Case 3 -
Germinoma of the Basal Ganglia
Gregory N. Fuller, MD Anderson Cancer Center, Houston, TX
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A 20-year-old man presented with a two-day history of intermittently slurred speech. There was no history of other signs or symptoms, including no history of headache, nausea, vomiting, motor or sensory deficits, visual disturbance, seizures or altered level of consciousness. A non-contrast CT scan performed in the Emergency Department revealed a 4-cm-diameter heterogeneous mass in the region of the left basal ganglia (putamen and globus pallidus). Subsequent MR imaging demonstrated that the basal ganglia mass displayed heterogeneous contrast enhancement, central hypointense areas of apparent necrosis, and surrounding vasogenic edema. Stereotactic biopsy was performed.
Case 3 - Slide 1
Case 3 - Figure 1
MRI. Axial T1-weighted image (T1WI) with contrast. A multicystic enhancing mass located in the left basal ganglia region is seen.
Case 3 - Figure 2
MRI. Coronal T1WI with contrast. A multicystic enhancing mass located in the left basal ganglia region is seen.
Case 3 - Figure 3
MRI. Sagittal T1WI with contrast. A multicystic enhancing mass located in the left basal ganglia region is seen.
Case 3 - Figure 4
MRI. Axial T2-weighted image (T2WI). Very little surrounding edema (hyperintensity on T2-weighted sequences) is seen.
Case 3 - Figure 5
H&E. Intraoperative consultation cytologic smear preparation shows a biphasic population, with large atypical germinoma cells interspersed with small reactive lymphocytes.
Case 3 - Figure 6
H&E. Intraoperative consultation frozen section confirms the representative nature of the smear prep, with clusters of large atypical germinoma cells interspersed with small reactive lymphocytes.
Case 3 - Figure 7
H&E. FFPE permanent tissue sections also exhibit characteristic architectural and cytologic features of germinoma.
Case 3 - Figure 8
CD117 (c-KIT). Germinoma shows strong reactivity for CD117 in a prominent membranous staining pattern with associated cytoplasmic positivity.
Case 3 - Figure 9
SALL4. The transcription factor SALL4 is strongly expressed in germinoma nuclei.
Case 3 - Figure 10
OCT4. The currently prerferred marker for confirming a diagnosis of germinoma is the transcription factor OCT4, which is a very robust marker showing strong nuclear positivity.
Case 3 - Figure 11
Placental alkaline phosphatase (PLAP). Once the mainstay of germinoma immunodiagnosis, PLAP is a relatively weak marker (compare this representative field with similar fields in figures 8, 9 and 10 showing OCT4, c-KIT, and SALL4 reactivity) that has fallen into disuse.
Case 3 - Figure 12
Beta-hCG. Germinomas are negative for CD30 (which is strongly and diffusely positive in embryonal carcinoma), alpha-fetoprotein (which is strongly and diffusely positive in yolk sac tumor) and beta-hCG (which is strongly and diffusely positive in choriocarcinoma), with the exception that many germinomas contain b-hCG-positive syncytiotrophoblastic cells (these were not seen in the present case).
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
The characteristic biphasic cell population, with large atypical germinoma cells interspersed with
small reactive lymphocytes on intraoperative consultation cytologic smear preparations often provides the
first strong indication of a diagnosis of germinoma. Confirmation of the diagnosis is provided by
demonstration of strong nuclear immunoreactivity for the robust transcription factor OCT4. Other
strongly positive markers include SALL4 (nuclear) and CD117 (c-KIT; membranous and cytoplasmic).
Placental alkaline phosphatase (PLAP) immunostaining formerly enjoyed widesprerad use to confirm a
diagnosis of germinoma, but this marker is notoriously capricious and, because reactivity is frequently
only patchy and/or pale, has fallen into desuetude with the arrival or far more robust markers such as
OCT4, CD117 and SALL4.
- Embryonal carcinoma
- Metastatic carcinoma
Germinoma of the Basal Ganglia
Germinoma is the most common germ cell tumor (GCT) of the central nervous system, followed by mixed
germ cell tumor, and then teratoma (with mature more common than immature). "Pure" embryonal carcinoma,
choriocarcinoma or yolk sac tumor do occur but are very rare, and when present usually comprise a
component of mixed germ cell tumor.
