The External Metastasis of The Central Nerve Yystem Germ Cell Tumors: Case Report and Review of Literature

doi:10.21203/rs.3.rs-94494/v1

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Case report

The External Metastasis of The Central Nerve Yystem Germ Cell Tumors: Case Report and Review of Literature

https://doi.org/10.21203/rs.3.rs-94494/v1

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posted 23 Oct, 2020

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Background: The central nervous system germ cell tumors (CNS GCTs) represent a class of rare tumors with incidences ranging from 3.6% in North America to 15.3% in some areas of Asia, and commonly occurring in children and adolescents[1]. According to the 2016 World Health Organization (WHO) classification, GCTs divided into germinomas, non-germinal germ cell tumors (NGGCT) and suprasellar with male prominent[2]. Common symptoms of GCTs include headache, dizziness, vomiting, thirst, heavy drinking, and precocious puberty[3]. Because of GCTs arising in the pineal region could compress the interventricular foramen with consequence obstructive hydrocephalus, leading to high intracranial pressure (HIP), the ventriculoperitoneal shunt is preferred to relieve severe HIP. Although CNS GCTs tend to spread through the subependymal lining and cerebrospinal fluid (CSF), the metastasis along the ventriculoperitoneal shunt is extremely rare[4]. Therefore, we reported two cases and a review of the literature.

Neurology

Chemotherapy

External metastasis

Germ cell tumor

Radiotherapy

The central nervous system germ cell tumors (CNS GCTs) represent a class of rare tumors with incidences ranging from 3.6% in North America to 15.3% in some areas of Asia, and commonly occurring in children and adolescents[1]. According to the 2016 World Health Organization (WHO) classification, GCTs divided into germinomas, non-germinal germ cell tumors (NGGCT) and suprasellar with male prominent[2]. Common symptoms of GCTs include headache, dizziness, vomiting, thirst, heavy drinking, and precocious puberty[3]. Because of GCTs arising in the pineal region could compress the interventricular foramen with consequence obstructive hydrocephalus, leading to high intracranial pressure (HIP), the ventriculoperitoneal shunt is preferred to relieve severe HIP. Although CNS GCTs tend to spread through the subependymal lining and cerebrospinal fluid (CSF), the metastasis along the ventriculoperitoneal shunt is extremely rare[4]. Therefore, we reported two cases and a review of the literature.

Case 1

A 13-year old Asian male presented with unsteady gait for four months, headache, nausea, drooping left eyelid, blurred version for 11 days and convulsions for three days. The MRI (Fig.1) scan revealed the occupation and HIP. The blood alpha-fetoprotein (AFP) was 188.2ng/ml (0-7ng/ml), blood chorionic gonadotropin β (β-HCG) was 716mIU/ml (0-2.6IU/ml). The AFP in CSF is 5.9ng/ml (0-7ng/ml), while the β-HCG is 542.9mIU/ml (0-2.6IU/ml). To relieve the HIP, the patient received ventriculoperitoneal shunt. Following the SIOP CNS GCT 96, the tumor was diagnosed as non-germinomatous germ cell tumors (NGGCTs). With establishing the diagnosis, the patient firstly received two cycles platinum-based chemotherapy followed by tumor resection and then completed left two courses of chemotherapy using the same regimen. Intraoperative pathological revealed hemorrhagic degeneration and necrosis, scattered in glands and heteronuclear cells, and cellular degeneration. Immunohistochemical display CK (+), AFP (+), HCG-β (+), Ki-67 (+), Syn (+), SMA (+), CD30 (+). Radiation therapy was given after chemotherapy, with the dose of 30.6Gy/17f Intensity modulated radiotherapy (IMRT) and PB 23.4Gy/13f (IMRT). However, the patient complained about cough, right costal margin and pain in the right clavicle with the blood β-HCG 742.1mIU/ml and AFP 873.3ng/ml in 8 months after the V-P shunt. The whole-body 18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) examination showed multiple intra-abdominal lesions demonstrating increased metabolic activity with a maximum standardized uptake value (Fig.4a). In combination with the imaging findings and laboratory results, we considered the extensive intraperitoneal metastasis (ENM) of CNS GCTs.

