UNEXPECTED ELEVATION OF KI-67 PROLIFERATION INDEX IN LOW GRADE TUMORS OF THE NERVOUS SYSTEM

1993 ◽  
Vol 52 (3) ◽  
pp. 290
Author(s):  
N. J. Hopf ◽  
H. H. Goebel ◽  
J. Bohl ◽  
A. Perneczky
Keyword(s):  
Nervous System ◽  
Proliferation Index ◽  
Low Grade ◽  
Ki 67

Umbrella Cells Mimicking Focal High-Grade Urothelial Carcinoma in Low-Grade Papillary Urothelial Carcinoma

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S121-S121
Author(s):  
Muhammad Masood Hassan ◽  
Tammey Naab ◽  
Ali Afsari
Keyword(s):  
Urothelial Carcinoma ◽  
Proliferation Index ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Prostate Hyperplasia ◽  
History Of ◽  
Papillary Urothelial Carcinoma ◽  
Artery Disease ◽  
Umbrella Cells

Abstract Objectives Low-grade papillary urothelial carcinoma (LGUC) has overall a preserved orderly appearance, minimal variability in architecture, and lack of significant cytologic atypia and mitotic activity without pleomorphism. A total of 53.8% of LGUC cases recur with 18.3% progression to high-grade UC. Even focal HGUC in LGUC can be a harbinger of progression. Accurate pathological interpretation is paramount in predicting recurrence and determining treatment. Methods A 63-year-old male with a past medical history of coronary artery disease, benign prostate hyperplasia, and obesity was referred to urology with a chief complaint of chronic hematuria. Cystoscopy with transurethral resection of bladder tumor was performed, which revealed mainly LGUC with focal high-grade-appearing UC. Results Histologic sections revealed papillary architecture with fused fronds, low-grade nuclear atypia, and scattered mitoses comprising 95% of the tissue submitted. No muscular wall invasion by carcinoma was seen. However, in one section, collections of large cells with well-defined cytoplasmic borders, multinucleation, and rare nuclear grooves were identified. The morphology raised the suspicion of a focal HGUC. Diffuse expression of CK20 and low Ki-67 proliferation index (1%) favored umbrella cells. Conclusion Our case reinforces the fact that sectioning can reveal foci, suspicious for HGUC, especially in urothelium. However, proper interpretation of morphology combined with the help of immunohistochemistry aids in accurate diagnosis, which is critical in determining proper clinical management of the patient.

Predictors of invasive breast cancer or DCIS recurrence in estrogen receptor positive (ER+) and estrogen receptor negative (ER-) ductal carcinoma in situ (DCIS) patients with and without associated invasive carcinoma (IC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11523-e11523 ◽  
Author(s):  
J. Picarsic ◽  
A. Brufsky ◽  
A. Onisko ◽  
M. Chivukula
Keyword(s):  
Estrogen Receptor ◽  
Biological Markers ◽  
Hormone Receptors ◽  
Invasive Carcinoma ◽  
Ductal Carcinoma ◽  
Response To Therapy ◽  
Proliferation Index ◽  
Low Grade ◽  
Ki 67 ◽  
Mib 1

