Introduction: There is no standard treatment paradigm for intracranial teratomas, a rare subset of primary intracranial non-germinomatous germ cell tumors (NGGCT), which comprise less than 1% of pediatric brain tumors. This case series retrospectively analyzes treatment and outcomes of pediatric intracranial teratomas from a single institution. Methods: Authors reviewed a comprehensive pathology database at Stanford’s Lucile Packard Children’s Hospital for intracranial teratomas in pediatric patients treated from 2006 to 2021; their demographics, treatment, and clinical course were analyzed. Results: Among 14 patients, median follow-up time was 4.6 years and mean age at diagnosis was 10.5 years. Ten had elevated tumor markers and underwent chemotherapy as initial treatment for NGGCT. Ultimately, these patients all required surgery for progressive or residual disease. Two patients did not undergo radiation. After biopsy or resection, 8 patients had pure mature teratoma, five had mixed germ cell tumor with teratoma component, and one had immature teratoma. The patient with immature teratoma died during chemotherapy from septic shock. No patients experienced recurrence. Common sequelae were endocrine (42.8%) and eye movement (50.0%) abnormalities. Discussion/Conclusion: We highlight the variable treatment course and outcome for pediatric patients with intracranial teratomas. Elevated tumor markers at presentation, along with imaging findings, favor chemotherapy initiation for presumed NGGCT. Resection of residual tumor is recommended even if tumor markers return to normal. Prognosis remains excellent; no patients had recurrence with a median follow-up of 4.6 years.

Primary intracranial non-germinomatous germ cell tumors (NGGCT) are rare, comprising less than 1–3% of pediatric brain tumors [1, 2]. NGGCT include mature (considered benign) teratoma, immature teratoma, and malignant teratoma, along with embryonal carcinoma, yolk sac tumor, choriocarcinoma, and mixed germ cell tumor [3].

In contrast to other NGGCT, mature teratoma consists of adult-type tissue derived from the three embryonic layers while immature teratoma comprises fetal tissue derived from the three embryonic layers [4]. Intracranial teratomas are primarily located in the pineal and suprasellar regions [5].

Following symptom presentation, diagnosis typically involves brain and spine imaging with an MRI along with evaluation of tumor markers [6]. NGGCT can be diagnosed with elevated tumor markers – alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (βHCG) – in serum and cerebrospinal fluid (CSF). These tumor markers can also be used to monitor disease course during and after treatment. However, in cases where tumor markers are inconclusive, patients undergo surgical biopsy for diagnosis.

There is no established standard treatment paradigm for intracranial teratomas, though surgical resection, with the goal of gross total resection (GTR), is part of curative treatment [7, 8]. Immature teratomas require chemotherapy and radiation in addition to surgery, although radiosurgery has also been considered adjuvant therapy [9, 10]. The 10-year survival rate for mature teratomas is 92.9%, while immature teratomas and lesions with malignant features have survival rates of 68–70.7% [8, 11].

This case series retrospectively analyzes treatment and outcomes from a single institution for patients under 18 years old diagnosed with intracranial teratomas between 2006 and 2021. Our goal was to understand the clinical characteristics of these tumors and the treatment courses for and the long-term outcomes of mature and immature teratomas as well as mixed germ cell tumor with teratoma components. We also propose a potential treatment algorithm.

The authors reviewed a comprehensive surgical neuropathology database at Stanford’s Lucile Packard Children’s Hospital for pathology diagnoses of intracranial teratoma in pediatric patients (age at diagnosis <18 years) treated from 2006 to 2021. After IRB approval, collected variables included age, sex, tumor location, serum and CSF marker levels, dates of procedures and treatments, recurrence, and date of last follow-up. Details of the patients’ treatment and clinical course were recorded for further analysis. All imaging studies were reviewed, and pathological diagnoses were confirmed with the electronic medical record. Written informed consent was obtained from the parent/legal guardian of the patient for publication of the details of their medical case and any accompanying images.

