IU Indianapolis ScholarWorks :: Browsing by Author "Cramer, Harvey M."

Browsing by Author "Cramer, Harvey M."

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Anaplastic Lymphoma Kinase Immunocytochemistry on Cell-Transferred Cytologic Smears of Lung Adenocarcinoma
(Karger, 2015-03) Zhang, Chen; Randolph, Melissa L.; Jones, Kelly J.; Cramer, Harvey M.; Cheng, Liang; Wu, Howard H.; Department of Pathology and Laboratory Medicine, IU School of Medicine
Background: Anaplastic lymphoma kinase (ALK) immunohistochemical staining on formalin-fixed paraffin-embedded tissue or cell blocks (CB) has been reported as an effective alternative to fluorescence hybridization in situ (FISH) for the detection of ALK gene rearrangement. However, CB frequently lack adequate cellularity even when the direct smears are cellular. This study aims to assess the utility of ALK immunocytochemical (ICC) staining on direct smears using the cell transfer (CT) technique for the detection of ALK rearrangement. Methods: Fine-needle aspiration (FNA) cases of lung adenocarcinoma in which the ALK status had been determined by FISH on CB or a concurrent biopsy were identified. ICC staining for ALK was performed on alcohol-fixed Papanicolaou-stained direct smears using the CT technique. ALK immunoreactivity was evaluated using a modified semiquantitative scale. Results were compared with those of FISH. Results: A total of 47 FNA specimens were included. Five of 7 FISH-positive cases showed positive ALK ICC staining (71.4%), and 39 of 40 FISH-negative cases were negative on ALK ICC staining (97.5%). The overall correlation between ALK ICC and FISH was 93.6%. Conclusion: ICC performed on FNA smears using the CT technique is an alternative method for the assessment of ALK rearrangement, especially when CB lack adequate cellularity.
The application of the Johns Hopkins Hospital Template on urine cytology
(Wiley, 2015-08) Wu, Howard H.; Redelman, Megan; Chen, Shaoxiong; Grignon, David J.; Cramer, Harvey M.; Department of Pathology and Laboratory Medicine, IU School of Medicine
Background To evaluate the utility of the Johns Hopkins Hospital (JHH) template in detection of high-grade urothelial carcinoma (HGUC). Methods A computerized search of our laboratory information system was performed for all urine cytology cases from 2009 to 2011 processed by the SurePath™. We included only cases with correlating surgical pathology within 6 months after the urinary samples were obtained. The original cytologic diagnoses were reclassified according to the JHH template, and these cytolog ic diagnoses were then correlated with the follow-up surgical pathology diagnoses. Results A total of 273 urine samples with histopathologic follow-up were identified. The reclassified cytologic diagnoses included negative for urothelial atypia or malignancy (NUAM) 110; atypical urothelial cells of undetermined significance (AUC-US) 83; atypical urothelial cells, cannot exclude high-grade urothelial carcinoma (AUC-H) 49; HGUC 29; and low-grade urothelial carcinoma (LGUC) 2. More than one-half of patients (58%) who had biopsy-confirmed high-grade urothelial lesions had a preceding cytologic diagnosis of AUC-H or HGUC. AUC-H and HGUC are associated with high-grade urothelial lesions in 80% and 90% of the cases and show statistical significance when compared with AUC-US or NUAM (P < 0.05). Conclusion The JHH template is useful and effective in identifying patients with high-grade urothelial lesions who need to undergo cystoscopy. Diagn. Cytopathol. 2015;43:593–597. © 2015 Wiley Periodicals, Inc.
