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Hindawi Case Reports in Oncological Medicine Volume 2020, Article ID 3787250, 5 pages https://doi.org/10.1155/2020/3787250 Case Report A Rare Case of Intracranial Nongerminomatous Germ Cell Tumor in a 21-Year-Old Romanian Male 1 1 1,2 1 3,4 Minesh Nandi , Rahul Anil, Edward Hamaty Jr., William Adams, David Stidd, 1 1 Krizelle Garde, and Hari Kandukuri Department of Neurological Critical Care Medicine, AtlantiCare Regional Medical Center, 1925 Paciﬁc Avenue, Atlantic City, NJ, USA Medical Neurological Critical Care, AtlantiCare Regional Medical Center, 1925 Paciﬁc Avenue, Atlantic City, NJ, USA Department of Neurosurgery, AtlantiCare Regional Medical Center, Atlantic City, NJ, USA Department of Neurological Surgery, Thomas Jeﬀerson University and Jeﬀerson Hospital for Neuroscience, Philadelphia, PA, USA Correspondence should be addressed to Minesh Nandi; firstname.lastname@example.org Received 24 March 2019; Revised 4 September 2019; Accepted 7 December 2019; Published 4 January 2020 Academic Editor: Giovanni Tallini Copyright © 2020 Minesh Nandi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Extragonadal germ cell tumors are a rare entity that is more prevalent in infants and young children, with preference to midline structures. The category of intracranial germ cell tumors is divided into pure germ cell tumors (GCTs) versus nongerminomatous germ cell tumors (NGGCTs). They are usually present in the second decade of life with a male preponderance. We present here a rare case of intracranial NGGCT in a 21-year-old Romanian male, who presented with complaints of emesis, ataxic gait, and diplopia. A computed tomography scan of the head in the emergency department revealed a pineal/suprapineal mass along with obstructive hydrocephalus and dilated lateral and third ventricles without any bleeding. MRI of the cervical, thoracic, and lumbar spine showed no evidence of leptomeningeal metastasis. The patient had elevated serum markers of beta-hCG and AFP, which pointed towards a diagnosis of nongerm cell tumor, as in pure GCTs, these markers are normal. To relieve the obstruction from the mass eﬀect, the patient had an endoscopic third ventriculostomy (EVT). However, after the procedure, he developed central diabetes insipidus as a complication with a triphasic response. Biopsy of the mass revealed atypical cells with granular architecture and atypical glands with positive immune histological markers for NGGCT. These ﬁndings supported the diagnosis of mixed germ cell tumor with yolk sac carcinoma and seminoma components. Patient’s transient central diabetes resolved with normalization in his urine output. He was eventually stabilized and returned to Romania for further management. In summary, intracranial germ cell tumors are rare brain tumors that should be distinguished based on histology and tumor markers as they will help in the guidance of therapy. An initial evaluation with neuroimaging, tumor markers, cytology from CSF, and biopsy is a must to distinguish further treatment and prognosis. 1. Introduction a male preponderance ratio of 3 : 1 . In North America, intracranial germ cell tumor represents 0.5-3% of pediatric central nervous system tumors . Patient’s clinical presen- Germ cell tumors (GCTs) can be gonadal or extragonadal depending upon the evidence of the existence of a primary tation varies by location and size including visual changes tumor in the testis or ovaries . GCTs are classiﬁed extrago- and signs of increased intracranial pressure . Neuroimag- nadal if there is no evidence of primary tumor in the gonads. ing techniques are useful in detecting the site; however, one Extragonadal germ cell tumor typically arises in locations cannot diﬀerentiate GCT types based on imaging alone, as a diagnosis usually requires histologic conﬁrmation. The that are midline, including anterior mediastinum, retroperi- toneum, pineal gland, and suprasellar regions . Distribu- molecular pathogenesis of intracranial GCT gain of chromo- tion