Bifocal germ cell tumor of pineal germinoma and neurohypophyseal embryonal carcinoma: illustrative case

Yu Naruse Departments of Neurosurgery

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Shinya Jinguji Departments of Neurosurgery

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Ryo Hiruta Departments of Neurosurgery

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Ayako Toda Departments of Neurosurgery

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Kenichiro Nagai Departments of Neurosurgery

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Shingo Kudo Pediatric Oncology, and

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Hideki Sano Pediatric Oncology, and

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Rei Sekine Diagnostic Pathology, Fukushima Medical University, Fukushima, Fukushima, Japan; and

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Osamu Suzuki Department of Diagnostic Pathology, Fukushima Medical University Aizu Medical Center, Aizuwakamatsu, Fukushima, Japan

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Mudathir Bakhit Departments of Neurosurgery

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Masazumi Fujii Departments of Neurosurgery

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BACKGROUND

Bifocal germ cell tumors, with primarily identical tissue composition, occur concurrently in the neurohypophyseal and pineal regions.

OBSERVATIONS

A 16-year-old male patient exhibited increased intracranial pressure symptoms, with concurrent tumors in the pineal and neurohypophyseal regions, causing obstructive hydrocephalus. His serum human chorionic gonadotropin level was elevated, measuring 506.6 mIU/mL. Upon gross endoscopic examination, the pineal tumor appeared white, whereas the neurohypophyseal tumor appeared red and hemorrhagic. Because of the limited sample size of the latter, a frozen section biopsy was feasible only for the pineal lesion, which indicated the presence of a germinoma. Subsequently, carboplatin and etoposide were administered, resulting in the reduction of the pineal tumor, but no effect was observed in the neurohypophyseal tumor. Histopathological analysis confirmed the pineal lesion as a germinoma, whereas the neurohypophyseal lesion was an embryonal carcinoma. Thus, the treatment was altered to ifosfamide, carboplatin, and etoposide (ICE), leading to a response in both tumors. The patient underwent three additional cycles of ICE therapy and high-dose chemotherapy, followed by whole craniospinal irradiation, achieving complete remission.

LESSONS

Although most bifocal germ cell tumors share the same histological tissue, occasional differences may arise, necessitating separate biopsies for accurate assessment.

ABBREVIATIONS

AFP = alpha-fetoprotein; CARE = carboplatin and etoposide; CNS = central nervous system; CSF = cerebrospinal fluid; CT = computed tomography; ETV = endoscopic third ventriculostomy; HCG = human chorionic gonadotropin; ICE = ifosfamide, carboplatin, and etoposide; GCT = germ cell tumor; MRI = magnetic resonance imaging; NGGCT = nongerminomatous germ cell tumor

BACKGROUND

Bifocal germ cell tumors, with primarily identical tissue composition, occur concurrently in the neurohypophyseal and pineal regions.

OBSERVATIONS

A 16-year-old male patient exhibited increased intracranial pressure symptoms, with concurrent tumors in the pineal and neurohypophyseal regions, causing obstructive hydrocephalus. His serum human chorionic gonadotropin level was elevated, measuring 506.6 mIU/mL. Upon gross endoscopic examination, the pineal tumor appeared white, whereas the neurohypophyseal tumor appeared red and hemorrhagic. Because of the limited sample size of the latter, a frozen section biopsy was feasible only for the pineal lesion, which indicated the presence of a germinoma. Subsequently, carboplatin and etoposide were administered, resulting in the reduction of the pineal tumor, but no effect was observed in the neurohypophyseal tumor. Histopathological analysis confirmed the pineal lesion as a germinoma, whereas the neurohypophyseal lesion was an embryonal carcinoma. Thus, the treatment was altered to ifosfamide, carboplatin, and etoposide (ICE), leading to a response in both tumors. The patient underwent three additional cycles of ICE therapy and high-dose chemotherapy, followed by whole craniospinal irradiation, achieving complete remission.

