Intracranial germ cell tumors (from Ackerman's Surgical Pathology)

• 95% arising along an axis extending from the suprasellar cistern to, and including, the pineal gland. most common neoplasms presenting in the latter location. A small subset involves the suprasellar and pineal regions simultaneously, exceptional examples lying in the basal ganglia, thalami, cerebral hemispheres, sella turcica, spinal cord, and lateral or fourth ventricles.
  
• The vast majority of intracranial germ cell tumors are diagnosed during the first three decades of life. Suprasellar examples produce visual field defects, diabetes insipidus, and hypothalamopituitary failure, whereas pineal region tumors compress the tectal plate and obstruct the aqueduct, presenting with symptoms and signs of hydrocephalus.
  
• Germinoma formerly designated as a variant of "pinealoma" because of its frequent location in the pineal region and fancied structural resemblance to that of the embryonic gland. Morphologically identical to the seminoma, germinomas in pure form constituted 65% of intracranial germ cell tumors.
  
• Bifocal tumors involving the pineal and suprasellar regions are nearly always germinomas.
  
• Although the histologic diagnosis is usually straightforward, a germinoma that has elicited a florid lymphocytic and granulomatous reaction may masquerade as tuberculosis, sarcoidosis, or another inflammatory process.

1: Childs Nerv Syst. 2006 Oct 21;

• Germinoma located in the basal ganglia in an 8-year-old girl.
  
  Klein O, Voirin J, Civit T, Auque J, Marchal JC.
  
  Department of Neurosurgery, Hopital Central, 29, Avenue du Marechal de Lattre de Tassigny, 54035, Nancy Cedex, France, o.klein@chu-nancy.fr.
  
  CASE REPORT: The authors describe a unique case of an 8-year-old girl with a germinoma located in the left basal ganglia. Medical history begins 5 months before with a central diabetes insipidus, loss of weight (5 kg at admission), vomiting and asthenia. Computed tomography (CT) and cranial magnetic resonance imaging (MRI) are performed and demonstrate a left basal ganglia tumour (nucleus lentiformis). Diabetes insipidus is considered as non-visible germinoma localization on the pituitary stalk rather than as a possible consequence of peri-tumoural oedema surrounding the hypothalamus. Spinal MRI is normal. Neurological as well as general examination is normal. DISCUSSION: The first hypothesis is low-grade glioma, but pathological examination following a stereotactic biopsy of the lesion reveals a cerebral germinoma. A few days before the biopsy, the girl experienced a mild left facial palsy, and CT scans at the time of biopsy reveals an intra-tumoural haemorrhage. Alpha fetoprotein and human chorionic gonadotrophin were negative as blood and cerebrospinal fluid markers, whereas placental alkaline phosphatase was positive on immunohistochemical profile of the tumour samples. Dedicated chemotherapy, followed by focal irradiation (40 Gy, 30 sessions, 45 days; SIOP CNS GCT 93 protocol), is performed with a complete response. The outcome is good (Glasgow Outcome Scale=I), without any cognitive impairment and the persistence of a mild facial palsy and a slight right arm dystonia on last neurological examination. There is still no evidence of tumour recurrence.

2: Cancer. 2006 Nov 1;107(9):2228-36.

• Focal and craniospinal irradiation for patients with intracranial germinoma and patterns of failure.
  
  Nguyen QN, Chang EL, Allen PK, Maor MH, Ater JL, Mahajan A, Wolff JE, Weinberg JS, Woo SY.
  
  Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
  
  BACKGROUND.: The authors compared the patterns of failure in patients with intracranial germinoma who were managed with either chemotherapy and focal irradiation or with craniospinal irradiation (CSI). METHODS.: A retrospective review was conducted on 21 patients with intracranial germinoma and treated with radiotherapy (RT) to the central nervous system at The University of Texas M. D. Anderson Cancer Center from 1981 to 2002. The study group was comprised of 13 males and 8 females with a median age at diagnosis of 19 years. Nine patients received chemotherapy prior to focal RT. Twelve patients received CSI. RESULTS.: The actuarial 10-year survival rate for all patients was 86%. The overall survival rate at 10 years was 89% for patients who received focal RT and 83% for patients who received CSI (P = .73). The 10-year local control rate in the brain for patients who received focal irradiation was 59% compared with 100% for patients who received CSI (P = .08). The rate of distant control in the spine at 5 years was 62% for patients who received focal irradiation and 100% for patients who received CSI (P = .04). CONCLUSIONS.: Although focal techniques of irradiation with chemotherapy are attractive methods that limited the volume irradiated, the strategy appeared to be associated with increased rates of failures in the brain and spine.

