2025 Volume 12 Pages 53-58
Central nervous system germ cell tumors are rare and account for 2% to 3% of all central nervous system tumors in Japan. Here, we report an extremely rare case of a primary spinal intramedullary mixed germ cell tumor. A 33-year-old man presented with a chief report of dysuria and numbness in the right lower extremity. Magnetic resonance imaging revealed a mass lesion on the left side of the intramedullary spinal cord at the Th10-11 vertebral body level with hyperintensity on T2-weighted images, isointensity on T1-weighted images, and uniform contrast in gadolinium. Cerebrospinal fluid examination revealed a few atypical cells. Although tumor removal using the posterior median sulcus approach was attempted, only a biopsy was performed because intraoperative rapid pathology suggested a possible diagnosis of germinoma. Permanent pathology revealed a mixed germ cell tumor (mainly comprising a germinoma with a yolk sac tumor). Postoperatively, cerebrospinal irradiation and 8 courses of the carboplatin and etoposide regimen were administered. No recurrence or new lesions were observed on magnetic resonance imaging at 94 months postoperatively. Our extensive literature search found only 4 cases of a mixed germ cell tumor of primary intramedullary origin in the spinal cord. Most spinal germ cell tumors described in the literature are either germinomas or mature teratomas; however, mixed germ cell tumors can also occur, albeit infrequently. Although additional cases need to be accumulated, our case suggests that yolk sac elements in spinal mixed germ cell tumors might not be directly associated with poor life expectancy.
Germ cell tumors comprise a group of diseases that occur predominantly in adolescents and young adults and are of various histologic types.1) It is less frequent than other central nervous system (CNS) tumors, with a frequency of 2% to 3% and 0.5% in Japan and the United States, respectively.2,3) Most CNS germ cell tumors arise in the suprasellar or pineal regions; they rarely originate in the spinal cord.4) The incidence of intracranial germ cell tumors is high in Asian populations. Therefore, guidelines for treatment of intracranial germ cell tumors have been published in Japan, and treatment strategies have been established to a certain extent.1) However, owing to the small number of cases, no standard treatment exists for primary mixed germ cell tumors of the spinal cord. In particular, primary intramedullary spinal cord mixed germ cell tumors are even rarer, with only 4 cases reported to date.5-8) We report a case of a primary intramedullary spinal mixed germ cell tumor (mainly comprising a germinoma with a yolk sac tumor) that was treated with whole-brain spinal cord irradiation and CARE therapy (carboplatin and etoposide) without recurrence for 94 months.
A 33-year-old man with no medical or family history presented to a local physician with the chief report of numbness in the entire right lower extremity for approximately 2 weeks. Spinal magnetic resonance imaging (MRI) revealed an intramedullary mass at the Th10-11 level. The patient was referred to our neurology department 1 month later for further examination.
At presentation, the patient had left-predominant lower-extremity muscle weakness (manual muscle testing [MMT] right/left] 4/5) and hyperreflexia of the deep tendon reflexes in the lower extremities with left dominance. In addition, hypothermia below the right Th11 and numbness in the entire right lower extremity and left toe were observed. Cerebrospinal fluid examination revealed a mildly elevated cell count of 29/μL and a protein level of 38 mg/dL. Almost all cells were mononuclear, with a small number of atypical cells. Although blood tests showed a mild elevation of neuron-specific enolase (14.4 ng/mL), no other abnormal findings were noted. Because an intramedullary tumor was suspected, the patient was referred to our department for further examination, which included a spinal cord biopsy.
After admission, the paralysis of the lower extremities progressed, and all lower extremity MMT scores were 1 (5 months after the initial symptoms). A bladder catheter was inserted because of urinary retention. The spinal MRI performed at our hospital showed a lesion with hyperintensity on T2-weighted images, isointensity on T1-weighted images, and uniform contrast in gadolinium in the Th10-11 intramedullary region. The lesions were unevenly distributed on the left side. The hyperintensity on T2-weighted images surrounding the mass was observed up to the Th8 vertebral body level (Fig. 1). Brain MRI and computed tomography of the trunk showed no neoplastic lesions.
Preoperative magnetic resonance imaging of the thoracic spine. (A) T2-weighted image showing a high-intensity mass lesion with spinal cord edema. (B), (C) T1-weighted image (B) and contrast-enhanced T1-weighted image (C) showing a mass lesion with enhancement at the Th10–Th11 level. (D), (E) T2-weighted (D) and contrast-enhanced T1-weighted (E) axial image showing a mass lesion distributed to the left spinal cord surface (arrows in D, E).