Patient Characteristics

We identified and reviewed data for 14 pediatric patients diagnosed with intracranial teratoma based on surgical pathology between 2006 and August 2021. Mean age at diagnosis was 10.5 years (range 4–18 years). All patients in this series were male and 42.9% were Caucasian, 21.4% Asian/Pacific Islander, and 35.7% Hispanic. Clinical presentation at the time of diagnosis varied and included nausea and emesis (57.1%), blurry vision or extraocular movement abnormalities (50%), headaches (35.7%), and diverse endocrinopathies (21.4%). One patient was diagnosed incidentally, after imaging for a mild traumatic brain injury.

One patient (7.1%) with an immature teratoma died of septic shock during his chemotherapy course, 6 months after initial surgery. No patients experienced disease recurrence after treatment, regardless of receiving radiation. Of note, 1 patient had concern for recurrence based on imaging concerning disease progression and returned for surgery, which revealed a granuloma, rather than recurrent teratoma.

Tumor Characteristics

Eight patients (57.1%) had pure mature teratomas. Five patients had mixed germ cell tumor with teratoma components as well as 1 case of an immature teratoma. Most teratomas were pineal lesions (71.4%), while others were located in the sella (35.7%), suprasellar region (35.7%), or presented in both the pineal and sellar/suprasellar regions (28.6%). One patient had a spinal drop metastasis, which was resected. Upon presentation, all patients had imaging of their entire neuraxis to assess for disease seeding. Only three patients (21.4%) had gonadal ultrasounds, which were all negative studies.

Tumor Markers

All patients had recorded serum and CSF AFP and βHCG data prior to treatment. Ten (71.4%) patients demonstrated elevated tumor markers of serum AFP or βHCG upon presentation. On the other hand, four patients (28.6%) had negative tumor markers in both serum and CSF. Two patients (16.7%) had extremely high CSF βHCG values (404–501 IU/L) but low serum AFP values (3–9 ng/mL).

Treatment Course

Eight patients (57.1%) were started on chemotherapy prior to surgical intervention based on elevated tumor markers. Three patients (21.4%) did not receive chemotherapy. The majority of patients (n = 10) underwent the North American Children’s Oncology Group (COG) ACNS1123 clinical trial protocol. These patients were placed on the trial’s stratum 1, which consisted of up to 6 cycles of carboplatin, etoposide, and ifosfamide followed by radiation if the tumor shrunk or disappeared. Of note, 6 patients in this group underwent initial surgical biopsy of their lesions. Ultimately, these patients all required surgical resection for progressive or residual disease following chemotherapy.

Radiation was typically recommended as consolidation treatment. Twelve patients (85.7%) completed radiation, which varied from whole ventricular radiation to tumor bed radiation.

Median follow-up time was 4.6 years (range 0.5–15.8 years). Following treatment, 50% of the cohort had extraocular movement deficits that were resolving and 6 patients (42.8%) also experienced endocrinological abnormalities and required supplementation. These postoperative sequelae were comparable between open and endoscopic surgical approaches.

Five patients (35.7%) required permanent CSF diversion with either an endoscopic third ventriculostomy (ETV) or placement of a ventriculoperitoneal shunt. Details of treatment course for each patient are in Table 1.

Table 1.

