Medulloblastoma (MB) is the most common malignant primary intracranial neoplasm diagnosed in childhood. Although numerous efforts have been made during the past few years to exploit novel targeted ...therapies for this aggressive neoplasm, there still exist substantial hitches hindering successful management of MB. Lately, progress in cancer biology has shown evidence that a subpopulation of cells within the tumour, namely cancer stem cells (CSCs), are thought to be responsible for the resistance to most chemotherapeutic agents and radiation therapy, accounting for cancer recurrence. Hence, it is crucial to identify the molecular signatures and genetic aberrations that characterise those CSCs and develop therapies that specifically target them. In this review, we aim to give an overview of the main genetic and molecular cues that depict MB-CSCs and provide a synopsis of the novel therapeutic approaches that specifically target this population of cells to attain enhanced antitumorous effects and therefore overcome resistance to therapy.
IMPORTANCE: Giant cell arteritis (GCA) is the most common systemic vasculitis in elderly individuals. Diagnosis is confirmed by temporal artery (TA) biopsy, although biopsy results are often ...negative. Despite the use of corticosteroids, disease may progress. Identification of causal agents will improve outcomes. Biopsy-positive GCA is associated with TA infection by varicella-zoster virus (VZV). OBJECTIVE: To analyze VZV infection in TAs of patients with clinically suspected GCA whose TAs were histopathologically negative and in normal TAs removed post mortem from age-matched individuals. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study for VZV antigen was performed from January 2013 to March 2015 using archived, deidentified, formalin-fixed, paraffin-embedded GCA-negative, GCA-positive, and normal TAs (50 sections/TA) collected during the past 30 years. Regions adjacent to those containing VZV were examined by hematoxylin-eosin staining. Immunohistochemistry identified inflammatory cells and cell types around nerve bundles containing VZV. A combination of 17 tertiary referral centers and private practices worldwide contributed archived TAs from individuals older than 50 years. MAIN OUTCOMES AND MEASURES: Presence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers. RESULTS: Varicella-zoster virus antigen was found in 45 of 70 GCA-negative TAs (64%), compared with 11 of 49 normal TAs (22%) (relative risk RR = 2.86; 95% CI, 1.75-5.31; P < .001). Extension of our earlier study revealed VZV antigen in 68 of 93 GCA-positive TAs (73%), compared with 11 of 49 normal TAs (22%) (RR = 3.26; 95% CI, 2.03-5.98; P < .001). Compared with normal TAs, VZV antigen was more likely to be present in the adventitia of both GCA-negative TAs (RR = 2.43; 95% CI, 1.82-3.41; P < .001) and GCA-positive TAs (RR = 2.03; 95% CI, 1.52-2.86; P < .001). Varicella-zoster virus antigen was frequently found in perineurial cells expressing claudin-1 around nerve bundles. Of 45 GCA-negative participants whose TAs contained VZV antigen, 1 had histopathological features characteristic of GCA, and 16 (36%) showed adventitial inflammation adjacent to viral antigen; no inflammation was seen in normal TAs. CONCLUSIONS AND RELEVANCE: In patients with clinically suspected GCA, prevalence of VZV in their TAs is similar independent of whether biopsy results are negative or positive pathologically. Antiviral treatment may confer additional benefit to patients with biopsy-negative GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.
OBJECTIVE:Varicella-zoster virus (VZV) infection may trigger the inflammatory cascade that characterizes giant cell arteritis (GCA).
METHODS:Formalin-fixed, paraffin-embedded GCA-positive temporal ...artery (TA) biopsies (50 sections/TA) including adjacent skeletal muscle and normal TAs obtained postmortem from subjects >50 years of age were examined by immunohistochemistry for presence and distribution of VZV antigen and by ultrastructural examination for virions. Adjacent regions were examined by hematoxylin & eosin staining. VZV antigen–positive slides were analyzed by PCR for VZV DNA.
RESULTS:VZV antigen was found in 61/82 (74%) GCA-positive TAs compared with 1/13 (8%) normal TAs (p < 0.0001, relative risk 9.67, 95% confidence interval 1.46, 63.69). Most GCA-positive TAs contained viral antigen in skip areas. VZV antigen was present mostly in adventitia, followed by media and intima. VZV antigen was found in 12/32 (38%) skeletal muscles adjacent to VZV antigen–positive TAs. Despite formalin fixation, VZV DNA was detected in 18/45 (40%) GCA-positive VZV antigen–positive TAs, in 6/10 (60%) VZV antigen–positive skeletal muscles, and in one VZV antigen–positive normal TA. Varicella-zoster virions were found in a GCA-positive TA. In sections adjacent to those containing VZV, GCA pathology was seen in 89% of GCA-positive TAs but in none of 18 adjacent sections from normal TAs.
CONCLUSIONS:Most GCA-positive TAs contained VZV in skip areas that correlated with adjacent GCA pathology, supporting the hypothesis that VZV triggers GCA immunopathology. Antiviral treatment may confer additional benefit to patients with GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.