3: Neurosurgery. 2006 Aug;59(2):267-77

• Neurofiberscopic biopsy of tumors of the pineal region and posterior third ventricle: indications, technique, complications, and results.
  
  Chernov MF, Kamikawa S, Yamane F, Ishihara S, Kubo O, Hori T.
  
  Department of Neurosurgery, Tokyo Women's Medical University, Tokyo, Japan.
  
  OBJECTIVE: Evaluation of results of the neurofiberscopic biopsy of tumors of the pineal region and posterior third ventricle. METHODS: From 2001 to 2004, 23 patients (mean age, 30.6 yr) with tumors located in the pineal region or posterior third ventricle underwent neurofiberscopic biopsy with simultaneous third ventriculostomy. The procedure was indicated for verification of the histological diagnosis of the neoplasm, which was planned to be treated by radiotherapy and/or chemotherapy without open surgery (eight patients), establishment of the pathological diagnosis for further choice of the most appropriate treatment strategy (11 patients), differentiation of the recurrent neoplasm and radiation necrosis (two patients), and decompression of the large tumor-associated cyst (two patients). In six previously shunted patients, substitution of the ventriculoperitoneal shunt on the third ventricle stoma was performed. RESULTS: There was no postoperative mortality or permanent morbidity. In all cases, the obtained tissue sample was sufficient for pathological diagnosis. Transient postoperative complications included fever (15 patients), nausea and vomiting (three patients), and diplopia (one patient). On the long-term follow-up, delayed third ventricular stoma failure caused by tumor regrowth and scar formation was found in one patient, and dissemination of the malignant glioma through the subarachnoid space was found in another patient. CONCLUSION: Neurofiberscopic biopsy represents a useful method for sampling of tumors of the pineal region and posterior third ventricle, which can be effectively used in both previously shunted and shunt-free patients.

4: Acta Neurochir (Wien). 2006 Aug;148(8):865-71

• Pure pineal germinomas: analysis of gender incidence.
  
  Cuccia V, Galarza M.
  
  Department of Neurosurgery, National Pediatric Hospital, Buenos Aires, Argentina. vcuccia@fibertel.com.ar
  
  OBJECTIVE: Pure pineal germinomas have been rarely reported in girls. Gender incidence and differences of pure pineal germinomas are not well known. The authors report a series of pure pineal germinoma and its gender characteristic is reviewed. METHODS AND RESULTS: Of a total of 50 germ cell tumors operated on between 1988 and 2004 we found 26 cases (median age at diagnosis, 12 years) of pineal germ cell tumors. Of these, 14 cases (male/female ratio: 13/1) were pure pineal germinomas, and 12 cases (male/female ratio: 12/0) were non-germinoma germ cell tumors. In pure pineal germinomas, the main clinical presentations were intracranial hypertension and cranial nerve dysfunction. Imaging studies disclosed a homogeneous type of tumor (n = 10) and associated hydrocephalus (n = 6). Cases were managed with biopsy and subsequent radiation therapy and chemotherapy. After a follow up of 10 years, pure germinoma cases have no neurological deficits and tumor recurrence. The literature on gender incidence of pure pineal germinomas is analyzed and possible causes are discussed. CONCLUSIONS: Although rare, pure pineal germinoma can be found in female subjects. On the basis of the literature review, the male/female ratio in cases of pure pineal germinoma is between 5:1 and 22:1 (mean 14:1). In our series, the male/female ratio was 13:1.

5: AJNR Am J Neuroradiol. 2006 Jun-Jul;27(6):1204-10

• Two patients with intraspinal germinoma associated with Klinefelter syndrome: case report and review of the literature.
  
  Nakata Y, Yagishita A, Arai N.
  
  Department of Neuroradiology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashi-dai, Fuchu, Tokyo 183-0042, Japan.
  
