Cortical Microhemorrhage Presentation of Small Vessel Primary Angiitis of the Central Nervous System.

OBJECTIVE: Primary angiitis of the central nervous system (PACNS) is a rare vasculitis restricted to the brain, spinal cord, and leptomeninges. This study aimed to describe the imaging characteristics of patients with small vessel PACNS (SV-PACNS) using 7 T magnetic resonance imaging (MRI). METHODS: This ongoing prospective observational cohort study included patients who met the Calabrese and Mallek criteria and underwent 7 T MRI scan. The MRI protocol includes T1-weighted magnetization-prepared rapid gradient echo imaging, T2 star weighted imaging, and susceptibility-weighted imaging. Two experienced readers independently reviewed the neuroimages. Clinical data were extracted from the electronic patient records. The findings were then applied to a cohort of patients with large vessel central nervous system (CNS) vasculitis. RESULTS: We included 21 patients with SV-PACNS from December 2021 to November 2023. Of these, 12 (57.14%) had cerebral cortical microhemorrhages with atrophy. The pattern with microhemorrhages was described in detail based on the gradient echo sequence, leading to the identification of what we have termed the "coral-like sign." The onset age of patients with coral-like sign (33.83 ± 9.93 years) appeared younger than that of patients without coral-like sign (42.11 ± 14.18 years) (P = 0.131). Furthermore, the cerebral lesions in patients with cortical microhemorrhagic SV-PACNS showed greater propensity toward bilateral lesions (P = 0.03). The coral-like sign was not observed in patients with large vessel CNS vasculitis. INTERPRETATION: The key characteristics of the coral-like sign represent cerebral cortical diffuse microhemorrhages with atrophy, which may be an important MRI pattern of SV-PACNS. ANN NEUROL 2024;96:194-203.

Is brain invasion sufficient as a stand-alone criterion for grading atypical meningioma?

OBJECTIVE: Despite the controversy surrounding brain invasion (BI) as the sole indicator used to diagnose atypical meningioma, this criterion was still incorporated in the 2021 WHO classification scheme. In this study, the authors investigated the reproducibility of this prognostic effect and the impact of BI on the prognosis in otherwise benign meningioma (benign meningioma with BI). METHODS: Patients (n = 1006) with a pathological diagnosis of benign or atypical meningioma according to the latest WHO classification criteria were enrolled in this study. In patients with atypical meningioma, the cases were further categorized as benign meningioma with BI and classical atypical meningioma. Clinical, pathological, and follow-up data were collected. Kaplan-Meier curves were compared with a log-rank test, and univariate and multivariate analyses were performed. RESULTS: The study patient cohort included 282 (28.0%) individuals who were pathologically confirmed as having BI among all 1006 patients with benign or atypical meningioma. A significant difference in recurrence-free survival was observed between patients who had benign meningioma with BI and those who had classical atypical meningioma (p < 0.001), as well as between patients with benign meningiomas and those without BI (p = 0.003). Multivariate Cox analysis indicated that BI was independently associated with increased risk of relapse in the entire population (HR 1.46, 95% CI 1.01-2.12, p = 0.049) and in the atypical meningioma subcohort (HR 2.21, 95% CI 1.32-3.71, p = 0.003), as well as the benign meningioma with and without BI subcohorts (HR 1.89, 95% CI 1.01-3.56, p = 0.049). Moreover, patients with classical atypical meningiomas had a risk of relapse four times higher than those who had benign meningioma with BI (p < 0.001). CONCLUSIONS: The findings demonstrate that benign meningioma with BI typically has an intermediate prognosis and can be differentiated from benign meningioma and classical atypical meningioma, which suggests that the importance of the diagnostic effect of BI is insufficiently accounted for in grading of atypical meningioma. Increased emphasis on the presence of BI in patients with atypical meningioma may be helpful in postsurgical decision-making and facilitating improvements in individual therapy.

Cellular senescence: a promising therapeutic target in colorectal cancer.

Colorectal cancer is one of the most malignant cancers worldwide, and efforts have been made to elucidate the mechanism of colorectal carcinogenesis. Cellular senescence is a physiological process in cell life, but it is also found in cancer initiation and progression. Lines of evidence show that senescence may influence the development and progression of colorectal carcinogenesis. Here, the authors review the characteristics of senescence and the recent findings of a relationship between senescence and colorectal cancer.

Cancer is a leading cause of death worldwide; out of the top ten most common cancers in 2020, the incidence and mortality rate of colorectal cancer (CRC) ranked third and second, respectively. Based on statistics, it was estimated that more than 1.9 million CRC cases occurred in 2020. In terms of CRC, a prominent risk factor is age, and studies suggest that the aging process plays a role in CRC initiation and progression. This review discusses how aging contributes to CRC carcinogenesis and summarizes recent findings on potential therapeutics.

