Tumors of the Pineal Region



Tumors of the Pineal Region





Pineocytoma (WHO Grade I), Pineal Parenchymal Tumor of Intermediate Differentiation (WHO Grade II to III), and Pineoblastoma (WHO Grade IV)

Pineal parenchymal tumors occupy a continuum of differentiation and clinical aggressiveness from the indolent pineocytoma to the overtly malignant pineoblastoma, with at least one category of intermediate differentiation. The criteria governing the boundaries within this spectrum remain undecided, complicating any effort to describe the component entities with accuracy. Nevertheless, enough of these rare cases have been amassed to establish a working approach to pathologic categorization that correlates with patient outcome. This approach was propounded by Jouvet et al. (1) and has been loosely adopted by the World Health Organization (WHO), as detailed later.


Clinical Context

Although mass lesions in and around the pineal gland are not uncommon, pineal parenchymal tumors are rather infrequent, constituting less than 1% of primary central nervous system (CNS) neoplasms and less than a third of pineal region tumors (1,2).

In general, both pineocytoma and pineal parenchymal tumor of intermediate differentiation (PPTID) are more likely to occur in young to middle-aged adults, but can also be seen in children. Pineoblastomas show the opposite distribution, with more cases occurring in childhood and early adulthood and fewer thereafter. No sex predilection exists for any category (1,2,3,4).

Pineal parenchymal tumors present with symptoms and signs similar to other pineal region tumors, the constellation of which may form Parinaud syndrome, an upward gaze paralysis with retraction nystagmus due to compression of the tectum. Acute obstructive hydrocephalus with signs of increased intracranial pressure is the most common presentation, which is likely due to the proximity of the cerebral aqueduct. Rarely, pineal parenchymal tumors present with spontaneous hemorrhage.

The most consistent association of pineal parenchymal tumors with a genetic syndrome is that of pineoblastoma with germline DICER1 mutations.
Certain inactivating DICER1 mutations cause a tumor predisposition syndrome in which the rates of pleuropulmonary blastoma, cystic nephroma, Wilms tumor, Sertoli–Leydig cell tumors, differentiated thyroid carcinoma, and pineoblastoma, among others (5). In one series, about a third of children diagnosed with pineoblastoma who were tested showed a germline DICER1 mutation, making the case that such patients and their families should be offered genetic counseling (6). Pineoblastomas are also occasionally seen in the context of retinoblastoma and/or germline RB1 mutations (7). In such cases, the retinoblastomas are generally bilateral with a synchronous pineoblastoma, termed “trilateral retinoblastoma” (8). Children with this presentation have a much worse prognosis than those with retinoblastoma alone. Pineoblastoma has been reported in familial adenomatous polyposis but is rare among those patients (9).

Pineocytomas are round, homogeneous, and hypodense on computed tomography (CT), sometimes with calcifications. Signal intensities on magnetic resonance imaging (MRI) are variable (10). The mass is circumscribed and compresses the surrounding tissue, whereas germ cell tumors tend to invade the brain (11). Because any pineal tumor can grow anteriorly, they may present as a posterior third ventricle mass. Small internal cystic spaces can be seen in pineal parenchymal tumors of any grade. However, an overall cystic construction should be approached with skepticism and suspicion of a pineal cyst.

Treatment approaches for pineal parenchymal tumors are not standardized, but include surgical excision for pineocytomas, with radiation added for most PPTIDs. Pineoblastomas are often treated with both chemotherapy and radiation, the latter frequently being craniospinal. Well-differentiated pineocytomas have 80% to 100% 5-year survival following resection, commensurate with their WHO grade I status (1,3,12). Those same series show a poor survival rate for pineoblastoma, about 10% at 5 years, whereas more recent series indicate median survivals around 50% to 70% at 5 years (13,14,15). One recent review of the literature found a median overall survival rate for PPTID of 14 years and progression-free survival of about 5 years among 127 reported patients (16).


Histopathology

Pineocytomas are formed of expanses of monotonous cells interrupted by small anucleate areas of felt-like cortical neuropil, very similar to those seen in some neurocytomas (Figure 12-1). Better-differentiated tumors tend to have greater amounts of these “pineocytomatous rosettes.” This classic architecture contrasts, with PPTIDs, which take on a lobular arrangement or diffuse, sheetlike growth.

The tumor cells are generally monotonous, with round regular nuclei that contain finely speckled chromatin and small, but easily found, nucleoli. A minority of pineocytoma and PPTID are pleomorphic with multinucleate, sometimes giant, tumor cells and irregular, hyperchromatic nuclei. Pleomorphism has not been shown to impact clinical outcomes, and
those cases behave according to the grade established by other criteria (17).






FIGURE 12-1 Pineocytomas usually contain areas of anucleate neuropil (pineocytomatous rosettes), similar to those seen in neurocytomas.

Mitosis (<1/10 HPF) and necrosis are not consistent with pineocytoma, WHO grade I (1). Ganglion cells are occasionally present, as in other tumors with neuronal or neurocytic differentiation. Lamellated calcifications with round or scalloped edges (corpora arenacea) are also seen and possibly represent overrun calcifications of the normal gland.

Pineoblastomas may closely resemble other malignant embryonal tumors and consist of sheets of small and poorly differentiated embryonal cells, frequently with necrosis, numerous mitoses, and vascular proliferation (Figure 12-2). Some cases may have large angular cells with prominent nucleoli and other features of anaplasia, the significance of which is unknown. Both lumen-forming (18) and fibrillary (Homer Wright) (19) rosettes sometimes appear. Pineoblastoma may also coexist with lower grade elements, in which case the tumor should still be classified pineoblastoma.

Some have observed heterologous elements within pineoblastoma, specifically skeletal muscle, cartilage, and melanotic epithelia. These cases resemble similar lesions of the retina and are called pineal anlage tumors (20,21). The significance of this exceptionally rare finding and how it relates to other pineoblastomas is unknown.


Grading

No formal WHO criteria exist by which to grade PPTs. One large series addressing the PPT grading suggests that they be divided into four categories based on mitotic figures and amount of neurofilament reactivity, with
PPTID occupying grades II and III. Pineocytomas should not contain mitosis or necrosis and should display strong and widespread neurofilament staining by immunohistochemistry. Grade II PPTIDs have pineocytomatous rosettes and 1 to 5 mitoses per 10 random 400× fields. Grade III is achieved with mitosis >6/10 HPF, or with loss of neurofilament expression. Pineoblastoma is patently malignant with sheets of small embryonal cells. Although not a formal criterion, the authors of this grading system did not observe necrosis in any grade I or grade II lesions, suggesting its utility as an adjunct criterion (1).

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Oct 22, 2018 | Posted by in NEUROLOGY | Comments Off on Tumors of the Pineal Region
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