is unimodal, with a sudden surge in frequency in early some 12p which is considered characteristic for germ cell pubertal years diagnosed between ages 10 and 21 years with tumor of the testes was observed . No diﬀerences were 2 Case Reports in Oncological Medicine (a) (b) (c) Figure 1: (a) Axial, (b) sagittal, and (c) coronal view of the intracranial germinoma. Note the obstructive pattern of the tumor giving obstructive hydrocephalus. found in genetic proﬁles of GCT versus NGGCT on compar- department and was administered a loading dose of Keppra ative genomic hybridization studies; however, average imbal- 1000 mg and a maintenance dose of 500 mg twice a day intra- ances occurred in the latter group . venously. The patient was then admitted to the neurological A meta-analysis comparing gonadal and extragonadal critical care unit for further monitoring. germ cell tumors revealed virtually no diﬀerence in geno- Neurosurgery evaluated the patient and recommended to mic alterations in the tumors . As per histologic classiﬁ- bolus 10 mg of IV dexamethasone and with the maintenance cation, approximately 25% of NGGCT are mixed, and they of 4 mg IV every 6 hours to prevent expansion and reduction contain more than one histologic component. These can of the cytotoxic edema from the mass eﬀect. Given his symp- include yolk sac, endodermal sinus, and syncytiotropho- toms of obstructive hydrocephalus with increased ICP of blast components. While parasellar tumors present with 22 mmHg, an endoscopic ventricular drain was placed for diabetes insipidus and hypothalamic-pituitary axis dysfunc- the drainage to relieve the pressure by the neurosurgeon. tion, the NGGCTs usually present as posterior third ventric- MRI of the brain revealed a pineal mass causing obstructive ular masses with obstructive hydrocephalus. Intracranial hydrocephalus via the compression of the cerebral aqueduct GCTs are divided further based on tumor markers in CSF likely from a possible underlying intracranial germ cell tumor and serum. These include alpha-fetoprotein (AFP) and beta (Figure 1, image R to L). MRI of the cervical, thoracic, and human chorionic gonadotropin (b-hCG) with immunohisto- lumbar spine was done with and without contrast. No chemical markers including alkaline phosphatase and c-kit enhancing lesions were visualized on these images, and there on the tumor cells . was no evidence of drop metastasis or discrete mass lesion or pathologic enhancement in the spinal system (Figure 2). A detailed MRI of the lesion revealed mass arising from the 2. Case Presentation pineal gland with a diameter of 3.6 cm and predominantly We present here a case of a 21-year-old right-handed Roma- solid component with discrete calciﬁcation inside the mass nian male, who was working in the United States on an (Figures 1(a)–1(c)). The tumor was causing compression of employer-sponsored visa and presented to the emergency the tectal plate of the midbrain and subjacent aqueduct, which was resulting in obstructive hydrocephalus. To further department of Atlantic Regional Medical Center in Atlantic City, New Jersey, with acute episodes of vomiting, diplopia, evaluate, we obtained serum beta-hCG and alpha-fetoprotein and ataxic gait and two episodes of tonic-clonic seizures. to distinguish if the mass was a pure extragonadal germ cell The patient was brought in by his acquaintances who tumor or NGGCT. Patient’s serum alpha-fetoprotein levels reported headaches for two weeks along with vision changes were elevated to 215.8 ng/mL (normal range of 0-8 ng/mL), and a slow decline in his mentation. His friends stated that and beta-hCG level was noted to be 35 mIU/mL (normal the patient was becoming more tired and lethargic with a range of 0-3 mIU/mL). Given the elevations of the tumor waxing and waning in mentation. Pertinent physical exam markers, this patient likely had an NGGCT; however, a deﬁnite diagnosis biopsy was needed. On day three of his revealed Parinaud’s syndrome with upward gaze palsy, diplo- pia, and unsteady gait. A CT