Case series of pediatric patients diagnosed with teratomas

CaseInitial tumor markersLocationSurgical pathologyInitial treatment courseSubsequent salvageable treatment courseCSF diversion neededClinical sequelaeFU, years
Serum βHCG: 44 IU/mL Pineal Mature teratoma/germinoma Biopsy, adverse effect from COG ACNS 1123 chemotherapy, progression on radiation, and GTR Cisplatin/vinblastine/bleomycin/paclitaxel chemotherapy No GH deficiency 15.8 
Serum AFP: 48 ng/mL 
CSF βHCG: 20 IU/mL 
CSF AFP: 9.43 ng/mL 
Serum βHCG: 12 IU/mL Pituitary/suprasellar Mature teratoma COG ACNS 1123 chemotherapy, GTR, and radiation (30.6 Gy ventricular +23.4 Gy boost to primary site) None No GH deficiency, DI, esotropia, and cognitive delay 4.2 
Serum AFP: 25 ng/mL 
CSF βHCG: <0.6 IU/mL 
CSF AFP: 26 ng/mL 
Serum βHCG: 30 IU/mL Pineal, pituitary, and spine Mature teratoma/germinoma Progression on COG ACNS 1123 chemotherapy, GTR, and brain/spine radiation (36 Gy CSI +54 Gy boost to suprasellar/pineal regions +45 Gy to spine) None Yes, VP shunt Panhypopituitary syndrome, DI, and abnormal EOM 0.5 
Serum AFP: 365 ng/mL 
CSF βHCG: 3.7 IU/mL 
CSF AFP: 11 ng/mL 
Serum βHCG: 51 IU/mL Pituitary and pineal Mature teratoma Residual after COG ACNS 1123 chemotherapy, GTR, and radiation (36 Gy CSI +18 Gy boost to primary site) None No GH deficiency, short stature, and Parinaud’s syndrome 4.8 
Serum AFP: 3 ng/mL 
CSF βHCG: 3.7 IU/mL 
CSF AFP: 11 ng/mL 
Serum βHCG: 108 IU/mL Pituitary/suprasellar Mature teratoma Residual after COG ACNS 1123 chemotherapy, GTR, and radiation (23.4 Gy CSI, 36 Gy ventricular +18 Gy boost to primary site) None No Panhypopituitary syndrome, bilateral optic atrophy, and hemianopsia 4.3 
Serum AFP: 9 ng/mL 
CSF βHCG: 501 IU/mL 
CSF AFP: 8 ng/mL 
Serum βHCG: 4.2 IU/mL Pineal and left thalamus Mature teratoma Biopsy (non-definitive), progression on COG ACNS 1123 chemotherapy, GTR, chemotherapy, and radiation (36 Gy CSI +54 Gy total boost to primary site) GTR surgery for presumed recurrence was confirmed as granuloma Yes, ETV and VP shunt Right hemiparesis, Parinaud’s syndrome, and precocious puberty 4.9 
Serum AFP: 429 ng/mL 
CSF βHCG: 4.4 IU/mL 
CSF AFP: 5.9 ng/mL 
Serum βHCG: <1 IU/mL Pineal Mature teratoma Surgeries (STR and GTR) None Yes, ETV Abnormal EOM 1.4 
Serum AFP: 1 ng/mL 
CSF βHCG: <0.6 IU/mL 
CSF AFP: <0.5 ng/mL 
Serum βHCG: 3 IU/mL Pineal and pituitary/suprasellar Mature teratoma Residual after COG ACNS 1123 chemotherapy, GTR, and radiation (36 Gy CSI +54 Gy total boost to primary site) None No Parinaud’s syndrome 0.9 
Serum AFP: 18 ng/mL 
CSF βHCG: 22 IU/mL 
CSF AFP: 19 ng/mL 
Serum βHCG: <1 IU/mL Pineal Mature teratoma/germinoma Biopsy (teratoma), GTR, COG ACNS 1123 chemotherapy, and radiation (24 Gy ventricular +36 Gy boost to primary site) None Yes, ETV Dry eyes 0.3 
Serum AFP: 3 ng/mL 
CSF βHCG: <0.6 IU/mL 
CSF AFP: <0.5 ng/mL 
10 Serum βHCG: normal Pineal Mature teratoma GTR None No Anxiety 4.8 
Serum AFP: normal 
11* Serum βHCG: <1 IU/mL Suprasellar Immature teratoma/PNET Surgeries and COG ACNS 0332 chemotherapy, and radiation (CSI) None No Left hemiparesis, DI, and hyperglycemia 0.5 
Serum AFP: 10 ng/mL 
CSF βHCG: 18 IU/mL 
CSF AFP: 9.1 ng/mL 
12 Serum βHCG: 14 IU/mL Pineal and bifrontal Mature teratoma and separate germinoma Biopsy (mature teratoma), residual after COG ACNS 1123 chemotherapy, GTR, and radiation (23.4 Gy CSI +12.6 Gy ventricular +18 Gy to primary site) Ifosfamide and etoposide chemotherapy No Parinaud’s syndrome 6.2 
Serum AFP: 2 ng/mL 
CSF βHCG: <0.6 IU/mL 
CSF AFP: <0.5 ng/mL 
13 Serum βHCG: <1 IU/mL Pineal Mature teratoma Biopsy (teratoma), GTR, and radiation (30.6 Gy ventricular) None Yes, VP shunt Seizures 6.9 
Serum AFP: 3 ng/mL 
CSF βHCG: <0.5 IU/mL 
CSF AFP: <0.5 ng/mL 
14 Serum βHCG: 35 IU/mL Pituitary/suprasellar Mature teratoma/germinoma/embryonal carcinoma GTR, COG ACNS 1123 chemotherapy, and radiation (36 Gy CSI +54 Gy to primary site) None No Panhypopituitary syndrome, DI, and cranial nerve VI palsy 4.8 
Serum AFP: 2 ng/mL 
CSF βHCG: 6.8 IU/mL 