Case 2

A 17-year-old Asian male presented with a longstanding history of generalized headache, diabetes insipidus and intermittent fever without obvious inducement. MRI examination (Fig.2) revealed hydrocephalus due to space-occupying lesions. The patient underwent VP shunt to face with the HIP. Moreover, the patient's blood β-HCG and AFP was negative. Based on the imaging feature and the patient's symptom, we believe that the patient had the GCTs with intraventricular dissemination. The patient received two circles with the regimen based on platinum. The blood tumor marker was negative and MRI revealed a 95% disappearance of the tumor after chemotherapy. Then the patient received and finished Whole Central Nerve System Irradiation with a dose of 40Gy/25f. After 32 months of chemoradiation therapy, the patient presented intermittent abdominal pain and right upper abdomen mass without obvious inducement. The blood tumor marker was negative and central nerve system MRI showed no evidence of tumor recurrence. Nevertheless, the MRI revealed the rough-edged masses in right upper abdominal (Fig.3). The patient then underwent PET-CT examination, PET-CT showed multiple site SUV elevation in the abdominal cavity, which was considered to be GCTs abdominal metastasis（Fig.4-b1-2）. Then the patient underwent tumor resection, and the immunohistochemical results are AE1/AE3 (+), CD117 (+), Ki67(70%), OCT3/4 (+), sall-4 (+). The patient began four courses platinum-based chemotherapy followed and it is in fair condition now.

Germ cell tumor is the most common tumor in the pineal region, but it is still a rare disease, accounting for less than 1% of all intracranial tumors[5]. Intracranial germ cell tumors are comparable to gonadal seminoma in histology. We reviewed the relevant data (Table.1) and found that Varan et al. 's team completed a retrospective study of 1011 cases[6], which is the most extensive retrospective study of germinoma. Among the 1011 patients, the longest survival time reached 32 years, but only ten patients developed ENM. Among the ten patients, 2 were germ cell tumors, 6 were neural tube cell tumors, 1 was ependymoma, and 1 was an atypical rod-shaped tumor. It can be seen that only 0.98% of patients had primary intracranial tumors with ENM[7]. Recently, Schmalisch et al. reported 2 cases of the pineal tumor[8]. As with the previous cases[5], these authors demonstrated the risk of metastasis caused by endoscopic biopsy. In contrast, although no endoscopic biopsy was performed in our patient, the v-p shunt was performed to alleviate the severe hydrocephalus in the patient. Although the cause of peritoneal implant metastasis in the patient is still unclear, we highly suspect that the cause of this situation is ventriculoperitoneal shunt[9].

Consider the whole medical treatment process, and it's entirely in line with the diagnosis and treatment standard that the initial diagnosis is suspected to be GCTS. Patients treated along this clinical pathway rarely have metastases outside the nervous system. These two patients developed extensive peritoneal metastasis 8 months and 32 months after VP shunt. Furthermore, we are wondering whether it is transferred by shunt. Unfortunately, no cytological analysis was performed on the CSF of the first patient after the operation, but the second patient's pathology revealed a metastasis GCTs.

Neuroaxial dissemination of iGCTs is common but distant metastases is rare; this is why we report the index two cases of iGCTs metastasizing through the VPS into the peritoneal cavity causing widespread intra‑abdominal carcinomatosis. According to Giuseppe Talamonti’s report, germ cell tumors could metastasis along the endoscopic biopsy pathway[5]. Instead of the biopsy, the patient in our case had VP shunt. As ENM through a VPS is an unusual phenomenon, whether or not the placement of a VPS increases the risk of a patient with a primary intracranial tumor developing ENM remains controversial. The lack of statistical evidence means that the management and treatment of patients who require a VPS should not be changed. Alternative means of CSF drainage or diversion such as endoscopic third vetriculosfomy (ETV) merit further discussion and risk‑benefit assessment. Meanwhile, clinicians should maintain a relatively high level of vigilance for patients with VPS and abdominal symptoms, upon which a low threshold for abdominopelvic imaging should be maintained.

