Pineal anlage tumor: clinical and diagnostic features, and rationales for treatment.

PURPOSE: To provide a treatment-focused review and develop basic treatment guidelines for patients diagnosed with pineal anlage tumor (PAT). METHODS: Prospectively collected data of three patients with pineal anlage tumor from Germany was combined with clinical details and treatment information from 17 published cases. RESULTS: Overall, 20 cases of PAT were identified (3 not previously reported German cases, 17 cases from published reports). Age at diagnosis ranged from 0.3 to 35.0 (median: 3.2 ± 7.8) years. All but three cases were diagnosed before the age of three years. For three cases, metastatic disease at initial staging was described. All patients underwent tumor surgery (gross-total resection: 9, subtotal resection/biopsy: 9, extent of resection unknown: 2). 15/20 patients were alive at last follow-up. Median follow-up for 10/15 surviving patients with available follow-up and treatment data was 2.4 years (0.3-6.5). Relapse was reported for 3 patients within 0.8 years after diagnosis. Five patients died, 3 after relapse and 2 from early postoperative complications. Two-year-progression-free- and -overall survival were 65.2 ± 12.7% and 49.2 ± 18.2%, respectively. All 4 patients who received intensive chemotherapy including high-dose chemotherapy combined with radiotherapy (2 focal, 2 craniospinal [CSI]) had no recurrence. Focal radiotherapy- and CSI-free survival rates in 13 evaluable patients were 46.2% (6/13) and 61.5% (8/13), respectively. CONCLUSION: PAT is an aggressive disease mostly affecting young children. Therefore, adjuvant therapy using intensive chemotherapy and considering radiotherapy appears to comprise an appropriate treatment strategy. Reporting further cases is crucial to evaluate distinct treatment strategies.

Pineal gland hypermetabolic involvement without central nervous system symptoms in a pediatric patient with primary nodular sclerosis subtype classical Hodgkin Lymphoma.

This case report presents the first reported pediatric case of primary classical nodular sclerosing Hodgkin Lymphoma (HL) with pineal gland involvement, presenting without CNS symptoms, which completely resolved after 2 cycles of chemotherapy. The 12 year-old male first presented with a right inguinal mass and external iliac lymphadenopathy accompanied by B symptoms. He was diagnosed with stage IV B classical HL, and as part of the staging work-up, a full-body PET/CT scan was performed. In addition to the right inguinal mass, the PET/CT demonstrated increased FDG uptake at the pineal gland along with level II lymph nodes. The patient was treated with ABVE-PC chemotherapy (Doxorubicin, Bleomycin, Vincristine, Etoposide, Prednisone, and Cyclophosphamide) as per standard arm of AHOD1331 COG protocol for newly diagnosed high-risk HL patients, which resolved the pineal mass after 2 cycles without requiring radiation therapy. Following 5 cycles, a full-body PET/CT showed no brain or neck activity, along with decreased size and activity of the right groin mass. To our knowledge, there are no other documented cases of primary HL with specific pineal involvement, and no cases that lack CNS symptoms altogether like this one did. Additionally, this is the third published pediatric case of primary CNS-HL, both of the previous cases were treated with radiotherapy and presented with CNS symptoms. Thus, this case demonstrates the importance of ordering a full-body PET/CT as part of the initial HL work-up and provides evidence that chemotherapy alone is a treatment option for some patients with primary intracranial HL.

Melatonin hormone as a therapeutic weapon against neurodegenerative diseases.

Brain disorders such as Alzheimer's and Parkinson's disease (PD) are irreversible conditions with several cognitive problems, including learning disabilities, memory loss, movement abnormalities, and speech problems. These disorders are caused by a variety of factors, mainly due to the toxic pollutants-induced biochemical changes in protein production, uncontrolled neuronal electrical activity, and altered neurotransmitter levels. Oxidative stress and toxicity associated with the increased glutamate levels decreased acetylcholine levels, and brain inflammation is the main contributing factor. Melatonin hormone is considered one of the potent treatment approaches for neurodegenerative disorders. Melatonin is released from the pineal gland and has a critical role in brain function regulation. Membrane receptors, binding sites, and chemical interaction mediate hormonal actions having multiple phenotypic expressions. It acts as a neurodegenerative agent against some neurological disorders such as Alzheimer's disease (AD), PD, depression, and migraines. Melatonin inhibits neurotoxic pollutants-induced Tau protein hyperphosphorylation, especially in AD. Other pivotal features of melatonin are its anti-inflammatory properties, which decrease pro-inflammatory cytokines expression and factors such as IL-8, IL-6, and TNF. Melatonin also reduces NO (an inflammation factor). In this review, we have highlighted the protective effects of melatonin, mainly spotlighting its neuroprotective mechanisms that will be beneficial to assess their effects in environmental pollution-induced neurodegenerative pathology.