Prognostic significance of locally invaded sites and tissue types in patients with nasal extranodal natural-killer/T-cell lymphoma: a single-center retrospective analysis.

BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. The International Prognostic Index is reported to be prognostically meaningful for ENKTL, but lacks discriminatory power for stage I/II ENKTL with extensive local invasion. This study aimed to evaluate the prognostic effects of local invasion by site and tissue type in patients with ENKTL. METHODS: We retrospectively analyzed data of 86 patients who were diagnosed with ENKTL by the Department of Pathology of Beijing Tongren Hospital from June 2002 to April 2016, and ascertained tumor infiltration of adjacent structures (AS), bone, and soft tissue for each patient, using physical findings and imaging scans. We used univariate and multivariate analysis to assess the association of each involved tissue or site with patients' overall survival (OS). RESULTS: Of the 86 patients, 71 (82.6%) experienced invasion of AS, 22 (25.6%) of soft tissue, and 26 (30.2%) had bone involvement. Overall, patients with AS involvement did not show significantly shorter survival than those without AS involvement (Log rank χ = 1.177, P = 0.278); however, patients who had involved eyeballs or brains showed significantly lower 2-year OS rates than those without eyeball involvement (Log rank χ = 4.105, P = 0.043) or brain involvement (Log rank χ = 7.126, P = 0.008). Patients with involved local soft tissue or bones, respectively, showed lower 2-year OS rates than those without involved local soft tissue (Log rank χ = 10.390, P = 0.001) or bones (Log rank χ = 8.993, P = 0.003). Multivariate analysis showed that involvement of the cheek or facial muscles (hazard ratio, HR = 5.471, 95% confidence interval [CI]: 1.466-20.416, P = 0.011) and the maxilla bone (HR = 6.120, 95% CI: 1.517-24.694, P = 0.011) were significantly independent predictors of lower 2-year OS rates. CONCLUSIONS: Imaging can accurately detect ENKTL invasion of AS, soft tissue, and bone. Involvement of local soft tissue or bone was significantly associated with lower 2-year OS rates. Involvements of the cheek or facial muscle, as well as maxilla bone, are independent predictors of lower 2-year OS rates in ENKTL patients.

Inflammatory myofibroblastic tumors of the nasal cavity and paranasal sinus: a clinicopathologic study of 25 cases and review of the literature.

Inflammatory myofibroblastic tumor (IMT) is rare in nasal cavity and paranasal sinus. The aim of this study was to describe the clinicopathological features of sinonasal IMT and analyze the relationship between the clinicopathological features and the prognosis. A retrospective study of 25 IMT patients between 2001 and 2012 was performed. Data on clinical features, treatment, and follow-up were recorded. The histological characters were observed. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan-Meier method. Clinically, the most common symptoms were nasal obstruction, facial pain, and toothache. Twenty patients received follow-ups 6-120 months after initial diagnosis. Fifteen (75 %) developed recurrence 1 or more times. One patient had left cervical lymph node metastasis (5 %). Five patients died of the tumor (25 %). Histologically, the IMTs composed of bland spindle cells admixed with a prominent infiltrate of plasma cells and lymphocytes and showed obvious atypia in recurrent cases. Histology with necrosis, mitosis (≥1/10 HPF), ganglion-like cells, histological pattern I or II and relapse (≥4 times) was significantly associated with poor OS and EFS. IMT of the nasal cavity and paranasal sinuses exhibits relatively bland histologic appearances, but can shows strongly aggressive behavior and relatively poor outcomes. Multiple relapse, necrosis, frequent mitosis, the presence of ganglion-like cells, and histological pattern might be associated with poor clinical outcomes.

Recurrent laryngeal inflammatory myofibroblastic tumor with positive anaplastic lymphoma kinase mimicking recurrent respiratory papillomatosis: a case report.

Inflammatory myofibroblastic tumor (IMT) of the larynx is an unusual lesion, particularly in the pediatric age group. Laryngeal IMTs in children follow a benign clinical course with reports of only rare recurrences and no metastases. Although anaplastic lymphoma kinase (ALK) has been associated with IMTs, there is only one pediatric laryngeal IMT reported to be ALK-positive with immunohistochemical staining. Here, we present a case of a 10-year-old boy with a laryngeal IMT that recurred four times and was misdiagnosed as recurrent respiratory papillomatosis after the initial three operations. ALK positivity was demonstrated by both immunohistochemical staining and fluorescence in situ hybridization. To the best of our knowledge, this case report is the first to describe a laryngeal IMT that recurred multiple times and was confirmed to be ALK-positive at the molecular level.