The most common location within the CNS in which germinoma arises is the pineal gland, followed by the
suprasellar region. The basal ganglia /thalamic region is third in frequency, with up to 15% of
germinomas arising in this location. Basal ganglia germinoma (BGG) can be difficult to diagnose for
three main reasons. First, because this location is a relatively rare site of origin, germinoma is often
not thought of when formulating the differential diagnosis. Secondly, the symptoms of germinoma of the
basal ganglia are often ill-defined and evolve slowly, usually with gradual onset of hemiparesis. And
thirdly, the initial imaging features of BGG frequently range from extremely subtle to virtually
undetectable unless there is a degree of suspicion on the part of the radiologist or surgical
pathologist. Moreover, rather presenting as a mass lesion, the initial imaging abnormality of many early
BGGs is exactly the opposite: hemiatrophy of the involved basal ganglia and ipsilateral cortex. Only
later in the course of the disease does a contrast- enhancing mass (as seen in the present case) evolve.
Recent imaging data suggest that susceptibility-weighted imaging (SWI) sequences may be the most
sensitive in detecting early, non-enhancing BGG. Even when BGG presents as an obvious enhancing mass,
because of its rarity, the clinical team may not think of it as an entity to be included in the
differential diagnosis unless one has been previously encountered. In the present case, BGG was not a
part of the initially formulated neuroimaging differential, which included such things as glioblastoma
and atypical lymphoma, and it was the surgical pathologist who suggested BGG as the most likely cause of
the mass at the time of intraoperative consultation. Young patient age in the10-20 year old range,
especially in male patients, coupled with a unilateral or bilateral lesion of the basal ganglia region is
a strong clue to include BGG in the preoperative differential diagnosis.
The gender incidence of CNS germinoma shows a definite overall male predeliction, but this is an
oversimplification because suprasellar germinomas actually exhibit a slight, but definite, female
prediliction. The common pineal germinoma shows a strong male prediliction, but the male predominance in
BGG is even more pronounced, with cases arising in females being the subject of case reports.
Most BGGs arise unilaterally, but bilateral BGG, occurring either synchronously or metachronously, are
well-recognized, and in fact represent the second most common multiple germinoma scenario after paired
pineal and suprasellar germinoma.
Other germ cell tumors (GCTs) may very rarely arise in the basal ganglia region, including mixed germ
cell tumors. In such instances, as in germ cell tumors arising at any body site, application of a panel
of immunomarkers generally provides a definitive diagnosis. The Table shows some of the most helpful
markers in current use. The SALL4 transcription factor is a genrerally excellent pan-germ cell tumor
maker that strongly labels the nuclei of germinoma, embryonal carcinoma and yolk sac tumor, albeit with
weaker nuclear staining seen in choriocarcinoma. SALL4 has also been claimed in recent studies to be a
more robust marker for yolk sac tumor than alpha- fetoprotein or glypican3. OCT4, another transcription
factor (and hence showing nuclear localization) is a very robust marker for germinoma and embryonal
carcinoma. These two germ cell tumors can usually be distinguished based on H&E features when
adequate well-preserved tissue is available; however, in the real world of shrinking biopsy size and
increasing surgical artifact optimal tissue is not always available, and the application of immunomarkers
greatly facilitates diagnosis – in this case use of CD117 (c- KIT) and CD30 will resolve the
differential, with CD117 strongly labeling germinoma, and CD30 strongly labeling embryonal carcinoma.
Yolk sac tumor (or a yolk sac tumor component of a mixed germ cell tumor) can be distinguished
immunophenotypically from germinoma and embryonal cacinoma by demonstrating expression of
alpha-fetoprotein. And finally, choriocarcinoma exhibits strong diffuse expression of beta-hCG to an
extent that is not seen in the other three tumors. Of note, placental alkaline phosphatase (PLAP),
formerly used to confirm germinoma, has been supplanted by the much more robust marker OCT4.