e11523 Background: DCIS is a heterogeneous pre-invasive carcinoma with a spectrum of clinical behavior. Patients with ER+ IC have better outcomes compared to ER- patients. FOXA1 and GATA 3 family of transcription factors have been shown to be associated with hormone receptors (ER and PR) and other variables of good prognosis with better overall and relapse-free survival rate. The specific aim of this study is to analyze the expression of these novel biological markers: FOXA1, GATA-3, with recognized markers: MIB-1(Ki-67) and HER2 /neu in DCIS patients with/without associated IC. Methods: Sixty-nine (69) cases of DCIS [(fifty two (52) cases in ER+; seventeen (17) in ER-] were retrieved from our Pathology database. The expressions of the biological markers are analyzed by using a panel of immunohistochemical stains. FOXA1, GATA 3, ER, PR are nuclear stains, a cumulative “H score” is derived based on proportionality (PS) and intensity scores (IS). A proliferation index (PI) is calculated for MIB-1 (Ki67) nuclear stain (low <10%, moderate 11–25%, high 26–50%, very high>50%). Her2/neu is scored as per guidelines for HercepTest (0, or 1+ =negative, 2+ =weakly positive, 3+ =strongly positive). Results: DCIS is categorized into low grade (LG) (nuclear grade 1 and 2), high grade (HG) (grade 3). In the HGDCIS (n=48), four (4) cases had IC after a mean of 7.75 years; three cases of recurrent DCIS after a mean 6 years. No recurrent IC or DCIS is seen in the LGDCIS (n=21) group. The results are shown in the Table . Conclusions: (1) Decreased expression of GATA 3 is observed in HGDCIS ER- group may be a contributor to higher recurrence observed in this group (14%) versus (0%) in ER+ group. (2) A strong expression of FOXA, GATA3, low Ki-67 index, absent Her 2 expression are characteristically seen in our ER+ DCIS group, as previously described in IC. 3. Comparing the response to therapy and outcome in the ER+ and ER- groups is on going. [Table: see text] No significant financial relationships to disclose.

scholarly journals HGG-06. REMARKABLE RESPONSE TO BRAF INHIBITOR IN AN INFANT WITH DISSEMINATED DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii345-iii345
Author(s):  
Le Le Aung
Keyword(s):  
Braf Inhibitor ◽  
Braf V600e ◽  
Proliferation Index ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
Braf Inhibitors ◽  
Visual Contact ◽  
Ki 67 ◽  
Low Grade Gliomas ◽  
Diffuse Leptomeningeal Glioneuronal Tumor

Abstract INTRODUCTION Diffuse Leptomeningeal Glioneuronal Tumor (DLGNT) are rare CNS tumors and in infants, they can be lethal. There are several anecdotal reports in infants with low grade gliomas (LGG) with treated with BRAF inhibitors. METHODS A six-month old baby girl presented with a 2-week history of absent visual contact and vomiting. Imaging revealed a large 4.7 X 4.2 X 2.8 cm suprasellar charismatic region mass and multiple small extra-axial plaques in spinal canal. The child developed significant ascites post VP shunt requiring shunt externalization, extensive protein infusion support and hospitalization for six weeks. Immunohisto-chemical staining revealed Olig-2 and S-100, GFAP and synaptophysin positive. EMA showed patchy cytroplasmic reactivity in stromal cells and CD99 showed diffuse reactivity in stromal and lesional cells. INI-1, IDH-1, and CD117 were negative. Ki-67 proliferation index was 8–10%. PCR for BRAF V600E/E2/D was detected and KIAA1549-BRAF fusion as negative. This was confirmed by Genome Wide Next Generation Sequencing. While waiting for GNS testing results, the baby received one dose of Vinblastine. However, within seven days of initiating Debrafenib, significant clinical and radiological responses were observed. CONCLUSION The baby continues safely on Debrafenib with continued dramatic radiological response. This suggest that there may be a role in early initiation of targeted therapy such as BRAF inhibitors rather than giving standard chemotherapy such as Vinblastine or Carboplatin-Vincristine in extremely ill infants with low grade gliomas.

scholarly journals Correlation of 11C-Methionine Combined Positron Emission and Computed Tomography and Ki-67 Proliferation Index in Pretreatment Assessment of Cerebral Gliomas

2021 ◽  
pp. 34-48
Author(s):  
T. Yu. Skvortsova ◽  
Zh. I. Savintceva ◽  
D. V. Zakhs ◽  
A. F. Gurchin ◽  
A. I. Kholyavin ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Proliferative Activity ◽  
Hot Spot ◽  
Proliferation Index ◽  
Low Grade ◽  
Normal Brain ◽  
Ki 67 ◽  
Positron Emission ◽  
Pet Ct ◽  
Cerebral Gliomas