[A clinical study of chromosome translocations in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in Chinese patients].

OBJECTIVE: To investigate the genetic aberrations in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphomas from different sites of the body in Chinese patients. METHODS: Two hundred and seventeen paraffin-embedded MALT lymphoma specimens from 11 major sites were studied with interphase fluorescence in situ hybridization (FISH) to detect t (11; 18) (q21; q21)/API2-MALT1, t (1; 14) (p22; q32)/IGH-BCL10, (14; 18) (q32; q21)/IGH-MALT1 and BCL6 gene involved chromosome translocations. RESULTS: These translocations were mutually exclusive and detected in 21% (46/217) of the cases, including t (11; 18) (q21; q21) API2-MALT1 13% (29/217), t (1; 14) (p22; q32) IGH-BCL10 in 1% (3/217), t (14; 18) (q32; q21) IGH-MALT1 1% (2/217), BCL6 involved translocation in 2% (4/217) and IGH-unknown translocation partner in 4% (8/217). t (11; 18) (q21; q21) API2-MALT1 was found with the highest frequency in MALT lymphoma from lungs (47%, 8/17) and small intestine (29%, 4/14), followed by salivary gland (17%, 1/6), stomach (14%, 12/84) and ocular adnexae (6%, 4/68). t (1; 14) (p22; q32) was only detected in lungs (12%, 2/17) and stomach (1%, 1/84). t (14; 18) (q32; q21) was mainly detected in lungs (6%, 1/17) and ocular adnexae (2%, 1/68). BCL6 gene involved translocation was detected in salivary gland (17%, 1/6) and stomach (4%, 3/84). CONCLUSIONS: It is demonstrated that the four translocations occur with markedly variable frequencies in MALT lymphoma of different sites in Chinese patients. The distributions of these chromosome translocations in Chinese patients are slightly different from those reported in western patients.

[Primary ocular adnexal lymphoproliferative lesions: clinicopathologic features and genetic alterations].

OBJECTIVE: To investigate clinicopathological and genetic characteristics of primary ocular adnexal lymphoproliferative lesions. METHODS: Clinical, morphological and immunohistochemical features of 37 archival cases of primary ocular adnexal lymphoproliferative lesions were studied including 5 cases of reactive lymphoid hyperplasia and 32 lymphomas retrospectively. Classification of the lymphomas were made according to the WHO classification of tumors of haematopoietic and lymphoid tissues. All cases were studied by interphase fluorescence in situ hybridization (FISH) using dual color break apart probes of IgH, MALT1, bcl-6, c-Myc, bcl-2, CCND1, bcl-10, and FOXP1 for detection of chromosomal aberrations involving IgH, MALT1, bcl-6, c-Myc, bcl-2, cyclinD1, bcl-10 and FOXP1 genes, respectively. FISH with IgH / bcl-2 dual color dual fusion probe was used for detection of t(14;18)(q32;q21)/IgH-bcl-2. CEP18 spectrum orange probe was used for detection of aneuploidy of the chromosome 18. RESULTS: Among 32 cases of lymphomas, 28 cases (87.5%) were extranodal marginal zone B-cell lymphomas of mucosa associated lymphoid tissue (MALT lymphoma), 2 cases were follicular lymphoma (FL) and 2 cases diffuse large B cell lymphoma (DLBCL). Among the 28 cases of MALT lymphoma, chromosomal aberrations were found in 60.7% (17/28) by interphase FISH analysis. One case showed positive IgH break-apart signal with unknown partner. 16 cases showed three copies of different genes, of which, three copies of MALT1, bcl-6, and c-Myc were identified in 7 cases (25%), 12 cases (43%), and 2 cases (8%) of MALT lymphomas, respectively. In addition, 5 cases showed two genes including three copies of bcl-6 and MALT1 in 4 cases, and three copies of bcl-6 together with c-Myc in one case. Furthermore, all cases with three copies of MALT1 had trisomy 18. t(14;18)(q32;q21) was detected in both follicular lymphomas. Of the 2 DLBCL cases, one showed three copies of bcl-6 together with trisomy 18 and the other one showed three copies of bcl-6 together with IgH and c-Myc rearrangements. Chromosomal aberration was not found in all 5 cases of reactive lymphoid hyperplasia. CONCLUSIONS: The most common entity of primary ocular adnexal lymphomas is MALT lymphoma and FISH is helpful for their differential diagnosis and classification. Trisomy 18 and three copies of bcl-6 are common chromosomal aberrations in primary ocular adnexal MALT lymphomas.