Robert J Tomsich Pathology And Laboratory Medicine Institute

Cleveland, OH, United States

Robert J Tomsich Pathology And Laboratory Medicine Institute

Cleveland, OH, United States
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Ali M.M.,Cleveland Clinic | Rybicki L.,Cleveland Clinic Lerner Research Institute | Nomani L.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Rouphail B.,Cleveland Clinic | And 6 more authors.
Clinical Lymphoma, Myeloma and Leukemia | Year: 2017

Background: Follicular lymphoma (FL) is heterogeneous. Although FL Grade 3B (FL3B) is treated as aggressive FL (aggFL), an optimal approach to FL Grade 3A (FL3A) remains unclear because few data exist on clinical outcomes on the basis of subclassification of FL Grade 3 (FL3) since the introduction of rituximab. We report outcomes of FL3 in the rituximab era. Patients and Methods: We identified and analyzed a retrospective cohort of 53 patients with FL3A, 3B, and FL Grade 3 with areas of diffuse large B-cell lymphoma (DLBCL). They were divided into 2 groups: aggFL (n = 21) included patients with FL3B (n = 10) and FL3 (A or B) with concomitant DLBCL (n = 11); indolent lymphoma (n = 32) included only FL3A. Results: Baseline characteristics did not differ between the groups. rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) was initial treatment in 15 (79%) of patients with aggFL and 21 (72%) of those with FL3A; rituximab was included in initial therapy in 18 (95%) and 24 (83%), respectively. Comparing aggFL and FL3A, 5-year overall survival was 90% versus 79% (P = .97) and 5-year progression-free survival (PFS) 44% versus 34% (P = .75), respectively. Conclusion: We conclude that outcomes for FL3, primarily treated with R-CHOP, do not differ between FL3A and aggFL (FL3B and FL3/DLBCL). The aggFL group showed a plateau in PFS confirming these should be treated with curative intent. FL3A patients, mainly managed with R-CHOP, also show an apparent plateau in PFS. Although longer follow-up and confirmation in other data sets is required, this indicates potential undertreatment of FL3A with less aggressive regimens often used for indolent lymphoma. © 2017 Elsevier Inc.


Underwood D.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Aramoni G.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Cash B.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Croyle M.,Robert J Tomsich Pathology And Laboratory Medicine Institute | And 9 more authors.
Cancer Cytopathology | Year: 2016

BACKGROUND: Gynecologic screening cytology is a complex task that includes microscopic activities and nonmicroscopic activities. The authors sought to determine the amount and percentage of time that cytotechnologists spend on those activities using the ThinPrep imaging system. METHODS: In arm 1, a total of 550 consecutive unselected slides were reviewed by 11 cytotechnologists, and the time used for individual subtasks of the screening process was recorded. In arm 2, a total of 20 unselected slides were each screened by 10 different cytotechnologists (200 slides in total) and total screening times and full manual review (FMR) times were recorded. RESULTS: In arm 1, cases with and without FMR required an average of 5.6 minutes and 3.0 minutes, respectively, to screen. Overall, review of fields of view (FOVs) took 95 seconds. FMR took an average of 2.6 minutes. The average screening times for FOV-only cases was significantly longer than the US Food and Drug Administration/Centers for Medicare and Medicaid Services (FDA/CMS) workload limit of 2.4 minutes (P=.005). However, in arm 2, the time needed to screen a case increased by an average of 1 minute compared with arm 1, including 1.1 minute for FOV-only cases and >2 minutes for FMR plus FOV cases. Approximately 100% of cases screened as FOV only exceeded the FDA/CMS workload limit of 2.4 minutes. CONCLUSIONS: The FDA/CMS workload limits for FOV-only cases appears to significantly underestimate the time needed to screen those cases, but seems to be appropriate for the majority of FMR plus FOV cases. Approximately 60% and 30% of the time designated to screening slides was spent on nonmicroscopic activities for FOV-only cases and FMR cases, respectively. © 2016 American Cancer Society.