The purpose of the study was to explore the correlation between 11С-methionine (Met) uptake measured by combined positron emission and computed tomography (PET/CT) in newly diagnosed cerebral gliomas and tumor proliferative activity as measured by Ki-67 labeling index (Ki-67 LI).The results of PET/CT with 11С-methionine (PET-Met) of 236 adult patients with pretreated glial brain tumors were included in retrospective analysis. The final diagnosis of glioma according to WHO classification of CNS tumors (2007) was based on both histology and immunohistochemistry using Ki-67 antibodies. On PET-Met tumor-to normal brain uptake ratio (TBR) was calculated by dividing maximum Met uptake in the tumor (hot spot 10 mm in diameter) to activity concentration in the contralateral cortex. The Spearmen rank correlation test was used to analyze the relationships between TBR and Ki-67 LI.PET-Met analysis showed that TBR increases with an increase in the aggressiveness of the glial tumor. The differences of TBR values between gliomas grade II vs III and grade III vs IV were significant (p < 0,001). Among grades II-III gliomas Met uptake was significantly higher in oligodendroglial and mixed gliomas than in astrocytomas (p < 0,001), but the differences did not depend on Ki-67 LI.Correlation analysis demonstrated significant correlation between Ki-67 LI and TBR values (r = 0,49, p < 0,05, Spearman rank test). With analyzing glioma subgroups TBR values correlated with Ki-67 LI in diffuse astrocytomas (r = 0,52, p < 0,05), oligodendrogliomas (r = 0,40, p < 0,05), oligoastrocytomas (r = 0,47, p < 0,05) and in high-grade gliomas (r = 0,45, p < 0,05) but not in low-grade gliomas. Comparison between TBR value and Ki-67 LI in each glioma showed a lack of coincidence in 22 % of cases (high Met uptake but low Ki-67 LI and vice versa). The main reasons for such discrepancies were tumor molecular biology or incorrect biopsy target.Met uptake in diffuse gliomas correlates with proliferative activity which justifies the use of PET-Met for glioma grading. In case of mismatch between two biomarkers one should rely on the indicator that implies a higher aggressiveness of the glioma.

scholarly journals Case Report: Multiple Chromosomal Translocations Including Novel CIITA-CREBBP Fusion and Mutations in a Follicular Lymphoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Huan-You Wang ◽  
Ethan S. Sokol ◽  
Aaron M. Goodman ◽  
Andrew L. Feldman ◽  
Carolyn M. Mulroney
Keyword(s):  
Follicular Lymphoma ◽  
Mhc Class Ii ◽  
Fusion Gene ◽  
B Cell Lymphoma ◽  
Class Ii ◽  
Chromosomal Translocations ◽  
Proliferation Index ◽  
Low Grade ◽  
Creb Binding Protein ◽  
Ki 67

The pathogenesis of follicular lymphoma is a multi-step process, in which chromosomal translocation between immunoglobulin heavy chain (IgH) and anti-apoptotic B-cell lymphoma 2 (BCL2), namely IgH-BCL2, is an earliest step, followed by other genetic/genomic alterations including but not limited to mutation of CREB binding protein (CREBBP). MHC class II transactivator (CIITA) is a transcription regulator responsible for expression of MHC class II molecules including HLA-DR in human. We report herein a novel fusion gene involving CIITA and CREBBP in a patient with a low-grade follicular lymphoma (FL) but with high Ki-67 proliferation index. In addition, our patient also harbors CREBBP mutation. Together, we postulate that total loss of CREBBP function may contribute, in part, to the lymphoma genesis. Furthermore, this patient has addition rare (TBL1XR1-TP63) and common (IgH-BCL2) chromosomal translocations and multiple mutations including BCL2, BRAF, MUTYH, and STAT6.