scan was done in the emergency admission, the patient received an endoscopic third ventricu- department that showed a pineal mass of 3×3×3:5 mm in lostomy to improve the obstructive hydrocephalus and help size along with obstructive hydrocephalus and dilatation of in the drainage of the cerebrospinal ﬂuid through the cerebral lateral and third ventricles without any evidence of bleeding. aqueduct system during which we also obtained a biopsy of the sample (Figure 3). The patient also had an episode of seizure in the emergency Case Reports in Oncological Medicine 3 (a) (b) (c) Figure 2: MRI of the cervical (a), thoracic (b), and lumbar spine (c) showing no evidence of leptomeningeal spread. (a) (b) (c) Figure 3: The image shows the endoscopic third ventriculostomy (EVT) procedure. However, after this procedure, the patient developed a Patient’s urine output decreased at a goal less than 3 L in 24 transient episode of central diabetes insipidus. On his labora- hours with a normal serum osmolality. Pathology report tory analysis, he was noted to have sodium level of came back, which revealed atypical cells were forming glan- dular architecture and solid area, which are all positive for 145 mEq/L (range 135 mEq/L-145 mEq/L) with a urine osmolality of 161 and serum osmolality of 298. Central dia- Sal-4 and negative for CD30 and GFAP (glial ﬁbrillary acidic betes insipidus is deﬁned as serum sodium concentration protein) (Figure 3). The atypical glands are positive for pan- higher than 142 mEq/L in a setting of polyuria of 3000 cc/day cytokeratin and glypican-3, and the solid area is positive for with a plasma osmolality of 295 and a low urine osmolality, OCT3/4 and CK117 (Figure 4). These ﬁndings supported a which were all noted in this patient. This was a complication diagnosis of mixed germ cell tumor with yolk sac carcinoma. likely from the EVT procedure. The patient was observed to However, due to the limited material, other components can- be in transient triphasic response with the polyuric phase not be ruled out. Patient’s electrolytes were normalized, and for ﬁve days, followed by an antidiuretic phase of 6 more he was medically cleared to travel back to Romania where days. We monitored his urine output very closely replacing he would be following up with neurosurgery for further man- agement of his NGGCT. cc per cc of volume by giving him by mouth and isotonic IV ﬂuids. The patient was started on desmopressin, which was administered in the intravenous form initially and then 3. Discussion converted to intranasal. The patient subsequently developed hyponatremia likely This case represents an acute presentation with challeng- also contributed from the desmopressin, and he was noted to ing complications in the management of location-sensitive develop cerebral salt wasting for which he was placed on intracranial germ cell tumor. The patient presented with hydrocortisone and later changed to ﬂudrocortisone. the symptoms of pineal mass, including diplopia, ataxia, 4 Case Reports in Oncological Medicine (a) (b) (c) (d) Figure 4: (a) Immunohistochemical stain of SALL-4, a marker for germ cell tumor. (b) Seminoma portion, 100x. (c) H&E of the whole biopsy. (d) Yolk sac carcinoma, 100x. Note the glands with atypical cells forming glandular architecture and solid area, which are all positive for Sal-4 and negative for CD30 and GFAP (glial ﬁbrillary acidic protein). The atypical glands are positive for pancytokeratin and glypican-3, and the solid area is positive for OCT3/4 and CK117. These ﬁndings supported a diagnosis of mixed germ cell tumor with yolk sac carcinoma. headaches, and vomiting, all which are signs of increased The tumor has homogeneous enhancement if no cysts intracranial pressure. Patient’s neuroimaging revealed a pic- are present or heterogeneous in appearance with the pres- ture of obstructive hydrocephalus. Given the CT scan and ence of cysts (Figure 1). As noted, our patient has a het- erogeneous MRI appearance of his mass with cystic MRI ﬁndings (Figures 1 and 2), prompt