Maternal pineal melatonin in gestation and lactation physiology, and in fetal development and programming.

Pregnancy and lactation are reproductive processes that rely on physiological adaptations that should be timely and adequately triggered to guarantee both maternal and fetal health. Pineal melatonin is a hormone that presents daily and seasonal variations that synchronizes the organism's physiology to the different demands across time through its specific mechanisms and ways of action. The reproductive system is a notable target for melatonin as it actively participates on reproductive physiology and regulates the hypothalamus-pituitary-gonads axis, influencing gonadotropins and sexual hormones synthesis and release. For its antioxidant properties, melatonin is also vital for the oocytes and spermatozoa quality and viability, and for blastocyst development. Maternal pineal melatonin blood levels increase during pregnancy and triggers the maternal physiological alterations in energy metabolism both during pregnancy and lactation to cope with the energy demands of both periods and to promote adequate mammary gland development. Moreover, maternal melatonin freely crosses the placenta and is the only source of this hormone to the fetus. It importantly times the conceptus physiology and influences its development and programing of several functions that depend on neural and brain development, ultimately priming adult behavior and energy and glucose metabolism. The present review aims to explain the above listed melatonin functions, including the potential alterations observed in the progeny gestated under maternal chronodisruption and/or hypomelatoninemia.

[Treatment outcomes in patients with central nervous system germinoma (neuro-ophthalmic aspects)]. / Rezul'taty kompleksnogo lecheniya bol'nykh s pervichnoi germinomoi TsNS (neirooftal'mologicheskie aspekty).

OBJECTIVE: The analyze the neuro-ophthalmic outcomes in patients with pineal and suprasellar germinoma after complex treatment. MATERIAL AND METHODS: There were 125 patients (88 males, 37 females) with primary CNS germinoma for the period 2008-2017. All patients were divided into 3 groups depending on the tumor localization: pineal area - 62 patients, suprasellar neoplasm - 38 patients, bifocal germinoma - 25 patients. Treatment was performed in accordance with the «Germinoma-2008¼ protocol. Tumors were histologically patients (partial - 32 cases, subtotal - 16 cases). Surgery was followed by postoperative chemotherapy and stereotactic radiotherapy. The results were evaluated by neuro-ophthalmological examination at all stages of complex treatment. RESULTS: Pineal germinoma resulted oculomotor and pupillary disorders (58 patients - 94%) and papilledema. The last one completely regressed under the treatment. Partial reduction of oculomotor and pupillary abnormalities occurred throughout chemotherapy (6 patients - 10%). More than half of patients (n=24, 63%) with suprasellar germinoma had visual impairment. Improvement of visual functions including severe visual disturbance was observed in 14 patients (58%). Predominantly, functional recovery occurred under chemotherapy (12 patients - 86%). Bifocal germinoma was followed by various combinations of oculomotor, pupillary and/or visual impairments. We observed regression of only mild visual disorders. Stereotactic radiotherapy did not ensure any changes in neuro-ophthalmic symptoms in all groups.

The paramedian supracerebellar infratentorial approach.

BACKGROUND: Lesions of the superior cerebellar surface, pineal region, lateral and dorsal midbrain and mesial temporal lobe are challenging to treat and often require neurosurgical intervention. METHODS: The paramedian variation of the supracerebellar infratentorial approach utilizes the downward slope of the cerebellum to facilitate exposure and the lower density of cerebellar bridging veins away from the midline decreases the need to sacrifice larger venous channels. We also discuss our experiences with the approach, and some of the drawbacks and nuances that we have encountered as it has evolved over the years. CONCLUSIONS: This approach is versatile and effective and the authors' surgical approach of choice for resecting these challenging lesions.

Pineal parenchymal tumours of intermediate differentiation - An evidence-based review of a new pathological entity.