Expression of Skp2, a p27Kip1 ubiquitin ligase, in malignant lymphoma: correlation with p27Kip1 and proliferation index

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2950-2956 ◽  
Author(s):  
Megan S. Lim ◽  
Ann Adamson ◽  
Zhaosheng Lin ◽  
Bayardo Perez-Ordonez ◽  
Richard C. K. Jordan ◽  
...  
Keyword(s):  
B Cell ◽  
Ubiquitin Ligase ◽  
Peripheral Blood Lymphocytes ◽  
Proliferation Index ◽  
Low Grade ◽  
B Cell Lymphomas ◽  
Ki 67 ◽  
Skp2 Expression ◽  
Aggressive Lymphomas ◽  
F Box Protein

Reduced levels of p27Kip1 are frequent in human cancers and have been associated with poor prognosis. Skp2, a component of the Skp1-Cul1-F-box protein (SCF) ubiquitin ligase complex, has been implicated in p27Kip1 degradation. Increased Skp2 levels are seen in some solid tumors and are associated with reduced p27Kip1. We examined the expression of these proteins using single and double immunolabeling in a large series of lymphomas to determine if alterations in their relative levels are associated with changes in cell proliferation and lymphoma subgroups. We studied the expression of Skp2 in low-grade and aggressive B-cell lymphomas (n = 86) and compared them with p27Kip1 and the proliferation index (PI). Fifteen hematopoietic cell lines and peripheral blood lymphocytes were studied by Western blot analysis. In reactive tonsils, Skp2 expression was limited to proliferating germinal center and interfollicular cells. Skp2 expression in small lymphocytic lymphomas (SLLs) and follicular lymphomas (FCLs) was low (mean percentage of positive tumor cells, less than 20%) and was inversely correlated (r = −0.67;P < .0001) with p27Kip1 and positively correlated with the PI (r = 0.82;P < .005). By contrast, whereas most mantle cell lymphomas (MCLs) demonstrated low expression of p27Kip1 and Skp2, a subset (n = 6) expressed high Skp2 (exceeding 20%) with a high PI (exceeding 50%). Skp2 expression was highest in diffuse large B-cell lymphomas (DLBCLs) (mean, 22%) and correlated with Ki-67 (r = 0.55;P < .005) but not with p27Kip1. Cytoplasmic Skp2 was seen in a subset of aggressive lymphomas. Our data provide evidence for p27Kip1 degradative function of Skp2 in low-grade lymphomas. The absence of this relationship in aggressive lymphomas suggests that other factors contribute to deregulation of p27Kip1 expression in these tumors.

Association of apparent diffusion coefficient with Ki-67 proliferation index, progesterone-receptor status and various histopathological parameters, and its utility in predicting the high grade in meningiomas

2020 ◽  
pp. 028418512092214
Author(s):  
Mustafa Bozdağ ◽  
Ali Er ◽  
Sümeyye Ekmekçi
Keyword(s):  
Diffusion Coefficient ◽  
Progesterone Receptor ◽  
Histological Grade ◽  
Proliferation Index ◽  
Proliferative Potential ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Apparent Diffusion ◽  
Adc Values

Background Accurate preoperative determination of the histological grade and cellular proliferative potential of meningioma by non-invasive imaging is of paramount importance. Purpose To evaluate the utility of apparent diffusion coefficient (ADC) in determining the histological grade of meningioma, and to investigate the correlation of ADC with Ki-67 proliferation index (PI), progesterone receptor (PR) status, and a number of other histopathological parameters. Material and Methods Histopathologically confirmed 94 meningioma patients (72 low-grade, 22 high-grade) who had undergone preoperative diffusion-weighted imaging were retrospectively evaluated. ADC values were obtained by manually drawing the regions of interest (ROIs) within the solid components of the tumor. The relationship between ADC and Ki-67 values, PR status, and multiple histopathological parameters were investigated, and the ADC values of high-grade and low-grade meningiomas were compared. Independent sample t-test, Mann–Whitney U test, receiver operating characteristic, Pearson correlation, and multiple logistic regression analysis were used for statistical assessment. Results All ADC and rADC values were significantly lower in high-grade meningiomas than in low-grade meningiomas (all P < 0.05). ADC values showed significantly negative correlations with Ki-67 and mitotic index ( P < 0.001 for each). Numerous ADC parameters were significantly lower in meningiomas demonstrating hypercellularity and necrosis features ( P < 0.05). ADC values did not show a significant correlation with PR score (all P > 0.05). Conclusion ADC can be utilized as a reliable imaging biomarker for predicting the proliferative potential and histological grade in meningiomas.

