MRI of pineal region tumors

The pineal region is a heterogeneous area that includes the pineal gland and several parapineal structures. Pineal region masses include germ cell tumors (GCTs), pineal parenchymal cell tumors, glioma, meningioma, metastases, and non-neoplastic masses such as pineal cysts, lipoma, epidermoid, vascular malformations. Although MRI has allowed an improvement in distinguishing true pineal masses from parapineal masses impinging into the region of the gland, it is still difficult to differentiate the pineal GCTs from pineal parenchymal tumors with only images, and the clinical informations such as age, sex, and the tumor markers are very important.     

Pathology of pineal region tumors

Various histological types of tumors arise in the pineal region. The most common tumors are pineal parenchymal tumors and germ cell tumors. Pineal parenchymal tumors are divided into pineocytoma, pineal parenchymal tumor with intermediate differentiation and pineoblastoma. Pineocytomas are well-differentiated tumors and retain the morphological and immunohistochemical features of pineal parenchymal cells. Lobular architectures and pineocytomatous rosettes are also typical features. In contrast, pineoblastomas are embryonal tumors resembling primitive neuroectodermal tumors (PNET). However, pineoblastomas are distinct from PNET in other sites due to their exhibiting photosensory differentiation including Flexner–Wintersteiner rosettes and fleurettes. Although pineal cysts are tumor-like lesions, and not true neoplasms, they are occasionally difficult to distinguish from pineocytoma and astrocytoma. From the therapeutic aspect, a precise differential diagnosis is critical.The pineal region is the most common site of the brain in which germ cell tumors occur. Germinoma, teratoma, embryonal carcinoma, yolk sac tumor and choriocarcinoma are encountered, and the latter three types of tumors usually constitute elements of mixed germ cell tumors. The morphological and immunohistochemical features of intracranial germ cell tumors are very similar to those of gonadal germ cell tumors, although there are some differences in germinoma. Pineal germinoma may exhibit carcinomatous differentiation.Other types of tumors are occasionally observed, including fibrillary and pilocytic astrocytoma, glioblastoma, ependymoma, melanoma, meningioma and so on. Metastatic pineal tumors are also rare. The most common site of origin for pineal metastasis is the lung.     

Surgical approaches to pineal region tumors

Direct surgical resection of pineal region tumors has become safer, more effective, and now plays an essential role in their management. Tissue diagnosis allows for the initiation of appropriate therapies and resection can be curative or improve the efficacy of adjuvant therapies. Several approaches have been reported. Based on our operative experience with 57 patients over a 20-year period, we conclude that the Infratentorial Supracerebellar and Parieto-Occipital Paramedian Transtentorial approaches provide excellent exposure while allowing minimally invasive, relatively low risk access to the majority of pineal region tumors. Indications, positioning, techniques, advantages, and disadvantages are discussed. A review of other approaches, pertinent historical remarks, and a discussion of the role of surgery in the contemporary management of pineal region tumors are presented.     

Neuroendoscopic anatomy and surgery in pineal region tumors

The therapeutic modalities for pineal region tumors in Western countries differ from those in far-eastern countries, that is, Japan and Korea, mainly because of the different patient populations. The majority of pineal region tumors in Japan and Korea are radio sensitive and/or chemosensitive, and adjuvant therapy rather than extensive surgery plays the main part in the treatment of these tumors. The authors have applied minimally-invasive preferential management in pineal region tumors in last 8 years. For the therapeutic regimen, if the tumor markers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were not detected in serum and there was significant ventricular dilation visualized on neuroimages, neuroendoscopic surgery was first applied for tumor debulking with tissue diagnosis and gross morphological analysis of the tumor and the intraventricular structures, followed by third-ventriculostomy. In the results, our minimally-invasive preferential regimen clarified the precise indication for neuroendoscopic procedures, and the majority of our patients with dilated ventricles and no evidence of tumor markers were treated satisfactorily with effective neuroendoscopic procedures as the initial procedure. Then avoided unnecessary craniotomy and radiotherapy and promised excellent therapeutic outcomes. Neuroendoscopic procedures have a great advantage in the management of chemo- or radiosensitive tumors, such as germinoma, pineoblastoma, or primitive neuroectodermal tumor. The neuroendoscopic anatomy including the lateral and third ventricles with a pineal region tumor with or without tumor dissemination was described in detail, together with the neuroendoscopic surgical technique.     