Practical Germ Cell Tumor Markers
|SALL4 ||OCT4 ||CD117 ||CD30 ||a-FP ||b-hCG|
|Germinoma|| ++++|| ++++ ||++++|| - ||- ||+/- syncyt|
|Embryonal ca ||++++ ||++++|| -|| ++++ ||- ||+/- syncyt|
|Yolk Sac Tumor ||++++ ||- ||- ||- ||+++ ||+/- syncyt|
|Choriocarcinoma ||++ ||-|| -|| -|| - ||++++|
Regarding beta-hCG expression, although diffuse positivity in a majority of tumor cells is
characteristic only of choriocarcinoma, scattered syncytiotrophoblasts can be seen in all types of GCTs,
including germinoma, and these cells exhibit strong reactivity for beta-hCG. The significance of the
presence of a beta-hCG-positive component of syncytiotrophoblasts in otherwise "pure" germinoma has been
extensively studied and debated, and in fact continues to be studied and debated. Many germinomas are
accompanied by elervated serum beta-hCG, and the question of what level correlates with the presence of a
choriocarcinoma component of a mixed GCT, and with a less favorable prognosis than "pure" germinoma,
remains debated and under study. Regarding biopsy interpretation, the current conventional wisdom favors
including germinoma with scattered syncytiotrophoblastic cells under the rubric of "pure" germinoma,
rather than classifying them as mixed GCTs; however, their presence should be noted in the pathology
report. Some clinical studies stratify GCT patients into three tiers, with the most favorable group
including "pure" germinoma and mature teratoma; an intermediate tier that includes germinoma with
elevated beta- hCG, mutifocal/disseminated germinoma, immature teratoma, and mixed germinoma with mature
teratoma; and a poor prognosis tier composed of "pure" embryonal carcinoma, choriocarcinoma or yolk sac
tumor and mixed GCTs in which any of these three tumors is a major component.
1. The basal ganglia/thalamic region is the 3rd most common site for germinoma of the CNS.
2. Early lesions may be very subtle and difficult to visualize on MR imaging studies, and imaging at
initial clinical presentation may may show hemiatrophy of the basal ganglia region and the ipsilateral
cerebral cortex, rather than a mass lesion
3. Even when presenting as a contrast-enhancing mass, basal ganglia germinoma requires knowledge of
the entity to raise the index od suspicion and include it in the differential diagnosis
4. In the context of a unilateral or bilateral lesion(s) localized to the basal ganglia, young
patient age (in the vicinity of 10-20 years old) and male gender should trigger inclusion of basal
ganglia germinoma high on the differential diagnosis.
- Wang XL, Li CJ. [The early diagnosis of juvenile germinoma originating from the basal ganglia and thalamus]. Zhonghua Nei Ke Za Zhi. 2011 Apr;50(4):307-10. Chinese. PubMed PMID: 21600150.
- Rasalkar DD, Chu WC, Cheng FW, Paunipagar BK, Shing MK, Li CK. Atypical location of germinoma in basal ganglia in adolescents: radiological features and treatment outcomes. Br J Radiol. 2010 Mar;83(987):261-7. Epub 2009 Sep 14. Review. PubMed PMID: 19752170.
- Lou X, Ma L, Wang FL, Tang ZP, Huang H, Cai YQ, Wong EH. Susceptibility-weighted imaging in the diagnosis of early basal ganglia germinoma. AJNR Am J Neuroradiol. 2009 Oct;30(9):1694-9. Epub 2009 Jul 6. PubMed PMID: 19581340.
- Hao S, Liu B, Tang J, Jia G, Zhang Y, Ma Z, Wang Z. Germinoma of basal ganglia in female: case report and review of the literature. Childs Nerv Syst. 2009 May;25(5):613-7. PMID: 19082612.
- Lee J, Lee BL, Yoo KH, Sung KW, Koo HH, Lee SJ, Choi JY, Lee KH, Lee JI, Shin HJ, Kim JH, Suh YL, Lee KH, Lee M. Atypical basal ganglia germinoma presenting as cerebral hemiatrophy: diagnosis and follow-up with 11C- methionine positron emission tomography. Childs Nerv Syst. 2009 Jan;25(1):29-37. PMID: 18712399.
- Sakai K, Shigeta H. Serial MR and CT features of primary germinoma originating in the basal ganglia. J Clin Neurosci. 1999 Mar;6(2):162-164. PMID:18639143.
