101 research outputs found
Better see to better agree: Phosphohistone H3 (PHH3) increases inter-observer agreement in mitotic count for meningioma grading and imposes new specific thresholds
No full textBackground: Mitotic count on hematoxylin and eosin (H&E)-stained slides is a crucial diagnostic criterion in meningioma grading. However, mitosis assessment on H&E slides can be impaired by technical factors and by pathologist's experience. Phosphohistone H3 (PHH3) serine-10 is a mitosis-specific antibody that has proven to facilitate mitotic count in various tumors. Methods: A series of 70 meningiomas (15 grade I, 40 grade II, 15 grade III) was used to validate PHH3 intra- and interobserver reproducibility and to identify PHH3-specific mitotic thresholds. Four pathologists with different experience in neuropathology counted mitoses on both H&E- and PHH3-stained slides. Results: H&E and PHH3 mitotic rates were highly correlated (Pearson's r = 0.92, P <. 0001). PHH3 mitotic counts had both a good mean interobserver correlation (Rm = 0.83) and a good intraclass correlation (0.78), higher than H&E mitotic indices (Rm = 0.77, intraclass correlation = 0.71). After further stratification of ..
Epidermal growth factor receptor and caveolin-1 coexpression identifies adult supratentorial ependymomas with rapid unfavorable outcomes
No full textSupratentorial ependymomas account for a minority of intracranial ependymomas, which still have uncertain prognostic markers. Among them, epidermal growth factor receptor (EGFR) overexpression correlates with a poor prognosis. In glioblastoma cells, EGFR function has been reported to be regulated by its migration from cell membrane infoldings called caveolae and by its colo-calization with the caveolae-associated protein caveolin-1 (cav-1). Therefore, we decided to investigate cav-1 expression and coexpression with EGFR in a series of adult intracranial ependymomas. We analyzed 22 adult supratentorial ependymomas and compared tumor grades as determined by the WHO classification and patient survival rates with the expression of EGFR, cav-1, and p53 and the values of the proliferation marker Ki-67, all tested by immunohistochemistry; in addition, we investigated the mutational profile of cav-1. The results demonstrate that the tumor grade is directly correlated with EGFR, Ki-67, and cav-1 expression only, whereas (by univariate analysis) the expression of all the studied markers, as well as the tumor histological grade, significantly correlated with the patient's overall survival (OS). By multivariate analysis using the Cox proportional hazards model, among all variables considered, cav-1 was the only independent prognostic marker related to OS (relative risk = 13.92; P =.013). Among grade II epen-dymomas, only cav-1 correlated with poor OS (P =.011), distinguishing 2 distinct subgroups of tumors with different outcomes despite sharing identical grading. All the patients studied carried wild-type cav-1 sequences, demonstrating that cav-1 overexpression is not driven by activating mutations, as previously reported in other tumor types. Interestingly, after stratifying all cases into 4 distinct groups according to cav-1 and EGFR expression (cav-1+/EGFR+, cav-1+/EGFR+, cav-1+/EGFR+, and cav-1+/EGFR+), the coexpres-sion of cav-1 and EGFR identified a subset of patients with definitively poor prognoses. Further studies are needed to support this evidence on a larger scale and to clarify how cav-1 and EGFR interaction can influence tumor aggressiveness. © The Author(s) 2010
Epidermal growth factor receptor and caveolin-1 coexpression identifies adult supratentorial ependymomas with rapid unfavorable outcomes
No full textSupratentorial ependymomas account for a minority of intracranial ependymomas, which still have uncertain prognostic markers. Among them, epidermal growth factor receptor (EGFR) overexpression correlates with a poor prognosis. In glioblastoma cells, EGFR function has been reported to be regulated by its migration from cell membrane infoldings called caveolae and by its colocalization with the caveolae-associated protein caveolin-1 (cav-1). Therefore, we decided to investigate cav-1 expression and coexpression with EGFR in a series of adult intracranial ependymomas. We analyzed 22 adult supratentorial ependymomas and compared tumor grades as determined by the WHO classification and patient survival rates with the expression of EGFR, cav-1, and p53 and the values of the proliferation marker Ki-67, all tested by immunohistochemistry; in addition, we investigated the mutational profile of cav-1. The results demonstrate that the tumor grade is directly correlated with EGFR, Ki-67, and cav-1 expression only, whereas (by univariate analysis) the expression of all the studied markers, as well as the tumor histological grade, significantly correlated with the patient's overall survival (OS). By multivariate analysis using the Cox proportional hazards model, among all variables considered, cav-1 was the only independent prognostic marker related to OS (relative risk = 13.92; P = .013). Among grade II ependymomas, only cav-1 correlated with poor OS (P = .011), distinguishing 2 distinct subgroups of tumors with different outcomes despite sharing identical grading. All the patients studied carried wild-type cav-1 sequences, demonstrating that cav-1 overexpression is not driven by activating mutations, as previously reported in other tumor types. Interestingly, after stratifying all cases into 4 distinct groups according to cav-1 and EGFR expression (cav-1+/EGFR+, cav-1-/EGFR-, cav-1+/EGFR-, and cav-1-/EGFR+), the coexpression of cav-1 and EGFR identified a subset of patients with definitively poor prognoses. Further studies are needed to support this evidence on a larger scale and to clarify how cav-1 and EGFR interaction can influence tumor aggressiveness
Cancers of unknown primary origin: current perspectives and future therapeutic strategies