Cellular pleomorphism in papillary tumors of the pineal region

Papillary tumor of the pineal region (PTPR) is a recently recognized entity. We present the pathologic findings of two cases of PTPR as examples, and discuss the presence of cellular pleomorphism in these tumors. Patient 1 is a 48-year-old man with a pineal region mass. The tumor had unique biphasic patterns, papillary/pseudopapillary areas, and increased mitotic activity. Juxtaposed areas had marked pleomorphism, including nuclear enlargement, smudgy chromatin, nuclear pseudoinclusions, and cytoplasmic vacuolation. Mitoses were absent in these areas. Immunohistochemical staining revealed strong S100 expression. CAM 5.2 and CK18 were strongly positive in a patchy fashion. MIB1 labeling indices were high in classic PTPR regions but very low in pleomorphic areas. Patient 2 was a 35-year-old male with a pineal region tumor characterized by papillary architecture and overall cellular monotony, rare mitoses, and pleomorphism as a more isolated finding, with associated nuclear enlargement and crowding. S100 and CAM 5.2 labeling were present, and MIB1 labeling index was very low throughout the tumor. We discuss the pathologic and phenotypic features of PTPR. Variable pleomorphism may be present, reflected in size variation and nuclear hyperchromasia, but was not accompanied by increased proliferative activity in these cases, suggesting a degenerative phenomenon.     

Long term outcomes following surgery for pineal region tumors

Journal of Neuro-Oncology - Pineal region tumors are surgically demanding tumors to resect. Long term neuro-oncologic outcomes following surgical excision of tumors from this region have been...     

松果体区肿瘤的放射治疗27例临床分析

 自1978年2月～1992年2月共收治松果体肿瘤患者27例。年龄分布9～36岁，其中25岁以下23例（85．2％），男女之比为2：1。有3例经组织学证实，18例采用脑室分流术加术后放疗，9例行单纯放疗。3年、5年生存率分别为66．7％（18／27）和55．6％（15/27），主要死因是局部复发。因为手术治疗本病有较高的并发症和死亡率，虽然大多数肿瘤不能全切，但对放射线敏感。因此，在无法取得组织寻诊断时，可采用脑室分流术和术后放疗。     

Epidemiology of germ cell tumors in Asia of pineal region tumor

A higher incidence of pineal region tumors in Asian countries compared to Western countries has been reported. In the Brain Tumor Registry of Japan (BTRJ), there were 38,273 primary brain tumors except those of unknown histology (1123 cases) registered in the period between 1984 and 1993, in which 807 pineal region tumors with 104 unknown histology were registered in BTRJ. Of these pineal region tumors, germ cell tumors had the highest frequency, 70.3%, followed by pineal parenchymal tumors, 12.0%; pineocytoma in 7.8% and pineoblastoma in 4.2%. Limited to germ cell tumors, germinoma was 68.0%, then teratoma including malignant teratoma, had the second high frequency, 14.7% in pineal region. While, data reported by Allaire et al. and Edwards et al. revealed that the incidence of germinoma was 88.6%, 52.4% of germ cell tumors in pineal region in France and in USA, respectively. Although number of cases is very small, it is suggested that the percentage of germinoma in germ cell tumors in the pineal region might be almost the same in Western countries as in Asian countries, and the occurrence of germ cell tumors in the pineal region was much higher than those in Asia. Age and gender distribution of pineal region tumors indicated that germ cell tumors and pineocytoma showed a high incidence in males and in children. Most of malignant pineal region tumors other than germinomas showed poor prognosis, but recent progress in surgical techniques and effective chemotherapy will improve the prognosis.     

