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Modern Pathology : An Official Journal... Dec 2022Central nervous system (CNS) germ cell tumors (GCTs) represent 2-3% of all primary CNS tumors. The majority are germinomas, which are radiosensitive and have an...
Central nervous system (CNS) germ cell tumors (GCTs) represent 2-3% of all primary CNS tumors. The majority are germinomas, which are radiosensitive and have an excellent prognosis. Contrarily, CNS non-germinomatous GCTs (NGGCTs) have less favorable prognosis and require more aggressive treatment. The expression of checkpoint/immune markers in CNS GCTs, particularly NGGCTs, is unknown. We previously reported a case of a patient whose intracranial NGGCT (predominantly choriocarcinoma) responded to immune checkpoint inhibition therapy. This case led us to evaluate our archive of intracranial GCTs for expression of PD-L1 and PD-1. With IRB approval, we searched the pathology archives at our institution for CNS GCTs. Demographic, radiologic, clinical, and histologic information was extracted from the medical records. Immunohistochemistry for lymphocytic markers (CD4, CD8, CD20), PD-1, and PD-L1 was performed. PD-L1 was considered positive if greater than 1% of tumor cells were positive and PD-1 was reported as a percentage of positive inflammatory cells. Fifty cases were identified, including 28 germinomas (mean age at diagnosis: 15.5 years; 17 males, 11 females), and 22 NGGCTs (mean age at diagnosis: 12.0 years, 21 males, 1 female). Germinomas were mostly suprasellar (17/28) and NGGCTs were predominantly pineal (17/22). Twenty-two germinomas (79%) were positive for PD-L1 expression, and 13 NGGCTs (57%) were positive for PD-L1. Cases of choriocarcinoma showed the most diffuse PD-L1 expression. PD-1 expression was seen in lymphocytes among 27/28 of the germinomas and 20/23 of the NGGCTs (ranging from 1-40% of lymphocytes). As expected, larger quantities of inflammatory cells were present in cases of germinoma. We demonstrate immune activity in CNS GCTs, and our results suggest that immune checkpoint inhibitors may be efficacious in the treatment of intracranial GCTs. Among NGGCTs, cases of choriocarcinoma showed the highest expression of PD-L1 in tumor cells, suggesting that this subtype may have the greatest benefit from checkpoint blockade.
Topics: Child; Male; Humans; Female; Adolescent; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Neoplasms, Germ Cell and Embryonal; Germinoma; Brain Neoplasms; Central Nervous System Neoplasms; Choriocarcinoma; Central Nervous System
PubMed: 36057740
DOI: 10.1038/s41379-022-01142-3 -
Cancers Jul 2022Pineal region tumors are rare intracranial tumors, accounting for less than 1% of all adult intracranial tumor lesions. These lesions represent a histologically... (Review)
Review
Pineal region tumors are rare intracranial tumors, accounting for less than 1% of all adult intracranial tumor lesions. These lesions represent a histologically heterogeneous group of tumors. Among these tumors, pineal parenchymal tumors and germ cell tumors (GCT) represent the most frequent types of lesions. According to the new WHO 2021 classification, pineal parenchymal tumors include five distinct histotypes: pineocytoma (PC), pineal parenchymal tumors of intermediate differentiation (PPTID), papillary tumor of the pineal region (PTPR), pinealoblastoma (PB), and desmoplastic myxoid tumor of the pineal region, SMARCB1-mutant; GCTs include germinoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, mixed GCTs. Neuroradiological assessment has a pivotal role in the diagnostic work-up, surgical planning, and follow-up of patients with pineal masses. Surgery can represent the mainstay of treatment, ranging from biopsy to gross total resection, yet pineal region tumors associated with obstructive hydrocephalus may be surgically managed via ventricular internal shunt or endoscopic third ventriculostomy. Radiotherapy remains an essential component of the multidisciplinary treatment approach for most pineal region tumors; however, treatment volumes depend on the histological subtypes, grading, extent of disease, and the combination with chemotherapy. For localized germinoma, the current standard of care is chemotherapy followed by reduced-dose whole ventricular irradiation plus a boost to the primary tumor. For pinealoblastoma patients, postoperative radiation has been associated with higher overall survival. For the other pineal tumors, the role of radiotherapy remains poorly studied and it is usually reserved for aggressive (grade 3) or recurrent tumors. The use of systemic treatments mainly depends on histology and prognostic factors such as residual disease and metastases. For pinealoblastoma patients, chemotherapy protocols are based on various alkylating or platinum-based agents, vincristine, etoposide, cyclophosphamide and are used in association with radiotherapy. About GCTs, their chemosensitivity is well known and is based on cisplatin or carboplatin and may include etoposide, cyclophosphamide, or ifosfamide prior to irradiation. Similar regimens containing platinum derivatives are also used for non-germinomatous GCTs with very encouraging results. However, due to a greater understanding of the biology of the disease's various molecular subtypes, new agents based on targeted therapy are expected in the future. On behalf of the EURACAN domain 10 group, we reviewed the most important and recent developments in histopathological characteristics, neuro-radiological assessments, and treatments for pineal region tumors.
