Immunohistochemical characterization of pineal parenchymal tumors using novel monoclonal antibodies to the pineal body

Abstract

To characterize the immunohistochemical nature of pineal parenchymal tumors (PPT), we examined nine cases of normal pineal bodies and 23 cases of PPT using several neuronal and glial antibodies and 10 novel monoclonal antibodies raised against human pineal tissue. The PPT were classified into four pineocytoma, five pineal parenchymal tumor of intermediate differentiation (Int-PPT), and 14 pineoblastoma. The pinealocytes, parenchymal cells of the pineal body, were labeled with five, neuronal and seven pineal monoclonal (from PP1 to PP7) antibodies in the normal pineal bodies. The subjects ranged from 3 to 85 years old, 12 female and eight male subjects were studied. Antibodies to glial cells PI1, PI2 and PX1, stained interstitial cells of the pineal body. Many of the PPT showed positive immunostaining for pinealocyte-associated antigens and neuronal markers. The intensity of immunostaining showed some association with the degree of differentiation of the tumor, but there was a considerable variety of staining from case to case. The pineocytomas are more immunopositive than are the Int-PPT or pineoblastoma for neuronal and pinealocyte-associated antibodies. In particular the neurofilament protein (NFP)68 kDa, PP1 and PP6 showed significant differences of reactivity between pineocytoma, Int-PPT and pineoblastoma, when compared in groups showing extensive positive staining (positive staining in almost all areas of the tumor). By using three representative antibodies, anti-NFP68kDa, PP1 and PP6, we were able to make a clear distinction between pineoblastoma, Int-PPT and pineocytoma. Glial fibrillary acidic protein (GFAP), PI1 and PI2 antibodies only occasionally showed a small number of positive cells in the tumor, and thus we considered these cells to be non-neoplastic interstitial cells or reactive astrocytes entrapped in the tumor. Our data suggest that the glial differentiation of PPT may occur, but that it seems to be a very rare event.

Pineal Parenchymal Tumors

“…6,[13][14][15] Age at presentation is variable for PPTs, with pineocytoma predominantly affecting adults (median age 38 years) whereas pineoblastoma most often affects a younger population (median age 18.5 years). 5,10,13,14,[16][17][18][19] No gender preference is apparent.…”

“…Among such tumors, some consist of cells with histological features intermediate between typical pineocytomas and pineoblastomas and thus are called PPTs of intermediate differentiation. 18 Rather, PPTs are believed to exist along a continuum. 39 PPTID may correspond to WHO grade 2 or 3 but definite grading criteria have yet to be established.…”

Histopathology of Tumors of the Pineal Region

“…PC cells can express serotonin [51] and TPH, which are involved in melatonin synthesis [52]. Intense immunostaining of PCs for pinealocyte-associated antigens (PP1 and PP6) has also been reported [53]. GFAP and S100P immunolabeling is usually positive in the interstitial cells in PCs [11,43].…”

Pathology of Pineal Parenchymal Tumors

“…The immunophenotype of pineoblastoma is similar to that of pineocytoma and includes reactivity for neuronal and photoreceptor markers, such as synaptophysin, neurofilaments, class III β-tubulin, chromogranin A, and retinal S-antigen [7,10,11,13,22,33]. However, reactivities are variable and usually lower in intensity than in other PPTs.…”