Preoperatively, a glioma such as astrocytoma was assumed, and tumor resection was performed on the lesion: Th9 partial laminectomy and Th10-11 total laminectomy were performed, followed by dural dissection. An intramedullary tumor was detected using a posterior median sulcus approach. The tumor was soft and pinkish gray (Fig. 2). Although total resection was initially planned, only a biopsy was performed because the diagnosis of germinoma was confirmed through an intraoperative rapid pathological examination. Postoperatively, no changes were observed in symptoms. Blood tumor marker levels showed no abnormal findings (human chorionic gonadotropin [hCG], 1.74 IU/L; β-hCG ≤ 0.1 ng/mL; and α-fetoprotein [AFP], 6.6 nm/mL).
Intraoperative photographs and histopathological examinations. (A) Photograph showing a slightly swollen spinal cord at the Th10 vertebral level without color abnormality on the spinal cord surface. (B) Pinkish-gray tumor identified in the spinal cord medulla. (C, D) HE staining showing diffuse proliferation of atypical cells with large chromatin-rich nuclei (C) and infiltration of lymphocyte so-called 2-cell pattern (D). (E-H) Immunostaining showing AFP- (E), glypican-3- (F), and keratin- (G) positive cells in part. (H) More than 90% of the tumor cells appear Spalt-like transcription factor 4.
AFP: α-fetoprotein; HE: hematoxylin and eosin
Permanent pathology specimens showed a diffuse proliferation of atypical cells with large chromatin-rich nuclei and scant cytoplasm. Although syncytiotrophoblastic giant cells were not observed, the hCG-positive cells were scattered. The histologic findings indicated mainly germinoma. Among these, a small region showing co-expression of AFP, glypican-3, and keratin, which are considered to be components of a yolk sac tumor, was observed. More than 90% of the tumor cells were Spalt-like transcription factor 4 positive (Fig. 2). The pathological diagnosis was a mixed germ cell tumor mainly comprising a germinoma with a yolk sac tumor.
The lesions were classified into the intermediate prognosis group in accordance with intracranial primary non-germinomatous germ cell tumors (NGGCT) and treated with radiation therapy and chemotherapy.9) Cerebrospinal irradiation was performed from postoperative day 11. The patient received a 23.4 Gy dose of whole-craniospinal irradiation delivered in 13 fractions, followed by local boost irradiation (27.0 Gy, 15 fractions) at the spinal cord lesion. Chemotherapy with the CARE regimen (carboplatin and etoposide) was initiated on postoperative day 19. The regimen comprised 600 mg (450 mg/m2) carboplatin (day 1) and 200 mg (150 mg/m2) etoposide (days 1-3). Owing to neutropenia and thrombocytopenia after the first course, radiotherapy was stopped until the neutrophil count recovered, and the dose in the second course was reduced to 480 mg/day carboplatin and 160 mg/day etoposide. However, neutropenia and thrombocytopenia recurred, and the dose was reduced even more to 480 mg/day carboplatin and 150 mg/day etoposide for the third course. The intramedullary spinal tumor disappeared after the third course of the CARE regimen (Fig. 3). The patient was then transferred to the convalescent ward.
Magnetic resonance imaging 4 months postoperatively. (A) T2-weighted image showing the improvement of the spinal cord swelling and atrophied spinal cord. (B) Contrast-enhanced T1-weighted image showing no residual tumors.
MRI performed 8 months after the biopsy revealed a disappearance of the intramedullary lesion at the Th10-Th11 level and no new intracranial lesion. Eight courses of the CARE regimen were administered 2 years postoperatively. Ninety-four months after the biopsy, complete paralysis of both lower extremities and bladder bowel disturbance persisted; however, follow-up MRI showed no recurrence.
Germ cell tumors originating from the spinal cord are rare, and approximately 100 cases of intramedullary primary germ cell tumors of the spinal cord have been reported.5-8,10-25) Germinoma (including those with syncytiotrophoblastic giant cells) and mature teratoma comprise the major portion of primary intramedullary germ cell tumors. We found only 4 primary intramedullary spinal mixed germ cell tumors, which are summarized in Table 1. We believe that our case, which mainly comprised germinoma with a partial yolk sac tumor, is the first report of a primary intramedullary spinal germ cell tumor.