Application of the Milan System for Reporting Salivary Gland Cytopathology: A Retrospective 12-Year Bi-institutional Study
(Oxford, 2019-06) Wu, Howard H.; Alruwaii, Fatimah; Zeng, Bao-Rung; Cramer, Harvey M.; Lai, Chiung-Ru; Hang, Jen-Fan; Pathology and Laboratory Medicine, School of Medicine
Objectives Multi-institutional studies are required for the validation of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). Methods A total of 1,560 fine-needle aspirations of the salivary glands were retrieved from two institutions for a 12-year period. The diagnoses were reclassified based on the MSRSGC. Risk of malignancy (ROM) for each category was calculated based on 694 histologic follow-up cases. Results The ROM for each category was: 18.3% for nondiagnostic, 8.9% for nonneoplastic, 37.5% for atypia of undetermined significance (AUS), 2.9% for benign neoplasm, 40.7% for salivary gland neoplasm of uncertain malignant potential (SUMP), 100% for suspicious for malignancy, and 98.3% for malignant. The sensitivity, specificity, positive predictive rate, and negative predictive rates were 89%, 99%, 98%, and 96%, respectively. Conclusions The results of the current study are in keeping with the MSRSGC. The indeterminate categories of AUS and SUMP showed intermediate ROMs at 37.5% and 40.7%, respectively.
Detection of BRAF Mutations on Direct Smears of Thyroid Fine Needle Aspirates through Cell Transfer Technique
(Oxford, 2015-04) Shi, Qiuying; Ibrahim, Ashley; Herbert, Kristi; Carvin, Marcia; Randolph, Melissa; Post, Kristin M.; Curless, Kendra; Chen, Shaoxiong; Cramer, Harvey M.; Cheng, Liang; Wu, Howard H.; Department of Pathology and Laboratory Medicine, IU School of Medicine
Objectives: To determine the utility of the cell transfer technique (CTT) for BRAF molecular testing on thyroid fine-needle aspiration (FNA) specimens. Methods: Polymerase chain reaction (PCR)–based BRAF molecular testing was performed on tissues obtained through CTT from both air-dried and ethanol-fixed direct smears of thyroid FNA specimens and then compared with the corresponding thyroidectomy formalin-fixed, paraffin-embedded (FFPE) tissues on 30 cases. Results: BRAF testing was successfully performed on 29 of 30 air-dried CTT, 27 of 30 ethanol-fixed CTT, and 27 of 30 FFPE tissues. The results exhibited 11, 13, and 13 BRAF mutations and 18, 14, and 14 wild types for the air-dried CTT, the ethanol-fixed CTT, and the FFPE tissues, respectively. The concordance rate was 96% between air-dried and ethanol-fixed CTT tissues, 88% between air-dried CTT and FFPE tissues, and 92% between ethanol-fixed CTT and FFPE tissues. Conclusions: PCR-based BRAF mutational testing can be reliably performed on the direct smears of the thyroid FNA specimens through the application of CTT.
Endoscopic ultrasound characteristics of pancreatic lymphoepithelial cysts: A case series from a large referral center.
(Wolters Kluwer, 2016) Dalal, Kunal S.; DeWitt, John M.; Sherman, Stuart; Cramer, Harvey M.; Tirkes, Temel; Al-Haddad, Mohammad A.; Department of Pathology and Laboratory Medicine, IU School of Medicine
BACKGROUND AND OBJECTIVES: Lymphoepithelial cysts (LECs) of the pancreas are benign lesions that can mimic cystic neoplasms on imaging. Endoscopic ultrasound (EUS) features have not been well described. We aimed to describe the clinical and EUS characteristics of LECs and the present outcomes of management at a high-volume referral center. MATERIALS AND METHODS: We identified patients who underwent EUS and were found to have LECs based on fine-needle aspiration (FNA) cytology or surgical pathology from existing databases. EUS features, imaging characteristics, and pathology results were described. RESULTS: Sixteen patients were found to have 17 LECs. The mean size was 33 mm ± 15 mm. Locations within the pancreas included 10 lesions in the tail, 3 in the body, 1 in the uncinate process; the remaining 3 were exophytic. Six lesions were anechoic, 6 were hypoechoic, and 5 had mixed echogenicity. Nine lesions had mixed solid/cystic components, 7 were purely cystic, and 1 was solid. Cyst fluid was thick or viscous in six cases and thin in three. Eleven patients had diagnostic cytopathology. Six patients ultimately underwent surgery due to symptoms, nondiagnostic FNA, or other clinical concerns for malignancy. CONCLUSIONS: Pancreatic LECs have variable morphology and echogenicity on EUS, but the appearance of a cyst with variable solid and cystic components combined with the appearance of thick, turbid, and viscous aspirate should raise suspicion for an LEC. The majority of patients with LECs at our center avoided surgery for LECs on the basis of diagnostic EUS-FNA.