Dermatopathic lymphadenopathy is a distinctive form of paracortical lymph node hyperplasia that usually occurs in the setting of chronic dermatologic disorders. The aim of this study is to update our ...understanding of the clinicopathologic and immunophenotypic features of dermatopathic lymphadenopathy. The study cohort was 50 lymph node samples from 42 patients diagnosed with dermatopathic lymphadenopathy. The patients included 29 women and 13 men with a median age of 49 years (range, 12-79). Twenty-two (52%) patients had a dermatologic disorder, including mycosis fungoides (n = 6), chronic inflammatory dermatoses (n = 13), melanoma (n = 1), squamous cell carcinoma (n = 1), and Kaposi sarcoma in the context of human immunodeficiency virus infection (n = 1). Twenty (48%) patients did not have dermatologic manifestations. Lymph node biopsy specimens were axillary (n = 22), inguinal (n = 21), cervical (n = 4), and intramammary (n = 3). All lymph nodes showed paracortical areas expanded by lymphocytes; dendritic cells, including interdigitating dendritic cells and Langerhans cells; and macrophages. Melanophages were detected in 48 (98%) lymph nodes. Immunohistochemical analysis provided results that are somewhat different from those previously reported in the literature. In the paracortical areas of lymph node, S100 protein was expressed in virtually all dendritic cells, and CD1a was expressed in a significantly greater percentage of cells than langerin (80 vs. 35%, p < 0.0001). These results suggest that the paracortical regions of dermatopathic lymphadenopathy harbor at least three immunophenotypic subsets of dendritic cells: Langerhans cells (S100
, CD1a
, langerin
), interdigitating dendritic cells (S100
, CD1a
, langerin
), and a third (S100
, CD1a
, langerin
) minor population of dendritic cells. Furthermore, in more than 60% of dermatopathic lymph nodes, langerin highlighted trabecular and medullary sinuses and cords, showing a linear and reticular staining pattern, which could be a pitfall in the differential diagnosis with Langerhans cell histiocytosis involving lymph nodes.
: Tracheal agenesis/atresia (TA) presents with respiratory distress at birth and subsequent difficulty in endotracheal intubation. The antenatal course is complicated by polyhydramnios and premature ...labor.
: We present a newborn baby boy with respiratory distress and unsuccessful intubation. Postmortem neck dissection revealed tracheal atresia with esophageal atresia and high tracheoesophageal fistula.
: In this variant of tracheal atresia, the coexistent esophageal atresia precluded the establishment of a functional air passage. This variant that does not fall into the any of the described categories in accepted classification systems. The lack of any distal communication makes this case inoperable and fatal.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
6.
Low-Grade Ductal Carcinoma In Situ Alghamdi, Sarah A; Krishnamurthy, Kritika; Garces Narvaez, Sofia A ...
American journal of clinical pathology,
02/2020, Letnik:
153, Številka:
3
Journal Article
Recenzirano
Abstract
Objectives
We aimed to determine the interobserver reproducibility in diagnosing low-grade ductal carcinoma in situ (DCIS). We also aimed to compare the interobserver variability using a ...proposed two-tiered grading system as opposed to the current three-tiered system.
Methods
Three expert breast pathologists and one junior pathologist identified low-grade DCIS from a set of 300 DCIS slides. Months later, participants were asked to grade the 300 cases using the standard three-tiered system.
Results
Using the two-tiered system, interobserver agreement among breast pathologists was considered moderate (κ = 0.575). The agreement was similar (κ = 0.532) with the junior pathologist included. Using the three-tiered system, pathologists’ agreement was poor (κ = 0.235).
Conclusions
Pathologists’ reproducibility on diagnosing low-grade DCIS showed moderate agreement. Experience does not seem to influence reproducibility. Our proposed two-tiered system of low vs nonlow grade, where the intermediate grade is grouped in the nonlow category has shown improved concordance.
Colorectal carcinoma is the second most common cause of cancer-related deaths in North America. Invasion of tumor cells into lymphatic and blood vessels is an imperative step in the metastatic ...progression of colorectal carcinoma.
This is a before-and-after study conducted by the Department of Pathology and Laboratory Medicine of Mount Sinai Medical Center of Florida to assess the impact on venous invasion (VI) detection by implementing routine elastin staining on all tumor-containing blocks per case, where feasible, in colorectal carcinoma (CRC) resection specimens.
Clinicopathological parameters of CRC specimens were collected from January until December 2021 (n = 93) for the pre-implementation cohort and from January until December 2022 (n = 61) for the post-implementation cohort.
VI detection was significantly increased in the post-implementation cohort at a rate of 50.8 % compared to only 18.6 % in the pre-implementation cohort. The majority of VI identified in the pre-implementation cohort was extramural (61.5 %), whereas in the post-implementation cohort it was intramural (41.9 %). On univariate analysis, implementation of routine elastin stain was associated with strikingly increased VI detection rates (OR = 4.5, p-value < 0.001). On multivariate analysis, after adjusting for other clinicopathologic variables, elastin staining retained its independent statistically significant impact on VI detection (OR = 2.6, p-value = 0.034). Of note, there were no significant differences in the pre- and post-implementation cohorts in the frequency of nodal metastases, tumor extent, histologic grade, perineural invasion, T stage or M stage.