LESSONS

Although most bifocal germ cell tumors share the same histological tissue, occasional differences may arise, necessitating separate biopsies for accurate assessment.

ABBREVIATIONS

AFP = alpha-fetoprotein; CARE = carboplatin and etoposide; CNS = central nervous system; CSF = cerebrospinal fluid; CT = computed tomography; ETV = endoscopic third ventriculostomy; HCG = human chorionic gonadotropin; ICE = ifosfamide, carboplatin, and etoposide; GCT = germ cell tumor; MRI = magnetic resonance imaging; NGGCT = nongerminomatous germ cell tumor

Central nervous system (CNS) germ cell tumors (GCTs) derive from primordial germ cells, with their inappropriate migration during embryonic development leading to the development of the ectopic embryonic cells within the brain, subsequently culminating in tumor formation.1 In the World Health Organization classification of tumors, CNS GCTs are histologically categorized into eight subtypes.2 In Western countries, these tumors have traditionally been divided into germinomas or nongerminomatous germ cell tumors (NGGCTs). However, in Japan, they are classified into three groups according to prognosis and optimal treatment: good, intermediate, or poor.3,4

CNS GCTs occur most frequently in the pineal region (53%–68%), followed by neurohypophysis (19%–37%) and basal ganglia (5%–10%).5,6 When CNS GCTs are detected simultaneously in the neurohypophysis and pineal region, they are termed bifocal GCTs, which account for 5.8% to 19.7% of all CNS GCTs.5,7,8 Bifocal GCTs, histologically predominantly comprised of germinoma in both the neurohypophyseal and pineal regions, have not exhibited any reported cases with varying histological types between these two regions.8,9 In this report, we present a rare case of a bifocal GCT, in which the pineal region was a germinoma, falling into the category of good prognosis. In contrast, the neurohypophyseal region was identified as an embryonal carcinoma, aligning with the poor prognosis group. Moreover, distinct responses to chemotherapy were observed in these two different lesions.

Illustrative Case

History and Examination

A 16-year-old male, previously diagnosed with autism spectrum disorder, sought medical attention due to symptoms including headache, nausea, vomiting, fatigue, blurred vision for a few days, and nocturnal polyuria persisting for a month. The patient exhibited full consciousness and lacked any signs of paralysis or sensory disturbance in the extremities. He displayed right abducens nerve palsy and a marked bilateral papilledema.

Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of tumors with the dimensions of 14 × 14 × 23 mm in the neurohypophyseal region and 31 × 26 × 31 mm in the pineal region (Fig. 1A–H). Although the pineal tumor displayed partial calcification, the neurohypophyseal tumor did not exhibit calcification (Fig. 1A). Both the pineal and neurohypophyseal tumors were isointense on T1- and T2-weighted MRI, and they demonstrated nearly uniform enhancement after gadolinium administration. However, the neurohypophyseal tumor displayed a slightly more contrast uptake (Fig. 1B–H). Notably, the neurohypophyseal tumor had extended from the sella turcica to the third ventricle (Fig. 1D and E). Meanwhile, the pineal tumor contained multiple small cysts, had an indistinct border with the bilateral thalamus, and obstructed the midbrain aqueduct, resulting in the enlargement of the bilateral lateral ventricles and the third ventricle (Fig. 1A and E–H).

FIG. 1
FIG. 1

Preoperative images. Sagittal plain CT image (A). Axial T1-weighted magnetic resonance (MR) images (B and F). Axial T2-weighted MR images (C and G). Axial gadolinium-enhanced T1-weighted MR images (D and H). Sagittal gadolinium-enhanced T1-weighted MR image (E). These images reveal the dimensions of the neurohypophyseal and pineal tumors, measuring 14 mm × 14 mm × 23 mm and 31 mm × 26 mm × 31 mm, respectively, as well as the presence of obstructive hydrocephalus due to the pineal tumor. Additionally, calcification is observed in the pineal tumor on the plain CT image (A). Both pineal and neurohypophyseal tumors show isointensity on T1- and T2-weighted MR images (B, C, F, and G) and demonstrate nearly homogeneous gadolinium uptake, with the neurohypophyseal tumor displaying slightly more pronounced contrast enhancement (D, E, and H).

