Altered expression pattern of integrin alphavbeta3 correlates with actin cytoskeleton in primary cultures of human breast cancer

Background: Integrins are transmembrane adhesion receptors that provide the physical link between the actin cytoskeleton and the extracellular matrix. It has been well established that integrins play a major role in various cancer stages, such as tumor growth, progression, invasion and metastasis. In breast cancer, integrin alphavbeta3 has been associated with high malignant potential in cancer cells, signaling the onset of widespread metastasis. Many preclinical breast cancer studies are based on established cell lines, which may not represent the cell behavior and phenotype of the primary tumor of origin, due to undergone genotypic and phenotypic changes. In the present study, short-term primary breast cancer cell cultures were developed. Integrin alphavbeta3 localization was studied in correlation with F-actin cytoskeleton by means of immunofluorescence and immunogold ultrastructural localization. Integrin fluorescence intensities were semi-quantitatively assessed by means of computerized image analysis, while integrin and actin expression was evaluated by Western immunoblotting. Results: In the primary breast cancer epithelial cells integrin alphavbeta3 immunofluorescence was observed in the marginal cytoplasmic area, whereas in the primary normal breast epithelial cells it was observed in the main cell body, i.e. in the ventrally located perinuclear area. In the former, F-actin cytoskeleton appeared well-formed, consisting of numerous and thicker stress fibers, compared to normal epithelial cells. Furthermore, electron microscopy showed increased integrin alphavbeta3 immunogold localization in epithelial breast cancer cells over the area of stress fibers at the basal cell surface. These findings were verified with Western immunoblotting by the higher expression of integrin beta3 subunit and actin in primary breast cancer cells, revealing their reciprocal relation, in response to the higher motility requirements, determined by the malignant potential of the breast cancer cells. Conclusion: A model system of primary breast cancer cell cultures was developed, in an effort to maintain the closest resembling environment to the tumor of origin. Using the above system model as an experimental tool the study of breast tumor cell behavior is possible concerning the adhesion capacity and the migrating potential of these cells, as defined by the integrin alphavbeta3 distribution in correlation with F-actin cytoskeleton

Predicting Survival of NSCLC Patients Treated with Immune Checkpoint Inhibitors: Impact and Timing of Immune-related Adverse Events and Prior Tyrosine Kinase Inhibitor Therapy

Introduction: Immune checkpoint inhibitors (ICIs) produce a broad spectrum of immune-related adverse events (irAEs) affecting various organ systems. While ICIs are established as a therapeutic option in non-small cell lung cancer (NSCLC) treatment, most patients receiving ICI relapse. Additionally, the role of ICIs on survival in patients receiving prior targeted tyrosine kinase inhibitor (TKI) therapy has not been well-defined. Objective: To investigate the impact of irAEs, the relative time of occurrence, and prior TKI therapy to predict clinical outcomes in NSCLC patients treated with ICIs. Methods: A single center retrospective cohort study identified 354 adult patients with NSCLC receiving ICI therapy between 2014 and 2018. Survival analysis utilized overall survival (OS) and real-world progression free survival (rwPFS) outcomes. Model performance matrices for predicting 1-year OS and 6-month rwPFS using linear regression baseline, optimal, and machine learning modeling approaches. Results: Patients experiencing an irAE were found to have a significantly longer OS and rwPFS compared to patients who did not (median OS 25.1 vs. 11.1 months; hazard ratio [HR] 0.51, confidence interval [CI] 0.39- 0.68, P-value \u3c0.001, median rwPFS 5.7 months vs. 2.3; HR 0.52, CI 0.41- 0.66, P-value \u3c0.001, respectively). Patients who received TKI therapy before initiation of ICI experienced significantly shorter OS than patients without prior TKI therapy (median OS 7.6 months vs. 18.5 months; P-value \u3c 0.01). After adjusting for other variables, irAEs and prior TKI therapy significantly impacted OS and rwPFS. Lastly, the performances of models implementing logistic regression and machine learning approaches were comparable in predicting 1-year OS and 6-month rwPFS. Conclusion: The occurrence of irAEs, the timing of the events, and prior TKI therapy were significant predictors of survival in NSCLC patients on ICI therapy. Therefore, our study supports future prospective studies to investigate the impact of irAEs, and sequence of therapy on the survival of NSCLC patients taking ICIs

Alternative lengthening of telomeres, ATRX loss and H3â K27M mutations in histologically defined pilocytic astrocytoma with anaplasia