Summary of cases of primary intramedullary spinal mixed germ cell tumor reported in the literature
| Authors | Year | Age | Sex | Pathology | Tumor location | Surgery | Radiotherapy (Gy) | Chemotherapy | Follow-up Period (months) | Status | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| CSI | Local | ||||||||||
| BEP, cisplatin, etoposide and bleomycin; CARE, carboplatin and etoposide; GTR, gross-total resection; ICE, cisplatin, ifosfamide, and etoposide; ICE (carbo), carboplatin, ifosfamide, and etoposide; STR, subtotal resection; TGN, paclitaxel, gemcitabine and nedaplatin * Tumor recurrence was suspected on MRI after the 2nd course of ICE (carbo). Therefore, the regimen was changed to ICE and radiotherapy was added. After ICE administration and irradiation, no recurrence of the tumor was detected. ** After the 3rd course of the BEP regimen, the regimen was changed to TGN because of residual thoracic spinal cord lesion. Considering radiotherapy and surgery, the patient denied treatment. New masses developed in the pituitary and pineal glands 59 months post-operatively. *** Remnant tumor was suspected at L2 lesion after the 3rd course of the ICE regimen. Salvage surgery was performed. |
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| Takahashi et al. | 2006 | 22 y | F | Germinoma, Choriocarcinoma | L1-2 | STR | Brain 30.6, Spine 27 | 30.6 | ICE (carbo) 2 cycles, ICE 1 cycle | 22 | No recurrence |
| Yamamoto et al. | 2013 | 42 y | F | Germinoma, Immature teratoma | L1-3 | GTR | 24* | 21* | CARE 2 cycles, ICE 4 cycles* | 26 | No recurrence |
| Nitta et al. | 2016 | 28 y | M | Embryonal carcinoma, Choriocarcinoma, Immature teratoma | C5-6, Th4-Cauda equina | Biopsy | -** | -** | BEP 3 cycles, TGN 13 cycles** | 120 | Intracranial recurrence** |
| Mukasa et al. | 2017 | 24 y | F | Yolk sac tumor, Mature teratoma | Th10, L2-3, Th12-L5 | Biopsy, GTR*** | 30 | 30 | ICE 8 cycles | 88 | No recurrence |
| Present case | 2024 | 33 y | M | Germinoma, Yolk sac tumor | Th10-11 | Biopsy | 23.4 | 27.0 | CARE 8 cycles | 94 | No recurrence |
No standard treatment strategy has been established for mixed germ cell tumors of spinal intramedullary origin. In Europe and the United States, germ cell tumors are categorized into 2 histologic groups-germinomas and NGGCT-to guide the selection of chemotherapy and radiation therapy protocols.26) In Japan, however, germ cell tumors are classified into 3 groups based on the prognostic implications of their histologic types. This classification informs the selection of treatment intensities.9,26,27) As for mixed germ cell tumors, the prognosis depends on whether the main components are germinoma (intermediate prognosis) or malignant germ cell tumors (poor prognosis).
Although it has not been established whether the treatment strategies for intracranial germ cell tumors can be directly applied to spinal germ cell tumors,24,28) we opted for CARE therapy in this case based on the classification system used in Japan and obtained effective tumor control. The present case exhibited components characteristic of a yolk sac tumor. Generally, yolk sac tumors are highly malignant; the 2 previously reported cases of pure spinal yolk sac tumors all produced extremely poor life outcomes.11,25) In contrast, our case, along with another reported case with a partial yolk sac tumor component,8) responded well to postoperative adjuvant therapy, achieving long-term tumor control exceeding 5 years. These 2 cases suggest that the yolk sac component may exhibit a relatively less aggressive behavior in spinal mixed germ cell tumors.
We treated an extremely rare case of a primary intramedullary spinal mixed germ cell tumor, mainly comprising germinoma and partial yolk sac tumor, with chemotherapy with CARE regimen and radiotherapy after biopsy. No recurrence was observed for 94 months postoperatively, suggesting that the treatment was effective. Despite the need for more case studies, our case, along with another case report, indicates that yolk sac components in spinal mixed germ cell tumors might not necessarily correlate with poor life outcome.
No financial assistance was obtained for this study.
The authors declare that data pertaining to this case report will be made available on request.
S Nakamura, H.S., and Y.G. wrote the report, conducted the literature search, extracted and analyzed the data, interpreted the results, and updated the reference lists. S Nakata, K.H., F.H., R.T., and J.H. were responsible for extracting and analyzing the data and interpreting the results. H.Y. and S.O. provided feedback on the reports.
Given this was a case report, informed consent was obtained from the patient for publication, and an institutional ethical review was deemed unnecessary.
All authors have no conflict of interest.