neurosurgical inter- vention was initiated, and the patient received an endoscopic enhancements. MRI of the entire spine is also necessary ventricular drain to relieve his obstruction and decrease the for the staging of intracranial GCTs as 15% of patients will intracranial pressure. Given his clinical signs of increased have leptomeningeal spread [1, 5]. intracranial pressure, imaging is a must. We did not perform Given the above-discussed markers, any tumors with ele- a lumbar puncture, and of note in cases such as this, lumbar vated AFP (>10 μg/L) can contain elements of endodermal puncture should be avoided in these patients due to risk of sinus tumor or a mature teratoma. Hence, if surgery is not herniation. Serum alpha-fetoprotein and beta-hCG levels possible for conﬁrmation of diagnosis, such masses should were elevated, pointing more towards the diagnosis of mixed be treated as having NGGCT. Serum AFP > 1000 μg/L has germ cell tumor or immature teratoma. For diagnosis and been identiﬁed as a poor prognostic indicator . However, staging, a histologic examination is needed to establish a a signiﬁcant portion of these tumors have mixed compo- deﬁnitive diagnosis of an intracranial GCT. Surgery to obtain nents, and hence, tumor markers should not be used for risk specimen is mandatory for patients with normal CSF, serum stratiﬁcation without an oﬃcial tissue diagnosis. AFP and alpha-fetoprotein, and beta-hCG as pure germ cell tumor or beta-hCG from CSF are more sensitive than serum, and both mature teratoma must be distinguished from other lesions should be obtained in the absence of clinical contraindica- since the therapeutic approaches are diﬀerent. tion. A lumbar puncture (LP), if not contraindicated, is more Regarding imaging, MRI is preferred for diagnosis and accurate for tumor markers and then ventricular CSF; how- staging, although CT is sensitive in detecting the lesions, as ever, if LP is contraindicated due to increased ICP, then tumor markers from ventricular CSF and serum can be used shown in Figure 1. During the evaluation of a sellar mass, it is imperative to obtain hormonal evaluation including serum for diagnostic purposes. A biopsy is challenging as the pineal prolactin, insulin-like growth factor, and 24-hour urinary gland is a deep structure surrounded by essential vasculature free cortisol for lactotroph, somatotroph, or corticotroph and is associated with complications. Immediate neurosurgi- adenomas. On MRI, the tumors appear isointense or hypoin- cal intervention is indicated for obstructive hydrocephalus from a pineal mass or acute visual deterioration from a tense on T1 sequences and hyperintense on T2 sequences. Case Reports in Oncological Medicine 5 suprasellar mass. As a result, our patient received an endo- References scopic third ventriculotomy procedure to relieve his  M. T. Jennings, R. Gelman, and F. Hochberg, “Intracranial obstruction (Figure 3). Surgical biopsies can yield small germ-cell tumors: natural history and pathogenesis,” Journal samples which can lead to inaccurate diagnosis depending of Neurosurgery, vol. 63, no. 2, pp. 155–167, 1985. on the area where the tissue was obtained from as mixed  M. E. Echevarria, J. Fangusaro, and S. Goldman, “Pediatric cen- tumors and contain various components, and a small area tral nervous system germ cell tumors: a review,” The Oncologist, biopsy may only include one part. As a result, when tissue vol. 13, no. 6, pp. 690–699, 2008. diagnosis is not reliable, treatment should be based upon  D. T. Schneider, S. Zahn, S. Sievers et al., “Molecular genetic the outcome associated with most malignant histology analysis of central nervous system germ cell tumors with com- and worse prognosis. parative genomic hybridization,” Modern Pathology, vol. 19, In such cases, for example, a tissue diagnosis of NGGCT no. 6, pp. 864–873, 2006. with normal AFP or beta-hCG levels should be treated as  H. Ogino, Y. Shibamoto, T. Takanaka et al., “CNS germinoma such and not a pure germ cell tumor. Given the location of