Keywords
pineal parenchymal tumors - pineal parenchymal tumor of intermediate differentiation
- tumor grade III
Introduction
Pineal tumors are rare, comprising 0.4 to 1% of brain tumors in adults and 3 to 8%
in children. The major categories of pineal tumors include germ cell tumors, pineal
parenchymal tumors (PPTs), and supporting tissue neoplasms (glial tumors).[1] Germinomas are the most common histologic type, comprising 50 to 60% of all pineal
tumors whereas PPTs aggregate about 30% of pineal region neoplasms.[1]
[2] PPTs are subdivided into pineocytoma, pineoblastoma, and pineal parenchymal tumor
of intermediate differentiation (PPTID). Pineoblastoma and pineocytoma aggregate about
45% each, and the remaining 10% are PPTID.[3]
[4] PPTID was recognized in 2007 by the World Health Organization (WHO) as a new pineal
parenchymal neoplasm intermediate in malignancy (WHO grades II and III) between pineocytoma
and pineoblastoma.[4]
These tumors are composed of diffuse sheets or lobules of monomorphic, uniform, round
cells with moderate to high cellularity, mild to moderate nuclear atypia, low to moderate
mitotic activity along with vascular proliferation, giant cells, and Homer Wright
rosettes. Despite that there is marked cellularity endothelial proliferation and necrosis
is seen rarely, when present, it is accompanied with other degenerative changes and
lacks peripheral nuclear palisading. Morphologically recognizable neuronal or ganglionic
differentiation occurs rarely.[5] In comparison with pineocytomas, they have higher potential for invasion, recurrence,
and leptomeningeal dissemination.
Very few cases are reported of PPTID and even more rarely of grade III. Therefore,
little is known about their clinical behavior and optimal management. Here, we present
a case of PPTID grade III large cell type in a young adult.
Case Report
A 35-year-old man presented in neurosurgery OPD of Uttar Pradesh University of Medical
Sciences, Saifai, Etawah, UP, India, with an intermittent headache, nausea, vomiting,
and giddiness for 1 year. Computed tomographic (CT) findings revealed a pineal gland
space occupying mass of about 4.5 × 4 cm size. It was solid, heterogeneously enhancing
mass with ill-defined margins. There was no evidence of calcification, but it was
obstructing the posterior third ventricle, to cause gross hydrocephalous. The patient
was further investigated to rule out secretory germ cell tumor. In view of hydrocephalous,
a cerebrospinal fluid (CSF) diversion procedure (right ventriculoperitoneal shunt)
was done, and the patient was taken for definitive surgery. At operation, tumor was
grayish, vascular, and soft to firm at places. Decompression and biopsy were done,
and the patient recovered following surgery.The received specimen was gray/brown soft
tissue bits aggregating 1/2 cc, and it was sent in 10% formal saline in histopathology
section of the pathology department. The tissue was processed, sectioned at 3 to 4
µm, and H&E stain was applied.
Section screened showed round to oval cells arranged in diffuse flat sheets with blood
vessels proliferation dominance. Cells were having larger nuclei, vesicular chromatin
pattern, ample cytoplasm, and focal neuropil-like stroma along with moderate atypia,
and mitotic activities were also appreciated, which was 3 to 5 mitotic figures per
10 hpf (high-power field) ([Fig. 1]). All these findings were suggestive of large cell-type PPTID. Immunohistochemistry
was found strongly positive for glial fibrillary acid protein (GFAP) and neuron-specific
enolase (NSE), variable for synaptophysin, and negative for epithelial membrane antigen
(EMA) and neurofilament ([Fig. 2]).
Fig. 1 H&E (10×)-stained section of pineal parenchymal tumor of intermediate differentiation
showing singly arranged cells. Cells had larger nuclei, vesicular chromatin pattern,
ample cytoplasm, and mitotic figures separated and supported by stromal elements with
vascular proliferation.
Fig. 2 Section showing negative immunostaining for neurofilament.
Based on its location, histomorphology, and immunohistochemistry analysis, it was
diagnosed as PPTID grade III large cell type.