The results of the serum tumor marker and the pituitary-related hormonal assay are described in Table 1. Human chorionic gonadotropin (HCG) levels were moderately elevated to 506.5 mIU/mL. Gonadotropin (luteinizing hormone and follicle-stimulating hormone) levels were suppressed at baseline, possibly due to negative feedback from HCG. Prolactin levels were slightly elevated above baseline values, possibly due to disturbance of prolactin-inhibiting factor.

TABLE 1

Results of the serum tumor marker and the pituitary-related hormonal assay

Laboratory testValueNormal Range
HCG (mIU/mL)506.50.0–9.9
AFP (ng/mL)4.30.0–9.9
CEA (ng/mL)<0.50.1–5.0
TSH (μIU/mL)0.7780.34–3.88
Free T3 (pg/mL)3.412.13–4.07
Free T4 (ng/dL)1.000.95–1.74
ACTH (pg/mL)44.607.2–63.3
Cortisol (μg/dL)12.935.3–22.5
PRL (ng/mL)64.793.7–16.3
GH (ng/mL)3.170–2.47
IGF-1 (ng/mL)402192–611
LH (mIU/mL)<0.070.1–8.7
FSH (mIU/mL)<0.302.0–8.3
Testosterone (ng/mL)23.61.31–8.71

ACTH = adrenocorticotropic hormone; CEA = carcinoembryonic antigen; FSH = follicle stimulating hormone; GH = growth hormone; IGF-1 = insulin-like growth factor–1; LH = luteinizing hormone; PRL = prolactin; TSH = thyroid stimulating hormone; T3 = triiodothyronine; T4 = thyroxine.

Progress of Treatment

Considering the imaging findings and tumor marker values, a diagnosis of GCT was suspected, leading to the decision to perform emergency procedures, including endoscopic third ventriculostomy (ETV), tumor biopsy, and ventricular drainage. During the operation, gross examination of the neurohypophyseal and pineal tumors revealed contrasting characteristics: the former displayed as red and firm, whereas the latter was white and soft (Fig. 2A and B). The pineal tumor exhibited a soft consistency and minimal bleeding, allowing for the acquisition of a sufficient tissue sample to establish a diagnosis. However, because of the firmness of the neurohypophyseal tumor and the bleeding encountered during the biopsy, only a limited tissue sample was obtained. Consequently, only tissue from the pineal tumor was subjected to a frozen section analysis, which ultimately showed the diagnosis of germinoma. The opening we established at the floor of the third ventricle turned out to be smaller than anticipated due to restrictions imposed by the neurohypophyseal tumor during our endoscopic maneuvering. A drain was inserted into the right lateral ventricle, and the surgical procedure was concluded.

FIG. 2
FIG. 2

Intraoperative images captured during the initial surgery (A and B) and the second surgery (C and D). During the initial surgery, the neurohypophyseal tumor is characterized by a red color and firm appearance, situated anterior to the third ventricular floor (A), while the pineal tumor exhibited a white color and soft texture (B). In the context of the second surgery, the neurohypophyseal tumor remains almost unchanged (C), whereas the pineal tumor has partially undergone degeneration into scar tissue (D).