scholarly journals Proliferation Index and Karyometric Features of Pancreatic Intraductal Proliferative Lesions

1999 ◽  
Vol 19 (3-4) ◽  
pp. 175-185 ◽  
Author(s):  
Romana Tomaszewska ◽  
Krzysztof Okoń ◽  
Krystyna Nowak ◽  
Jerzy Stachura
Keyword(s):  
Pancreatic Cancer ◽  
Proliferative Activity ◽  
Diagnostic Value ◽  
Pancreatic Disease ◽  
Proliferation Index ◽  
Low Grade ◽  
Cell Nuclei ◽  
Ki 67 ◽  
Single Feature ◽  
Papillary Hyperplasia

The increasing frequency and poor prognosis in pancreatic cancer prompt us to search for morphological lesions being a substrate for its development. Studies of autopsy and surgically resected material as well as recent molecular studies have proved that one of the possible pathways of pancreatic neoplasia is the intraepithelial proliferation – dysplasia – cancer sequence. In the present paper we studied the proliferative activity (Ki‐67 index) in pancreatic intraepithelial proliferative lesions and its correlation with geometric features of cell nuclei as signs of increasing dysplasia. The studies were carried out in a group of 35 patients operated on for pancreatic cancer, chronic pancreatitis and other conditions not associated with the pancreas. We used immunohistochemical methods and basic morphometric parameters. The results of our studies indicate that the cell proliferative activity depends both on the type of epithelial proliferation and underlying pancreatic disease. The values of Ki‐67 index are significantly different in low‐grade proliferation (flat and papillary hyperplasia) and high‐grade proliferation (atypical papillary hyperplasia and carcinomain situ). A set of karyometric features correlates with Ki‐67 index but there is no single feature which would have a diagnostic value.

Primary Dural Lymphoma Masquerading as a Meningioma: A Rare Clinical Entity

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S114-S114
Author(s):  
Sakshi Sakshi ◽  
Ashish Bains
Keyword(s):  
B Cell ◽  
Dura Mater ◽  
Occipital Lobe ◽  
B Cell Lymphoma ◽  
Mass Effect ◽  
Proliferation Index ◽  
Right Visual Field ◽  
Pcr Analysis ◽  
Low Grade ◽  
Ki 67

Abstract Primary dura mater–based lymphomas are extremely uncommon and when detected are often clinically and radiologically misidentified. As per literature search, they account for <0.1% of all non-Hodgkin lymphomas; however, a precise incidence is unknown since only a few cases have been described in the literature. Here we report a case of a 64-year-old female who presented for evaluation of a newly diagnosed left tentorial tumor, diagnosed as “consistent with meningioma” on imaging studies with significant mass effect on the left occipital lobe and left cerebellum with effacement of the fourth ventricle. She had been experiencing disabling headaches, balance dysfunction, and reduced vision. On examination, the patient had right visual field defect with wide-based gait. No evidence of systemic lymphoma or clinically suspicious lymphadenopathy was documented. An intraoperative consultation revealed sheets of lymphocytes, rather highly concerning for lymphoma. H&E sections showed dense fibroconnective tissue heavily infiltrated by mature small- to intermediate-sized lymphocytes with irregular nuclei and condensed chromatin without a discernible architecture. Only sparse and scattered larger lymphocytes were seen. Flow cytometry identified a subset of B cells with lambda-restricted immunophenotype expressing CD19+, CD20+, CD10+, CD5–, and CD23–. On tissue sections, Ki-67 showed an overall proliferation index of 10% to 20%. However, no residual follicular dendritic cell meshwork was detected by CD21 or CD23. PCR analysis detected clonal B-cell IgH and IgKappa gene rearrangements. A diagnosis of low-grade CD10-positive B-cell lymphoma (likely follicle center-cell origin) was made and the patient was discharged after 3 days of surgery for outpatient follow-up and treatment. In conclusion, low-grade dural-based lymphomas are extremely rare and often misdiagnosed as meningiomas clinically and radiologically. Additionally, it is important distinguish lymphomas of the dura mater, which are excluded from the definition of primary CNS lymphomas and may have a different clinical management and outcome.

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