PubMed: 35954310
DOI: 10.3390/cancers14153646 -
Cancers Jul 2022Background: CNS germinoma, being marker-negative, are mainly diagnosed by histological examination. These tumors predominantly appear in the suprasellar and/or pineal...
Background: CNS germinoma, being marker-negative, are mainly diagnosed by histological examination. These tumors predominantly appear in the suprasellar and/or pineal region. In contrast to the suprasellar region, where biopsy is the standard procedure in case of a suspected germ-cell tumor to avoid mutilation to the endocrine structures, pineal tumors are more accessible to primary resection. We evaluated the perioperative course of patients with pineal germinoma who were diagnosed by primary biopsy or resection in the SIOP CNS GCT 96 trial. Methods: Overall, 235 patients had germinoma, with pineal localization in 113. The relationship between initial symptoms, tumor size, and postoperative complications was analyzed. Results: Of 111 evaluable patients, initial symptoms were headache (n = 98), hydrocephalus (n = 93), double vision (n = 62), Parinaud syndrome (n = 57), and papilledema (n = 44). There was no significant relationship between tumor size and primary symptoms. A total of 57 patients underwent primary resection and 54 underwent biopsy. Postoperative complications were reported in 43.2% of patients after resection and in 11.4% after biopsy (p < 0.008). Biopsy was significantly more commonly performed on larger tumors (p= 0.002). Conclusions: These results support the practice of biopsy over resection for histological confirmation of pineal germinoma.
PubMed: 35884617
DOI: 10.3390/cancers14143555 -
Neuro-ophthalmology (Aeolus Press) 2022Suprasellar germinomas can present with non-diagnostic, or even normal results on imaging. The spectrum of reported cases ranges from normal imaging, thickened pituitary...
Suprasellar germinomas can present with non-diagnostic, or even normal results on imaging. The spectrum of reported cases ranges from normal imaging, thickened pituitary stalks, to discrete tumour growths. This similar phenomenon is less commonly seen in the pineal region, or bifocal germinomas, and the literature is sparse with only a few case series or reports mentioning a similar presentation of signs and symptoms preceding radiological evidence of diagnosis. We report a case of pineal germinoma presenting with dorsal midbrain syndrome with no evidence of tumour growth on initial imaging despite symptoms. For patients presenting with this clinical radiological latent period, follow-up imaging is useful to identify interval development of germinomas. This applies to patients with dorsal midbrain syndrome, or even other unexplained ophthalmoplegia, as the initial sign of pineal region germinoma, despite normal imaging.
PubMed: 35859628
DOI: 10.1080/01658107.2022.2034890 -
Child's Nervous System : ChNS :... Sep 2023Resecting pineal region tumors in children is often challenging. Several approaches have been proposed and practiced. A personal series of pediatric pineal region tumors...