Because the initial surgery showed that the opening of the third ventricular floor may be insufficient, initiation of chemotherapy was advised, aiming to reduce the tumor size. Treatment with carboplatin 300 mg/m2 on days 1–3 and etoposide 150 mg/m2 on days 1–2 carboplatin and etoposide (CARE) was started on postoperative day 5, with the hope that the pineal tumor would shrink and the obstructed cerebral aqueduct would open. At the end of the first cycle of CARE therapy, serum HCG decreased to 215.3 mIU/mL, and serum alpha-fetoprotein (AFP) remained within the normal range at 2.9 ng/mL. The histopathological confirmation of the diagnosis was achieved 12 days after the initial surgery. Based on the results of histopathological examinations, including the immunostaining, the pineal tumor was diagnosed as a germinoma, and the neurohypophyseal tumor was identified as embryonal carcinoma (Fig. 3). MRI conducted after the initial CARE therapy (13 days after the initial surgery) indicated a significant reduction in the size of the pineal tumor. However, there was no improvement in the obstructive hydrocephalus due to the presence of membranous-like structures blocking the cerebral aqueduct. The neurohypophyseal tumor showed a minimal reduction in size, but contrast uptake in the intrasellar region was decreased (Fig. 4A–C).

FIG. 3
FIG. 3

Histopathological examination. This figure presents the results of the histopathological examination, with hematoxylin and eosin staining and immunohistochemistry performed on samples collected from the pineal tumor (A, B, E–J) and the neurohypophyseal tumor (C, D, K–P). The pineal tumor shows a two-cell pattern marked by a significant proliferation of large, round, and atypical cells, accompanied by a small lymphocytic infiltration (A, bar = 100 µm). Among these large cells, there is a noticeable appearance of pale pink cytoplasm and enlarged, oval-shaped nuclei containing one to three prominent nucleoli each (B, bar = 20 µm). The neurohypophyseal tumor shows large, round, epithelial-like atypical cells with some glandular or papillary changes and a small lymphocytic proliferation (C, bar = 100 µm). The nuclei were large and irregular. Multinucleated cells and apoptotic bodies were readily visible (D, bar = 20 µm). Immunostaining for the pineal tumor (E–J, bar = 50 µm) was positive for placental alkaline phosphatase (PLAP) (E), SALL4 (F), and c-kit (G) and negative for CD30 (H), HCG (I), and AFP (J). Immunostaining for the neurohypophyseal tumor (K–P, bar = 50 µm) was positive for SALL4 (L) and CD30 (N), slightly positive for PLAP (K), c-kit (M), and HCG (O), and negative for AFP (P).

FIG. 4
FIG. 4

MR images obtained during the treatment process. Gadolinium-enhanced sagittal T1-weighted MR images (A, D, and G) and gadolinium-enhanced axial T1-weighted MR images (B, C, E, F, H, and I) taken at different stages of the treatment process. Gadolinium-enhanced T1-weighted images following the first cycle of CARE therapy (A–C) reveal a reduction in the size of the pineal tumor, with minimal change in the neurohypophyseal tumor. After four cycles of ICE therapy (D–F), there is a slight residual presence of both tumors. After high-dose chemotherapy, autologous peripheral blood stem cell transplantation, and whole craniospinal irradiation, both tumors are no longer visible (G–I).

Because the obstructive hydrocephalus persisted, a second surgical procedure was performed 14 days after the initial surgery. This entailed ETV and replacement of the ventricular drain (Fig. 2C and D). Intraoperative observations revealed a substantial reduction in the pineal tumor, with some parts degenerating into scar tissue. The cerebral aqueduct was visible but narrow and surrounded by membranous degenerative tissue. The neurohypophyseal tumor remained red, firm, and prone to bleeding, similar to its condition during the initial surgery. The opening in the floor of the third ventricle was small and exhibited weak pulsations, necessitating further enlargement. The neurohypophyseal and pineal tumors underwent a second biopsy, with the diagnoses aligning with the initial findings.