CSF AFP: <0.5 ng/mL 
CaseInitial tumor markersLocationSurgical pathologyInitial treatment courseSubsequent salvageable treatment courseCSF diversion neededClinical sequelaeFU, years
Serum βHCG: 44 IU/mL Pineal Mature teratoma/germinoma Biopsy, adverse effect from COG ACNS 1123 chemotherapy, progression on radiation, and GTR Cisplatin/vinblastine/bleomycin/paclitaxel chemotherapy No GH deficiency 15.8 
Serum AFP: 48 ng/mL 
CSF βHCG: 20 IU/mL 
CSF AFP: 9.43 ng/mL 
Serum βHCG: 12 IU/mL Pituitary/suprasellar Mature teratoma COG ACNS 1123 chemotherapy, GTR, and radiation (30.6 Gy ventricular +23.4 Gy boost to primary site) None No GH deficiency, DI, esotropia, and cognitive delay 4.2 
Serum AFP: 25 ng/mL 
CSF βHCG: <0.6 IU/mL 
CSF AFP: 26 ng/mL 
Serum βHCG: 30 IU/mL Pineal, pituitary, and spine Mature teratoma/germinoma Progression on COG ACNS 1123 chemotherapy, GTR, and brain/spine radiation (36 Gy CSI +54 Gy boost to suprasellar/pineal regions +45 Gy to spine) None Yes, VP shunt Panhypopituitary syndrome, DI, and abnormal EOM 0.5 
Serum AFP: 365 ng/mL 
CSF βHCG: 3.7 IU/mL 
CSF AFP: 11 ng/mL 
Serum βHCG: 51 IU/mL Pituitary and pineal Mature teratoma Residual after COG ACNS 1123 chemotherapy, GTR, and radiation (36 Gy CSI +18 Gy boost to primary site) None No GH deficiency, short stature, and Parinaud’s syndrome 4.8 
Serum AFP: 3 ng/mL 
CSF βHCG: 3.7 IU/mL 
CSF AFP: 11 ng/mL 
Serum βHCG: 108 IU/mL Pituitary/suprasellar Mature teratoma Residual after COG ACNS 1123 chemotherapy, GTR, and radiation (23.4 Gy CSI, 36 Gy ventricular +18 Gy boost to primary site) None No Panhypopituitary syndrome, bilateral optic atrophy, and hemianopsia 4.3 
Serum AFP: 9 ng/mL 
CSF βHCG: 501 IU/mL 
CSF AFP: 8 ng/mL 
Serum βHCG: 4.2 IU/mL Pineal and left thalamus Mature teratoma Biopsy (non-definitive), progression on COG ACNS 1123 chemotherapy, GTR, chemotherapy, and radiation (36 Gy CSI +54 Gy total boost to primary site) GTR surgery for presumed recurrence was confirmed as granuloma Yes, ETV and VP shunt Right hemiparesis, Parinaud’s syndrome, and precocious puberty 4.9 
Serum AFP: 429 ng/mL 
CSF βHCG: 4.4 IU/mL 
CSF AFP: 5.9 ng/mL 
Serum βHCG: <1 IU/mL Pineal Mature teratoma Surgeries (STR and GTR) None Yes, ETV Abnormal EOM 1.4 
Serum AFP: 1 ng/mL 
CSF βHCG: <0.6 IU/mL 
CSF AFP: <0.5 ng/mL 
Serum βHCG: 3 IU/mL Pineal and pituitary/suprasellar Mature teratoma Residual after COG ACNS 1123 chemotherapy, GTR, and radiation (36 Gy CSI +54 Gy total boost to primary site) None No Parinaud’s syndrome 0.9 
Serum AFP: 18 ng/mL 
CSF βHCG: 22 IU/mL 
CSF AFP: 19 ng/mL 
Serum βHCG: <1 IU/mL Pineal Mature teratoma/germinoma Biopsy (teratoma), GTR, COG ACNS 1123 chemotherapy, and radiation (24 Gy ventricular +36 Gy boost to primary site) None Yes, ETV Dry eyes 0.3 
Serum AFP: 3 ng/mL 
CSF βHCG: <0.6 IU/mL 
CSF AFP: <0.5 ng/mL 
10 Serum βHCG: normal Pineal Mature teratoma GTR None No Anxiety 4.8 
Serum AFP: normal 
11* Serum βHCG: <1 IU/mL Suprasellar Immature teratoma/PNET Surgeries and COG ACNS 0332 chemotherapy, and radiation (CSI) None No Left hemiparesis, DI, and hyperglycemia 0.5 
Serum AFP: 10 ng/mL 
CSF βHCG: 18 IU/mL 
CSF AFP: 9.1 ng/mL 
12 Serum βHCG: 14 IU/mL Pineal and bifrontal Mature teratoma and separate germinoma Biopsy (mature teratoma), residual after COG ACNS 1123 chemotherapy, GTR, and radiation (23.4 Gy CSI +12.6 Gy ventricular +18 Gy to primary site) Ifosfamide and etoposide chemotherapy No Parinaud’s syndrome 6.2 
Serum AFP: 2 ng/mL 
CSF βHCG: <0.6 IU/mL 
CSF AFP: <0.5 ng/mL 
13 Serum βHCG: <1 IU/mL Pineal Mature teratoma Biopsy (teratoma), GTR, and radiation (30.6 Gy ventricular) None Yes, VP shunt Seizures 6.9 
Serum AFP: 3 ng/mL 
CSF βHCG: <0.5 IU/mL 
CSF AFP: <0.5 ng/mL 
14 Serum βHCG: 35 IU/mL Pituitary/suprasellar Mature teratoma/germinoma/embryonal carcinoma GTR, COG ACNS 1123 chemotherapy, and radiation (36 Gy CSI +54 Gy to primary site) None No Panhypopituitary syndrome, DI, and cranial nerve VI palsy 4.8 
Serum AFP: 2 ng/mL 
CSF βHCG: 6.8 IU/mL 
CSF AFP: <0.5 ng/mL 