Kligman F.L.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Kottke-Marchant K.,Case Western Reserve University
Journal of Biomedical Materials Research - Part A | Year: 2015

Expanded polytetrafluoroethylene (ePTFE) grafts were coated on the luminal surface with a cell-adhesive fluorosurfactant (FSP) polymer to promote endothelialization, followed by ethanol hydration to degas the pores and subsequent cell-adhesive, enzymatically degradable poly(ethylene glycol)-based hydrogel incorporation into the graft interstices to accommodate potential smooth muscle cell integration in the graft wall. The FSP coating on ePTFE was stable as demonstrated by a significantly reduced receding water contact angle on FSP-coated ePTFE (14.5±6.4°) compared to uncoated ePTFE (105.3±4.5°, P<0.05) after ethanol exposure. X-ray photoelectron spectroscopy analysis of the same surfaces confirmed FSP presence. Localization of the FSP and hydrogel within the ePTFE graft construct was assessed using fluorescently labeled polymers, and demonstrated hydrogel infiltration throughout the thickness of the graft wall, with FSP coating limited to the lumen and adventitial surfaces. FSP at the luminal surface on dual-coated grafts was able to bind endothelial cells (EC) (98.7±23.1 cells/mm2) similar to fibronectin controls (129.4±40.7 cells/mm2), and significantly higher than uncoated ePTFE (31.6±19 cells/mm2, P<0.05). These results indicate that ePTFE grafts can be simultaneously modified with two different polymers that have potential to directly address both endothelialization and intimal hyperplasia. Such a construct is a promising candidate for an off-the-shelf synthetic graft for small-diameter graft applications. © 2015 Wiley Periodicals, Inc.


French C.A.,Brigham and Women's Hospital | Rahman S.,Harvard University | Walsh E.M.,Brigham and Women's Hospital | Kuhnle S.,Harvard University | And 11 more authors.
Cancer Discovery | Year: 2014

NUT midline carcinoma (NMC) is an aggressive subtype of squamous cell carcinoma that typically harbors BRD4/3-NUT fusion oncoproteins that block differentiation and maintain tumor growth. In 20% of cases, NUT is fused to uncharacterized non-BRD gene(s). We established a new patient-derived NMC cell line (1221) and demonstrated that it harbors a novel NSD3-NUT fusion oncogene. We find that NSD3-NUT is both necessary and sufficient for the blockade of differentiation and maintenance of proliferation in NMC cells. NSD3-NUT binds to BRD4, and BRD bromodomain inhibitors induce differentiation and arrest proliferation of 1221 cells. We find further that NSD3 is required for the blockade of differentiation in BRD4-NUT-expressing NMCs. These findings identify NSD3 as a novel critical oncogenic component and potential therapeutic target in NMC. SIGNIFICANCE: The existence of a family of fusion oncogenes in squamous cell carcinoma is unprecedented, and should lead to key insights into aberrant differentiation in NMC and possibly other squamous cell carcinomas. The involvement of the NSD3 methyltransferase as a component of the NUT fusion protein oncogenic complex identifies a new potential therapeutic target. © 2014 American Association for Cancer Research.


Przybycin C.G.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Przybycin C.G.,Cleveland Clinic | Magi-Galluzzi C.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Magi-Galluzzi C.,Cleveland Clinic | And 2 more authors.
Advances in Anatomic Pathology | Year: 2013