PURPOSE
Resecting pineal region tumors in children is often challenging. Several approaches have been proposed and practiced. A personal series of pediatric pineal region tumors resected through craniotomy with posterior interhemispheric occipital transtentorial (OT) approach are reviewed. We present the surgical techniques, pitfalls, and their results.
MATERIAL AND METHODS
Eighty patients ranging in age from 3 months to 21 years old, and treated over 3 decades were reviewed. Hydrocephalus caused the main presenting symptoms and was noted in 74 patients. It was treated prior to the craniotomy for tumor resection with endoscopic third ventriculostomy (ETV) in 33, external ventricular drainage in 26, and precraniotomy shunt in 15. Nine patients had ETV together with endoscopic biopsy. All patients had a parieto-occipital craniotomy in a prone position. Through a tentorial section, a gross total resection of the tumor was attempted except for germinomas.
RESULTS
The tumor pathology showed 32 germ cell tumors (GCT), 22 benign astrocytomas, 13 pineal parenchymal tumors, 5 ATRTs, 3 papillary tumors, and 5 others. Of GCTs, 18 were teratomas. The extent of resection consisted of 55 gross total resections, 13 subtotal resections, 10 partial, and 2 biopsies with one postoperative death. Hemiparesis in 2, cerebellar ataxia in another 2, and hemiballismus in 1 were transient and improved over time. One had permanent hemisensory loss and another patient had bilateral oculomotor palsy. Postoperative homonymous hemianopia occurred in 2 patients but subsided over a short period of time. Parinaud's sign was noted in 24 patients, of which 16 were transient.
CONCLUSION
The posterior interhemispheric OT approach provides a safe route and comfortable access to the pineal region in children. A great majority of postoperative neurological complications are the results of direct manipulations of the midbrain at tumor resection. Identification and preservation of the tumor-brain interface are of paramount importance. GCTs other than teratomas are treated with neoadjuvant chemotherapy and may eliminate the need for craniotomy. Exophytic midbrain JPAs are amenable to resection.
Topics: Child; Humans; Pinealoma; Retrospective Studies; Brain Neoplasms; Pineal Gland; Postoperative Complications; Teratoma
PubMed: 35821434
DOI: 10.1007/s00381-022-05595-4 -
Journal of the ASEAN Federation of... 2022We report a case of a 24-year-old Filipino male who complained of general weakness, polydipsia, weight loss, bitemporal headaches, loss of libido and behavioral changes....
We report a case of a 24-year-old Filipino male who complained of general weakness, polydipsia, weight loss, bitemporal headaches, loss of libido and behavioral changes. Endocrine work-up revealed neurogenic diabetes insipidus and panhypopituitarism. Brain MRI showed multiple intracranial tumors in the left frontal lobe, pineal and suprasellar region with moderate non-communicating hydrocephalus. Intracranial mass biopsy with ventriculo-peritoneal shunting was done. Histopathology of the mass and CSF revealed a germinoma. He underwent chemoradiotherapy while on maintenance hormone replacement.
Topics: Male; Adult; Humans; Young Adult; Hypopituitarism; Germinoma; Brain Neoplasms; Treatment Outcome; Diabetes Insipidus, Neurogenic
PubMed: 35800587
DOI: 10.15605/jafes.037.01.12 -
Radiology Case Reports Sep 2022Patients with pineal tumors are often asymptomatic and the symptoms depend on the location of the mass. In fact, around 3%-8% of pediatric brain tumor cases are pineal...
Patients with pineal tumors are often asymptomatic and the symptoms depend on the location of the mass. In fact, around 3%-8% of pediatric brain tumor cases are pineal tumors. Children with pineal tumors may present with dizziness and vertigo as early signs. These symptoms are common conditions among 5-15 years old children and could probably lead to misdiagnoses. We present a case of 14-year-old who came to the emergency room of DR. Soetomo Hospital Surabaya with neurotologic symptoms. After a series of radiographic and laboratory examinations, he was diagnosed with germinoma. A ventriculoperitoneal shunt was performed in the emergency room and intravenous dexamethasone was administered.