132例松果体区肿瘤的临床研究

Objective To review the clinical manifestations, imaging, tumor markers, treatment methods, pathology results and clinical curative effects of pineal region tumors and to evaluate the characteristics and intervention strategies for those tumors. Methods The clinicopathological data of 132 patients with pineal region tumor treated in our department between January 2000 and May 2008 were retrospectively studied.Results A moderate predominance in males was presented. The clinical manifestations of the disease included increased intracranial pressure and ocular movement impairment. There were some features but no regularity and specific appearance on imaging including CT and MRI. 88. 6% of patients associated with hydrocephalus. A high serum level of alpha-fetoprotein (AFP) was presented in 14 cases and high HCG in 9 cases.Eighteen cases received direct radiation therapy and 7 had radiotherapy post biopsy. 107 cases were treated surgically and 63 cases received postoperative adjuvant treatment. 114 cases had pathology results including 56 germ cell tumors. The patients were followed up for 12 ～ 132 months. Recurrence developed in 23 cases and 12 cases died.The 5-year survival rate was 89. 3%. Conclusion Pineal region tumors are often associated with hydrocephalus and this makes preoperative diagnosis difficult. Imaging examination may help diagnosis but less specific. Germ cell tumors may diagnosed by some tumor markers. Radiation therapy is the choice of treatment for pure germinomas.Other types of pineal region tumors should receive surgical treatment. Postoperative adjuvant treatment based on pathology can provide a good prognosis in pineal region tumor.     

132例松果体区肿瘤的临床研究

目的 研究松果体区肿瘤的临床表现、影像学特征、肿瘤标记物、病理特征、治疗方法 和临床疗效,探讨其特点和治疗策略.方法 回顾性分析2000年1月至2008年5月间住院治疗的132例松果体区肿瘤患者的资料.结果 132例松果体区肿瘤患者中,男性98例,女性34例,男女之比为2.9:1.临床表现以颅内压升高、眼球运动障碍为主.CT和MRI检查有一定特征,但缺乏特异性的影像表现.132例患者中,合并腩积水117例,占88.6%.甲胎蛋白(AFP)升高14例,人绒毛膜促性腺激素(HCG)升高9例.132例患者中,直接放疗18例,病理活检后放疗7例,手术切除107例.有病理诊断结果 者114例,其中生殖细胞源性肿瘤56例.随访12～132个月,肿瘤复发23例,死亡12例.132例患者的5年牛存率为89.3%.结论 松果体区肿瘤常合并脑积水,定性诊断较困难,影像学检查有助于诊断,但特异性较差.结合肿瘤标记物可诊断生殖细胞源性肿瘤.纯生殖细胞瘤可直接选择放化疗,其他类型肿瘤均应开颅行手术治疗.应根据患者的病理诊断结果 ,施行联合放化疗,效果较好.     

132例松果体区肿瘤的临床研究

Objective To review the clinical manifestations, imaging, tumor markers, treatment methods, pathology results and clinical curative effects of pineal region tumors and to evaluate the characteristics and intervention strategies for those tumors. Methods The clinicopathological data of 132 patients with pineal region tumor treated in our department between January 2000 and May 2008 were retrospectively studied.Results A moderate predominance in males was presented. The clinical manifestations of the disease included increased intracranial pressure and ocular movement impairment. There were some features but no regularity and specific appearance on imaging including CT and MRI. 88. 6% of patients associated with hydrocephalus. A high serum level of alpha-fetoprotein (AFP) was presented in 14 cases and high HCG in 9 cases.Eighteen cases received direct radiation therapy and 7 had radiotherapy post biopsy. 107 cases were treated surgically and 63 cases received postoperative adjuvant treatment. 114 cases had pathology results including 56 germ cell tumors. The patients were followed up for 12 ～ 132 months. Recurrence developed in 23 cases and 12 cases died.The 5-year survival rate was 89. 3%. Conclusion Pineal region tumors are often associated with hydrocephalus and this makes preoperative diagnosis difficult. Imaging examination may help diagnosis but less specific. Germ cell tumors may diagnosed by some tumor markers. Radiation therapy is the choice of treatment for pure germinomas.Other types of pineal region tumors should receive surgical treatment. Postoperative adjuvant treatment based on pathology can provide a good prognosis in pineal region tumor.     

