Key-words:
Malignant tumor - papillary tumor of the pineal region - pineal gland
Introduction
Papillary tumors of the pineal region are located in the pineal gland which is located
in the center of the brain. Papillary tumors of the pineal region (PTPRs) were first
described by A. Jouvet et al. in 2003 and were introduced in the World Health Organization
(WHO) classification of central nervous system (CNS) in 2007. Papillary tumors of
the CNS and particularly of the pineal region are very rare, and therefore, diagnosing
them is extremely difficult.[[1]]
Case Report
A 5-year-old male child presented with worsening headaches, abnormally enlarged head
since birth, and visual disturbances of several months duration. Noncontrast computed
tomography (CT) revealed a 2.5 cm × 2.8-cm mass near the posterior aspect of the third
ventricle, which resulted in obstructive hydrocephalus. The third and lateral ventricles
were enlarged. Brain magnetic resonance imaging (MRI) was subsequently performed.
A precontrast sagittal T1-weighted image showed a mass in the region of the pineal
gland, which was isointense on T1 and T2-weighted images. The mass was enhancing avidly
on contrast [[Figure 1]]. The patient underwent a gross-total surgical resection of pineal mass through
a suboccipital supra-cerebellar approach. The patient tolerated the procedure well
and tissue was sent for histopathological examination and diagnosed papillary tumor
pineal region which was further confirmed on immunohistochemical. Histopathologically,
the tumor displayed distinctive features described for PTPR. This tumor was an epithelial-appearing
lesion with focal papillary architecture, as well as other densely cellular areas
that showed ependymal-like differentiation. Within the cellular areas, true rosettes
and tubules were identified, consisting of cells with clear or vacuolated cytoplasm.
Nuclei were round to oval with stippled chromatin in the papillary sites, vessels
were layered with large, pale to eosinophilic columnar cells. Mitotic activity is
reported to vary from 4 to 10 per 10 HPF, and necrotic foci were identified. Occasionally,
PAS-positive islands were found. While microvascular proliferation was absent, vessels
were hyalinized with a clear demarcation between the tumor and the residual normal
pineal gland [[Figure 2]] and [[Figure 3]].
Figure 1: (a) Sagittal T1-weighted contrast magnetic resonance imaging showing a mass in the
region of the pineal gland, with a thin rim of intrinsic signal hyperintensity. (b)
Coronal T1-weighted contrast magnetic resonance imaging showing a mass in the region
of the pineal gland, with a thin rim of intrinsic signal hyperintens
Figure 2: Hematoxylin and Eosin stain in Papillary tumor of the Pineal Region (˟400) Extensive
papillary formation lined by cuboidal to columnar cells with maintained basal polarity
with mild to minimal atypia
Figure 3: (a) Cytokeratin 18 Positivity in cells on immunohistochemistry. (b) Epithelial membrane
antigen positivity in cells on immunohistochemistry
The evolution in the classification of pineal tumors has led to the emergence of PTPR.
Discussion
Based on a series of six tumors with identical histological features, PTPR was first
described as a distinct entity in 2003.[[2]] To date, there are now 59 reported cases, including six cases. In children under
the age of 16 years (10.2%),[[3]],[[4]] PTPR generally presents with nonspecific symptoms, including headache and visual
disturbances due to obstructive hydrocephalus.[[5]] Neuroimaging usually displays a large (2–4 cm), well-circumscribed contrast-enhancing
tumor, which occasionally has cystic elements.[[6]],[[7]] Previous MRI literature has reported a heterogeneously enhancing mass in the pineal
region.[[2]],[[8]] PTPR is prone to local recurrence, even after surgery chemotherapy, or radiotherapy.
PTPR is now viewed as a separate entity from choroid plexus papilloma and ependymoma,
although there is significant overlap.[[5]] PTPR displays prominent decoration with cytokeratins, which are most characteristically
seen in papillary structures. CK18 is the cytokeratin most often associated with PTPR,
although KL1, AE1/AE3, and CAM 5.2 also commonly decorate these tumors. Due to the
rarity of PTPRs, no set positive or negative cutoffs have been established for these
markers.[[5]] In PTPR, staining is also seen with NSE and S-100. Focal decoration with chromogranin,
synaptophysin, and EMA is also described. In contrast to the strong GFAP decorations
in ependymomas, GFAP immunoreactivity in PTPR is usually focal or absent.[[8]],[[9]] Choroid plexus tumors frequently stain for membranous Kir 7.1 or cytoplasmic stanniocalcin-1;
however, these two markers are absent in the majority of PTPR.[[5]] Transthyretin is more often expressed in choroid plexus tumors as well. Because
of the few reported cases of PTPR, there are no current standard treatment options
beyond gross total resection. New areas of interest in the diagnosis and prognosis
of PTPR continue to develop as pathologists further delineate this newly described
entity. Measurements of melatonin levels, as well as the elucidation of the enzymes
in melatonin synthesis of pineal tumors, have been recently explored as possible diagnostic
and treatment indicators. As more pathologists have become familiarized with the cytological
presentation of PTPR, the ability to diagnose the tumor on intraoperative smear preparations
has increased. By combining observations such as smear population, architecture, background,
calcification, single cells, cell morphology, location, and radiology, the addition
of cytologic imprints can help improve the intraoperative diagnostic power over frozen
section alone.[[10]]
