awoke with no further neurological deficits.
Histologic examination revealed a tumor composed of large epithelioid cells with large pleomorphic nuclei and a prominent lymphoplasmacytic infiltrate. Immunohistochemical staining of the tumor cells was positive for C-kit, placental alkaline phosphatase, and D2-40 and negative for keratin and S100. CD45 immunostain highlighted the lymphocytes (Fig. 2). This was consistent with a diagnosis of germinoma (Fig. 2).
The patient underwent fractionated radiation therapy (24 Gy to the periventricular area with a boost of 45 Gy to the primary tumor in 30 cycles). She did develop panhypopituitarism. One year after surgery, the patient's vision was counting fingers, right eye and 20/40, left eye. Her left visual field showed a temporal hemianopia. Both optic discs were pale. There was no evidence of tumor by MRI (Fig. 3).
The majority of intracranial germ cell tumors (GCTs) have been reported in suprasellar, pineal, or basal ganglia locations (1). Some have been reported with unique presentations including metastasis (2,3), orbital involvement (4), and cranial nerve involvement (5,6). There are several debated theories of the genesis of intracranial GCTs, but they all share the same principle in which germ cells during embryogenesis migrate aberrantly into the head or are misplaced within the mesoderm in the region of the optic nerves.
According to our literature search, there are only 2 reports of germinomas within the optic nerve(s) and 7 optic chiasmal germinomas, all of which were nonexophytic (Table 1). The mean age at diagnosis in reported cases is approximately 24 years, with 90% found in men.
Patients with a suprasellar GCT typically present with a triad of DI, visual changes, and endocrine abnormalities. Of the cases reported with optic nerve and chiasm germinoma, 100% suffer from visual deficits, 54.5% were diagnosed with DI, and 63.6% reported some form of endocrine abnormalities. DI often starts before the visual changes are detected (1). Laboratory studies reveal endocrine abnormalities, such as prolactinemia, hypotestosteronism, hypothyroidism, and panhypopituitarism. Alpha fetal protein, beta human chorionic gonadotropin (bHCG), and lactate dehydrogenase have been reported within normal limits, except for 1 study with elevated bHCG (2). Sodium levels have been reported to be either high or low. Lumbar puncture, when performed, is usually unremarkable except for 1 study with a peculiar finding of oligoclonal banding and persistent immunoglobulin G synthesis in the cerebrospinal fluid independent of a demyelinating process (9).
Magnetic resonance imaging in all studies revealed the tumor to be of high signal intensity on T2, with either marked enhancement or a heterogeneous ring enhancing lesion on the optic chiasm and/or optic nerves. Similarly, our patient's MRI findings were characterized by an enhancing mass involving the optic chiasm.
The MRI findings alone yield a broad differential diagnosis including chiasmal glioma, craniopharyngioma, ectopic pituitary adenoma, infundibuloma, neurosarcoidosis and tuberculum sella meningioma. The GCT often appears well circumscribed on imaging but in reality it may actually infiltrate the surrounding nerve fibers of the optic nerves/chiasm without clear distinction. With biopsy, it is important to restrict the sampling to the obviously abnormal tissue without causing further damage to the surrounding visual pathways.
Surgical biopsy was performed in 82% reported cases of optic nerve and chiasm germinoma of which the vast majority also received radiation therapy. One third of the reports used a concomitant chemotherapy regimen of carboplatin etopiside and ifosfamide (2,8). Recurrence was reported in 2 patients who were treated with combined radiation and chemotherapy without surgery (2).
Visual function may or may not improve (1), and given the paucity of reported cases, it is still unclear whether radiation therapy causes significant damage to the optic fibers. Vision is more likely to improve in true suprasellar GCT's after surgery and radiation therapy, in contrast to optic nerve and chiasmal GCT's with an infiltrative lesion, because removal of the tumor in the former case leads to the loss of the compressive mass effect it had caused (8,9,11).
1. Bowman CB, Farris BK. Primary chiasmal germinoma. A case report and review of the literature. J Clin Neuroophthalmol. 1990;10:9–17.
2. Nakajima T, Kumabe T, Jokura H, Yoshimoto T. Recurrent germinoma in the optic nerve: report of two cases. Neurosurgery. 2001;48:214–217; discussion 217–218.
3. Rath S, Vemuganti GK, Biswas G, Mod H. Optic nerve and chiasmal germinoma. Ophthal Plast Reconstr Surg. 2009;25:161–163.
4. Perrini P, Ventura L, Ricci A, Galzio R. Primary germinoma of the orbit. Neurosurgery. 2005;57:E813.
5. Lima BR, Schoenfield L, Rychwalski PJ. Germinoma presenting as a fourth cranial nerve palsy in a patient with adenomatous polyposis coli (APC) gene mutation. J AAPOS. 2011;15:71–73.
6. Aguila LA, Chou SM, Bay JW. Primary intracranial germinoma presenting as lower cranial nerve involvement: case report and review of the literature. Neurosurgery. 1984;14:475–479.
7. Xia C, Liu Z, Zhang R, Mao Y, Wang Y. Primary intrinsic optic chiasm germinoma. J Clin Neurosci. 2011;18:860–862.
8. DiLuna ML, Two AM, Levy GH, Patel T, Huttner AJ, Duncan CC, Piepmeier JM. Primary, non-exophytic, optic nerve germ cell tumors. J Neurooncol. 2009;95:437–443.
9. Krolak-Salmon P, Androdias G, Honnorat J, Caudie C, Bret P, Hernette D, Vighetto A. Beware of optic neuritis! Lancet Neurol. 2002;1:516–517.
10. Wilson JT, Wald SL, Aitken PA, Mastromateo J, Vieco PT. Primary diffuse chiasmatic germinomas: differentiation from optic chiasm gliomas. Pediatr Neurosurg. 1995;23:1–5; discussion 6.
11. Nadkarni TD, Fattepurkar SC, Desai KI, Goel A. Intracranial optic nerve germinoma. J Clin Neurosci. 2004;11:559–561.
12. Iizuka H, Nojima T, Kadoya S. Germinoma of the optic nerve: case report. Noshuyo Byori. 1996;13:95–98.