Neoplasms of the pineal gland

Neoplasms discussed in this chapter are pineal parenchymal neoplasms, the papillary tumor of the pineal region, and primary central nervous system (CNS) germ cell neoplasms. Nearly all primary CNS germ cell neoplasms arise in the pineal or suprasellar regions but very rare examples occur in other midline regions of the neuraxis, such as the spinal cord. Gliomas, meningiomas, and metastatic tumors may all occur in the region of the pineal gland, but are considered in other chapters.

NEOPLASMS IN THE PINEAL GLAND

These may present with:

Raised intracranial pressure due either to mass effect or aqueduct compression and subsequent hydrocephalus.

Brain stem compression, producing Parinaud syndrome (paralysis of gaze in the vertical plane), other gaze palsies, nystagmus, ataxia, or long tract signs.

PINEAL PARENCHYMAL NEOPLASMS

Approximately 20% of pineal parenchymal neoplasms are pineocytomas, 30% are pineoblastomas, and 50% are intermediate neoplasms.

Pineal parenchymal neoplasms represent 15–30% of pineal tumors, but only 0.5% of intracranial tumors.

Patients presenting with pineal parenchymal neoplasms are mostly in their 3 rd or 4th decade.

There is an equal incidence of pineal parenchymal neoplasms in males and females.

Pineoblastomas occur at a younger mean age (approximately 20 years of age) than pineocytomas (approximately 40 years of age).

Rarely, pineoblastomas are associated with bilateral retinoblastomas in children.

Classic pineocytomas respond relatively well to surgery and focal radiotherapy.

Other pineal parenchymal neoplasms may metastasize through cerebrospinal fluid pathways, and show a variable response to surgery and adjunctive therapies.

PINEAL PARENCHYMAL NEOPLASMS

The developed pineal gland consists of nests of pineocytes enclosed by fibrovascular septa. Pineocytes are neuroepithelial cells, contain abundant secretory granules, and have elongated processes with club-like endings that extend towards blood vessels. Melatonin, a hormone with effects on the sleep–wake cycle, and serotonin are the major products of the pineal gland and, like cells in the retina, pineocytes can produce S antigen. The principal types of pineal parenchymal tumor are:

pineocytoma

pineal parenchymal tumor of intermediate differentiation

pineoblastoma.

Many pineal parenchymal neoplasms are not readily classified as pineocytomas or pineoblastomas and end up in the intermediate category. The mixed pineal parenchymal tumor combines features of a pineocytoma and pineoblastoma and is very rare. The term pinealoma should no longer be used.

MACROSCOPIC APPEARANCES

Pineocytomas are firm gray neoplasms. Pineoblastomas are softer and sometimes gelatinous in texture and may contain areas of hemorrhage and necrosis. Although both types of neoplasm may be circumscribed, pineocytomas usually compress surrounding tissues (Fig. 39.1), while pineoblastomas tend to infiltrate the midbrain, third ventricle, or sometimes the thalamus and hypothalamus. Pineoblastomas frequently disseminate throughout the CNS along CSF pathways.

39.1 Pineocytoma.
Arising from the pineal gland, this neoplasm has partly invaded and distorted the rostral brain stem.

The pineocytoma consists predominantly of small monomorphic cells set in a fibrillary background (Fig. 39.2). The cells are generally arranged in sheets, though a nodular pattern may occasionally be evident. A characteristic feature is the formation of pineocytomatous rosettes, which are relatively large zones of fine, fibrillary processes surrounded by an oval arrangement of neoplastic cell nuclei (see Fig. 39.5). The neoplastic cells generally resemble the cells of normal pineal gland, with their argyrophilic processes which may have club-like terminal expansions. Their processes express NSE and synaptophysin, and at the ultrastructural level contain microtubules and a few dense core vesicles. Some cells label with antibodies to S antigen.

39.2 Pineocytoma.
(a) Pineocytomatous rosettes dominate this region of a typical pineocytoma. (b) In a smear preparation, the cells of this pineocytoma are characterized by uniformity, delicate cytoplasmic processes, and tiny nucleoli. (c) Silver impregnation of the neuritic processes in a pineocytomatous rosette. (d) Cytologic pleomorphism as marked as here may be seen in pineocytomas and intermediate pineal parenchymal neoplasms. In an otherwise typical pineocytoma with pineocytomatous rosettes, but without mitoses and focal increases in nuclear:cytoplasmic ratio, it is not thought to be an adverse prognostic sign. (e) Widespread immunoreactivity for neurofilament proteins is typical of pineocytomas.

Cytologic pleomorphism, manifesting occasionally as giant cells with misshapen, hyperchromatic nuclei, may be found in scattered groups of cells. Provided these cells are not accompanied by mitoses and other atypical cells with a high nuclear:cytoplasmic ratio, they are not thought to be an adverse prognostic sign. Mitoses are exceptional in pineocytomas. Ganglion cells may be found in some pineocytomas.

Cells in a pineocytoma are usually immunoreactive for neurofilament proteins. Immunolabeling for GFAP is confined to reactive astrocytes. Electron microscopy may reveal cilia with a 9 + 0 configuration, as well as dense core vesicles.

Intermediate or mixed pineal parenchymal neoplasms

Intermediate and mixed pineal parenchymal tumors occupy a middle ground between pineocytoma and pineoblastoma:

The pineal parenchymal tumor of intermediate differentiation is characterized by a syncytial or occasionally lobular architecture (Fig. 39.3). Some of its cells may resemble those of a pineocytoma, but it lacks the well-differentiated features of this tumor, including pineocytomatous rosettes. Collections of ‘blast’ cells are also missing. Cytologic pleomorphism is variable, but usually not marked. Mitoses are readily found. Ganglion cells and giant cells are occasionally evident. Immunoreactivity for neuronal markers may be prominent. This variant sometimes metastasizes throughout the CNS. Indicators of a more favorable outcome among intermediate tumors are immunoreactivity for neurofilament proteins, and a mitotic count of less than 6/10 hpfs.

39.3 Two examples of the intermediate pineal parenchymal tumor (a) and (b). These lacked pineocytomatous rosettes and embryonal cells and had a higher cell density than exhibited by pineocytomas. The expression of neurofilament proteins is variable, but was strong and widespread in this example associated with survival over more than 10 years (c). Mitotic figures are present, but usually not numerous, and Ki-67 immunolabeling is moderate (d), intermediate between levels seen in pineocytomas and pineoblastomas.

The rare mixed pineocytoma/pineoblastoma is characterized by groups of small, rapidly proliferating cells in a neoplasm which otherwise has the architecture and cytology of a pineocytoma. The small ‘blast’ cells confer the behavioral properties of a pineoblastoma upon this neoplasm.

Pineoblastoma

The pineoblastoma resembles the classic (non-desmoplastic) medulloblastoma, and was previously grouped with other embryonal neoplasms of neuroepithelial lineage in the broad category of primitive neuroectodermal tumors (Chapter 38). It contains round or polyhedral cells with a high nuclear:cytoplasmic ratio, which are arranged in sheets or lobules (Fig. 39.4). Mitoses and apoptotic bodies are generally plentiful. Neuroblastic (Homer Wright) and Flexner–Wintersteiner rosettes may occasionally be found, but pineocytomatous rosettes are not a feature of the typical pineoblastoma (Fig. 39.5), being found only in the rare mixed tumor. Necrosis and hemorrhage are common, while melanin-producing cells or signs of mesenchymal differentiation, such as striated muscle or cartilage, are exceptional. Immunoreactivity for neuronal markers may be local or widespread (Fig. 39.4), and pineoblastomas may label with antibodies to retinal S antigen.