Cysts of the Pineal Gland: a Review of the Literature Concerning the Incidence, Classifications, Diagnosis, Treatment, Physiology, and Anatomy

Family Practice Clerkship Summer 2005 Anatomy and Physiology. The pineal gland, situated at the, “posteriodorsal aspect of the diencephalons, [with] proximal portion […] invaginated by the pineal recess of the third ventricle, (Rowland, 2000)” and weighing ~130 mg, with a length of ~1 cm, is also a highly vascularized organ, served by the, “posterior choroidal branches of posterior cerebral arteries (Rowland, 2000).” The pineal gland functions both as an endocrine and neural organ and acts either directly or indirectly to impact all organs of the human body (Rowland, 2000). The pineal gland, acted on by norepinephrin, yields pineal indoleamines (Rowland, 2000). Innervation is by axons from brain via the pineal stalk, in addition to sympathetic innervation by: postganglionic axons perikarya from the superior cervical ganglia (Rowland, 2000). Cell bodies of the pineal gland communicate with the preganglionic fibers ending in ganglia of the intermediolateral cell column upper thoracic of spinal cord (Rowland, 2000). The neurons of intermediolateral cell column of spinal cord end in terminals from perikarya, hypothalamus, and paraventricular nuclei are connected suprachiasmatic nuclei that receive signals from ganglion cells of retinas via retinohypothalamic neural tract (Rowland, 2000). Incidence. Sawamura et al. (1996) found, in discounting cysts less than 0.5 mm, in their review of 6023 patients and 8623 MRI studies, an overall frequency of 1.3% of pineal region cysts. They speculate that pineal cysts begin forming, in women during adolescence, as its use wanes. Sawamura et al. (1996) noted pineal cysts are most frequent 5.82% amongst young (21-70) women, and using the chi square analysis found that young women had a p value of <0.001>Diagnosis Sagittal MRI to evaluate for the possibility of obstruction or occlusion of the proximal aqueduct and anatomical relationships relative to the pineal gland is indicated either when otherwise unexplained clinical symptoms are manifested, or previous CAT scan or MRI warrants such (Fetell et al., 1986). Clinical symptoms associated with pineal cysts represent both neural and endocrine function of the pineal gland. Rowland (2000) delineated (Appendix A, Table 1.) three symptom categories based on impairment and type of involvement, which include: increased intracranial pressure resultant of hydrocephalus, brainstem and cerebellar compression, and endocrine abnormalities. The following clinical symptoms have been most frequently found in association with pineal cysts and may occur in widely varying degrees and configurations, with regard to one another: Parinaud’s syndrome; headache, migraine without aura, migraine with aura, chronic migraine, hemicrania continna, unilateral headache; scotoma and transient inferior field deficit; paroxysmal papillary dilatations and contractions; mass effect; mesencephalic; diplopia; vertige; ataxia; long pathways deficit (Peres et al., 2004; Michielsen et al., 2002; Tartara et al., 1999; Konovalov et al., 1998). Imaging. Fleege, et al. (1995), via CAT and MRI studies, examined nineteen patients presenting with symptomatic pineal cysts, aged 15-46 years, comprising five male and fourteen women. Fleege et al. (1995) concluded, citing the broad spectrum of configurations observed regarding the pineal cysts, distinction could not be made, via MRI or CAT studies of the pineal cyst in question, between a benign cyst and a pineal region neoplasm. Barboriak et al. (2001) showed 75% of pineal cysts changed <2>Pathophysiology and Anatomy of Pineal Region Cysts. Todo et al. (1991) noted three primary defining characteristics of large benign pineal cysts in a study of two middle-aged patients in whom the cysts were an incidental MRI finding. These characteristics include: a three-layered cyst wall, including: (1) collagen fibrous layer, (2) gliaic layer, (3) and pineal cell layer; cysts walls typically measure 100-300 microns; calcification was found associated with the first layer of cyst walls. Tamaki et al. (1989) found pineal cysts have greater opacification than cerebrospinal fluid and less than other regional anatomical structures using T1-weighted images were used in MRI, and smooth margins and homogenous contents were observed using T2-weighted images in