Anaplasia may be identified in a subset of tumors with a presumed pilocytic astrocytoma (PA) component or piloid features, which may be associated with aggressive behavior, but the biologic basis of this change remains unclear. Fiftyâ seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3â 75) were included. A clinical diagnosis of NF1 was present in 8 (22%). Alternative lengthening of telomeres (ALT) was assessed by telomereâ specific FISH and/or CISH. A combination of immunohistochemistry, DNA sequencing and FISH were used to study BRAF, ATRX, CDKN2A/p16, mutant IDH1 p.R132H and H3â K27M proteins. ALT was present in 25 (69%) cases and ATRX loss in 20 (57%), mostly in the expected association of ALT+/ATRXâ (20/24, 83%) or ALTâ /ATRX+ (11/11, 100%). BRAF duplication was present in 8 (of 26) (31%). H3â K27M was present in 5 of 32 (16%) cases, all with concurrent ATRX loss and ALT. ALT was also present in 9 (of 11) cases in the benign PA precursor, 7 of which also had ATRX loss in both the precursor and the anaplastic tumor. In a single pediatric case, ALT and ATRX loss developed in the anaplastic component only, and in another adult case, ALT was present in the PAâ A component only, but ATRX was not tested. Features associated with worse prognosis included subtotal resection, adult vs. pediatric, presence of a PA precursor preceding a diagnosis of anaplasia, necrosis, presence of ALT and ATRX expression loss. ALT and ATRX loss, as well as alterations involving the MAPK pathway, are frequent in PA with anaplasia at the time of development of anaplasia or in their precursors. Additionally, a small subset of PA with anaplasia have H3â K27M mutations. These findings further support the concept that PA with anaplasia is a neoplasm with heterogeneous genetic features and alterations typical of both PA and diffuse gliomas.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/1/bpa12646_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/2/bpa12646.pd

Evaluation of Somatic Mutations in Solid Metastatic Pan-Cancer Patients

Metastasis continues to be the primary cause of all cancer-related deaths despite the recent advancements in cancer treatments. To evaluate the role of mutations in overall survival (OS) and treatment outcomes, we analyzed 957 metastatic patients with seven major cancer types who had available molecular testing results with a FoundationOne CDx® panel. The most prevalent genes with somatic mutations were TP53, KRAS, APC, and LRP1B. In this analysis, these genes had mutation frequencies higher than in publicly available datasets. We identified that the somatic mutations were seven mutually exclusive gene pairs and an additional fifty-two co-occurring gene pairs. Mutations in the mutually exclusive gene pair APC and CDKN2A showed an opposite effect on the overall survival. However, patients with CDKN2A mutations showed significantly shorter OS (HR: 1.72, 95% CI: 1.34–2.21, p \u3c 0.001) after adjusting for cancer type, age at diagnosis, and sex. Five-year post metastatic diagnosis survival analysis showed a significant improvement in OS (median survival 28 and 43 months in pre-2015 and post-2015 metastatic diagnosis, respectively, p = 0.00021) based on the year of metastatic diagnosis. Although the use of targeted therapies after metastatic diagnosis prolonged OS, the benefit was not statistically significant. However, longer five-year progression-free survival (PFS) was significantly associated with targeted therapy use (median 10.9 months (CI: 9.7–11.9 months) compared to 9.1 months (CI: 8.1–10.1 months) for non-targeted therapy, respectively, p = 0.0029). Our results provide a clinically relevant overview of the complex molecular landscape and survival mechanisms in metastatic solid cancers

Immunohistochemical and biochemical investigation of the expression of the O-linked N-acetylglucosamine containing epitope H in the brain