Based on our results and what has been published recently, we confirm an increase in the VI detection rate after implementing routine elastin staining on all tumor-containing blocks in CRC resection specimens.
•Lymphatic and blood vessel invasion is an imperative step in the metastatic progression of colorectal carcinoma.•Improving venous invasion detection in colorectal carcinoma may influence the oncologists' clinical decision.•The routine use of elastin stain significantly improves the detection rates of venous invasion in colorectal carcinoma.•Routine elastin stain is associated with 4.5 times increased venous invasion detection rates in colorectal carcinoma.
Background: Multiparametric (mp) magnetic resonance imaging (MRI)-ultrasound fusion-targeted biopsy (TB) has improved the detection of clinically significant prostate cancer (csCaP) using the ...Prostate Imaging Reporting and Data System (PI-RADS) reporting system, leading some authors to conclude that TB can replace the 12-core systematic biopsy (SB). We compared the diagnostic performance of TB with SB at our institution.
Methods: Eighty-three men with elevated prostate-specific antigen levels (6.6 ng/mL, interquartile range IQR 4.5-9.2) and abnormal mp-MRI (127 lesions, PI-RADS ≥3, median size: 1.1 cm, IQR 0.8-1.6) underwent simultaneous TB and SB. Diagnosis of any CaP (Gleason score, GS ≥6) and csCaP (GS ≥7) was compared using the McNemar's exact test.
Results: SB showed higher, but not statistically significant, detection rates of any CaP and csCaP (51.8% and 34.9%) versus TB (44.6% and 28.9%) (P = 0.286 and P = 0.359, respectively). TB outperformed SB in the quantification of 56.6% CaP and detecting cancer in anterior sectors (7.2%). Compared to SB, TB missed twice the amount of any CaP and csCaP. SB alone detected 22.2% of all csCaPs and upgraded 20.6% of TB-detected CaP. SB identified cancer invisible on mp-MRI (13.7% of all CaP) or missed by TB due to a small size (<1 cm) and sampling error (7% of lesions).
Conclusion: A combination of SB with TB remained necessary for achieving the highest cancer detection rates. Limiting prostate biopsy to TB alone can miss csCaP due to the presence of synchronous high-grade cancer invisible on MRI or failure to hit the target. TB is the best approach for anterior lesions and tumor quantification.
Neuroendocrine carcinomas (NECs) arise from neuroendocrine cells present throughout the body, and often present with metastases even with small and undetectable primary tumors. Additionally, ...neuroendocrine differentiation can be seen in carcinomas of non-neuroendocrine origin further complicating the landscape of metastatic NECs. Organ specific immunohistochemical markers such as TTF1, CDX2 and PAX8 are often lost in high grade tumors and may be non-contributory in localizing the primary site.
Though NECs share a common cellular origin, they exhibit great variability in biologic behavior, prognosis and treatment based on the primary organ of origin.
Twenty one cases of metastatic NECs were retrieved from our archives and were classified based on location of the primary tumor derived from clinical and radiological findings. Next generation sequencing data was retrieved and analyzed for recurrent genetic abnormalities in these cases. Statistical analysis was performed using IBM SPSS25 software.
RB1 mutations were exclusive to NECs metastasizing from lung primary and were detected in 5 of 12 (41.6 %) cases (p = 0.04). CDKN gene family (CDKN1B and 2 A) mutations were limited to metatstatic NECs of non-pulmonary origin and were detected in 4 of 9 (44.4 %) cases (p = 0.02).
The location of the primary tumor in metastatic NECs appears to have significant prognostic and therapeutic implications. But due to the morphological homogeneity, higher grade of tumor, variable sensitivity of immunohistochemical markers, and small, often undetectable primary tumors, the localization of the primary tumor in cases of metastatic NECs is a challenge. In this study, RB1 and CDKN gene family mutations are identified as possible markers for differentiating pulmonary and non-pulmonary origin in metatstatic NECs.
Brain tumors in adults may be infrequent when compared with other cancer etiologies, but they remain one of the deadliest with bleak survival rates. Current treatment modalities encompass surgical ...resection, chemotherapy, and radiotherapy. However, increasing resistance rates are being witnessed, and this has been attributed, in part, to cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells that reside within the tumor bulk and have the capacity for self-renewal and can differentiate and proliferate into multiple cell lineages. Studying those CSCs enables an increasing understanding of carcinogenesis, and targeting CSCs may overcome existing treatment resistance. One approach to weaponize new drugs is to target these CSCs through drug repurposing which entails using drugs, which are Food and Drug Administration–approved and safe for one defined disease, for a new indication. This approach serves to save both time and money that would otherwise be spent in designing a totally new therapy. In this review, we will illustrate drug repurposing strategies that have been used in brain tumors and then further elaborate on how these approaches, specifically those that target the resident CSCs, can help take the field of drug repurposing to a new level.
PDF