Pineal region lesions are uncommon, and pineal parenchymal tumours (PPT) account for 20-30% of tumours in this area of which pineocytomas (PCs) and pineoblastomas (PBs) are more prevalent. In 2007, the World Health Organisation (WHO) reclassified PPT from two subgroups (PC and PB) into four, including pineal parenchymal tumours of intermediate differentiation (PPTID). PPTID have been further divided into low- and high-grade lesions (WHO II and III), but due to their rarity have proven difficult lesions to diagnose and a paucity of literature means their optimal treatment options are a challenge to define. This article is a review of the literature of PPTID highlighting diagnostic criteria, a discussion on the role of surgery and radiotherapy, including treatment paradigms and reported outcomes for these problematic neoplasms.

[Age-associated reproductive cycle hypothalamic regulation impairment and its correction].

This review covers present-day ideas of the female organism reproductive system neuroendocrine regulation in aging. The literature data on the key role of the hypothalamus in formation, organization and age-related decline of the reproductive function in both mammals and humans are considered in detail. Special focus is on catecholamines, peptides and other biologically active compounds acting in these processes. The authors discuss data showing interaction between the suprachiasmatic nuclei of the hypothalamus and the pineal gland synchronizing circadian and diurnal rhythms of gonadotropine-releasing hormone being normally synthesised and secreted during the reproductive period, but failing in aging or under the influence of neurotoxic compounds. Molecular mechanisms of ovarian cycle hypothalamic regulation impairment and possible ways of its correction by means of melatonin and peptide preparations from the pineal gland are described. The data presented may be of utility to prevent premature aging of reproductive function.

Pediatric papillary tumors of the pineal region: to observe or to treat following gross total resection?

INTRODUCTION: Papillary tumors of the pineal region (PTPR) are rare brain tumors characterized by frequent local recurrences. Standardized treatment strategies are not yet defined. CASE REPORT: We present the case of a 3-year-old girl diagnosed with PTPR. Due to her young age, adjuvant radiotherapy was omitted after gross total tumor resection. Thirty-six months later, local tumor recurrence occurred. Considering the possible risks of secondary surgery, the recurrent tumor was irradiated with proton radiotherapy. Three months later, the tumor showed near-complete remission. DISCUSSION: Based on this experience and other pediatric case reports from the literature, local radiotherapy might be suggested also after complete tumor resection.

The endoscopic intraventricular management of pineal cysts: a minimally invasive modus operandi.

BACKGROUND: The management of pineal cysts is still debatable, especially for asymptomatic incidental ones. For symptomatic cysts associated with hydrocephalus, the surgical management is mandatory and may include either classical microsurgical approaches to the pineal region or endoscopic trans-ventricular approaches in a minimally invasive philosophy. METHOD: The authors expose a stepwise technique to treat a pineal cyst associated with an obstructive hydrocephalus in one procedure gathering a third ventriculostomy followed by an intraventricular marsupialisation of the pineal cyst. CONCLUSION: This endoscopic approach allows the treatment of the hydrocephalus and the pineal cyst in one short minimally invasive procedure.

Potential role of melatonin in prevention and treatment of lung cancer.

Lung cancer is the second most common cancer and the most lethal cancer worldwide. Melatonin, an indoleamine produced in the pineal gland, shows anticancer effects on a variety of cancers, especially lung cancer. Herein, we clarify the pathophysiology of lung cancer, the association of circadian rhythm with lung, and the relationship between shift work and the incidence of lung cancer. Special focus is placed on the role of melatonin receptors in lung cancer, the relationship between inflammation and lung cancer, control of cell proliferation, apoptosis, autophagy, and immunomodulation in lung cancer by melatonin. A review of the drug synergy of melatonin with other anticancer drugs suggests its usefulness in combination therapy. In summary, the information compiled may serve as a comprehensive reference for the various mechanisms of action of melatonin against lung cancer, as a guide for the design of future experimental research and for advancing melatonin as a therapeutic agent for lung cancer.

Pineal cyst apoplexy: report of an unusual case managed conservatively.

Pineal cyst apoplexy is a very rare entity with previously reported symptoms of severe frontal or occipital headache, gaze paresis and visual field defects, nausea or vomiting, syncope, ataxia, hearing loss and sudden death. The treatment options for symptomatic pineal cysts are observation, shunting, aspiration via stereotactic guidance or endoscopy, third ventriculostomy, ventriculocysternostomy, and/or surgical resection by craniotomy and microsurgery. Here, the authors report an unusual case of a 28-year-old male patient with pineal cyst apoplexy, presenting with headache, insomnia, and sexual dysfunction symptoms who is being managed conservatively and observed for two years by an academic tertiary care unit.