The epitope H contains an O-Linked N-acetylglucosamine residue in a specific conformation and/or environment recognized by the mouse IgM monoclonal antibody H. The antibody H was raised against lamb oligodendrocytes. In the present study the distribution of the epitope H was investigated, by using the indirect immunoperoxidase method, in 190 formalin-fixed, paraffin embedded specimens including, 30 cases of normal human brains, 30 cases of normal lamb brains, 30 cases of normal rabbit brains, 30 cases of normal rat brains, 10 human brains of old persons with atrophy, 10 brains of infants with lesions of anoxic encephalopathy, 2 brains of premature neonates with anoxic encephalopathy, 9 specimens of human embryos in different weeks of gestation, 10 cases of gemistocytic astrocytomas, 10 cases of pilocytic astrocytomas, 10 cases of subependymal giant cell astrocytomas occurring in children with tuberous sclerosis, 5 cases of medulloblastomas and 1 case of PNET. In addition fresh frozen tissues of lamb brains and mixed cultures of lamb astrocytes and oligodendrocytes were stained using the double indirect immunofluorescence method and the primaxy IgM monoclonal mouse antibody H and the polyclonal rabbit anti-GFAP antibody. Finally, by using the Western-blot, immunoblot -method the localization of the epitope H was investigated, in the cultures of human astrocytoma U87 and D54 cell lines. In the immunoperoxidase stain the expression of the epitope H was graded as follows: Negative expression (-) when all cells were unstained, very low expression when less than 5% of the cells were stained, low expression when 5-30% of the cells were stained, moderate expression when 30-75% of the cells were stained and high expression when more than 75% of the cells were stained. The results of the present study are as follows: 1) All types of neurons of human, lamb, rabbit and rat brains remained negative for the epitope H. 2) The microglial cells of all brain specimens remained negative for the epitope H. 3) The oligodendrocytes of all brain specimens remained negative for the epitope H. 4) All the oligodendrocytes in the lamb tissue cultures revealed strong cell body and process staining for the epitope H. 5) The myelin of all brain specimens remained negative for the epitope H. 6) All the astrocytes in the lamb tissue cultures revealed strong cell body and process staining. 7) The astrocytes of the external glia limitans (surface of the brain) of all normal brain specimens showed high expression for the epitope H. 8) The protoplasmic astrocytes of the cerebral cortex and basal ganglia (cerebral hemispheric nuclei) of all normal brain specimens showed very low expression for the epitope H. 9) The fibrous astrocytes of the white matter of all normal brain specimens showed low expression for the epitope H. 10) The ependymal cells of the lamb, brains showed low expression for the epitope H. 11) The ependymal cells of the normal rabbit, rat and human brain specimens showed very low expression for the epitope H. 12) The ependymal cells of the normal human embryos remained negative for the epitope H. 13) The cells of the neural tube of the human embryos remained negative for the epitope H, except in two cases where they showed very low expression for the epitope H. In the 27 day-old human embryo the cell processes of the peripheral marginal zone showed strong stain and high expression for the epitope H. 14) The neural crest and its derivatives showed variable expression for the epitope H, in the human embryos. On the 26-day all cells