*The patient passed away during chemotherapy.

Dx, diagnosis; FU, follow-up; βHCG, β-human chorionic gonadotropic; AFP, alpha fetoprotein; CSF, cerebrospinal fluid; CSI, craniospinal irradiation; COG, Children’s Oncology Group; GTR, gross total resection; STR, subtotal resection; VP, ventriculoperitoneal; ETV, endoscopic third ventriculostomy; DI, diabetes insipidus; EOM, extraocular movements; GH, growth hormone.

An 8-year-old healthy boy presented with 9 days of headache, nausea, and worsening blurry vision. MRI demonstrated obstructive hydrocephalus and heterogeneously enhancing pineal/third ventricular and sellar/suprasellar masses with a mid-thoracic intradural, extramedullary spinal nodule, as shown in Figure 1a and b. Tumor markers were elevated (serum b-HCG 30 IU/L [normal 2–5 IU/L]; serum AFP 365 ng/mL [normal 10–20 ng/mL]; CSF b-HCG 3.7 IU/L [normal <2 ng/mL]; CSF AFP 11 ng/mL [normal <1.5 ng/mL]), indicating NGGCT pathology. Following placement of a ventriculoperitoneal shunt, the patient underwent urgent chemotherapy.

Fig. 1.

MRI brain and spine for illustrative case. a Pre-treatment sagittal T1 post-contrast with pineal/third ventricular and sellar/suprasellar masses (denoted by black stars). b Pre-treatment sagittal T2 FIESTA post-contrast with mid-thoracic spine mass (denoted by white arrow). c Sagittal T2 CUBE post-contrast with growing suprasellar lesions and the resected pineal mass. d Post-treatment sagittal T2 CUBE post-contrast with no disease recurrence. e Pineal tumor section consistent with mixed germ cell tumors (99% mature teratoma and <1% germinoma; H&E). f Pineal tumor section consistent with mixed germ cell tumors, with immunostaining for Oct3/4 showing nuclear positivity in the germinoma cells.