After the histopathological diagnosis of the neurohypophyseal tumor and the ineffectiveness of CARE therapy in reducing its size, the patient’s chemotherapy regimen was changed to ifosfamide 1800 mg/m2 on days 1 to 5, carboplatin 400 mg/m2 on days 1 to 2, and etoposide 100 mg/m2 on days 1 to 5 (ICE) starting from the second course. The initial ICE therapy not only proved effective in shrinking the pineal tumor but also yielded positive results for the neurohypophyseal tumor, leading to its reduction in size. Consequently, three additional courses of ICE were administered. After the third course of chemotherapy, the serum AFP and HCG levels were within normal range. After a total of five courses of chemotherapy, including one course of CARE and four courses of ICE, both the neurohypophyseal and pineal tumors had nearly completely regressed (Fig. 4D–F). Upon completion of five courses of chemotherapy, the patient’s bilateral papilledema and right abducens nerve palsy improved, and diplopia resolved. However, hypopituitarism and central diabetes insipidus became evident, promoting the initiation of treatment with hydrocortisone 20 mg/d, levothyroxine 50 mg/d, and desmopressin 180 mg/d. Subsequently, the patient underwent high-dose chemotherapy with autologous peripheral blood stem cell transplantation (thiotepa 200 mg/m2 on days 1–4 and melphalan 70 mg/m2 on days 1–3), followed by cerebrospinal irradiation, with doses of 30.8 Gy/17 fractions, 9.0 Gy/5 fractions for whole brain, and a 14.4–Gy/8 fractions boost focused on the neurohypophyseal and pineal tumor bed.

At the 15-month mark after the initial surgery, both the neurohypophyseal and pineal tumors had completely resolved (Fig. 4G–I), and there were no indications of elevated tumor markers.

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Observations

The important and interesting aspect of this case is the presence of bifocal GCTs displaying distinct histological types, specifically embryonal carcinoma and germinoma in the neurohypophyseal and pineal regions, respectively. These differing histological types were reinforced by distinct intraoperative characteristics and disparate responses to the shared chemotherapy regimen, CARE therapy.

In cases of CNS GCTs where bifocal tumors are observed in imaging studies, when both serum and cerebrospinal fluid (CSF) AFP are within normal range, and there is only a slight elevation in serum or CSF levels of HCG, the diagnosis of germinoma can often be made without the need for biopsy.9,10 However, it should be noted that not all bifocal tumors can be confirmed as germinomas without a tissue biopsy. In rare cases, NGGCTs, including teratoma or embryonal carcinoma, can manifest as bifocal tumors even in the absence of elevated tumor markers.8,9,11 In Japan, it is a common practice to administer radiochemotherapy to patients with brain tumors who have a serum HCG level of 2,000 mIU/mL or higher or a serum AFP level of 2000 ng/mL or higher. Even without a confirmed tissue diagnosis, this approach is commonly adopted due to the perceived poorer prognosis associated with these elevated levels. Elevated serum AFP levels above the normal range categorize the patient into the intermediate or poor prognostic group. However, there are no well-defined criteria for serum HCG values that can reliably distinguish between the good prognostic group (pure germinoma) and intermediate or poor prognostic group when serum HCG is less than 2,000 mIU/mL.4 In this particular case, the serum HCG was elevated at 506.5 mIU/mL, which is considerably high for secretion from a germinoma. It is our contention that this elevated HCG level may have been produced by an embryonal carcinoma located in the neurohypophyseal region.12,13