were negative, on the 27-day the cells showed high expression, at seven weeks rare elongated cells were positive in the spinal ganglia, at eight weeks the spinal ganglia showed a positive paranuclear cytoplasmic spot in many cells. At 12 weeks the neurons and their satellite cells were negative for the epitope H, whereas the cells of the capsule and a good number of elongated cells within the ganglion were strongly stained for the epitope H. The schwann cells up to the 13th week up to which we had data remained negative for the epitope H. 15) The epithelial cells of the choroid plexus of the normal human brain specimens revealed high expression for the epitope H. 16) The epithelial cells of the choroid plexus of the lamb and rabbit brains revealed low expression for the epitope H. 17) The hypertrophic reactive astrocytes of the external glia limitans of the atrophic brains of old human persons revealed strong cytoplasmic stain and high expression for the epitope H. 18) The ependymal cells of the premature neonates and of the infants who died with signs of anoxic encephalopathy showed high expression for the epitope H. 19) The ten cases of gemistocytic astrocytomas showed high expression for the epitope H. 20) The ten cases of subependymal giant cell astrocytomas occurring in tuberous sclerosis showed high expression for the epitope H. 21) The ten cases of pilocytic astrocytomas showed a biphasic pattern of expression for the epitope H. The dense areas composed of elongated pilocytic astrocytes showed high expression and the loose areas composed of stellate (protoplasmic) astrocytes showed low expression. 22) The five cases of medulloblastomas and the one case of PNET remained negative for the epitope H. 23) The U87 and D54 human astrocytoma cell lines, with the method Western-blot – immunoblot revealed that the epitope H is present at four polypeptides on each cell line. The three polypeptides have similar molecular weights on both cell lines and these are 106KD, 56KD and 54 KD. There is a fourth polypeptide with 32KD in the U87 cell line and a fourth polypeptide with 33KD in the D54 cell line which bear the epitope H.Το επιτόπιο Η αναγνωρίζεται από το μονοκλωνικό αντίσωμα Η. Το μονοκλωνικό αντίσωμα Η είναι της τάξεως IgM και δημιουργήθηκε σε ποντικό μετά από ένεση ολόκληρων σωμάτων ολιγοδενδρογλοιακών κυττάρων προβάτου. Το επιτόπιο Η περιλαμβάνει το σάκχαρο Ν-ακετυλογλυκοζαμίνη αλλά και άλλα στοιχεία τα οποία μπορεί να είναι ή το παρακείμενο τμήμα της πολυπεπτιδικής αλύσου ή ο τρόπος που τοποθετείται το σάκχαρο στο μόριο της πολυπεπτιδικής αλύσου ή ο συνδυασμός και των δύο παραπάνω καταστάσεων. Έτσι το μονοκλωνικό αντίσωμα Η δεν αναγνωρίζει όλα τα πολυπεπτίδια που φέρουν το σάκχαρο Ν-ακετυλογλυκοζαμίνη, αλλά αναγνωρίζει έναν υποπληθυσμό αυτών των πολυπεπτιδίων που φέρουν το σάκχαρο με τις προϋποθέσεις που απαιτούνται για να δημιουργηθεί το επιτόπιο Η. Σε αυτή την μελέτη εξετάσθηκε η κατανομή του επιτοπίου Η με τη μέθοδο της έμμεσης ανοσοϋπεροξειδάσης σε 190 δείγματα τα οποία μονιμοποιήθηκαν σε φορμόλη και σκηνώθηκαν σε παραφίνη. Στα 190 δείγματα περιλαμβάνονται: 30 φυσιολογικοί εγκέφαλοι, ανθρώπων, 30 φυσιολογικοί εγκέφαλοι προβάτου, 30 φυσιολογικοί εγκέφαλοι κουνελιού, 30 φυσιολογικοί εγκέφαλοι επίμυων, 10 εγκέφαλοι υπερηλίκων ανθρώπων με ατροφία, 10 εγκέφαλοι βρεφών με ανοξική εγκεφαλοπάθεια, 2 εγκέφαλοι πρόωρων νεογνών με ανοξική εγκεφαλοπάθεια, 9 περιπτώσεις ανθρωπίνων εμβρύων σε διαφορετικά στάδια κυήσεως, 10 περιπτώσεις γεμιστοκυτταρικών, 10 περιπτώσεις τριχοκυτταρικών, 10 περιπτώσεις υποεπενδυματικών