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According to the Global Cancer Statistics 2020, colorectal cancer (CRC) represents the third most frequent malignancy worldwide, and is the second in terms of mortality [1]. Since the early 2000s, screening programs and the consequent early identification and removal of pre-cancerous lesions, together with the shift to a healthier lifestyle, have reduced the frequency of CRC cases in high-incidence areas [2,3]. Another mechanism of drug resistance may also be related to the therapy-induced selection of cancer stem cells, which represent tumor cells that are able to self-renew and to generate tumor cells harboring different genetic alterations [20]. [...]understanding their molecular features may be useful for developing therapeutic strategies that are able to target cancer stem cells and to overcome drug resistance. [...]although the knowledge of the mechanisms underlying the pathogenesis, progression, and metastasization of CRC has greatly expanded in recent decades, many aspects still remain to be clarified.

When they restricted the analysis to the 76 patients with primary, untreated tumors, only seven meningiomas had complete loss of H3K27me3 [3]. Among 2448 meningiomas operated in our institution between 2004 and 2020, 12 were anaplastic due to a mitotic index of ≥ 20 mitoses per 10 high power fields. Declarations Conflict of interest We have no conflict of interest to declare.

Atypical meningiomas are diagnosed in the presence of: (1) three or more of the following minor atypical criteria: increased cellularity, small cells with a high nuclear/cytoplasmic ratio, prominent nucleoli, sheeting, and foci of spontaneous or geographic necrosis; (2) mitotic count ≥ 4 mitoses per 10 HPF (high mitotic index); (3) brain invasion. The 5-year disease-free survival (DFS) is around 50%. Due to their heterogeneous behavior, the post-surgical treatment of atypical meningiomas is controversial. This study investigated the ability of histopathological features to predict recurrence risk of atypical meningiomas. Meningiomas classified as atypical only on minor atypical criteria had low recurrence risk. Brain invasion, high mitotic index and sheeting were significantly associated with shorter disease-free survival (DFS) ( P  = 0.001; P  = 0.01; P  = 0.01). The presence of brain invasion and the co-presence of sheeting and high mitotic index had the highest ability to identify recurring meningiomas ( P  = 0.0001) (sensitivity: 90.9%; specificity: 86.7%). Our results suggest reconsideration of classification of meningiomas as atypical based only on minor atypical criteria. The presence of brain invasion and the co-occurrence of sheeting and high mitotic count may be useful to identify high risk cases, which may benefit from adjuvant treatments.

Neoangiogenesis has been correlated to biological aggressiveness and an adverse clinical course of several neoplasias. Its prognostic role in meningiomas appears to be controversial. Nonetheless, if adequately quantified with specific markers and appropriate scoring methods, angiogenesis seems to be significantly associated with a high growth fraction, development of recurrences and shorter overall survival of meningiomas. As a consequence, neoangiogenesis may represent a target for therapies aimed at reducing the growth of inoperable meningiomas or recurrence risk of totally resected tumors. Even more significantly, the identification of the factors that mediate angiogenesis in meningiomas could help us to determine appropriate novel anti-angiogenic therapies for these tumors. Herein the methods for quantification of angiogenesis as well as its regulating factors in meningiomas are reviewed.

Reactive oxygen species (ROS) represent reactive products belonging to the partial reduction of oxygen. It has been reported that ROS are involved in different signaling pathways to control cellular stability. Under normal conditions, the correct function of redox systems leads to the prevention of cell oxidative damage. When ROS exceed the antioxidant defense system, cellular stress occurs. The cellular redox impairment is strictly related to tumorigenesis. Tumor cells, through the generation of hydrogen peroxide, tend to the alteration of cell cycle phases and, finally to cancer progression. In adults, the most common form of primary malignant brain tumors is represented by gliomas. The gliomagenesis is characterized by numerous molecular processes all characterized by an altered production of growth factor receptors. The difficulty to treat brain cancer depends on several biological mechanisms such as failure of drug delivery through the blood-brain barrier, tumor response to chemotherapy, and intrinsic resistance of tumor cells. Understanding the mechanisms of ROS action could allow the formulation of new therapeutic protocols to treat brain gliomas.

Tumor budding is a long-established independent adverse prognostic marker in colorectal cancer, yet methods for its assessment have varied widely. In an effort to standardize its reporting, a group of experts met in Bern, Switzerland, in 2016 to reach consensus on a single, international, evidence-based method for tumor budding assessment and reporting (International Tumor Budding Consensus Conference [ITBCC]). Tumor budding assessment using the ITBCC criteria has been validated in large cohorts of cancer patients and incorporated into several international colorectal cancer pathology and clinical guidelines. With the wider reporting of tumor budding, new issues have emerged that require further clarification. To better inform researchers and health-care professionals on these issues, an international group of experts in gastrointestinal pathology participated in a modified Delphi process to generate consensus and highlight areas requiring further research. This effort serves to re-affirm the importance of tumor budding in colorectal cancer and support its continued use in routine clinical practice.