In previous reports, the diagnosis of bifocal GCTs was frequently established through tissue biopsy, either due to uncertainty regarding the biopsy site or because only one of the two sites was biopsied. Yet, both sites were diagnosed as having the same histological tissue. In some cases, even when the histology appeared identical, a closer examination revealed that the two tissues were mixed germ cell tumors.9,14,15 To our knowledge, this is the first report documenting a simultaneous biopsy of a lesion from the pineal and neurohypophysis areas, each exhibiting different histological characteristics, specifically germinoma and embryonal carcinoma. It is not rare for CNS GCTs to have a mixed histology.10,16 In the present case, the amount of tissue obtained from each site was small, and it is possible that both or one of the pineal and neurohypophyseal regions were mixed GCTs containing germinoma and embryonal carcinoma components. However, the intraoperative observations in this case distinctly set the two tumors apart: the neurohypophyseal tumor displayed a red coloration, was prone to hemorrhaging, and exhibited firmness, while the pineal tumor appeared white, had a soft consistency and presented typical characteristics of a germinoma. Furthermore, the response to the initial course of CARE therapy showed limited shrinkage of the neurohypophyseal tumor but a marked reduction in the size of the pineal tumor. Germinoma is highly sensitive to radiochemotherapy, and its standard treatment is whole ventricle irradiation with CARE therapy to reduce the risk of late sequelae associated with radiotherapy.17 In contrast, NGGCTs such as embryonal carcinoma, yolk sac tumor, and choriocarcinoma fall into the category of poor prognostic groups, exhibiting lower survival rates compared to germinomas. Within this category, prioritizing tumor control takes precedence over functional prognosis. Hence, a common approach involves the utilization of whole craniospinal irradiation combined with intense chemotherapy.4 The neurohypophyseal tumor showed a limited response to CARE therapy but exhibited a favorable response upon transitioning to ICE therapy, with carboplatin as a more intensive chemotherapy regimen. Although cisplatin traditionally served as the primary platinum agent in ICE therapy, recent practice also incorporates the use of carboplatin.18–21 In this particular case, we administered 900 mg/m2 of carboplatin per course during CARE therapy and 800 mg/m2 of carboplatin per course during ICE therapy. Despite the similar carboplatin doses, our observations indicated that ifosfamide was notably more effective against embryonal carcinoma. Aside from the histological diagnosis, these findings suggest that each site’s tissues differed.

Some reports have documented the metachronous occurrence of GCTs with different histological types in the pineal and neurohypophyseal regions. This includes a case of a germinoma emerging after total resection of a pineal mature teratoma, which might be indicative of a recurrence potentially attributed to the absence of radiochemotherapy.16,22 In a prior report, we presented a case of pure germinomas in the neurohypophysis and cervical spinal cord. This case emerged long after treatment of a mixed GCT, including a yolk sac tumor and germinoma in the pineal region. In this report, we postulate in alignment with “the germ cell theory” that each tumor was multicentric in nature, originating de novo.16 The germ cell theory postulates that CNS GCTs originate from preexisting primordial germ cells within the CNS. These primordial germ cells have the potential to differentiate into all histological types of GCTs. This potential is thought to underlie the development of de novo metachronous GCTs.1

Even in the current case under consideration, in which two different tumors occurred simultaneously, the germ cell theory remains in accord with the notion of the multicentric occurrence of different histological tumor types within the pineal and neurohypophyseal regions. There have been several reported cases of extracranial GCTs of primary gonadal origin that occur simultaneously and with different tissues in the left and right testes.23–25 Given the absence of vascular or lymphatic connections between the left and right testes, it is postulated that each testis gives rise to GCTs independently.23,26 This suggests that intracranial GCTs with multicentric and different histological types may also develop simultaneously. Hence, it is important to recognize that in some cases of bifocal GCT, as in our case, GCTs with different histological types may occur concurrently in each respective location.

Transventricular endoscopic surgery offers the advantage of conducting relatively minimally invasive biopsies in the neurohypophysis and pineal regions.27,28 In the case of bifocal GCTs, it is important to perform biopsies at each site to ensure proper diagnosis and, consequently, appropriate treatment plans. This is crucial due to the rare likelihood of histological differences between the two sites, which could lead to varying responses to treatment.

Lessons

The current report is the first to document a bifocal GCT with distinct histological subtypes in the neurohypophyseal and pineal regions, as confirmed through endoscopic biopsies of each respective region. Initially, the patient underwent CARE chemotherapy before the histopathological diagnosis was established, resulting in insufficient treatment. Subsequently, after the confirmation of the tissue diagnosis, ICE therapy was administered, coupled with high-dose chemotherapy and radiotherapy, culminating in the patient achieving complete remission.

