The human pineal gland is shaped like a pine cone, with a length, width and thickness of about 7 mm × 5 mm × 4 mm and a mass of 140-200 mg. It is located above the superior colliculus of the midbrain, covered by the posterior part of the corpus callosum and connected to the 3rd ventricle by a thin stalk. The tumor occurs in the hypothalamus and anterior part of the 3rd ventricle and can invade the hypothalamus and spinal cord and the central nervous system. Metastasis to the skin, lungs or liver is rare. It accounts for less than 1% of intracranial tumors and is most commonly seen in boys.
Disease Description
The human pineal gland resembles a pine cone, with a length, width, and thickness of about 7 mm × 5 mm × 4 mm, and a mass of 140-200 mg. It is located above the superior colliculus of the midbrain, covered by the posterior part of the corpus callosum, and connected to the third ventricle by a thin stalk. The pineal gland is mainly innervated by norepinephrinergic fibers in the superior cervical ganglion, and the norepinephrine (NE) released from nerve fiber endings acts to the pineal gland by osmosis, and animal experiments have confirmed that light stimulation inhibits the release of NE. Stimuli such as olfactory, auditory, and temperature sensations can affect the function of the pineal gland. The syndrome was introduced by Pellizzi in 1972 and is also known as precocious puberty syndrome and precocious giant genitalia syndrome. It refers to the increased secretion of gonadotropins and sex hormones caused by pineal tumors (the secretion of the pineal gland is functionally antagonistic to that of the pituitary gland). Common tumors include adult pineal cell tumor, pineal cell tumor, glioblastoma, teratoma, germ cell tumor, seminomatous cell tumor, astrocytoma, and ectopic pineal tumor. They account for less than 1% of intracranial tumors and are mostly seen in boys.
Symptoms and signs
The clinical manifestations of tumors in the pineal region vary depending on the location of the lesion. The clinical manifestations largely depend on the size of the tumor and the degree of invasion of the surrounding neural structures.
Brain edema Tumor in the pineal region invades the third ventricle and causes obstruction, resulting in increased intracranial pressure, with common symptoms of lethargy, headache, vomiting and mental abnormalities. Generally speaking, the more acute the obstruction is, the more sudden and obvious the symptoms occur.
2.Neurological symptoms The neurological symptoms of pineal tumor are related to the infiltrated and compressed nerves and conduction pathways. Thalamic infiltration can lead to hemiplegic incomplete paralysis, intermittent pain and sensory abnormalities. Erosion of the internal capsule causes lateral incomplete palsy. Involvement of the basal ganglia causes extrapyramidal syndrome or motor deficits and visual field defects. Tumors compressing the pineal region of the tegmentum can cause Parsingino syndrome. This syndrome includes paralysis of upward gaze, dull pupillary reflex to light, convergence palsy, and wide gait.
3. Hypothalamic pituitary hypofunction performance Tumor in pineal gland area may cause hypothalamic damage and uremia, hyperphagia, lethargy, obesity and behavioral abnormalities, and may be accompanied by visual field damage, water regulation and thermoregulation imbalance and pituitary hypofunction performance.
Precocious puberty Pineal tumors often cause precocious puberty, most of them occur in males. If calcification of pineal tumors occurs, calcified spots can be seen on cranial radiographs. The possible reason for precocious puberty is that the tumor destroys the pineal gland to produce and release a substance that inhibits the secretion of gonadotropin by the pituitary gland, and then the inhibitory effect disappears and precocious puberty occurs. Precocious puberty can also occur when the tumor overtakes the pineal region and damages the hypothalamus. Pineal tumor causes delayed puberty is rare, but there are individual cases of gonadal hypogonadism related to pineal tumor.
