Germ Cell Tumors



Germ Cell Tumors





Clinical Context

Extragonadal germ cell neoplasms are uncommon in the central nervous system (CNS), accounting for less than 1% of all primary CNS tumors in the United States (1) and around 4% of primary CNS tumors in children (2). They recapitulate many of the features of extragonadal germ cell tumors at other sites, being midline, mostly in adolescent or young adult males and mostly seminoma/germinoma histology. CNS germ cell tumors include germinoma, immature and mature teratoma, choriocarcinoma, yolk sac (endodermal sinus) tumor, and embryonal carcinoma, with many lesions exhibiting a combination of histologies (mixed malignant germ cell tumor). Clinically, CNS germ cell tumors are grouped broadly into pure germinomatous and nongerminomatous types, based on prognosis and response to therapy.

CNS germ cell tumors most commonly affect males (∼3:1 male:female) and have an increased incidence among people of Asian descent, accounting for up to 15% of all primary brain tumors in Taiwan (3). The incidence for CNS germ cell tumors peaks in the second decade when most cases occur, with a median age around 17 years regardless of sex or race (4,5). Although very rare, CNS germ cell tumors also occur in older adults, reported up to 86 years of age (5).

Although germ cell tumors can occur at any level of the neuraxis, the vast majority occur in the midline, with only rare cases found laterally. The most common sites for germ cell tumors within the CNS are the pineal gland and suprasellar region, with the anatomic distribution varying by sex. In males, pineal cases outnumber all other CNS sites, whereas females tend to develop suprasellar lesions (4). When considering only lesions of the pineal gland, the germ cell tumor patient population skews even further toward males, giving a ratio of 15:1 (5). Multifocal disease, usually pineal and suprasellar, is present in a minority of cases, around 15% (6,7).

Neuroimaging of germ cell tumors yields varying results, with no reliable features for distinguishing any one of them. Signal characteristics are variable and heterogeneous on both T1- and T2-weighted series, with occasional intratumoral cysts and calcification that may suggest teratoma, although both can be seen in other lesions (6). Germinomas occasionally extend along the ventricular walls in a plaque-like fashion,
radiologically simulating the periventricular distribution of some primary CNS lymphomas.

The clinical workup for CNS germ cell tumors includes examination of cerebrospinal fluid (CSF) and blood for markers of differentiation, specifically β-hCG and α-fetoprotein (AFP). In cases where surgery is contraindicated, they may form the diagnostic basis for aggressive treatment (8). β-hCG in the CSF is presumptive evidence that the tumor contains choriocarcinoma elements, and AFP indicates yolk sac or immature teratoma elements. The prognostic impact of these tumor markers in the CSF is incompletely understood, but they may be associated with a small decrease in survival in patients with nongerminomatous lesions (9). One series showed frequent production of β-hCG by histologically pure germinomas that was associated with higher rates of recurrence (10).

Treatment for germ cell tumors in the CNS depends on tumor type. Pure germinomas, which are exquisitely radiosensitive, typically receive radiotherapy that is targeted to include the third ventricle, whole brain, or the entire craniospinal axis to treat potential microscopic dissemination (11). Because of greater side effects in children from cerebral irradiation, some dose-sparing approaches utilizing pre-radiation chemotherapy have been developed and show promise in reducing radiation exposure in that population (12,13). Given their rarity and heterogeneous compositions, other malignant germ cell tumors do not receive any standard regimen, except that most cases are treated with some form of radiation therapy. Pure mature teratomas are the only CNS germ cell tumor that can be approached successfully with resection alone (14).

The outcomes for pure germinomas and mature teratomas are favorable, with greater than 90% survival for both in one large series. Immature teratomas and other malignant germ cell tumors, however, had survival rates of 70% or less at 3 years (7). The presence of choriocarcinoma, yolk sac tumor, or embryonal carcinoma was associated with 38% 5-year survival in another series (15).


Germinoma

Primary CNS germinomas resemble those at other extragonadal sites, with large round cells containing moderate amounts of clear or partially clear cytoplasm around large nuclei with vesicular chromatin and prominent eosinophilic nucleoli (Figure 15-1). The cells vary in distribution from solid sheets with few other cell types to individually scattered almost imperceptibly among inflammatory cells and native tissue, traversed by delicate collagenous septa. Germinomas are among the few nonneuroepithelial CNS neoplasms that can infiltrate over limited distances as single cells into the surrounding tissue.

Germinoma is particularly susceptible to crush artifact and the lesion’s overall histology can be obscured by it. Careful handling can minimize this effect. Immunostaining crushed areas can demonstrate distorted
positivity for germinoma markers (Figure 15-2), but diagnosing based on such findings is risky, especially with CD117, which is also expressed by mast cells.

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Oct 22, 2018 | Posted by in NEUROLOGY | Comments Off on Germ Cell Tumors
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