Neuroendocrine, immunohistochemical, and ultrastructural study of pineal region tumors

Abstract

Thirteen patients with tumors in the pineal region were submitted to pre- and post-operative blood sampling (08:00, 14:00, 20:00, and 02:00 hr) for three or four consecutive days. A single cerebrospinal fluid (CSF) sample was collected at surgery, and melatonin levels determined. In all patients, serum and CSF beta subunit of human chorionic gonadotrophin (betaHCG), carcino embryonic antigen (CEA), and alpha-fetoprotein (AFP) levels were measured. Histology revealed four pineocytomas, one pineoblastoma, four germinomas, one immature teratoma, one pilocytic astrocytoma, one lymphoma, and one meningioma. Serum and CSF levels of serological biomarkers were normal, except for one of the germinoma cases. In most patients, alteration either in the circadian rhythm or in the melatonin concentration was observed before surgery. In benign neoplasms the circadian rhythm was conserved. In pineoblastoma, lymphoma, and three out of four germinomas, melatonin concentrations were undetectable. In one case of germinoma, melatonin levels were high, with the circadian rhythm being abolished. According to conventional histology, all germinomas were similar. Therefore, in a rare case of pineal germinoma with high melatonin levels, the tissue was subjected to an in depth investigation (immunohistochemical and ultrastructural) in order to determine the pathology and the possible differences from the other typical germinomas. Results were compared to those provided from other pineal neoplasms. Electron microscopy examination detected the presence of clusters of intermediate filaments and numerous electrondense granules only in the case of a germinoma producing melatonin.

Histopathology of Tumors of the Pineal Region

“…The endogenous rhythm of secretion is generated by the hypothalamic suprachiasmatic nuclei and activated by the light/dark cycle [17,18]. The pattern of melatonin secretion in patients with a histologically identified PRT has only been reported in a small number of patients [19][20][21]. The melatonin secretion rhythm has been reported to be dramatically reduced in undifferentiated or invasive tumors [21].…”

Biomarkers of Pineal Region Tumors: A Review

“…17 We applied the pineal region tumor classification system to determine the percent distribution of pineal region masses in 6 historic case series (Table 1). 15,16,[18][19][20][21]…”

“…Many case reports and series from the 1960s describe abnormalities in melatonin secretion in the setting of pineal masses. 13,18,[39][40][41][42][43][44][45][46][47][48] In a review completed in 2015, Rousselle and colleagues concluded that few if any pineal parenchymal cell tumors consistently produce a hypomelatoninemic or hypermelatoninemic state. 49 They suggest that reported symptoms of pineal masses such as sleep or behavioral problems represent hypothalamic extension rather than abnormalities of melatonin secretion.…”

Measurement of melatonin in body fluids: Standards, protocols and procedures

“…The elevated diurnal melatonin levels reported in some initial studies [54, 56] were not verified in later descriptions of relatively larger series of pineal region neoplasms [58]. For example, in two series of tumors that included four [59] and five pineal parenchymal neoplasms [57] only one of the patients displayed high diurnal levels of melatonin.…”