Fig. 1.

MRI brain and spine for illustrative case. a Pre-treatment sagittal T1 post-contrast with pineal/third ventricular and sellar/suprasellar masses (denoted by black stars). b Pre-treatment sagittal T2 FIESTA post-contrast with mid-thoracic spine mass (denoted by white arrow). c Sagittal T2 CUBE post-contrast with growing suprasellar lesions and the resected pineal mass. d Post-treatment sagittal T2 CUBE post-contrast with no disease recurrence. e Pineal tumor section consistent with mixed germ cell tumors (99% mature teratoma and <1% germinoma; H&E). f Pineal tumor section consistent with mixed germ cell tumors, with immunostaining for Oct3/4 showing nuclear positivity in the germinoma cells.

Close modal

However, surveillance MRI performed 2 weeks later showed continued growth of both intracranial masses with symptomatic mass effect on the brainstem, and the patient was brought to the operating room for GTR of the pineal/third ventricular mass, which was confirmed as mature teratoma with 1% germinoma on pathology shown in Figure 1e and f. The patient resumed chemotherapy, and tumor markers had normalized by this point. Given the mixed pathology from the first operation and continued growing teratoma syndrome, the patient also then underwent GTR of the thoracic spine mass and suprasellar mass, which were both mature teratomas in Figure 1c. By 8 months after the initial diagnosis, the patient had completed six cycles of chemotherapy and 36 Gy cranial/spinal proton radiation with 54 Gy boost to the suprasellar and pineal primary sites and 45 Gy to the region of spinal disease. At most recent follow-up, the patient is 9 months post-diagnosis and 1 month post-treatment with residual central panhypopituitarism, shown in Figure 1d.

Intracranial teratoma is a rare entity that has no standard treatment paradigm. We present a single-institution case series of 14 pediatric patients with intracranial teratoma confirmed on surgical pathology and treated between 2006 and 2021. The few case series on intracranial teratoma establish its low prevalence among brain tumors, which ranges from 1 to 7% for children [12‒17]. Demographic and tumor characteristics of our cohort are reflected in other studies. Most intracranial teratomas are diagnosed in males [14, 15, 17, 18]. Likewise, other series also report high incidence of pineal and suprasellar locations of teratomas with diverse neurologic and endocrine-related presentations [14, 15].

Initial diagnosis includes imaging of the neuraxis to rule out drop metastases and characterize the intracranial lesion, though there may not be pathognomonic radiographic features differentiating NGGCT subtypes from germinoma [19]. Gonadal ultrasound was uncommonly utilized in our case series, even though many extracranial teratomas arise from the testes or ovaries in adults [20]. AFP and βHCG tumor markers in serum and CSF are necessary to diagnose and monitor tumors throughout the treatment course [4]. Elevated AFP or βHCG is a strong predictor of NGGCT, though germinomas may also display elevated βHCG, and different groups have advocated for disparate diagnostic thresholds [7, 19]. In our cohort, most patients began treatment with chemotherapy prior to surgery for presumed NGGCT based on elevated tumor markers according to COG recommendations.

Neurosurgery has a role in diagnosis, treatment, and symptom management for patients with intracranial teratomas. Depending on tumor location, various open craniotomy approaches are available, including transcallosal or suboccipital supracerebellar approach for pineal teratomas and transcranial approaches for suprasellar/sellar tumors. Now, with developments in endoscopic surgery, neurosurgeons can perform more minimally invasive biopsies or resections in addition to CSF diversion with ETV safely and efficiently [21, 22]. Biopsies in the setting of elevated tumor markers are not uniformly recommended and do not necessarily always yield accurate diagnoses due to technical margins of error [19, 23]. Malignant tumors require radical surgical resection, and NGGCT in general undergo definitive histopathologic diagnosis with biopsy or resection, especially if tumor marker levels normalize following chemotherapy without complete response [19, 24]. Pure mature teratomas respond poorly to chemotherapy alone and therefore eventually require GTR surgical resection for cure. Patients with normal initial tumor markers and GTR of mature teratoma may be managed conservatively without adjuvant chemoradiation.