- Fujii Y, Saito Y, Ogawa T, Fujii S, Kamitani H, Kondo S, Horie Y, Togawa M, Senda M, Maegaki Y, Ohno K. Basal ganglia germinoma: diagnostic value of MR spectroscopy and (11)C-methionine positron emission tomography. J Neurol Sci. 2008 Jul 15;270(1-2):189-93. PMID: 18371980.
- Villani A, Bouffet E, Blaser S, Millar BA, Hawkins C, Bartels U. Inherent diagnostic and treatment challenges in germinoma of the basal ganglia: a case report and review of the literature. J Neurooncol. 2008 Jul;88(3):309-14. PMID: 18365143.
- Wong TT, Chen YW, Guo WY, Chang KP, Ho DM, Yen SH. Germinoma involving the basal ganglia in children. Childs Nerv Syst. 2008 Jan;24(1):71-8. Epub 2007 Sep 29. PubMed PMID: 17906866.
- Rossi A, Garrè ML, Ravegnani M, Nozza P, Abbruzzese A, Giangaspero F, Tortori-Donati P. Bilateral germinoma of the basal ganglia. Pediatr Blood Cancer. 2008 Jan;50(1):177-9. PubMed PMID: 16700048.
- Okamoto K, Ito J, Ishikawa K, Morii K, Yamada M, Takahashi N, Tokiguchi S, Furusawa T, Sakai K. Atrophy of the basal ganglia as the initial diagnostic sign of germinoma in the basal ganglia. Neuroradiology. 2002 May;44(5):389-94. PMID: 12012122.
- Elizabeth J, Menon G, Bhattacharya RN, Radhakrishnan VV. Germinoma of the basal ganglia: a case report and review of literature. Neurol India. 2002 Mar;50(1):84-6. PubMed PMID: 11965648.
- Sugimoto K, Nakahara I, Nishikawa M. Bilateral metachronous germinoma of the basal ganglia occurring long after total removal of a mature pineal teratoma: case report. Neurosurgery. 2002 Mar;50(3):613-6; discussion 616-7. PubMed PMID: 11841731.
- Liu E, Robertson RL, du Plessis A, Pomeroy SL. Basal ganglia germinoma with progressive cerebral hemiatrophy. Pediatr Neurol. 1999 Apr;20(4):312-4. PMID: 10328283.
- Wong LW, Jayakumar CR. Germinoma of the basal ganglia and thalamus-- CT and MRI findings. Singapore Med J. 1997 Oct;38(10):444-6. PMID: 9529959.
- Kobayashi T, Kageyama N, Kida Y, Yoshida J, Shibuya N, Okamura K. Unilateral germinomas involving the basal ganglia and thalamus. J Neurosurg. 1981 Jul;55(1):55-62. PMID: 7241216.
- Yamada H, Imamura K, Sakai N, Ando T, Hirata T, Misao H, Sakata K, Shimokawa K. [Intracerebral germinoma developing in the right basal ganglia- -report of a case followed up by CTscan and review of the literature (author's transl)]. No To Shinkei. 1980 Apr;32(4):387-92. Japanese. PMID: 7378202.
- Villani A, Bouffet E, Blaser S, Millar BA, Hawkins C, Bartels U. Inherent diagnostic and treatment challenges in germinoma of the basal ganglia: a case report and review of the literature. J Neurooncol. 88:309-14, 2008. PMID: 18365143.
- Wong TT, Chen YW, Guo WY, Chang KP, Ho DM, Yen SH. Germinoma involving the basal ganglia in children. Childs Nerv Syst 24:71-78, 2008. PMID: 17906866.
- Rossi A, Garrè ML, Ravegnani M, Nozza P, Abbruzzese A, Giangaspero F, Tortori-Donati P. Bilateral germinoma of the basal ganglia. Pediatr Blood Cancer 50:177-179, 2008. PMID: 16700048.
- Cao D Li J, Guo CC, Allan RW, Humphrey PA. SALL4 is a novel diagnostic marker for testicular germ cell tumors. Am J Surg Path 33:1065-1077, 2009.
- Mei K, et al. Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: a study of 77 cases. Modern Pathol 22:1628-1636, 2009.
- Hattab EM. Germ cell tumors. Chapter 15 in: Perry A, Brat D, eds. Practical Surgical Neuropathology. Philadelphia: Elsevier, 2010.