Discussion
The pineal gland is a small, red brown, pine-shaped endocrine gland located in the
vicinity of the posterior third ventricle. Its size ranges between 10 and 14 mm. Tumors
of the pineal gland are classified as germ cell tumors, parenchymal tumors, and malformative
tumors. The other pathologies include astrocytoma, meningiomas, ependymomas, metastatic
brain tumors, and epidermoid and dermoid cyst. PPTIDs are the tumors that are intermediate
in nature clinically and on microscopy. It constitutes approximately 10% of PPTs.
Clinical profile of PPTID is similar to that of other pineal region tumors. Diplopia
and headache are the common findings that are followed by Parinaud’s syndrome. Parinaud’s
syndrome is vertical gaze disturbance that occurs due to compression of the tectal
plate. If the tumor mass is large enough, it may cause hydrocephalous further leading
to elevated intracranial pressure and ataxia.[6] In one case series, it was found that 80% of PPTIDs have local invasion.[7] Rarer complications include intracranial dissemination and CSF spread to the spine.
The 5-year survival rate is 39 to 74%.[3] Tumor grade, extent of resection, and neuraxis spread were prognostic factors for
freedom from progression and overall survival whereas high-grade histology and subtotal
resection were the variables that negatively influenced an overall survival. Mallick
et al[8] found that the progression-free survival was 5.17 years and overall survival was
14 years. The possibilities of recurrence and spread are always there, including local,
spinal, and leptomeningeal metastasis. Jouvet et al[2] reported PPT with intermediate differentiation and graded it on the basis of mitosis
and neurofilament staining. Patil and Karandikar[9] reported PPTID grade II along with metastasis in the thoracic and lumbosacral region.
Khaled et al[10] and Kiyici and Sanal[11] also reported PPTID. Raleigh et al[12] classified PPTIDs on their cell morphology and categorized them into small and large
cell types, which had distinct clinical outcomes. Large cell types possibly have more
adverse effects. The accurate frequency of occurrence is difficult to evaluate because
of diagnostic difficulties both clinically and pathologically and also subjective
to the pathologist. Imaging in these tumors is also supplementary for diagnosis. CT
results vary from heterogenous to uniform enhancement whereas on magnetic resonance
imaging, tumors are heterogenous hypointense on T1WI and heterogenous hyperintense
on T2WI. Therefore, there is no single neuroimaging feature that is pathognomic of
PPTID.[13] This category was first introduced by Schild et al in 1993,[14] and this tumor occurs in all age groups from childhood to adult and the peak incidence
early adults.[5] This case was diagnosed in a 35-year-old man. Jouvet et al[2] proposed a new prognostic grading grade I pineocytoma, grade IV pineoblastoma, and
grades II and III are for PPTID that lies between pineocytoma and pineoblastoma. The
grade II have less than 6 mitotic figures per 10 hpf, with positive immune labeling
for neurofilament and grade III being defined as having 6 or more mitotic figures
per 10 hpf or less than 6 mitotic figures but without immune staining for neurofilament.
In PPTIDs, the expression of neuronal markers is variable. Staining for synaptophysin
is mainly diffuse, cytoplasmic, and variable in intensity. Neurofilament protein expression
is variable. GFAP and S-100 protein staining are also positive. Chromogranin A can
be expressed with pseudo-stratified architecture.[9]
[10]
[14] Immunohistostaining is not significant to differentiate small and large cell-type
PPTIDs.[12]
We present the case report of large cell-type PPT grade III. This case should be discussed
as it is valuable because accurate diagnosis is mandatory for the further management.
Conclusion
Diagnosing PPTID can be difficult, and histopathologic findings are not pathognomonic.
Histopathology along with immune histochemistry must be done to diagnose and rule
out differential. As accurate grading is essential for such rare tumors for their
optimal therapeutic management and prognosis that depend on the histopathologic grading.
CSF analysis and spinal screening with clinical follow-up should be done because the
possibilities of dissemination. More study should be carried out on this tumor to
better interpret the nature of PPTID, especially large cell types as they are associated
with poor prognosis.