Choosing a treatment course therefore depends on initial tumor markers, imaging findings, and subsequent tumor evolution. Overall, NGGCT are less sensitive to chemotherapy and radiation than germinomas, potentially due to teratoma components, though there is currently no consensus on optimal chemoradiation regimens [4, 11]. Current chemotherapy protocols for NGGCT in general include cisplatin or carboplatin along with etoposide, cyclophosphamide, or ifosfamide; high-dose chemotherapy is reserved for recurrent cases, although novel agents are currently under investigation [4]. NGGCT patients are typically started on chemotherapy based on concerning tumor markers as part of their treatment regimen, with ‘second look’ surgery recommended for persistent disease burden and negative tumor marker profiles [4, 7].

Intracranial immature teratomas are extremely rare, though the few case series commenting on this pathology report no recurrence following treatment with surgery and neoadjuvant therapies [14]. Some tumors contain mixed components, such as teratoma with germinoma, comprising 25–32% of intracranial germ cell tumors [14]. For these patients with tumors with mixed components, radiation is helpful as adjuvant therapy. In addition, the “growing teratoma syndrome” phenomenon refers to patients with enlarging tumor elements despite chemo- or radiotherapy [12, 16]. A few patients in our series demonstrated such tumor growth, requiring salvage surgery. Patient 3 (Table 1) is one example where urgent surgeries were warranted to address the multiple tumors. Radiation was also recommended as consolidation treatment. Based on our case series and findings, we propose a potential treatment paradigm for pediatric intracranial teratoma, shown in Figure 2.

Fig. 2.

Flowchart for the treatment approach to intracranial teratoma. CSF, cerebrospinal fluid.

Fig. 2.

Flowchart for the treatment approach to intracranial teratoma. CSF, cerebrospinal fluid.

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With no disease recurrence in our cohort, prognosis is overall excellent for intracranial teratomas. Prior literature describes 5-year survival rates as 100% for mature teratomas and 67% for immature teratomas [25]. Ten-year survival rates are 92.9% for pure mature teratomas and 70.7% for malignant immature teratomas [8]. Surgical resection is a key component of definitive treatment of NGGCT, including teratomas [26]. CSF diversion procedures are common to treat obstructive hydrocephalus, a frequent sequelae of the disease process, with our case series (35.7%) as well as others other series reporting need for ventriculoperitoneal shunt placement or ETV in 85.7% of cases [14]. Radiation alone can lead to metastatic recurrence, though adjunct radiation therapy is helpful, particularly for mixed germ cell tumor and patients with immature teratoma or NGGCT that is not solely mature teratoma, in order to ensure no disease recurrence [26, 27].

Intracranial teratomas are rare diagnoses for children with no clearly established standard treatment paradigm. Elevated tumor markers, along with imaging findings, favor chemotherapy initiation for presumed NGGCT. Although markers may normalize after treatment, surgery with goal of GTR is recommended for residual tumor. Based on our single-institution case series on intracranial teratomas, prognosis is excellent following GTR along with chemotherapy and radiation therapy for mature teratomas and mixed tumors, with no disease recurrence over a median follow-up of 4.6 years.

The study was conducted with approval of Stanford Institutional Review Board (IRB#57363). The Board determined that written informed consent was not required. Written informed consent was obtained from the parent/legal guardian of the patient for publication of the details of their medical case and any accompanying images.

The authors of this study have no conflicts of interest to report.

AW is supported by the Agency for Healthcare Quality and Research under award F32HS028747.

Dr. Wu had full access to all of the data in this study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Wu, Jin, Prolo, and Grant. Acquisition, analysis, and interpretation of data and critical revision of the manuscript for important intellectual content: Wu, Jin, Vogel, Hiniker, Campen, Prolo, and Grant. Drafting of the manuscript: Wu. Statistical analysis of data: Wu and Jin. Administrative, technical, or material support: Vogel, Hiniker, Campen, Prolo, and Grant. Supervision: Wu, Prolo, and Grant.

The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from A.W.

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