γιγαντοκυτταρικών αστροκυτωμάτων, 5 περιπτώσεις μυελοβλαστωμάτων και 1 περίπτωση PNET. Ακόμα με τη μέθοδο του έμμεσου ανοσοφθορισμού βάφηκαν μεικτές καλλιέργειες αστροκυττάρων και ολιγοδενδροκυττάρων προβάτου καθώς και τομές κρυοστάτου εγκεφάλων προβάτου. Με τη μέθοδο του Western-blot – immunoblot μελετήθηκε η κατανομή του επιτοπίου Η στα πολυπεπτίδια των κυτταρικών σειρών των ανθρωπίνων αστροκυτωμάτων U87 και D54. Τα αποτελέσματα της μελέτης είναι τα ακόλουθα: 1) Τα νευρικά κύτταρα όλων των εγκεφάλων του ανθρώπου, του προβάτου, του κουνελιού και του επίμυος παρέμειναν αρνητικά για το επιτόπιο Η. 2) Το ολιγοδενδρογλοιακά κύτταρα των εγκεφάλων όλων των ειδών παρέμειναν αρνητικά για το επιτόπιο Η. 3) Τα μικρογλοιακά κύτταρα των εγκεφάλων όλων των ειδών παρέμειναν αρνητικά για το επιτόπιο Η. 4) Η μυελίνη των εγκεφάλων όλων των ειδών παρέμεινε αρνητική για το επιτόπιο Η. 5) Τα ινώδη αστροκύτταρα της λευκής ουσίας των φυσιολογικών εγκεφάλων όλων των ειδών παρουσίασαν χαμηλή έκφραση για το επιτόπιο Η. 6) Τα αστροκύτταρα της εξωτερικής επιφάνειας των φυσιολογικών εγκεφάλων όλων των ειδών, τα οποία σχηματίζουν τον έξω αφοριστικό νευρογλοιακό υμένα παρουσίασαν υψηλή έκφραση για το επιτόπιο Η. 7) Τα πρωτοπλασματικά αστροκύτταρα του φλοιού και των βασικών γαγγλίων των εγκεφαλικών ημισφαιρίων όλων των ειδών των εγκεφάλων παρουσίασαν πολύ χαμηλή έκφραση για το επιτόπιο Η. 8) Τα επενδυματικά κύτταρα των εγκεφάλων του προβάτου παρουσίασαν χαμηλή έκφραση για το επιτόπιο Η. 9) Τα επενδυματικά κύτταρα των φυσιολογικών εγκεφάλων του ανθρώπου του κουνελιού και του επίμυος παρουσίασαν πολύ χαμηλή έκφραση για το επιτόπιο Η. 10) Τα επενδυματικά κύτταρα του Κ.Ν.Σ των ανθρωπίνων εμβρύων παρέμειναν αρνητικά για το επιτόπιο Η. 11) Τα επιθηλιακά κύτταρα του χοριοειδούς πλέγματος του φυσιολογικών εγκεφάλων του ανθρώπου παρουσίασαν υψηλή έκφραση για το επιτόπιο Η. 12) Τα κύτταρα του νευρικού σωλήνα των ανθρωπίνων εμβρύων παρουσίασαν αρνητική έκφραση για το επιτόπιο Η εκτός από μια περίπτωση που παρουσίασε χαμηλή έκφραση. 13) Τα επενδυματικά κύτταρα των εγκεφάλων των βρεφών που απεβίωσαν από ανοξική εγκεφαλοπάθεια παρουσίασαν υψηλή έκφραση για το επιτόπιο Η. 14) Τα αντιδραστικά υπερτροφικά αστροκύτταρα του έξω αφοριστικού νευρογλοιακού υμένα των ατροφικών εγκεφάλων των υπερηλίκων παρουσίασαν υψηλή έκφραση για το επιτόπιο Η. 15) Οι δέκα περιπτώσεις γεμιστοκυτταρικών και υποεπενδυματικών γιγαντοκυτταρικών αστροκυττωμάτων παρουσίασαν υψηλή έκφραση για το επιτόπιο Η. 16) Οι δέκα περιπτώσεις τριχοκυτταρικών (πιλοκυτταρικών) αστροκυττωμάτων παρουσίασαν διφασική έκφραση για το επιτόπιο Η με τις πυκνές περιοχές να παρουσιάζουν υψηλή και τις αραιές περιοχές χαμηλή έκφραση για το επιτόπιο Η. 17) Οι πέντε περιπτώσεις μυελοβλαστωμάτων και η μία περίπτωση PNET παρέμειναν αρνητικές για το επιτόπιο Η. 18) Οι σειρές των U87 και D54 των αστροκυτωμάτων με τη μέθοδο του Western-blot, immunoblot παρουσίασαν τέσσερα πολυπεπτίδια η κάθε μία που φέρουν το επιτόπιο Η. Τα τρία πρώτα με μοριακά βάρη 106KD, 56KD, 54KD είναι κοινά και στις δύο σειρές. Η σειρά U87 παρουσιάζει ένα τέταρτο πολυπεπτίδιο με μοριακό βάρος 32KD που φέρει το επιτόπιο Η και η σειρά D54 ένα τέταρτο πολυπεπτίδιο με μοριακό βάρος 33KD που φέρει το επιτόπιο Η. 19) Τα ολιγοδενδροκύτταρα του προβάτου στις κυτταροκαλλιέργειες παρουσίασαν έντονη χρώση του σωματικού κυτταροπλάσματος και των αποφυάδων τους για το επιτόπιο Η. 20) Τα αστροκύτταρα του προβάτου τόσο με τις πλατειές όσο και με τις στενές αποφυάδες στις κυτταροκαλλιέργειες παρουσίασαν έντονη χρώση του κυτταροπλάσματος για το επιτόπιο Η