Müllerianosis was first described as a rare entity consisting of an admixture of cervical, tubaric, or endometrial epithelium within the lamina propria and muscularis propria of the urinary bladder. This lesion occurs mainly in the dome or posterior wall of the urinary bladder in women of fertile age. Its clinical presentation is characterized by hematuria, pelvic pain, and dysuria, nonspecific symptoms that are related to the responsiveness of müllerian glands to hormonal stimuli. The major interest of müllerianosis resides in its similarity, from clinical, cytologic, and histologic viewpoints, to more threatening conditions, such as neoplasias. The clinical context and the identification of periglandular endometrial stroma at histologic examination with conventional hematoxylin-eosin stain, as well as the immunohistochemical demonstration of estrogen and progesterone receptors in the glands, are of diagnostic utility in the differential diagnosis. Müllerianosis may be responsive to gonadotropin-releasing hormone agonists. Surgical resection may be justified in the case of clinical symptoms refractory to hormone therapy.

The fifth edition of the World Health Organization (WHO) classification of central nervous system (CNS) tumors introduced the new tumor type CNS tumor with BCOR internal tandem duplication (ITD), characterized by a distinct DNA methylation profile and peculiar histopathological features, including a circumscribed growth pattern, ependymoma-like perivascular pseudorosettes, microcystic pattern, absent or focal GFAP immunostaining, OLIG2 positivity, and BCOR immunoreactivity. We describe a rare case of a CNS tumor in a 45-year-old man with histopathological and immunohistochemical features overlapping the CNS tumor with BCOR internal tandem duplication (ITD) but lacking BCOR immunostaining and BCOR ITD. Instead, the tumor showed CREBBP::BCORL1 fusion and pathogenic mutations in BCOR and CREBBP , along with a DNA methylation profile matching the “CNS tumor with EP300:BCOR(L1) fusion” methylation class. Two CNS tumors with fusions between CREBBP , or its paralog EP300 , and BCORL1 , and approximately twenty CNS tumors with CREBBP/EP300::BCOR fusions have been reported to date. They exhibited similar ependymoma-like features or a microcystic pattern, along with focal or absent GFAP immunostaining, and shared the same DNA methylation profile. Given their morphological and epigenetic similarities, circumscribed CNS tumors with EP300/CREBBP::BCOR(L1 ) fusions and CNS tumors with BCOR ITD may represent variants of the same tumor type. The ependymoma-like aspect coupled with the lack of diffuse GFAP immunostaining and the presence of OLIG2 positivity are useful clues for recognizing these tumors in histopathological practice. The diagnosis should be confirmed after testing for BCOR(L1) gene fusions and BCOR ITD.

Abstract The use of adjuvant radiotherapy is controversial in patients with atypical meningiomas treated with gross total resection (GTR). This study aimed to determine whether clinico-pathological features could be helpful to predict the recurrence risk in this group of patients and to identify high-risk ones who could benefit from adjuvant treatment. We collected 200 patients with primary atypical meningiomas treated with GTR but with no adjuvant radiotherapy from 5 different centers. A risk score, formulated by assigning 1 point for the presence and 0 points for the absence of 5 high-risk parameters (male sex, parasagittal site, Simpson grade 3, mitotic index ≥ 6/10 HPF, and sheeting), was the most significant predictor of recurrence. A score ≥2 was associated with 4.7 risk of shorter disease-free survival (p < 0.0001). Our findings indicate that the presence of at least 2 clinico-pathological high-risk factors predicts recurrence of totally resected primary atypical meningiomas and could be helpful for identifying patients who could benefit from adjuvant radiotherapy.

Oligodendroglioma is defined by IDH mutation and 1p/19q codeletion. The latter is mutually exclusive to ATRX immunohistochemical loss and has been recently associated with the loss of H3K27me3 immunostaining. We aimed to assess the diagnostic and prognostic value of H3K27me3 immuno-expression in diffuse gliomas with oligodendroglial or mixed oligoastrocytic morphology. H3K27me3 immunostaining was performed in 69 diffuse gliomas with oligodendroglial (n = 62) or oligoastrocytic (n = 7) morphology. The integration with routinely assessed IDH mutations, ATRX immunostaining, and 1p/19q codeletion classified these cases as 60 oligodendroglial and 9 astrocytic. H3K27me3 was lost in 58/60 oligodendrogliomas with retained (n = 47) or non-conclusive (n = 11) ATRX staining, 3/6 IDH-mutant astrocytomas with ATRX loss, and 3/3 IDH-wt astrocytomas. H3K27me3 was retained in 2/60 oligodendrogliomas with retained ATRX, and in 3/6 IDH-mutant astrocytomas, two of which had lost and one retained ATRX. The combination of H3K27me3 and ATRX immunostainings with IDH mutational status correctly classified 55/69 (80%) cases. In IDH-mutant gliomas, ATRX loss indicates astrocytic phenotype, while ATRX retention and H3K27me3 loss identify oligodendroglial phenotype. Only 14 (20%) IDH-mutant cases with retained ATRX and H3K27me3 or inconclusive ATRX immunostaining would have requested 1p/19q codeletion testing to be classified. Furthermore, H3K27me3 retention was associated with significantly shorter relapse-free survival (P < 0.0001), independently from IDH mutation or 1p/19q codeletion (P < 0.005). Our data suggest that adding H3K27me3 immunostaining to the diagnostic workflow of diffuse gliomas with oligodendroglial or mixed morphology is useful for drastically reducing the number of cases requiring 1p/19q codeletion testing and providing relevant prognostic information.