PubMed: 35789558
DOI: 10.1016/j.radcr.2022.06.001 -
Radiology Case Reports Sep 2022Primary intracranial germ cell tumors are rare, often affecting children and young patients. Germinomas are the most common type of germ cell tumors. We present the case...
Primary intracranial germ cell tumors are rare, often affecting children and young patients. Germinomas are the most common type of germ cell tumors. We present the case of a 10-year-old child, who was admitted with decreased visual acuity, asthenia, polyuro-polydipsic syndrome, and gait disorder. His biological assessment showed an hypocortisolemia and diabetes insipidus. Imaging found a bifocal process in the suprasellar and pineal region, suggestive of a bifocal germinoma. Imaging data and the positivity of human chorionic gonadotrophin in the cerebrospinal fluid were in favor of the diagnosis of bifocal germinal tumor confirmed by biopsy. Currently the patient is hospitalized in pediatric oncology department. The diagnosis of germ cell tumors is based on imaging, tumor marker assays, and biopsy. They are treated by radiation therapy alone or in combination with reduction chemotherapy, and surgery for tumor residues. The location of the tumor usually makes surgery difficult.
PubMed: 35755113
DOI: 10.1016/j.radcr.2022.05.080 -
Radiology Case Reports Sep 2022Tumors of the pineal region are a rare clinical entity, comprising approximately 3%-8% of pediatric tumors. Based on their histopathological features, they are typically...
Tumors of the pineal region are a rare clinical entity, comprising approximately 3%-8% of pediatric tumors. Based on their histopathological features, they are typically classified as pineal parenchymal tumors and germ cell tumors, with the latter being more prevalent. Clinical presentation is heterogeneous, with symptoms arising either due to tumor invasion or compression of adjacent neurovascular structures and increased intracranial pressure. Imaging studies are paramount in evaluating pineal region lesions and establishing an accurate diagnosis, with MRI representing the gold standard. Herein, we present the case of a 16-year-old boy presented with recurrent headaches. A head MRI revealed a pineal gland lesion. Histopathological examination confirmed the diagnosis, and the patient underwent a successful gross total resection (GTR) of the tumor. This case report seeks to draw attention to the elusive clinical presentation and management of this infrequently encountered tumor, as well as emphasize the importance of considering pineal gland tumors in the differential diagnosis of recurrent, chronic headaches in pediatric patients.
PubMed: 35755097
DOI: 10.1016/j.radcr.2022.05.024 -
American Journal of Ophthalmology Case... Sep 2022To report a case of bilateral ocular paraneoplastic syndrome by seminoma/germinoma in thymus and pineal glands, two primary lesions.
PURPOSE
To report a case of bilateral ocular paraneoplastic syndrome by seminoma/germinoma in thymus and pineal glands, two primary lesions.
OBSERVATIONS
A 18-year-old male presented at a local clinic complaining of just floaters in left eye without any other clinical signs and symptoms. The treating ophthalmologist found bilateral uveitis, and referred to our hospital. Bilateral retinal periphlebitis and optic disc swelling were shown. Vitreous opacity was found in left eye. We started ocular and systemic examinations to identify the cause of the uveitis, and also initiated oral steroid therapy. The survey using aqueous humor and blood samples showed no specific results for his uveitis. Computer tomography (CT) and magnetic resonance imaging (MRI) detected tumors in thymus and pineal glands. Five months after his first visit, the tumor in his thymus was resected, and was diagnosed as a seminoma/germinoma by pathological examination. Three months later, the tumor in the pineal gland was diagnosed as a germinoma by biopsy followed by chemotherapy and focal radiotherapy. Finally no abnormal ocular finding but slight optic disc atrophy was ascertained.
CONCLUSIONS AND IMPORTANCE
This is a case of ocular paraneoplastic syndrome induced by seminoma/germinoma in thymus and pineal glands, two primary lesions. Systemic screening by CT and MRI enables prompt diagnosis, treatment and favorable clinical course for such pathogenesis.
PubMed: 35647392
DOI: 10.1016/j.ajoc.2022.101589