MRI. Fain et al. (1994) redefined the second layers as follows: (2) pineal parenchymal cells with calcifications possible, (3) hypocellular glial tissue with or without Rosenthal fibers including, or occurring individually, granulations. It was also observed the cyst walls ranged from 0.5-2.0 mm (Fain et al., 1994). Lee et al. (1987) noted that in their fifteen patients cysts were midline, with flattening of the superior colliculi and no mass effect. Hardy (1996) notes intracystic bleeding is a major contributory factor in cyst growth. Mario et al. (2004) speculates that dysfunction in melatonin production and secretion may be associated with pineal region cysts. Treatment. In the literature the two most frequently addressed interventions are “open-surgical” and stereotactic methods and likewise are most prominently addressed here with regards to the other currently employed procedures. Treatment can include: radiotherapy; chemotherapy; open surgical resection via infratentorial, supracerebellar, suboccipital craniotomy, or occipital-transtentorial; endoscopicopy, via either free-hand method, or stereotactic biopsy, with possible shunt placement in patients with recurrence, or in asymptomatic patients, cautious clinical monitoring, with no intervention until symptoms present. Although 33.3% of pineal region tumors are benign and curable with complete surgical resection, rarely are symptomatic pineal region cysts benign (Rowland, 2000). Prognosis for such patients is heavily contingent upon the histopathology of the cystic tumor (Rowland, 2000). Radiotherapy, 5,500 cGy total focused on the cranium, and partially in the pineal region, is standard for all pineal region malignancies (Rowland, 2000). Unless metastasis is indicated radiographically, the vertebral column is generally not targeted in such therapeutic interventions (Rowland, 2000). Chemotherapy of pineal region malignancies is employed often in concert with radiotherapy regarding nongerminomatous malignant GCTs, using variations of cisplatin, vinblastine, and bleomycin or cisplatin and etoposide (Rowland, 2000). Musolino et al. (1987) cites the possible risks of surgical intervention, but as demonstrated by Konovalov et al. (1998) and Maurer et al (1990), these views are largely unfounded; whereas, there is a significant risk of recurrence and complication from such associated with stereotactic diagnosis and treatment method. With complete surgical resection, both complete diagnostic studies and one-time complete treatment is achieved, without the possibility of follow-up measures, the exception being chemotherapy and radiotherapy of malignant cysts. Mena et al. (1997) provided evidence in support of surgical resection of pineal cysts, showing that one patient who had stereotactic treatment, suffered recurrence and another who had no treatment died of associated cystic complications. Konovlov et al. noted that surgical outcomes for resection could be very good in the above noted approaches and made recommendations accordingly. Tartara et al. (2000) recommend the infratentorial-supracerebellar approach, which allows the best and safest entry. Fetell et al. (1991) reports on nine patients who underwent uneventful suboccipital craniotomy and suffered no mentioned complications. MacKey et al. reported on a 7-year-old-boy who underwent occipital-transtentorial resection of a pineal cyst. The authors make strong recommendations for surgical intervention for the following reasons: (1) resect with wide margins, (2) mitigate recurrence, (3) limit other future cystic complications, (4) mitigate need for shunt placement in patients with hydrocephalus, (5) increase sample size for testing, including histoimmuniochemical and biocytopathologic analysis. They especially point to the potential for stereotactic biopsy to not meet the above-noted criteria; thereby, necessitating further invasive intervention. Michielsen et al. (2002) makes recommendations for rigid endoscopic treatment of pineal cysts. In review of seven symptomatic patients, of which four were treated endoscopically, three free-handed and one stereotactically. Two patients underwent ‘open surgical resection.’ The mean follow-up period was 29 months, with the endoscopic patients were asymptomatic and the other two patients symptomatic. Musolino et al. (1993) noted stereotactic biopsy is effective in diagnosis and treatment of pineal cysts and they point out that is does so without many of the risks associated with conventional surgery or radiotherapy. Stern and Ross (1993) describe the stereotactic treatment of two patients, in which a shunt was employed in the one after recurrence and the other remained well for the 30-month follow-up period. Both patients had benign cysts, of which was comprised ‘brown-yellowish’ fluid. Cytologic and histoimmuniochemical studies confirmed the nature of the cysts. Behrems and Ostertag (1993) retrospectively reviewed seven patients who underwent stereotactic biopsy, five of whom had, ‘clinical recovery or marked improvement,’ over the 20-month mean follow-up period. The authors make recommendations for stereotactic treatment based on the notion confirmatory diagnostic tests can be conducted with sample aspirated, in a minimally invasive procedure. References. Baboriak, D. P., Lee, L., Provenzale, J. M.: Serial MR imaging of pineal cysts: implications for natural history and follow-up. AJR. 176:737-743, 2001. Behrens, P., Ostertag, C. B.: [Stereotactic procedure in pineal cysts] [Article in German] Fortschr Neurol Psychiatr. 61(8):284-9, 1993. Fain, J. S., Tomlinson, F. H., Scheithauser, B. W., Parisi, J. E., Fletcher, G. P., Kelly, P. J., Miller, G. M.: Symptomatic glail cysts of the pineal gland. Neurosurgy. 32(2):315-20; discussion 320-321, 1993. Fetell, M. R., Bruce, J. N., Burke, A. M., Cross, D. T., Torres, R. A., Powers J. M., Stein B. M.: Non-neoplastic pineal cysts. American Journal of Neuroradiology, 7(6):1081-1086, 1986. Fleege, M. A., Miller, G. M., Fletcher, G. P., Fain, J. S., Scheithauser, B. W.: Benign glial cysts of the pineal gland: unusual imaging characteristics with histologic correlation. Pediatr Radiol. 25(4): 254-248, 1995. Konovalov, A. N., Spallone, A., Pitzkhelauri, D. I.: Pineal epidermoid cysts: diagnosis and management. J Neurosurg. 91(3):370-4, 1999. Lee, D. H., Norman, D., Newton, T. H.: MR imaging of pineal cysts. J Comput Assist Tomogr. 11(4):586-90, 1987. MacKay, C. I., Baeesa, S. S., Ventureyra, E. C. G.: Epidermoid cysts of the pineal region. Mena, H., Armonda, R. A., Ribas, J. L., Ondra, S. L., Rushing, E. J.: Nonneoplastic pineal cystics: a clinicopathologic study of twenty-one cases. Journal of Neurology, Neurosurgy, & Psychiatry. 56:207-208, 1993. Michielsen, G., Benoit, Y., Baert, E., Meire, F., Caemaert, J.: Symptomatic Pineal Cysts: Clinical Manifestations and Management. Acta Neurochirurgica. 144(3):233-242, 2002. Mondera, M., Marcol, W., ska-Macyszyn, G. B., Kluczewska, E.: Pineal cysts in childhood. 2003. Musolino, A., Cambria, S., Rizzo, G., Cambria, M.: Symptomatic cysts of the pineal gland: stereotactic diagnosis and treatment of two cases and review of the literature. J Comput Assist Tomogr. 11(4):586-590, 1987. Peres, M. F. P., Zukerman, E., Porto, P. P., Brandt, R. A.: Headaches and Pineal Cyst: A (More Than) Coincidental Relationship? Headache: The Journal of Head and Face Pain. 44(9):929 2004. Petiteolin, V., Garcier, J. M., Mohammedi, R., Ravel, A., Mofid, R., Viallet, J. F., Vanneuville, G., Boyer, L.: [Prevalence and morphology of pineal cysts discovered on pituitary MRI: review of 1844 examinations] [Article in French] Neurosurgy. 32(2):310-314, 1993. Rowland, L. P.: Merritt’s Neurology (10th ed.). Lippincott Wiliams & Wilkins, 2000. Pp. 99-103; 342-347. Sawamura, Y., Ikeda, J., Ozawa, M., Minoshima, Y., Saito, H., Abe, H.: Magnetic resonance images reveal a high incidence of asymptomatic pineal cysts in young women. Journal of Clinical Pathology. 49:267-269, 1996. Stern, J. D., Ross, D. A.: Stereotactic management of benign pineal region cysts: report of two cases. Neurosurgery. 32(2):310-4, 1993. Tamaki, N., Shirataki, K., Lin, T. K., Masumura, M., Katayama, S., Matsumoto, S.: Cysts of the pineal gland. A new clinical entity to be distinguished from tumors of the pineal region. Childs Nerv Syst. 5(3):172-6, 1989. Tartara, F., Regolo, P., Terreni, M. R., Giovanelli, M.: Glial cyst of the pineal gland: case report and considerations about surgical management. J Neurosurg Sci. 44(2):89-93, 2000. Todo T., Kondo, T., Shinoura, N., Yamada, R.: Large cysts of the pineal gland: report of two cases. Neurosurgery. 29(1):101-5, 1991. Vajtai, I., Bodosi, M., Vargaa, Z., Ormos, J., Varos, E. [Symptomatic glial cysts of the pineal gland: report of two cases and review of the literature.] [Article in Hungarian] J Neurosurg. 80(3):454-460, 1994.