5, abnormal secretion and regulation of melatonin can lead to many clinical diseases. The secretion of melatonin in normal people has a circadian rhythm, with the highest serum melatonin levels after 10 pm and before early morning, while the rhythmic secretion of melatonin disappears in Alzheimer’s patients. Melatonin’s antioxidant, anti-glutamate excitotoxicity and direct regulation of apoptotic gene expression can prevent apoptosis in neural tissues and contribute to the treatment of Alzheimer’s disease and Parkinson’s disease, brain injury, stroke and epilepsy.
Disease etiology
Both teratomas of the pineal gland with chorionic tissue and germ cell tumors can secrete HCG and secrete enough of the hormone to cause precocious puberty. Such tumors have the histological and functional characteristics of choriocarcinoma. Pineal tumors causing precocious puberty may be due to tumor compression or disruption affecting the regulatory function of the hypothalamus or HCG secretion. Neuroendocrine anatomical findings suggest that precocious puberty is caused by the expansion of other tumors of the brain extending into the pineal gland. Another possible cause of precocious puberty is due to the production of a substance by the pineal gland that inhibits the secretion of gonadotropins by the pituitary gland, and if the pineal gland is destroyed, the inhibitory effect is lost and precocious puberty occurs. It is also possible that the tumor may go beyond the pineal region and cause fluid accumulation in the third ventricle or damage the hypothalamus, thus causing precocious puberty.
Pathophysiology
The pineal gland is associated with sexual function and development. The pineal gland can inhibit gonadotropin secretion, and precocious puberty can occur in animals with disruption of the pineal gland. Melatonin can reduce plasma LH levels and inhibit GH secretion in normal subjects. Darkness stimulates the secretion of melatonin hormone, which is presumed to be a drowsy substance.
The rhythmic activity of the pineal gland can be summarized into 3 types.
The main physiological factor affecting the pineal MLT rhythm is the stimulation of light. The main physiological factor influencing the pineal MLT rhythm is the stimulation of light. The peak value of MLT is at night due to the signal of dark light stimulation.
②Monthly rhythm: MLT fluctuations in female blood are synchronized with the menstrual cycle. The decrease in MLT may have a “permissive” effect on ovulation.
(iii) Annual rhythm: The reproductive year is characterized by alternating between the climax of fertility and the quiescence of the pituitary and gonadal systems. This alternation may be due to the length of the daylight period affecting the reproductive system through the pineal gland.
Diagnostic tests
Diagnosis: The diagnosis of tumors of the pineal region must be based on the pathological-histological classification, because the treatment options and prognosis of each type of tumor vary greatly, and the greatest difficulty is still the difficulty in obtaining histological specimens, thus emphasizing the importance of stereotactic pineal region lesion biopsy.
Laboratory tests: measurement of pituitary hormones and their dynamic function tests are useful in the identification of pituitary adenomas, especially hormone-secreting pituitary adenomas. Blood and cerebrospinal fluid HCG measurements are useful in the diagnosis of germ cell tumors. Sensitive immunoassay for AFP and β-HCG is used as a routine method to diagnose pineal tumors.
1. Patients with hormone-secreting germ cell tumors of the pineal region have increased levels of HCG-β and AFP in the cerebrospinal fluid.
2.Cerebrospinal fluid exfoliation cytology examination is most valuable for diagnosing germ cell tumor and pineoblastoma because these two tumor cells are easily shed and appear to be implanted in the cerebrospinal fluid. If pathological cells are found in cerebrospinal fluid exfoliation cytology examination, a clear diagnosis can be made. The intracerebrospinal fluid implantation can stimulate the secretion of excessive cerebrospinal fluid from the ventricular choroid plexus and lead to hydrocephalus, so the tumor can be combined with significant hydrocephalus when it is small.
In situ hybridization analysis by Tsumanuma et al. of three cases of pinealoblastoma and five cases of pineal cell tumor revealed that these two types of tumor cells preserve the function of expressing HIOMT mR-NA. elevated levels of MIOMT can help diagnose the extent of pineal parenchymal tumor.
Other ancillary tests.