Table.1 Review of 18 cases of ventriculoperitoneal shunt‑related intra‑abdominal metastasis reported between 1979 to 2020.
Author	Age	Sex	Histological type	Treatment	Initial position	Metastatic area	V-P shunt	Time to metastatic	Initial symptoms	Survival after metastatic
F.Lesoin[10]	4	M	Pineal tumor	Radiotherapy	posterior part of the 3rd-ventricle	intracranial and abdominal(mesenteric)	Y	12mo	bilateral,symmetrical, cerebellar syndrome bilateral papilledema, Parinaud‘s syndrome	10mo
F.Lesoin[10]	3	F	pinealoblastoma	Subtotal resection and radiotherapy	third ventricle	behind the bladder, internal mammary glands and subhepatic pulmonary	Y	8mo	character disorders, cerebellar syndrome	>18 months
F.Lesoin[10]	12	M	pinealoblastoma	Subtotal resection and radiotherapy	pineal	pulmonary	Y	12mo	static,symmetricla, bilateral,cerebellar syndrome	68mo
Belongia and Jogal[7]	7	M	Mixed malignant	Chemotherapy	N/A	Multiple intra‑abdominal masses	Y	5mo	Asymptomatic, incidental finding on spinal imaging	10 months
Murray et al.[11]	13	F	Pineal germinoma	Resection of mass and chemotherapy	pineal	Ascites, pelvic,mass, peritoneal,nodules	Y	17mo	Abdominal distension	>34 months
Altundag et al.[12]	23	M	Pineal germinoma	Chemotherapy	pineal	Ascites, pelvic,mass, multiple,liver nodules	Y	24mo	Abdominal distension	>36 months
Back et al.[13]	10	M	Pineal germinoma	Chemoradiotherapy and resection of mass	pineal	Abdominal mass	Y	13mo	Abdominal pain and distension	>4 months
Ung et al.[14]	13	M	Pineal germinoma	Resection of mass and chemotherapy	pineal	Abdominal mass	Y	37mo	Abdominal pain	>24 months
Pallini et al.[15]	15	M	Pineal germinoma	subtotal resection and radiotherapy	pineal and 3rd ventricle	Pelvic mass, peritoneal nodules	Y	2mo	headache,lethargy, limitation,upward gaze, diabetes insipidus	4 months
Kim et al.[16]	36	M	Pineal germinoma	Chemotherapy	Pineal	Ascites, peritoneal nodules	Y	12mo	Abdominal distension, vomiting	>6 months
Devkota et al.[17]	12	M	Pineal germinoma	N/A	Pineal	Pelvic mass, peritoneal nodules	Y	24mo	Abdominal pain, distension,vomiting	<1 month
Haimovic et al.[18]	27	M	Pineal germinoma	Radiotherapy	posterior 3rd-ventricle	right abdominal palpable rectal	Y	36mo	bifrontal, headaches, diplopia, nausea, dizziness, hydrocephalus, duration	NA
Kun et al.[19]	14	M	Germinoma	Radiotherapy	NA	Pelvic mass	Y	14mo	Abdominal pain, constipation	>38 months
Triolo and Schulz[20]	15	M	Pineal germinoma	N/A	Pineal	Pelvic abdominal mass peritoneal and omental nodules	Y	N/A	Constipation, weight loss	21 months
Wood et al.[21]	11	M	Pineal germinoma	Chemoradiotherapy	Pineal	Pelvic mass	Y	36mo	Rectal discomfort	>24month
Wood et al.[21]	13	F	Pineal germinoma	N/A	Pineal	Pelvic mass	Y	10mo	N/A	<1month
Wood et al.[21]	15	M	Pineal germinoma	Chemotherapy	Pineal	Fluid collection	Y	36mo	Abdominal pain distension	N/A

central nervous system germ cell tumors (CNS GCTs), World Health Organization (WHO), non germinal GCTs (NGGCTs), high intracranial pressure (HIP), cerebrospinal fluid (CSF), alpha-fetoprotein (AFP), chorionic gonadotropin β (β-HCG), ventriculoperitoneal (VP), Immunohistochemical (IHC), 18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT), extensive intraperitoneal metastasis (EIM), endoscopic third vetriculosfomy (ETV).

Declarations of interest: None.

Ethics approval and consent to participate：Not applicable

Consent for publication：Agreed

Availability of data and material：Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Competing interests：The authors declare that they have no competing interests.

Funding：This report did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions: Writing - original draft preparation: Peng Wang; Resources: Yanong Li; Writing - review and editing: Xiaoguang Qiu

Acknowledgements：The authors thank the patient for their contributions. Also thank my roommates for being quite when I was writing my manuscript, especially Bowei Xiao.

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The External Metastasis of The Central Nerve Yystem Germ Cell Tumors: Case Report and Review of Literature

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Abstract

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Background

Case Report

Discussion

Conclusion

Abbreviations

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