Even in cases with typical bifocal GCT imaging findings and mildly elevated HCG in serum or CSF, it is imperative to recognize that not all such cases are germinomas. They may encompass NGGCTs such as embryonal carcinoma or teratoma, or they might exhibit different histologies between the neurohypophysis and pineal regions. In particular, embryonal carcinoma is highly malignant and requires more intensive radiochemotherapy than germinoma to achieve remission. Consequently, obtaining a histological diagnosis at each site in bifocal GCTs is of utmost importance in tailoring appropriate treatment regimens according to the GCT grade and enhancing the patient’s prognosis.

Author Contributions

Conception and design: Naruse, Jinguji. Acquisition of data: Naruse, Jinguji, Hiruta, Toda, Nagai, Kudo, Sano, Sekine. Analysis and interpretation of data: Naruse, Jinguji, Hiruta, Toda, Nagai, Kudo, Sekine. Drafting the article: Naruse, Jinguji, Hiruta, Toda, Nagai, Kudo, Sano, Sekine, Bakhit. Critically revising the article: Naruse, Jinguji, Hiruta, Nagai, Kudo, Sekine, Bakhit, Fujii. Reviewed submitted version of manuscript: Naruse, Jinguji, Hiruta, Toda, Nagai, Sekine, Bakhit. Approved the final version of the manuscript on behalf of all authors: Naruse. Administrative/technical/material support: Fujii. Study supervision: Jinguji, Sano, Fujii. Diagnosis of the case: Suzuki.

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    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Coli A, Bigotti G, Dell’Isola C, Castri F, Rulli F, Massi G Synchronous bilateral testicular germ cell tumor with different histology. Case report and review of the literature. Urol Int. 2003;71(4):412417.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Zequi SdeC, da Costa WH, Santana TB, Favaretto RL, Sacomani CA, Guimaraes GC Bilateral testicular germ cell tumours: a systematic review. BJU Int. 2012;110(8):11021109.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Symeonidis EN, Tsifountoudis I, Anastasiadis A, et al. Synchronous bilateral testicular cancer with discordant histopathology occurring in a 20-year-old patient: a case report and review of the literature. Urologia. 2023;90(2):434441.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Matsushima M, Fukasawa K, Kawahara M, et al. Synchronous bilateral testicular tumors of different cell types on each side. Urology. 1987;30(2):180182.

  • 27

    Somji M, Badhiwala J, McLellan A, Kulkarni AV Diagnostic yield, morbidity, and mortality of intraventricular neuroendoscopic biopsy: systematic review and meta-analysis. World Neurosurg. 2016;85:315-24.e2.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Kinoshita Y, Yamasaki F, Tominaga A, et al. Pitfalls of neuroendoscopic biopsy of intraventricular germ cell tumors. World Neurosurg. 2017;106:430434.

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  • FIG. 1

    Preoperative images. Sagittal plain CT image (A). Axial T1-weighted magnetic resonance (MR) images (B and F). Axial T2-weighted MR images (C and G). Axial gadolinium-enhanced T1-weighted MR images (D and H). Sagittal gadolinium-enhanced T1-weighted MR image (E). These images reveal the dimensions of the neurohypophyseal and pineal tumors, measuring 14 mm × 14 mm × 23 mm and 31 mm × 26 mm × 31 mm, respectively, as well as the presence of obstructive hydrocephalus due to the pineal tumor. Additionally, calcification is observed in the pineal tumor on the plain CT image (A). Both pineal and neurohypophyseal tumors show isointensity on T1- and T2-weighted MR images (B, C, F, and G) and demonstrate nearly homogeneous gadolinium uptake, with the neurohypophyseal tumor displaying slightly more pronounced contrast enhancement (D, E, and H).