Atypical teratoid/rhabdoid tumors with multilayered rosettes in the pineal region

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly malignant tumor of the central nervous system (CNS) that typically occurs during infancy. These tumors exhibit morphologic heterogeneity and differentiate along multiple lineages, thus posing a diagnostic challenge. Here, we present two cases of AT/RT with a primitive neuroectodermal component and histological pattern resembling an embryonal tumor with multilayered rosettes (ETMR), a rare but distinctive embryonal entity with different therapeutic implications. Patient 1, a 23-month-old girl, presented with a history of gait unsteadiness and headache; cranial computed tomography (CT) identified a mass in the pineal and third ventricular regions. Patient 2, a 26-month-old girl, presented with headache and vomiting; CT revealed a mass in the posterior third ventricle. Both patients were treated via gross total tumor resection. Although histologically, AT/RT cases variably comprise primitive neuroectodermal, mesenchymal, and classic rhabdoid cells, the most striking feature of both cases was the presence of multilayered rosettes with a few Homer Wright rosettes and occasional primitive neuroepithelial tubes in focal primitive component areas. Immunohistochemistry revealed considerable heterogeneity within the tumors. We further present our findings in the context of the relevant literature.     

Contribution of the daily melatonin profile to diagnosis of tumors of the pineal region

Tumors of the pineal region (TPR) include different entities: germ cell tumors (GCT), pineal parenchymal tumors (PPT), meningiomas, and glial tumors. Except for GCT, there are no peripheral markers and histopathological diagnosis needs biopsy or surgery. We studied daily melatonin variations in twenty-nine patients with TPR and five with tectal plate glioma (TPG), used as controls, before and/or after surgery. Before surgery, a melatonin nycthemeral rhythm was observed in patients with TPG and TPR (one cyst, three PPT, one papillary tumor of the pineal region, two meningiomas, six gliomas). Melatonin rhythm was dramatically reduced for undifferentiated or invasive tumors. After surgery, the absence of melatonin variation in some cases could be the consequence of pineal damage by surgery. The contribution of determination of melatonin profiles to the diagnosis of TPR remains limited but of interest. The evidence for melatonin deficiency could justify melatonin administration to prevent the postpinealectomy syndrome. Bruno Claustrat and Michelle Fèvre-Montange contributed equally to this work.     

Gliomas of the pineal region

Although several series of pineal region tumors are available, the issue of pineal gliomas has been scarcely faced in the literature. Gliomas are usually included in largest series of pineal neoplasms. Therefore, whether pineal gliomas share the biological behavior of either hemispheric gliomas or other midline lesions is not yet defined. The aim of this retrospective study is to analyze long-term morbidity and mortality of these lesions. In English published literature gliomas account for about 14–22 % of all pineal region tumors. Most of these tumors are pilocytic astrocytomas, while glioblastoma multiforme is rare. We retrospectively analyzed all pineal region tumors operated on in our department in the last 28 years, and identified eight pineal astrocytomas, accounting for 14.03 % of all pineal tumors. The series includes four pilocytic astrocytomas, two grade II diffuse astrocytomas, and two anaplastic astrocytomas. A comprehensive review of the available literature data shows that the mean survival time of WHO grade II gliomas is shorter when tumor grows in the pineal region than for hemispheric locations, although the limited amount of available data prevents a rigorous statistical analysis. This difference might be due to the peculiar infiltrating behavior of pineal tumors, which often can’t be satisfactorily resected from vital structures.     