A Case Report of Immunotherapy-Resistant MSI-H Gastric Cancer with Significant Intrapatient Tumoral Heterogeneity Characterized by Histologic Dedifferentiation

We describe a patient with both gastric adenocarcinoma and metastatic squamous cell carcinoma (SCC) of unknown primary site. The possibility of a single malignant clonal process as opposed to differing primaries was supported by the finding of both histologies exhibiting high microsatellite instability. Despite evidence of tumor microsatellite instability, the patient’s disease process did not respond to immune checkpoint inhibition. Our pursuit of whole-exome sequencing and comparing the single-nucleotide variant profiles of both tumors supported a single clonal process with the development of significant intratumoral heterogeneity. High intratumoral heterogeneity has posed a challenge to precision medicine approaches, but we also provide a review of the literature of this phenomenon mediating resistance to immunotherapy strategies

Glioblastoma, IDH-Wildtype With Epithelioid Morphology and a BCR::NTRK2 Fusion

Glioblastoma, IDH-wildtype (GBM) is a high-grade astrocytic glioma that accounts for the majority of malignant brain tumors in adults. Within this entity, epithelioid GBM represents a histological subtype characterized by a loosely cohesive aggregate of large cells with abundant cytoplasm, and vesicular nuclei that usually harbors the BRAF V600E mutation. Molecular alterations in GBMs are frequent and play an important role in the diagnosis of this entity. Among the many genetic alterations reported, NTRK fusions are rare and account for <2% of gliomas. Furthermore, NTRK2 fusions are most seen in pediatric populations. Recent approval of the TRK inhibitor larotrectinib by the Food and Drug Administration (FDA) has brought interest in the study and recognition of NTRK fusions in multiple types of tumors. Trials that assess the response to this drug in cancers carrying NTRK fusions have yielded favorable results. We discuss a rare presentation of an adult-type GBM with epithelioid morphology and a BCR::NTRK2 gene fusion.Revisión por pare

The O-Linked N-Acetylglucosamine Containing Epitope H (O-GlcNAcH) is Upregulated in the Trophoblastic and Downregulated in the Fibroblastic Cells in Missed Miscarriage Human Chorionic Villi With Simple Hydropic Degeneration

Epitope H contains an O-linked N-acetylglucosamine (O-GlcNAcH) residue in a specific conformation and/or environment recognized by the mouse monoclonal antibody H. O-GlcNAcH is present in several types of cells and in several polypeptides, including cytokeratin 8 and vimentin, on the latter in cells under stress. In the present work, we examined the expression of the O-GlcNAcH in 60 cases of endometrial curettings from missed miscarriage cases containing normal and simple hydropic degenerated chorionic villi in each case, using monoclonal antibody H and indirect immunoperoxidase and Western blot immunoblot. In all cases examined the expression of the O-GlcNAcH was cytoplasmic as follows: (1) syncytiotrophoblastic cells showed very low expression in chorionic villi (CV) with nonhydropic degeneration (NHD) and high expression in hydropic degenerated (HD) CV; (2) cytotrophoblastic cells showed low expression in CV with NHD and high expression in HD CV; (3) fibroblastic cells showed high expression in CV with NHD and very low expression in HD CV; (4) histiocytes showed very low expression in both types of CV; (5) endothelial cells showed high expression in both types of CV. An immunoblot of CV from one case of a legal abortion from a normal first-trimester pregnancy showed 5 polypeptides with 118.5, 106.3, 85, 53, and 36.7 kD bearing the epitope H and the 53 kD corresponded to cytokeratin 8. The expression of the O-GlcNAcH is upregulated in the trophoblastic cells and downregulated in the fibroblastic cells in the HD CV in comparison to the NHD CV

Scrotal Apocrine Adenocarcinoma with Pagetoid Phenomenon and Inguinal Lymph Node Metastases.

We report a case of scrotal apocrine adenocarcinoma in a 72-year-old Caucasian male which was initially presented as a reddish superficial lesion which in time became an ulcerated nodule. The initial pathological examination showed an apocrine adenocarcinoma with pagetoid phenomenon. The tumor recurred after four months and then excision biopsy showed tumor with pagetoid phenomenon which reached all the surgical margins. Three months later an ulcerated nodule in the scrotum and greatly enlarged ipsilateral inguinal lymph nodes were noticed. The final pathological examination showed multiple separated malignant foci, some with overlying pagetoid phenomenon and inguinal lymph node metastases. Immunohistochemistry showed positivity for Gross Cystic Disease Fluid Protein-15 (GCDFP-15), androgen receptors, and score 3+ for the Human Epidermal growth factor Receptor-2 (HER2). The aggressive behavior of the present tumor goes along with previous reports showing that HER2 high score cases exhibit a worse prognosis

Hemorrhagic chondrosarcoma in a patient with Ollier disease: Case report and literature review

We present a rare case of skull-base hemorrhagic chondrosarcoma in a patient with Ollier disease. Chondrosarcomas complicated by intracranial hemorrhage are very uncommon, with few reported cases in the literature. To our knowledge, this is the first such reported case