No full textAbstract It is widely accepted that systemic neoplastic spread is a late event in tumour progression. However, sometimes, rapidly invasive cancers are diagnosed because of appearance of metastatic lesions in absence of a clearly detectable primary mass. This kind of disease is referred to as cancer of unknown primary (CUP) origin and accounts for 3-5% of all cancer diagnosis. There is poor consensus on the extent of diagnostic and pathologic evaluations required for these enigmatic cases which still lack effective treatment. Although technology to predict the primary tumour site of origin is improving rapidly, the key issue is concerning the biology which drives early occult metastatic spreading. This review provides the state of the art about clinical and therapeutic management of this malignant syndrome; main interest is addressed to the most recent improvements in CUP molecular biology and pathology, which will lead to successful tailored therapeutic options.</p
Primary bladder phaeochromocytoma diagnosed by a vet
No full textBladder phaeochromocytomas are rare neuroendocrine neoplasms whose diagnosis can be missed in spite of their rather suggestive presentation. It is mandatory to collect a thorough medical history and to recognize their typical symptoms. This study reports the case of a woman, treated for hypertensive crisis, who was diagnosed with bladder phaeochromocytoma thanks to a vet noting her fainting after micturitio
Histology far away from Flatland: 3D roller-coasting into grade-dependent angiogenetic patterns in oligodendrogliomas
No full textIntrathoracic splenosis: A case report and an update of invasive and noninvasive diagnostic techniques
No full textIntrathoracic splenosis is a rare condition resulting from autotransplantation of splenic tissue into the left side of the chest, usually after diaphragmatic and splenic rupture after blunt or penetrating abdominal trauma. Patients are often free of symptoms, and nodules are usually discovered at computed tomographic scan. Owing to the rarity of the condition (30 cases in the literature so far), most patients undergo thoracotomy before final diagnosis. We present a case of thoracic splenosis that recently came to our attention
"Benign" metastatic meningioma: clinico-pathological analysis of one case metastasising to the lung and overview on the concepts of either primitive or metastatic meningiomas of the lung.
No full textLung '' metastases '' of benign meningiomas are rarely described events of biological and clinical interest. We, here, report of a 70-year-old healthy woman found by CT scan to have multiple lesions, the two largest in the right lung on routine examination. Anamnesis revealed that the patient underwent a surgical resection of cerebral meningioma 12 years before. The larger lung lesion was a 3-cm node located in the right lung and was removed by wedge resection. Macroscopically, it showed well-defined borders, whitish colour and firm consistency; histologically, it was uniformly composed by spindle meningothelial cells arranged in fascicules including psammoma bodies. The morphological and immunohistochemical features of this lesion, together with the similarity with the original cerebral tumour and its indolent evolution, led to a final diagnosis of '' benign '' meningioma metastatic to the lung. Lung metastatic meningiomas may be a diagnostic challenge because of their unusual site of presentation and the possible confusion with primitive lung meningiomas or primary mesenchymal lung lesions. They represent a typical example of '' benign '' tumours that may implant to the lung similar to other tumours, definitely considered benign but reported to rarely present unusual secondary localization
Intrathoracic splenosis: a case report and an update of invasive and noninvasive diagnostic techniques.
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Caveolin-1 expression is variably displayed in astroglial-derived tumors and absent in oligodendrogliomas: concrete premises for a new reliable diagnostic marker in gliomas.
No full textCaveolins are basic constituents of flask-shaped cell membrane microdomains (caveolae), which are involved in many cell functions, including signalling, trafficking, and cellular growth control. The distribution of caveolae within the normal brain and in brain tumors is controversial. In the present study, we describe the expression of caveolin-1 (cav-1) in 64 brain tumors of different grade, of either astroglial or oligodendroglial origin. All studied astrocitomas of any grade (from II to IV) were cav-1 positive, displaying staining patterns and intensity specifically associated to the different tumor grades. In all glioblastomas and gliosarcomas, cav-1 staining was extremely intense, typically localized at the cell membrane and recognized a variable percentage of cells, including the majority of spindle cells and palisade-oriented perinecrotic cells. In anaplastic astrocytomas, a less intense membrane staining or a cytoplasmic dotlike immunoreactivity were present, the latter being almost the exclusive pattern observed in diffuse astrocitomas grade II. In contrast to astroglial tumors, the striking totality of grade II oligodendrogliomas and the large majority of grade III were lacking cav-1 expression. Interestingly, a cav-1 distribution overlapping the pattern described in tissues was observed also in primary cell cultures of human glioblastomas and astrocytomas, and also in one established glioblastoma cell line (U251 MG), analyzed by means of confocal microscopy and flow cytometry. In conclusion, among astroglial tumors cav-1 expression varies in distribution, pattern, and intensity specifically according to tumor types and grades. The association between tumor progression and a more structured membranous pattern of cav-1 expression could suggest the hypothesis of a neoplastic shift towards a mesenchymal phenotype, whose behavioral and biologic significance worth further studies. Finally, the lack of cav-1 immunoreactivity in oligodendrogliomas suggests its concrete application as a useful diagnostic marker
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