Rosette-Forming Glioneuronal Tumor in the Pineal Region: A Series of 6 Cases and Literature Review.

Resected lesions from the pineal region are rare specimens encountered by surgical pathologists, and their heterogeneity can pose significant diagnostic challenges. Here, we reviewed 221 pineal region lesions resected at New York-Presbyterian Hospital/Columbia University Irving Medical Center from 1994 to 2019 and found the most common entities to be pineal parenchymal tumors (25.3%), glial neoplasms (18.6%), and germ cell tumors (17.6%) in this predominantly adult cohort of patients. Six cases of a rare midline entity usually found exclusively in the fourth ventricle, the rosette-forming glioneuronal tumor, were identified. These tumors exhibit biphasic morphology, with a component resembling pilocytic astrocytoma admixed with variable numbers of small cells forming compact rosettes and perivascular pseudorosettes. Targeted sequencing revealed a 100% co-occurrence of novel and previously described genetic alterations in the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling pathways, suggesting a synergistic role in tumor formation. The most common recurrent mutation, PIK3CA H1047R, was identified in tumor cells forming rosettes and perivascular pseudorosettes. A review of the literature revealed 16 additional cases of rosette-forming glioneuronal tumors in the pineal region. Although rare, this distinctive low-grade tumor warrants consideration in the differential diagnosis of pineal region lesions.

Concurrent uveoretinitis and pineocytoma in a child suggests a causal relationship.

Uveoretinitis was observed in a 9-year-old girl 6 months prior to the clinical appearance of a pineal tumour. Surgical removal was not successful but biopsy revealed a parenchymal neoplasm with differentiated pinealocytes and absent mitotic activity. Some of the tumour cells contained S-antigen, rhodopsin, and serotonin. Systemic glucocorticoid therapy followed by radiation therapy caused considerable reduction in size of the tumour and a complete normalisation of all eye symptoms. This report demonstrates for the first time that a pineocytoma can occur together with uveoretinitis in humans. The latter resembles the experimentally induced autoimmune uveoretinitis described in animals. It is speculated that the retinitis might reflect an autoimmune response to S-antigen present in some tumour cells of the pineocytoma.

Cerebrospinal fluid placental alkaline phosphatase in the intracranial germinomas: results of enzyme antigen immunoassay.

The authors investigated the placental alkaline phosphatase (PALP) activity in cerebrospinal fluid (CSF) by enzyme-antigen immunoassay using polyclonal antibody as a marker for intracranial germinomas in 17 patients with germ cell tumors and 20 with other disorders. The detection limit of PALP activity was 0.072 optical density units equivalent to 5.9 ng/ml. Five of nine germinomas demonstrated high CSF PALP activities before treatment. These high PALP activities became undetectable following radiation therapy. The other tumors were small or had no CSF contact. CSF PALP activity is a useful tumor marker for pure germinomas.

Immunohistochemical and in vitro functional analysis of pineal-germinoma infiltrating lymphocytes: report of a case.

The present study describes the phenotypic and functional analysis of tumor-infiltrating lymphocytes isolated from a germinoma located in the pineal region. Tumor-infiltrating lymphocytes were separated from the germinoma and cultured in medium containing IL-2 (1000 U/ml). An immunohistochemical analysis of frozen sections revealed that 90% of the germinoma-infiltrating lymphocytes were CD3-positive T cells expressing CD4, CD8, and HLA Class I and Class II antigens, but were negative for CD16, CD20, CD23, CD25 and CD14 antigens. After in vitro cultivation in the presence of high concentrations of IL-2, the lymphocytes proliferated for 2 weeks, showing marked DNA synthesis. In addition, the lymphocytes could lyse NK-resistant allogeneic target cells. These results provide evidence for a potential role of germinoma-infiltrating lymphocytes in vivo, and suggest that the lymphocytes may control the growth of autochthonous tumor cells by killing those that are not restricted to the major histocompatibility complex.

Immunoreactive S-antigen in cerebrospinal fluid: a marker of pineal parenchymal tumors?

This investigation evaluated the possibility that the occurrence of S-antigen in cerebrospinal fluid (CSF) might be used as a preoperative marker of pineal parenchymal tumors (pineoblastoma and pineocytoma). Such a marker could provide a means of preoperatively differentiating these neoplasms from pineal region tumors of other origin. The S-antigen, also known as the 48-kD protein or arrestin, is a highly antigenic protein originally found in the retina and pineal gland. In the retinal photoreceptors and submammalian pineal photoreceptors the protein is thought to be involved in phototransduction; its function in the mammalian pinealocyte is unknown. S-Antigen immunoreactivity also occurs in certain neoplastic cells of retinoblastomas, pineocytomas, pineoblastomas, and cerebellar medulloblastomas. This study included a group of 13 patients with tumors of the pineal region. Samples of CSF were obtained preoperatively and analyzed for the S-antigen using western blot technology. Tumor biopsy material was classified according to conventional neurohistological criteria and was also examined by immunocytochemical techniques for the presence of the S-antigen. S-Antigen immunoreactivity was found in the preoperative CSF of the one patient found to have pineocytoma; tumor tissue removed from this patient was the only neoplastic tissue examined in this study which contained S-Antigen immunoreactive tumor cells. Furthermore, hydroxyindole-O-methyltransferase activity was detectable in the pineocytoma but not in three other pineal tumors, and melatonin levels in the CSF of the pineocytoma patient were the highest in the patient group examined. These preliminary results suggest that testing for S-antigen in CSF might be useful in characterizing and treating tumors of the pineal region and, when identified in conjunction with other markers, it might also help to better define pineal parenchymal tumors. This study needs confirmation with a larger number of patients. If this approach is eventually found to be a reliable predictor of pineal cell tumors, it may supplant the need for surgical biopsies before initiating appropriate adjunctive therapy.