Many hereditary tumor syndromes are associated with neoplasms of the kidney. It is becoming increasingly well recognized that a given familial tumor syndrome may be very heterogenous in clinical appearance and that unrecognized patients may present initially for the treatment of a renal mass. It is therefore important for surgical pathologists to be aware of the specific gross and microscopic findings in the kidney that suggest a possible syndromic association. In this review, we detail the histologic features of syndromic- associated renal neoplasms, describe the presence of characteristic changes in the background renal parenchyma, and provide an update on associated extrarenal manifestations for each of the following syndromes: von Hippel-Lindau disease, hereditary papillary renal cell carcinoma (RCC), hereditary leiomyomatosis-RCC, Birt-Hogg-Dubé syndrome, tuberous sclerosis complex, germline succinate dehydrogenase mutation, hereditary nonpolyposis colorectal cancer syndrome, hyperparathyroidism-jaw tumor syndrome, PTEN hamartoma syndrome, constitutional chromosome 3 translocation, and familial nonsyndromic clear cell RCC. We also include a synopsis of renal medullary carcinoma because of its association with hereditary hemoglobinopathies. Copyright © 2013 by Lippincott Williams & Wilkins.


Watts K.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Li J.,Cleveland Clinic | Magi-Galluzzi C.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Zhou M.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Zhou M.,New York University
Histopathology | Year: 2013

Aims: Intraductal carcinoma of the prostate (IDC-P) is a distinct clinicopathological entity and is associated with aggressive, high-grade and high-volume prostate carcinoma (PCa). The incidence, clinicopathological characteristics and prognostic significance of IDC-P have not been reported in prostate biopsies (PBx) that surgical pathologists encounter in their daily practice. Methods and results: In 1176 prospectively collected PBx, 33 IDC-P cases were identified (2.8%). The mean age of patients with IDC-P was 65 (range 46-79) years and mean serum prostate-specific antigen was 16.2 (range 0.4-105.6) ng/ml. Three (0.26%) IDC-P cases did not have a concomitant invasive PCa. Of 30 cases with concomitant invasive PCa, Gleason score was 7 in 16 (53.3%), 8 in four (13.3%) and 9 in 10 (33.3%) cases. The mean number of biopsy cores involved by PCa was 7.2 (range 1-14). Nine patients were treated with radical prostatectomy. Seminal vesicle invasion was found in four of nine (44%) cases, significantly higher than the risk of 12% predicted by Partin Tables (P = 0.016). Conclusions: This is the first prospective study that has investigated the incidence and prognostic significance of IDC-P diagnosed in PBx encountered in daily practice. It is critical for surgical pathologists to diagnose and report IDC-P in PBx. © 2013 John Wiley & Sons Ltd.


Procop G.W.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Yerian L.M.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Yerian L.M.,Cleveland Clinic | Wyllie R.,Cleveland Clinic | And 2 more authors.
American Journal of Clinical Pathology | Year: 2014

Objectives: Duplicate laboratory tests that are unwarranted increase unnecessary phlebotomy, which contributes to iatrogenic anemia, decreased patient satisfaction, and increased health care costs. Materials and Methods: We employed a clinical decision support tool (CDST) to block unnecessary duplicate test orders during the computerized physician order entry (CPOE) process. We assessed laboratory cost savings after 2 years and searched for untoward patient events associated with this intervention. Results: This CDST blocked 11,790 unnecessary duplicate test orders in these 2 years, which resulted in a cost savings of $183,586. There were no untoward effects reported associated with this intervention. Conclusions: The movement to CPOE affords real-time interaction between the laboratory and the physician through CDSTs that signal duplicate orders. These interactions save health care dollars and should also increase patient satisfaction and well-being. © American Society for Clinical Pathology.


Minca E.C.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Lanigan C.P.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Reynolds J.P.,Robert J Tomsich Pathology And Laboratory Medicine Institute | Wang Z.,Robert J Tomsich Pathology And Laboratory Medicine Institute | And 5 more authors.
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer | Year: 2014