Spontaneous regression of germinoma in the pineal region before endoscopic surgery: a pitfall of modern strategy for pineal germ cell tumors

Since its introduction in the neurosurgical field, neuroendoscopy has played an important role in the treatment of pineal germ cell tumors. The authors report a case of pineal germinoma revealing spontaneous regression before neuroendoscopic surgery. A 15-year-old boy presented with chronic headache, deterioration of his visual acuity, and diplopia. Head magnetic resonance imaging (MRI) revealed a large tumor in the pineal region and triventricular hydrocephalus due to occlusion of the aqueduct. As levels of tumor markers in serum and cerebrospinal fluid, including those of alpha-fetoprotein, carcinoembryonic antigen, human chorionic gonadotropin (hCG), and the beta-subunit of hCG, were all within the normal ranges, endoscopic surgery for biopsy and third ventriculocisternostomy was performed. Under endoscopic view, the tumor was revealed to be smaller than expected from preoperative images. MRI obtained 14 days after admission disclosed marked shrinkage of the tumor. The histopathological diagnosis was pure germinoma, and the patient underwent chemotherapy combined with fractionated radiotherapy. The tumor disappeared, and the patient did not show any signs of relapse. Spontaneous regression is a very rare phenomenon in malignant brain tumors, and in the literature it has been uncommonly described in pineal germ cell tumors. Our case disclosed a pitfall of modern strategy for this pathology with neuroendoscopy. Dilated ventricles and a certain amount of lesion are factors for safe endoscopic biopsy of pineal tumors. Radiographic images shortly before surgery are warranted, especially in patients whose symptoms of intracranial hypertension have already improved before surgery.     

Glioblastoma multiforme of the pineal region

Glioblastoma multiforme (GBMs) tumors are exceedingly rare tumors in the pineal region. We present three cases in which patients presented with a pineal/posterior third ventricular region mass and review all the previously reported cases in the literature. Pineal region GBM seems to be a very aggressive tumor with a high rate of leptomeningeal and ependymal metastatic disease. Patients usually present with signs and symptoms of hydrocephalus and Parinaud’s syndrome. The clinical and radiological characteristics of pineal GBM do not differentiate it from other malignancies of this region, thus surgical biopsy is generally required for definitive diagnosis. Glioblastoma should be considered in the differential diagnosis of the pineal region tumors, especially when evidence of leptomeningeal or ependymal metastatic disease is present.     

Molecular genetics of pineal region neoplasms

A large variety of mass lesions have been reported in the region of the pineal gland. Pineal parenchymal tumors and germ cell tumors (GCTs) are especially characteristic of this region. Despite their rarity, a number of excellent studies on the cytogenetics and molecular genetics of pineal parenchymal tumors and pineal region GCTs have been published. These studies draw attention to a number of distinct genomic regions recurrently involved in the various subtypes of malignancies of the pineal gland. Outcomes for tumors in this location vary widely between patients and among differing histologies. Development of novel therapies for patients with poor prognoses will depend on the acquisition of a more detailed understanding of the molecular basis associated with the etiopathogenesis of these neoplasms. We review the literature on cytogenetics, familial syndromes, animal models and molecular genetics of pineal region neoplasms.     

Papillary tumor of the pineal region

Tumors of the pineal region are rare in adulthood, accounting for approximately 1% of intracranial neoplasms in this age range. Papillary tumor of the pineal region (PTPR) was first described by Jouvet et al. in 2003. In 2007, PTPR was included by the World Health Organization as a distinct entity in their new classification of central nervous system tumors. We report a case of PTPR, and undertake a literature review of this rare neuroepithelial neoplasm. Patients with PTPR need long-term follow up, and new cases should be well documented so that we can gain a better understanding of this neoplasm.