S-antigen immunoreactivity in trilateral retinoblastoma.

Using monoclonal antibody MAbA9-C6, which identifies an antigenic determinant of S-antigen retained in fixed tissue sections, we investigated S-antigen immunoreactivity in the ocular and brain tumors of four cases of trilateral retinoblastoma. In the eye, S-antigen immunoreactivity was present in all retinoblastomas examined, as well as one retinocytoma characterized by benign appearing cells including fleurettes. S-antigen immunoreactivity was focally present in two of the four brain tumors examined. Additionally, two intraocular medulloepitheliomas, one of which contained well-defined rosettes, and 16 primary intracranial tumors, including seven pineal gland tumors and nine other lesions, some of which histopathologically may resemble retinoblastoma, were examined. S-antigen immunoreactivity was observed in two pineal gland tumors but not the remaining nine primary intracranial neoplasms or the two intraocular medulloepitheliomas. Our results further substantiate the immunologic relationship between the retina and the pineal gland, and tumors originating in these tissues.

S-antigen-like immunoreactivity in a human pineocytoma.

A pineocytoma was investigated by means of immunocytochemistry with the use of a polyclonal antibody against bovine retinal S-antigen. Several cells of this tumor displayed strong S-antigen-like immunoreaction in analogy to certain pinealocytes in normal human pineal organs. This study indicates that S-antigen immunocytochemistry may be applied to characterize tumors of the pineal region.

S-antigen immunoreactivity in human pineal glands and pineal parenchymal tumors. A monoclonal antibody study.

Using a four-step immunoperoxidase (PAP) method and the monoclonal antibody MAbA9-C6 (MAbA9-C6), which defines an epitope of the retinal S-antigen (S-Ag), we investigated the S-Ag immunoreactivity in human fetal, newborn, infantile and adult pineal glands and in 13 human pineal parenchymal tumors. S-Ag immunoreactivity was demonstrated in a few cells in one of the four fetal and in both infantile glands. Eight of nine adult pineal glands contained isolated MAbA9-C6-positive cells. In two of seven pineocytomas showing neuronal or gangliogliomatous differentiation a few scattered cells displayed S-Ag positivity; two of four pineoblastomas contained small groups of strongly immunoreactive neoplastic cells; two malignant pineocytomas did not demonstrate any S-Ag immunoreactivity. Our results indicate that isolated cells in human pineal gland retain some of the cytochemical characteristics of photoreceptor cells recognized by the MAbA9-C6, and that S-Ag immunoreactivity may be occasionally expressed in pineal parenchymal tumors.

Immune responses in patients with brain tumors. Factors such as anti-convulsants that may contribute to impaired cell-mediated immunity.

The responsiveness of lymphocytes obtained from patients with brain tumors to in vitro stimulation with mitogenic lectins was examined. The previously reported finding of decreased responsiveness was confirmed. To investigate the factors responsible for the hyporesponsiveness, mitogen (phytohemagglutinin and pokeweed mitogen) induced lymphocyte activation was evaluated using lymphocytes from 22 patients with brain tumors and 22 normal individuals. Lymphocytes from 13 patients with brain tumors, showed depressed responsiveness when cultured in autologous serum; in eight this was marked and in five moderate. Normal, rather than autologous, serum corrected lymphocyte function from only one of the markedly hyporesponsive patients, suggesting the existence of an intrinsic lymphocyte abnormality in some patients with brain tumors. However, serum from the hyporesponsive patients depressed mitogen-induced activation of lymphocytes from both tumor patients and normals. The presence of suppressive serum factors could not be related to the nature of the tumor (benign versus malignant, site, cell type or degree of anaplasia). The present studies showed that significant depression of in vitro lymphocyte responsiveness occurred with exposure to two anti-convulsant agents (phenytoin and phenobarbital) and dexamethasone. Thus, impaired lymphocyte function in patients with brain tumors may have a complex explanation with drug (corticosteroids, anticonvulsants) induced suppression playing a significant role.

Suprasellar germinomas (ectopic pinealomas): aspects of immunological characterization and successful chemotherapeutic responses in recurrent disease.

Two patients with suprasellar germinomas were initially treated successfully with radiotherapy, but subsequently they developed recurrent tumor 2 1/2 and 12 years later. The recurrent tumor was solely extraneural in the first patient because of seeding from a ventriculoperitoneal shunt, and in the second patient the tumor recurred as its initial site as well as in the 4th ventricle. Both tumors secreted the beta-subunit of human chorionic gondadotropin. A dramatic tumor response was seen in both patients with systemic chemotherapy consisting of a combination of cis-platinum, bleomycin, and vinblastine. The "small cells" in one of the suprasellar germinomas were shown to be predominately T lymphocytes on the basis of an examination of the cell surface markers on these cells. (Neurosurgery, 7: 352-358, 1980).

Presence of lymphocyte membrane surface markers on "small cells" in a pineal germinoma.

A 16-year-old boy was operated on via an occipital transtentorial craniotomy for a pineal tumor. Routine histological examination of the tissue revealed it to be a germinoma, as characterized by the presence of two cell populations: large cells and small, lymphoid-appearing cells. The cells were evaluated in a single-cell suspension for the presence of lymphocyte membrane surface markers; small cells exclusively were found to have such markers. A T-lymphocyte membrane marker was present in 51% of the small cells, whereas 15 to 18% of the small cells had a B-lymphocyte membrane marker.