Patterns of Care and Age-Specific Impact of Extent of Resection and Adjuvant Radiotherapy in Pediatric Pineoblastoma.

BACKGROUND: Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. Controversy remains regarding optimal disease management. OBJECTIVE: To evaluate patterns of care and optimal clinical management of pediatric pineoblastoma. METHODS: A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics. RESULTS: Older patients (age ≥ 4 yr) experienced improved overall survival compared to younger patients (age < 4 yr) (hazard ratio [HR] = 0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR = 3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR = 0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P = .041); extent of resection was not associated with survival in younger patients (P = .880). CONCLUSION: Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.

Intravascular Papillary Endothelial Hyperplasia of the Pineal Region: A Case Report and Review of the Literature.

BACKGROUND: Intravascular papillary endothelial hyperplasia (IPEH) is a benign vascular lesion that is uncommon in the central nervous system. To our knowledge, there has been only one previous report of occurrence in the pineal region. We present a second case and a review of the literature. CASE DESCRIPTION: A 28-year-old woman presented with 1 month of headaches and visual auras. Brain magnetic resonance imaging scan demonstrated a 2.6- × 1.8- × 1.3-cm nonenhancing T1-hypointense, T2-/fluid-attenuated inversion recovery-hyperintense pineal region mass with cerebral aqueduct obstruction and hydrocephalus. She underwent placement of a right extraventricular drain followed by complete surgical resection. Histologic analysis was consistent with IPEH. CONCLUSIONS: Although rare, IPEH is an entity that should be considered in the differential diagnosis for intracranial masses with radiographic features characteristic of vascular lesions. Tissue sampling is imperative for distinction from more malignant entities. Complete resection is curative and is the standard of care when feasible. Given the risk of local progression and neurologic compromise with subtotal resection of central nervous system lesions, further study regarding adjuvant treatment options is warranted.

Pineal Region Tuberculoma Caused by Mycobacterium bovis as a Complication of Bacille Calmette-Guérin Vaccine: Case Report and Review of the Literature.

BACKGROUND: Brain tuberculoma is a rare manifestation of tuberculosis especially in immunosuppressed patients. The definitive diagnosis may be difficult owing to mimicking brain tumors and the absence of the common presentation. Bacille Calmette-Guérin (BCG) vaccine is used for protection against tuberculous meningitis and miliary disease, more so in children, and also for the treatment of bladder cancer. CASE DESCRIPTION: The following case of brain tuberculoma is a boy aged 6 months who was presented to our hospital with poor feeding, nausea and vomiting, and confusion lasting 1 month. A brain magnetic resonance imaging scan showed a large mass lesion in the pineal region with generalized hydrocephaly in which polymerase chain reaction assays of the tissue was positive for Mycobacterium bovis and had a good response to antituberculosis drugs and surgery. CONCLUSIONS: We present a case of brain tuberculoma as the complication of BCG vaccine. To our knowledge, this case is the first case of brain tuberculoma after BCG vaccination. We should consider brain tuberculoma that presents with a similar presentation in any infants with a history of BCG vaccination.

Response of an adult patient with pineoblastoma to vorinostat and retinoic acid.

We report the case of an adult patient with pineoblastoma (PBL) who had a complete radiographic response following treatment with vorinostat and retinoic acid. This regimen was used to treat bulky residual tumor that persisted despite radiation therapy (RT) and two cycles of cytotoxic chemotherapy. Vorinostat and retinoic acid were chosen as an alternative to cytotoxic chemotherapy, which our patient was unable to tolerate, based on preclinical data suggesting efficacy of this combination. MRI demonstrated a complete response to this regimen, which continues to remain stable without evidence of recurrence.

[Case of pineocytoma causing repetitive subarachnoid hemorrhage for 43 years].

A 61-year-old woman had suffered from severe headache and nausea over 20 times during the last 43 years. An subarachnoid hemorrhage (SAH) was detected by spinal puncture in some other hospitals, but the source of hemorrhage remained unknown in spite of repeated angiography. At the age of 61, she was diagnosed as having normal pressure hydrocephalus, and received a ventriculo-peritoneal shunt. She suffered from sudden headache 12 days after surgery. A CT scan showed a SAH and enlargement of the pineal mass. The tumor was totally removed via the occipital interhemispheric transtentorial approach and was diagnosed histologically as a pineocytoma. She has been free from SAH for three years since removal of the tumor. Pineal apoplexy should be considered as a cause of SAH.