High Apoptotic Index in Urine Cytology Is Associated with High-Grade Urothelial Carcinoma
(Wiley, 2016-08) Yang, Chi-Shun; Chen, Shaoxiong; Cramer, Harvey M.; Wu, Howard H.; Department of Pathology and Laboratory Medicine, IU School of Medicine
BACKGROUND The significance of apoptosis and its association with high-grade urothelial carcinoma (HGUC) in urine cytology has yet to be determined. METHODS A computerized search of the study laboratory information system was performed over a 3-year period for all urine cytology specimens processed using the SurePath liquid-based preparation technique. Only those cases with correlating surgical pathology obtained within 6 months after the urine cytologic samples were included in the current study. Cases from ileal conduit samples were excluded. A semiquantitative numerical scoring system (apoptotic index) was used to assess the amount of pyknosis or karyorrhexis, with 0 indicating none, 1 indicating < 10 per 10 high-power fields, 2 indicating 10 to 30 per 10 high-power fields, and 3 indicating > 30 per 10 high-power fields. Statistical analysis using the Pearson chi-square test was performed. RESULTS A total of 228 cases including 105 benign cases, 79 cases of HGUC, and 44 cases of low-grade urothelial carcinoma (LGUC) diagnosed on follow-up surgical pathology were selected. A score of 0 was observed in 70 benign, 11 HGUC, and 8 LGUC cases; a score of 1 was observed in 31 benign, 21 HGUC, and 23 LGUC cases; a score of 2 was observed in 3 benign, 27 HGUC, and 9 LGUC cases; and a score of 3 was observed in 1 benign, 20 HGUC, and 4 LGUC cases. CONCLUSIONS Excluding ileal conduit urine specimens, the finding of a high apoptotic index (score ≥ 2) with the presence of pyknosis or karyorrhexis in ≥10 per 10 high-power fields in the urine cytology appears to be significantly associated with HGUC (P<.05).
TCGA data and patient-derived orthotopic xenografts highlight pancreatic cancer-associated angiogenesis
(Impact Journals, LLC, 2015-04-10) Gore, Jesse; Craven, Kelly E.; Wilson, Julie L.; Cote, Gregory A.; Cheng, Monica; Nguyen, Hai V.; Cramer, Harvey M.; Sherman, Stuart; Korc, Murray; Department of Medicine, IU School of Medicine
Pancreatic ductal adenocarcinomas (PDACs) overexpress pro-angiogenic factors but are not viewed as vascular. Using data from The Cancer Genome Atlas we demonstrate that a subset of PDACs exhibits a strong pro-angiogenic signature that includes 37 genes, such as HDAC9, that are overexpressed in PDAC arising in KRC mice, which express mutated Kras and lack RB. Moreover, patient-derived orthotopic xenografts can exhibit tumor angiogenesis, whereas conditioned media (CM) from KRC-derived pancreatic cancer cells (PCCs) enhance endothelial cell (EC) growth and migration, and activate canonical TGF-β signaling and STAT3. Inhibition of the type I TGF-β receptor with SB505124 does not alter endothelial activation in vitro, but decreases pro-angiogenic gene expression and suppresses angiogenesis in vivo. Conversely, STAT3 silencing or JAK1-2 inhibition with ruxolitinib blocks CM-enhanced EC proliferation. STAT3 disruption also suppresses endothelial HDAC9 and blocks CM-induced HDAC9 expression, whereas HDAC9 re-expression restores CM-enhanced endothelial proliferation. Moreover, ruxolitinib blocks mitogenic EC/PCC cross-talk, and suppresses endothelial p-STAT3 and HDAC9, and PDAC progression and angiogenesis in vivo, while markedly prolonging survival of KRC mice. Thus, targeting JAK1-2 with ruxolitinib blocks a final pathway that is common to multiple pro-angiogenic factors, suppresses EC-mediated PCC proliferation, and may be useful in PDACs with a strong pro-angiogenic signature.