with elevated serum human chorionic gonadotropin level: clin- the tumor along with surgical complication, a gross resection ical characteristics and treatment outcome,” International Jour- of the mass is generally not recommended. As emphasized, nal of Radiation Oncology, Biology, Physics, vol. 62, no. 3, before the distinction of a true germinoma from NGGCT is pp. 803–808, 2005. crucial. Pure germ cell tumors are sensitive to radiation ther-  G. Calaminus, D. Frappaz, R. D. Kortmann et al., “Outcome of apy with long-term progression-free survival rates greater patients with intracranial non-germinomatous germ cell than 90% in those patients after radiation therapy . In a tumors-lessons from the SIOP-CNS-GCT-96 trial,” Neuro- study with 48 patients that were conﬁrmed by histology to Oncology, vol. 19, no. 12, pp. 1661–1672, 2017. have a primary CNS germ cell tumor, it was revealed that  M. G. Haddock, S. E. Schild, B. W. Scheithauer, and P. J. Schom- treatment with radiation with doses higher than 40 Gy to berg, “Radiation therapy for histologically conﬁrmed primary the primary tumor was associated with better control . central nervous system germinoma,” International Journal of Prior treatment of the localized germinoma included receiv- Radiation Oncology, Biology, Physics, vol. 38, no. 5, pp. 915– ing craniospinal irradiation CSI 36 Gy with a boost to the pri- 923, 1997. mary tumor of 50 Gy; however, studies demonstrated that  M. Bamberg, R. D. Kortmann, G. Calaminus et al., “Radiation with whole-brain or whole-ventricle irradiation resulted in therapy for intracranial germinoma: results of the German spinal failure rates less than 10% . cooperative prospective trials MAKEI 83/86/89,” Journal of As a result, the current standard of care for radiation Clinical Oncology, vol. 17, no. 8, pp. 2585–2592, 1999. alone for localized germinoma is 21-24 Gy to the whole ven-  Y. Shibamoto, M. Takahashi, and K. Sasai, “Prognosis of intra- tricle with the boost to the tumor for a total dose of 40-40 cranial germinoma with syncytiotrophoblastic giant cells 5 Gy. Due to the prevalence of NGGCT much less common treated by radiation therapy,” International Journal of Radia- tion Oncology, Biology, Physics, vol. 37, no. 3, pp. 505–510, 1997. than pure germinoma, there are no signiﬁcant studies avail- able to interpret the treatment. NGGCTs are mostly not sen-  G. Calaminus, M. Bamberg, D. Harms et al., “AFP/beta-HCG sitive to radiation with a small series study showing patient secreting CNS germ cell tumors: long-term outcome with respect to initial symptoms and primary tumor resection. treated alone with radiation therapy, and craniospinal irradi- Results of the cooperative trial MAKEI 89,” Neuropediatrics, ation with a boost to the local tumor site had a survival rate of vol. 36, no. 2, pp. 71–77, 2005. 20-40% . As a result, in the absence of randomized studies, the current standard of care for patients with intracranial NGGCTs is neoadjuvant chemotherapy, followed by cra- niospinal irradiation. The tumors are more sensitive to a platinum-based compound, including cisplatin or carbopla- tin along with etoposide . Studies had shown that neoad- juvant therapy before initiation of radiation therapy resulted in long-term survival (60-70% of cases) . In SIOP CNS GCT study, the magnitude of alpha-fetoprotein elevation was correlated with adverse prognostic indicator with AFP > 1000 U/L revealing a progression-free survival rate of 32% versus 76% in those with AFP < 1000 U/L . Another potential prognostic indicator is the presence of residual disease upon completion of neoadjuvant chemo- therapy. In the SIOP CNS 96 trial, the progression-free sur- vival was 85% for dose with no residual tumors versus 48% for those with residual tumors . Also, in patients with recurrent NGGCTs, prognosis is poor. Conflicts of Interest The authors declare that they have no conﬂicts of interest. 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Published: Jan 4, 2020
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