1. pneumoencephalography used in the past was eliminated due to many complications and low sensitivity, nowadays CT or MRI is mostly chosen according to clinical manifestations. ct is the examination of choice for pineal tumors and can be done with enhancement and coronal scans. ct-guided biopsy can obtain tissue locally at the lesion and clarify the pathological diagnosis. fedorcsak et al. performed 523 ct-guided targeted biopsies between 1989 and 1996 and concluded that this method is completely accurate. The method was considered to be completely effective and necessary for the histological diagnosis of intracranial tumors and the development of appropriate treatment plans.
MRI shows the high signal of the pineal tumor area and the extent of tumor invasion into the third ventricle.
3. Head radiography shows large (>15mm) flocculent pineal calcifications or signs of cerebral edema.
Differential diagnosis
The differential diagnosis should pay attention to distinguish tumors occurring outside the pineal region, such as meningioma and hemangioma; tumors in adjacent areas, such as brainstem and cerebellar earth; pineal cysts, etc. The distinction between these diseases and pineal tumors is mainly based on imaging, and if there is precocious puberty, germ cell tumors are more likely. The final diagnosis depends on pathological examination.
Treatment options
Surgical treatment of tumors of the pineal region has a mortality rate of 14-37%. Radiation therapy can be applied to most patients with pineal tumors. However, there is no consensus on the standard radiation therapy for this tumor. Chemotherapy is preferred for patients with pineal tumors, and studies have shown that the pineal gland does not have a blood-cerebrospinal fluid barrier, which makes it more appropriate for treating cases of tumor recurrence or metastasis. Chemotherapy with cisplatin, bleomycin, and vincristine (or vincristine) is often used clinically. For germ cell tumors of the pineal gland and choriocarcinoma chemotherapy is an even more effective approach.
Complications
1.If the tumor compresses the cerebral aqueduct, it may cause intracranial hypertension, and the tumor compresses the tetraspanic body, it may cause Parinaud syndrome (inability to see upward, disappearance of pupillary reflex to light, inability of both eyes to converge and large gait).
2. Tumors in the pineal gland can cause hypothalamic damage and uveitis.
Prognosis and prevention
Prognosis: Pineoblastoma, teratoma and germ cell tumor are sensitive to chemotherapy. Teratomas are insensitive to radiotherapy while chemotherapy can have a better outcome. For example, the CEB regimen is carboplatin, etoposide, bleomycin for teratoma and germ cell tumors, etoposide and cisplatin for teratoma after radiotherapy; vincristine, carboplatin, etoposide and cyclophosphamide for pineal cell tumors before radiotherapy; ECOMB regimen for teratoma. Chemotherapy is only part of the treatment regimen, and patients often require additional surgery or radiation therapy. A small number of patients with germ cell tumors receive high-dose chemotherapy followed by bone marrow transplantation, which can significantly prolong the patient’s life.
The prognosis of patients with tumors of the pineal region varies according to their histological type, severity of disease, and treatment, with patients with germ cell tumors having a better prognosis (5-year survival rate of 83% has been reported) and patients with pineoblastoma and mixed germ cell tumors having a worse prognosis. Pineal cell tumors with less than 6 mitotic cells under light microscopy and positive neurofilament immunostaining were classified as grade II; pineal cell tumors with greater than or equal to 6 mitotic cells under light microscopy or negative neurofilament immunostaining were classified as grade III; and pineoblastomas had the worst prognosis and were classified as grade IV.
Epidemiology
The incidence of pineal tumors is quite inconsistent across countries, with the United States reporting 0.2% to 1% of brain tumors and Japan 4%. The tumors that occur are teratomas (germ cell tumors), pineal tumors, glioblastomas, and cysts. Pineal tumors are solid cellular tumors. The most common pineal tumor is the ovarian germ cell tumor. This tumor occurs in the hypothalamus and anterior part of the 3rd ventricle and can invade the hypothalamus and spinal cord and the central nervous system. Metastasis to the skin, lungs or liver is rare.