  • FIG. 2

    Intraoperative images captured during the initial surgery (A and B) and the second surgery (C and D). During the initial surgery, the neurohypophyseal tumor is characterized by a red color and firm appearance, situated anterior to the third ventricular floor (A), while the pineal tumor exhibited a white color and soft texture (B). In the context of the second surgery, the neurohypophyseal tumor remains almost unchanged (C), whereas the pineal tumor has partially undergone degeneration into scar tissue (D).

  • FIG. 3

    Histopathological examination. This figure presents the results of the histopathological examination, with hematoxylin and eosin staining and immunohistochemistry performed on samples collected from the pineal tumor (A, B, E–J) and the neurohypophyseal tumor (C, D, K–P). The pineal tumor shows a two-cell pattern marked by a significant proliferation of large, round, and atypical cells, accompanied by a small lymphocytic infiltration (A, bar = 100 µm). Among these large cells, there is a noticeable appearance of pale pink cytoplasm and enlarged, oval-shaped nuclei containing one to three prominent nucleoli each (B, bar = 20 µm). The neurohypophyseal tumor shows large, round, epithelial-like atypical cells with some glandular or papillary changes and a small lymphocytic proliferation (C, bar = 100 µm). The nuclei were large and irregular. Multinucleated cells and apoptotic bodies were readily visible (D, bar = 20 µm). Immunostaining for the pineal tumor (E–J, bar = 50 µm) was positive for placental alkaline phosphatase (PLAP) (E), SALL4 (F), and c-kit (G) and negative for CD30 (H), HCG (I), and AFP (J). Immunostaining for the neurohypophyseal tumor (K–P, bar = 50 µm) was positive for SALL4 (L) and CD30 (N), slightly positive for PLAP (K), c-kit (M), and HCG (O), and negative for AFP (P).

  • FIG. 4

    MR images obtained during the treatment process. Gadolinium-enhanced sagittal T1-weighted MR images (A, D, and G) and gadolinium-enhanced axial T1-weighted MR images (B, C, E, F, H, and I) taken at different stages of the treatment process. Gadolinium-enhanced T1-weighted images following the first cycle of CARE therapy (A–C) reveal a reduction in the size of the pineal tumor, with minimal change in the neurohypophyseal tumor. After four cycles of ICE therapy (D–F), there is a slight residual presence of both tumors. After high-dose chemotherapy, autologous peripheral blood stem cell transplantation, and whole craniospinal irradiation, both tumors are no longer visible (G–I).

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    Han L, Song Y, Fang L, Qi S Multiple ectopic recurrent germ cell tumors after total pineal mature teratoma removal: a case report and literature review. Front Oncol. 2023;13:1094231.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Coli A, Bigotti G, Dell’Isola C, Castri F, Rulli F, Massi G Synchronous bilateral testicular germ cell tumor with different histology. Case report and review of the literature. Urol Int. 2003;71(4):412417.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Zequi SdeC, da Costa WH, Santana TB, Favaretto RL, Sacomani CA, Guimaraes GC Bilateral testicular germ cell tumours: a systematic review. BJU Int. 2012;110(8):11021109.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Symeonidis EN, Tsifountoudis I, Anastasiadis A, et al. Synchronous bilateral testicular cancer with discordant histopathology occurring in a 20-year-old patient: a case report and review of the literature. Urologia. 2023;90(2):434441.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Matsushima M, Fukasawa K, Kawahara M, et al. Synchronous bilateral testicular tumors of different cell types on each side. Urology. 1987;30(2):180182.

  • 27

    Somji M, Badhiwala J, McLellan A, Kulkarni AV Diagnostic yield, morbidity, and mortality of intraventricular neuroendoscopic biopsy: systematic review and meta-analysis. World Neurosurg. 2016;85:315-24.e2.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Kinoshita Y, Yamasaki F, Tominaga A, et al. Pitfalls of neuroendoscopic biopsy of intraventricular germ cell tumors. World Neurosurg. 2017;106:430434.

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