Occurrence of Pineal Gland Tumors in Combined Chronic Toxicity/Carcinogenicity Studies in Wistar Rats

Abstract

Pineal gland tumors are very rare brain lesions in rats as well as in other species including humans. A total of 8 (out of 1,360 examined) Wistar rats from 3 different combined chronic toxicity/carcinogenicity or mere carcinogenicity studies revealed pineal gland tumors. The tumors were regarded to be spontaneous and unrelated to treatment. The morphology and immunohistochemical evaluation led to the diagnosis malignant pinealoma. The main characteristics that were variably developed within the tumors were the following: cellular atypia, high mitotic index, giant cells, necrosis, Homer Wright rosettes, Flexner-Wintersteiner rosettes and pseudorosettes, positive immunohistochemical reaction for synaptophysin, and neuron-specific enolase. The pineal gland is not a protocol organ for histopathological examination in carcinogenicity studies. Nevertheless, the pineal gland can occasionally be encountered on the routine brain section or if it is the origin of a tumor protruding into the brain, the finding will be recorded. Therefore, although known to be a rare tumor in rats, pineal neoplasms should be included in the list of possible differential diagnoses for brain tumors, especially when the tumor is located in the region of the pineal body.

The morphological and functional characteristics of the pineal gland

“…The incidence of these tumors is under 1% of central nervous system primitive tumors [57,72,73]. These tumors can be well differentiated, like the pineocytoma, or poorly differentiated, as the pinealoblastoma.…”

“…These tumors can be well differentiated, like the pineocytoma, or poorly differentiated, as the pinealoblastoma. The pineocytoma has a tendency to be well differentiated, with a slow growth rate, with Homer-Wright or Flexner-Wintersteiner rosette formation, [73,74] while the pinealoblastoma is poorly delimitated and with a rapid growth pattern [53] with a marked hypercellularity of small, round cells with a poor cytoplasm and hyperchromatic and round nucleus [74]. An intermediate form tumor is also reported, with a mixed architecture, with uniform cells in an abundant stroma.…”

“…Intermediate pineal tumor is positive for Synaptophisin, Chromogranin A and Neurofilament and a Ki-67 index of 1–30%. Pineoblastoma is positive to NSE, Synaptophysin, Chromogranin A, Neurofilament, partially to GFAP and has a very high Ki-67 index [56,71,73,74].…”

Nonproliferative and Proliferative Lesions of the Rat and Mouse Endocrine System

“…( Al Zubaidy and Malinowski 1984 ; Botts et al 1994 ; Capen et al 2001 ; Coca et al 1992 ; Fraser 1986 ; Furukawa et al 1999 ; Götz et al 1992 ; Heath and Winokur 1998 ; Hirato and Nakazato 2001 ; Jouvet et al 2006 ; Koestner and Solleveld 1996 ; Korf et al 1990 ; Krinke et al 1985 ; Krinke et al 2000 ; Maekawa et al 1984 ; Rubinstein 1972 ; Schachner et al 1984 ; Treumann et al 2015 ; Vogel and Fuller 2003 ; Walker et al 1994 ; Yamamoto et al 1991 )…”

Malignant pinealoma observed in the deep cerebral parenchyma of a male Wistar rat

“…In contrast, the tumor classification of rodent species generally classifies tumors occurring in the pineal region as pinealoma, and those with high histological grade referred to as malignant pinealoma 4,8 . Pinealomas derived from parenchymal cells of the pineal gland have been reported in various strains of rats, including Sprague-Dawley 9 , F344 10,11 , Wistar [12][13][14] , and Osborne Mendel 15 rats, and are characterized by an expansive growth of tumor cells in the area between the posterior-dorsal median line of the cerebrum and the cerebellum, where the pineal gland is located. In rats, the highest incidence of spontaneous pinealomas (1%) has been reported in Wistar rats 14 ; however, the incidence in other reports is generally lower 10,12,15 .…”