INTRODUCTION: Oncogenic anaplastic lymphoma kinase (ALK) gene rearrangements in non-small-cell lung carcinomas (NSCLC) provide the basis for targeted therapy with crizotinib and other specific ALK inhibitors. Treatment eligibility is conventionally determined by the Food and Drug Administration-approved companion diagnostic fluorescence in situ hybridization (FISH) assay on paraffin-embedded tissue (PET). On limited samples such as fine needle aspiration-derived cytoblocks, FISH for ALK is often uninformative. FISH performed on liquid-based ThinPrep slides (ThinPrep-FISH) may represent a robust alternative.METHODS: Two hundred thirty cytology samples from 217 patients with advanced NSCLC, including a consecutive series of 179 specimens, were used to generate matched ThinPrep slides and paraffin cytoblocks. The same ThinPrep slides used for cytologic diagnosis were assessed by standard ALK break-apart two-color probe FISH, after etching of tumor areas. Ultrasensitive ALK immunohistochemistry (IHC) on corresponding cytoblocks [D5F3 antibody, OptiView signal amplification] served as the reference data set.RESULTS: ThinPrep-FISH ALK signals were robust in 228 of 230 cases and not compromised by nuclear truncation inherent in paraffin-embedded tissue-FISH; only two samples displayed no signals. Nine of 178 informative cases (5%) in the consecutive series and 18 of 228 informative cases (7.8%) overall were ALK rearranged by ThinPrep-FISH. In 154 informative matched ThinPrep-FISH and cytoblock-IHC samples, 152 were concordant (10, 6.5% ALK status positive; 142, 92.2% ALK status negative), and two (1.3%) were ThinPrep-FISH positive but IHC negative (sensitivity 100%, specificity 98.6%, overall agreement 98.7%).CONCLUSION: Detection of ALK gene rearrangements in liquid cytology ThinPrep slides derived from patients with NSCLC can be confidently used for clinical ALK molecular testing.


PubMed | Robert J Tomsich Pathology And Laboratory Medicine Institute
Type: Journal Article | Journal: Histopathology | Year: 2014

Intraductal carcinoma of the prostate (IDC-P) is a distinct clinicopathological entity and is associated with aggressive, high-grade and high-volume prostate carcinoma (PCa). The incidence, clinicopathological characteristics and prognostic significance of IDC-P have not been reported in prostate biopsies (PBx) that surgical pathologists encounter in their daily practice.In 1176 prospectively collected PBx, 33 IDC-P cases were identified (2.8%). The mean age of patients with IDC-P was 65 (range 46-79) years and mean serum prostate-specific antigen was 16.2 (range 0.4-105.6) ng/ml. Three (0.26%) IDC-P cases did not have a concomitant invasive PCa. Of 30 cases with concomitant invasive PCa, Gleason score was 7 in 16 (53.3%), 8 in four (13.3%) and 9 in 10 (33.3%) cases. The mean number of biopsy cores involved by PCa was 7.2 (range 1-14). Nine patients were treated with radical prostatectomy. Seminal vesicle invasion was found in four of nine (44%) cases, significantly higher than the risk of 12% predicted by Partin Tables (P = 0.016).This is the first prospective study that has investigated the incidence and prognostic significance of IDC-P diagnosed in PBx encountered in daily practice. It is critical for surgical pathologists to diagnose and report IDC-P in PBx.


PubMed | Robert J Tomsich Pathology And Laboratory Medicine Institute
Type: Journal Article | Journal: Seminars in thrombosis and hemostasis | Year: 2014

There are many unique issues that may make a pathologists consultation helpful in hemostasis testing. Besides the rapidly expanding knowledge of both bleeding and thrombotic disorders and a wide test menu, hemostasis testing is very sensitive to preanalytical issues (hemolysis, fill volume, time, temperature, storage conditions) and the interference of many commonly prescribed drugs. The pathologist can serve an important role in the evaluation of a patient for a bleeding or thrombotic disorder. Using defined algorithms, hemostasis testing can proceed in a logical fashion and be reported using patient-specific comments that take into account clinical history and medication therapy. This approach can improve the diagnostic process, preventing misdiagnoses and leading to a decreased time to diagnosis and an improved utilization of laboratory resources.

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