PLAGIARISM SCAN REPORT

Date 2020-06-04

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Introduction: Pilocystic astrocytoma is a brain tumor that occurs more in children and young adults. They usually araise from the
cerebelum,near the brainstem in the hypothalamic region. These tumors are usually slow growing and benign. Definition of Pilocytic
astrocytoma Pilocytic astrocytoma, the most common childhood brain tumor, is typically associated with mitogen-activated protein kinase
(MAPK) pathway alterations. Surgically inaccessible midline tumors are therapeutically challenging, showing sustained tendency for
progression and often becoming a chronic disease with substantial morbidities. accounting for ~20% of all pediatric brain tumors. Tumor
locations in our cohort reflect the fact that pilocytic astrocytomas occur throughout the CNS, with about half arising outside the cerebellum.
Extra-cerebellar tumors are often surgically inaccessible, leading to a chronic disease with multiple recurrences, visual and neurological
impairment, and/or side-effects of therapy. Histopatholgy of Pilocytic astrocy toma Health Organization (WHO) as grade I neoplasms, which
typically have an excellent prognosis. In this regard, tumors amenable to gross total resection (GTR) are considered "cured”, with low risk of
tumor recurrence following resc-tion. However, PAs arising in the optic pathway,brainstem, and diencephalon are not usually amenable to
GTR. Surgery for tumors in these regions is typically sub-total in order to avoid complications, such as visual Weld loss, third nerve palsy,
endocrine deWcits, hypothalamic obesity, and death. In these situations where GTR is not possible, there is signiWcant variability in the
behavior of PAs. The diYculty in predicting clinical outcome for such patients underscores the need for prog-nostic genetic or histopathologic
biomarkers. To identify histopathologic features associated with tumor recurrence, we performed detailed clinical, routine pathologic, and
immunohistochemical analyses on a series of PAs from 107 patients where the clinical course was known. To our knowledge, this is one of
the largest series examining the clinical signiWcance of these variables in PAs. In this report, we speciWcally found that the presence of
necrosis, oligodendroglioma-like cytology, vascular hya- linization, and calciWcation were each associated with reduced event-free survival
(EFS). In addition, the increase of CD68+ cells showed a trend towards worse EFS. This intriguing Wnding suggests that elements of the
tumor envi-ronment, such as actively proliferating monocytic or microglial cells may contribute to tumor growth in this oth- erwise benign
neoplasm. In addition to standard histologic review, the maximal number of mitoses per ten consecutive high powered fields (HPF) was
determined on a careful search of all available slides, and the MIB-1 (Ki-67) proliferative labeling index (LI) was calculated for each specimen.
The latter was calculated as a maximal labeling index (percentage) by counting the fraction of immunopositive nuclei among 500–1000 non-
endothelial cells (1–3 HPF) within “hot spots” identified on low-magnification scanning. High proliferative indices were defined as >1 mitosis/10
HPF or >0.5% MIB-1 LI . Slides were also specifically examined for the presence or absence of biphasic pattern, microcyst formation,
Rosenthal fibers, eosinophilic granular bodies, oligodendroglioma-like cytology, vascular hyalinization, chronic inflammation,
microcalcifications, hemorrhage, microvascular proliferation (e.g., glomeruloid vessels with multiple lumens and endothelial prominence),
necrosis, leptomeningeal invasion, and perivascular pseudorosettes such as those seen more extensively in pilomyxoid astrocytomas. Who
grading? Pilocytic astrocytomas WHO grade I (PA I) and diffuse astrocytomas WHO grade II (A II) exhibit characteristic morphological
features allowing to distinguish these tumors in most instances .While, PA I usually are of low cellularity and are characterized by elongated or
bipolar tumor cells accompanied by Rosenthal fibers and a typical vascular pattern with hyalinized and sometimes glomeruloid vessels, A II
mostly present with uniform and moderately dense astrocytic cells in a loosely structured often microcystic stroma with inconspicuous vessels.
However, morphological variety and limited material at examination could result in major difficulties to distinguish PA I from A II. For example,
rare variants of PA I such as the so-called diffuse pilocytic astrocytoma of the cerebellum mimicking the histology of A II are difficult to discern
on morphological grounds only. Another frequent obstacle for straightforward diagnosis is small sample size due to tumor localization in
sensitive areas or due to techniques such as stereotactic biopsy. In such cases, additional tumor specific markers besides histological
features would greatly assist diagnosis. Mutations in the gene encoding human cytosolic NADP+ dependent isocitrate dehydrogenase (IDH1)
recently have been reported to be very frequent, approaching 70–80% in A II, while being rare in PA I. On the other hand, novel findings
established a DNA copy number gain at chromosomal band 7q34 including the human v-raf murine sarcoma viral oncogene homolog B1 gene
(BRAF) as a typical lesion for PA I, seen in approximately 70%, but much less frequent in A II Recent studies have found that copy number
gain at 7q34 is due to a tandem duplication resulting in fusion of BRAF and KIAA1549 genes, which lacks the auto-inhibitory domain of wild
type BRAF . This event results in activation of the ERK/MAPK pathway and promotes G2/M transition in the cell cycle . Gross features In
1953, a 9 y.o. boy was examined at our institution because of headaches, nausea, vomiting and ataxia. A pneumoventriculography revealed a
subtentorial space occupying mass, which was surgically explored. During surgery a large cystic cavity was disclosed in the midline, with a
solid mural nodule clinging to the lateral wall. Ac-cording to the surgeon's opinion, the solid nodule was entirely re-moved. The cystic wall had
the aspect of normal cerebellar cortexand was not removed. Surgical samples were processed for light mi-croscopy. Bouin ®xative was used
immediatly after surgical removal.4mm para½n embedded sections were stained with haematein-phloxin-saphran, Masson's trichrome and
PAS. Immunohisto-chemical test (anti-GFAP) was performed 45 years later. Histo-logical examination was characterized by two patterns: a
loosely knittissue and a more compact one. The former was composed of stellate astrocytic cells, GFAP-positive, in areas ®lled with
mucinous back-ground; the latter contained piloid elements with Rosenthal ®bersand brightly eosinophilic granular bodies. Nuclear
polymorphism was common, concolusion pilocystic astrocytomas are the most common pediatric brain tumors in our population. Complete
resection is the best treatment option but some tumors are aggrassive and recurrence.

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