  We report 2 cases of intraspinal germinoma associated with Klinefelter syndrome. In one patient, spinal cord atrophy was observed at the upper and lower ends of the intraspinal tumor. Brain atrophy was observed in both cases. Germinoma should be included in the differential diagnosis if an intraspinal tumor is observed in a patient with Klinefelter syndrome.

6: J Neurooncol. 2006 Sep;79(3):255-8.

• Primary midbrain cystic germinoma mimicking glioma: a case with neuroendoscopic biopsy.
  
  Uchino M, Haga D, Mito T, Kuramitsu T, Nakamura N.
  
  Department of Neurosurgery, Saiseikai Yokohama-shi Nambu Hospital, Yokohama-shi, Kanagawa-ken, Japan. uchino0717@yahoo.co.jp
  
  Intracranial germinoma arising primarily in the midbrain is extremely rare. We present the first reported case of cystic midbrain germinoma that lacked evident solid components and mimicked a midbrain glioma. In a 22-year-old man with headache and diplopia, magnetic resonance imaging showed a ring-enhancing lesion in the midbrain. The preoperative diagnosis included brain stem glioma, metastasis, and neuroepithelial cyst. A neuroendoscopic biopsy specimen provided a histologic diagnosis of germinoma. The patient responded well to chemotherapy and radiotherapy. The case illustrates the diagnostic value of neuroendoscopic biopsy in the differential diagnosis of brainstem lesions in adult. The possibilities considered should now include germinoma.

7: J Neurosurg. 2006 Feb;104(2 Suppl):143-8

• Germinoma: unusual imaging and pathological characteristics. Report of two cases.
  
  Rushing EJ, Sandberg GD, Judkins AR, Vezina G, Kadom N, Myseros JS, Packer RJ, Santi M.
  
  Department of Neuropathology and Ophthalmic Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA. rushinge@afip.osd.mil
  
  Primary germ cell neoplasms of the central nervous system typically develop as midline mass lesions during the first three decades of life. The authors present two cases with atypical clinicopathological features that stimulate discussion on the diagnosis and management of these tumors. The first patient was an 11-year-old boy of Japanese-American heritage who presented with a 6-month-long history of cognitive decline, difficulty swallowing, unsteady gait, and intermittent right-sided posturing. The initial magnetic resonance (MR) image of the brain displayed a mildly increased T2 signal in the cerebral peduncles, putamen, and globus pallidus bilaterally. Follow-up MR images showed an increase in the T2 signal abnormality in the left basal ganglia. The second patient was a 10-year-old Caucasian boy who presented with diabetes insipidus and subsequently displayed progressive fatigue, involuntary eye and mouth movements, and obsessive-compulsive behavior. An MR image demonstrated signs of mineral deposition and foci of increased T2 signal in both basal ganglia. Follow-up MR images demonstrated a progressive increase in the T2 signal (which was then located within the mesial temporal lobe). A biopsy performed on the left thalamic lesion in the first patient revealed a germinoma. The patient was treated with chemotherapy and died 2 years later. The second patient underwent a lumbar puncture, which demonstrated an elevated level of beta-human chorionic gonadotropin. Despite the lack of a mass on MR images in this child, the need for a tissue diagnosis prompted the authors to perform an anterior temporal lobectomy. The diagnosis of diffuse germinoma was confirmed, and the patient was treated with adjunctive chemotherapy. Although uncommon, germ cell tumors can present outside the midline and exhibit a multifocal growth pattern.

8: J Neurooncol. 2005 Nov;75(2):163-7.

• C-kit expression in germinoma: an immunohistochemistry-based study.
  
  Nakamura H, Takeshima H, Makino K, Kuratsu J.
  
  Department of Neurosurgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, 860-8556 Kumamoto, Japan. hnakamur@fc.kuh.kumamoto-u.ac.jp
  
  In our immunohistochemical study of 25 human primary intracranial germinomas and germinomas with syncytiotrophoblastic giant cells (STGC), we stained the same sections for c-kit and placental alkaline phosphatase (PLAP). Immunohistochemical expression was graded using a semi-quantitative scoring system where 3+ =51-75%, and 4+ =76-100%. Of the 25 cases, 7 (28%) were graded 3+ and 18 (72%) 4+ for c-kit; 8 (32%) were 3+ or 4+ for PLAP. All 3 cases negative for PLAP-staining were strongly positive and all embryonal carcinomas, immature teratomas, and yolk sac tumors were negative for c-kit staining. The soluble isoform of c-kit (s-kit) is reportedly detectable in cerebral spinal fluid of patients with germinomas and germinomas with STGC. C-kit and s-kit may be powerful tumor markers for germinomas with or without STGC.