The Role of Fluorescence In Situ Hybridization in Pancreatobiliary Brushing Cytology: A Large Retrospective Review with Histologic Correlation
(MDPI, 2022-10-14) Khan, Jaffar; De la Sancha, Carlo; Saad, Mohammed; Alkashash, Ahmad; Ullah, Asad; Alruwaii, Fatimah; Velasquez Zarate, Luis; Cramer, Harvey M.; Wu, Howard H.; Pathology and Laboratory Medicine, School of Medicine
(1) Background: Although the specificity of brush cytology for the detection of malignant pancreaticobiliary strictures is high, its sensitivity is low. Fluorescence in situ hybridization (FISH) can be used to detect chromosomal aneuploidy in biliary brushing specimens, and when used as an adjunct to routine cytology, it significantly improves diagnostic sensitivity. (2) Methods: We searched our laboratory information system to identify all bile duct brush cytology cases with follow-up surgical pathology between January 2001 and September 2019. Cytologic diagnoses were classified as negative, atypical, suspicious, or malignant. Correlated surgical pathological diagnoses were classified as benign or malignant. FISH test results were obtained for a subset of cytology cases with concurrent FISH testing, and the sensitivity, specificity, positive predictive value, and negative predictive value in identifying malignancy for cytology alone, FISH alone, and combined cytology and FISH were calculated. (3) Results: A total of 1017 brushing cytology cases with histologic correlation were identified. A total of 193 FISH tests were performed concurrently with cytological specimens. Malignant diagnoses were identified in 623 of 1017 patients, while 394 patients had benign strictures. The sensitivity, specificity, positive predictive, and negative predictive rate were 65%, 78%, 83%, and 49% for cytology alone; 72%, 67%, 63%, and 68% for FISH alone; and 85%, 42%, 60%, and 74% for combined cytology and FISH, respectively. Among FISH-positive cases, the risk of malignancy for polysomy was 82% and 32% for trisomy. (4) Conclusions: FISH improves the sensitivity and negative predictive rate of bile duct brush cytology. The combination of cytology and FISH has increased the sensitivity from 65% to 85% and the negative predictive rate from 49% to 74% when compared to cytology alone. A patient with a polysomy FISH result had a significantly higher risk of malignancy than a patient with a trisomy 7 result (82% vs. 32%, p < 0.00001).
World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading in fine‐needle aspiration biopsies of renal masses
(Wiley, 2018-11) Perrino, Carmen M.; Cramer, Harvey M.; Chen, Shaoxiong; Idrees, Muhammad T.; Wu, Howard H.; Pathology and Laboratory Medicine, School of Medicine
Background Utilization of fine‐needle aspiration (FNA) biopsy for the evaluation of renal masses has been increasing at our institution. At times diagnostic material on direct smears is superior to that in the cell block/core biopsy, therefore assigning an accurate nuclear grade in the cytopathology report would provide useful prognostic information. Methods Search of the pathology database identified renal FNAs performed during an 11‐year period (2006–2017). Corresponding core biopsies and resections were identified. Cases with a diagnosis of primary renal neoplasia on FNA, core biopsy, and/or resection were included. Two pathologists reviewed all cases and assigned a World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade to each FNA, core biopsy, and resection case. Results A total of 162 kidney FNAs were identified. Primary renal neoplasia was diagnosed in 137 cases on core biopsy/resection. Among diagnostic FNAs of clear cell RCC and papillary RCC with core biopsy/resection specimens for re‐review (n = 52), reviewers assigned a concordant WHO/ISUP grade to 83% (43/52) of cases. Among 9 cases with discrepant scores, all had a discrepancy of 1 grade and were undergraded on FNA. Using a two tier grading system (low vs. high grade), reviewers assigned a concordant grade to 88% (46/52) of cases. Among 6 cases with discrepant scores, all were classified as low grade (WHO/ISUP grade 2) on FNA versus high grade (WHO/ISUP grade 3) on resection. Conclusion The WHO/ISUP grade assigned on FNA shows good concordance with subsequent resection/core specimens (83%), with all discrepant cases being undergraded by one grade.

Browsing by Author "Cramer, Harvey M."

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