9: Neurol Med Chir (Tokyo). 2005 Aug;45(8):415-7

• Pineal Germinoma with granulomatous reaction: case report.
  
  Nishibayashi H, Uematsu Y, Terada T, Itakura T.
  
  Department of Neurological Surgery, Wakayama Medical University, Japan. hirokin@wakayama-med.ac.jp
  
  A 20-year-old man presented with diplopia. Neurological examination revealed mild skew deviation and upbeat nystagmus. Computed tomography showed a clover-shaped isodense mass in the pineal region with homogeneous enhancement. The lesion was isointense on both T(1)- and T(2)-weighted magnetic resonance (MR) imaging with homogeneous enhancement by gadolinium-diethylenetriaminepenta-acetic acid. Cerebral angiography showed no tumor staining. Serum and cerebrospinal fluid were negative for beta-human chorionic gonadotropin, alpha-fetoprotein, and placental alkaline phosphatase. Open biopsy was performed using a right occipital transtentorial approach. Histological examination revealed a tumor consisting of clusters of germinoma cells, but with prominent infiltration of lymphocytes, plasma cells, and macrophages, and proliferation of small vessels. The histological diagnosis was germinoma with granulomatous reaction. MR imaging showed complete disappearance of the tumor after chemoradiotherapy. Neurosurgeons should be aware of this rare tumor to avoid misdiagnosis as granulomatous inflammation.

10: Pediatr Blood Cancer. 2006 Mar;46(3):363-6

• Central diabetes insipidus: Is it Langerhans cell histiocytosis of the pituitary stalk? A diagnostic pitfall.
  
  Prosch H, Grois N, Bokkerink J, Prayer D, Leuschner I, Minkov M, Gadner H.
  
  Children's Cancer Research Institute, Vienna, Austria.
  
  Central diabetes insipidus (CDI) is a rare disorder that may be caused by a variety of diseases. In pediatric and adolescent patients the most common causes for CDI are Langerhans cell histiocytosis (LCH) and germinoma. To avoid a potentially hazardous biopsy of the hypothalamic pituitary region it is recommended to evaluate patients with CDI carefully to identify potential extracranial lesions. Since LCH is the most common systemic disease that may cause CDI, special focus is paid to the identification of LCH lesions. We report on a 9(1/2) year old girl who presented with central diabetes insipidus and a thickening of the pituitary stalk on magnetic resonance imaging. Diagnostic workup revealed a history of recurrent ear infections and a compressed 6th thoracic vertebral body on radiographs. Based on these findings LCH was anticipated. Upon growth of the pituitary stalk lesion the patient was treated with LCH standard chemotherapy. After an initial shrinkage of the lesion, a further growth of the pituitary stalk lesion was observed and the tumor was resected. Histopathology revealed germinoma. This case underscores the importance of a istopathologically proven diagnosis in patients with HPR tumors before the initiation of a specific therapy, even if the clinical findings are highly suggestive.

11: Indian Pediatr. 2005 Apr;42(4):376-9.

• Synchronous germinomas in the pineal and suprasellar region.
  
  Haque F, Zahid M, Ahmad SA, Naseem S.
  
  Department of Radiodiagnosis, Jawahar Lal Nehru Medical College, Aligarh Muslim Univerity, Aligarh 202 002, U.P., India. faisalhaquel@rediffmail.com
  
  Synchronous primary intracranial germ cell tumors are rare. Only 5-10% of all germ cell tumors are found as synchronous lesion in pineal and suprasellar region. They are also known by the entity "double mid-line atypical teratoma". An 11-year-old male child presented with polyuria, polydipsia and features of raised intracranial tension. CT scan head revealed well-defined homogenously enhancing lesions in the pineal and suprasellar region. Histopathology examination showed the lesion to be of germ cell origin.