Browsing by Author "Wu, Howard H."

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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.
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    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.
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    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.
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    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.
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    The Dilemma of the Dilated Main Pancreatic Duct in the Distal Pancreatic Remnant After Proximal Pancreatectomy for IPMN
    (Springer, 2019-08) Simpson, Rachel E.; Ceppa, Eugene P.; Wu, Howard H.; Akisik, Fatih; House, Michael G.; Zyromski, Nicholas J.; Nakeeb, Attila; Al-Haddad, Mohammad A.; DeWitt, John M.; Sherman, Stuart; Schmidt, C. Max; Surgery, School of Medicine
    Objective(s) A dilated main pancreatic duct in the distal remnant after proximal pancreatectomy for intraductal papillary mucinous neoplasms (IPMN) poses a diagnostic dilemma. We sought to determine parameters predictive of remnant main-duct IPMN and malignancy during surveillance. Methods Three hundred seventeen patients underwent proximal pancreatectomy for IPMN (Indiana University, 1991–2016). Main-duct dilation included those ≥ 5 mm or “dilated” on radiographic reports. Statistics compared groups using Student’s T/Mann-Whitney U tests for continuous variables or chi-square/Fisher’s exact test for categorical variables with P < 0.05 considered significant. Results High-grade/invasive IPMN or adenocarcinoma at proximal pancreatectomy predicted malignant outcomes (100.0% malignant outcomes; P < 0.001) in remnant surveillance. Low/moderate-grade lesions revealed benign outcomes at last surveillance regardless of duct diameter. Twenty of 21 patients undergoing distal remnant reoperation had a dilated main duct. Seven had main-duct IPMN on remnant pathology; these patients had greater mean maximum main-duct diameter prior to reoperation (9.5 vs 6.2 mm, P = 0.072), but this did not reach statistical significance. Several features showed high sensitivity/specificity for remnant main-duct IPMN. Conclusions Remnant main-duct dilation after proximal pancreatectomy for IPMN remains a diagnostic dilemma. Several parameters show a promise in accurately diagnosing main-duct IPMN in the remnant.
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    Fine needle aspiration cytology of hepatic metastases of neuroendocrine tumors: A 20‐year retrospective, single institutional study
    (Wiley, 2018-01) Saeed, Omer A.; Cramer, Harvey; Wang, Xiaoyan; Wu, Howard H.; Pathology and Laboratory Medicine, School of Medicine
    Background Fine needle aspiration (FNA) is considered an excellent technique for documenting metastatic neuroendocrine tumors (NETs). This study aims to evaluate the accuracy of FNA in diagnosing metastatic NETs to the liver and determining the grade and origin of these metastases. Methods Our laboratory information system was searched from 1997 to 2016 to identify all cases of metastatic NETs to the liver that were sampled by FNA. The cytopathology and surgical pathology reports as well as the patients' electronic medical records were reviewed. The cytohistologic type and grade of the metastatic NETs, as well as the site of the patient's primary were recorded. Results High‐grade NETs, including small cell and poorly differentiated neuroendocrine carcinomas, constituted 62% (167/271) of the cases, while low‐grade NETs, including well differentiated NET (grade1 and grade 2), pheochromocytomas, paragangliomas, and carcinoid tumors of lung, constituted 38% (104/271) of cases. The most common diagnosis was metastatic small cell carcinoma accounting for 45% (122/271) of cases. The most common primary sites were lung (44%; 119/271) followed by pancreas (19%; 51/271). The FNA diagnosis was confirmed by histopathology in 121 cases that had a concurrent biopsies or resection specimens. Conclusions FNA is an accurate method for diagnosing metastatic NETs to the liver. There were significantly more high‐grade (62%) than low‐grade (38%) metastatic NETs to the liver. In our practice, lung (44%) and pancreas (19%) were the most common primary sites of metastatic NETs involving the liver. In 16% of the cases, a primary site could not be established.
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    Fine Needle Aspiration Cytology of Metastatic Plasmacytoid Urothelial Carcinoma- Report of Four Cases Including a Case of Mixed Plasmacytoid and Micropapillary Morphology
    (Karger, 2015-05) Wu, Howard H.; Kao, Chia-Sui; Grignon, David J.; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Objectives: The aim of this study was to report a small series of fine-needle aspiration (FNA) cytology of the plasmacytoid variant of urothelial carcinoma (PVUC). Study Design: A computerized search of our laboratory information system was performed for the 5-year period between January 2008 and January 2013 to identify all FNA cases in which the corresponding surgical pathology cases were diagnosed as PVUC. Results: The 4 cases identified were from 2 men (aged 56 and 64 years) and 2 women (aged 72 and 46 years). The FNA smears demonstrated low-to-moderate cellularity and consisted predominantly of single and dyshesive, medium-sized tumor cells with eccentrically located nuclei and a moderate-to-abundant dense cytoplasm. The nuclei were oval with slightly irregular nuclear membranes and contained coarse granular chromatin with inconspicuous or small nucleoli. There was moderate nuclear variation in size. The nuclear-to-cytoplasmic ratio ranged from <1 to 3. Binucleation, cytoplasmic vacuoles, and perinuclear hof were occasionally seen. Conclusions: FNA cytology of PVUC shares features with plasma cell neoplasms, lobular carcinoma of the breast, and signet ring cell carcinoma of the stomach. Being aware of the patient's clinical history and the potential diagnostic pitfall of this rare variant of urothelial carcinoma is important for an accurate diagnosis on FNA biopsy.
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    Fine-Needle Aspirates of Thyroid Microcarcinoma
    (Elsevier, 2017) Partyka, Kristen L.; Wu, Howard H.; Department of Pathology and Laboratory Medicine, School of Medicine
    Introduction Widespread use of ultrasound allows for detection of smaller thyroid nodules and preoperative evaluation with fine-needle aspiration (FNA). Both incidental and non-incidental microcarcinoma can be found, leading to uncertainty with clinical management. Materials and methods A retrospective analysis of thyroid FNAs performed at our institution was conducted for the 5-year period from 2010 to 2014. Aspirates were categorized using the Bethesda System for Reporting Thyroid Cytopathology. Cytologic diagnoses were then correlated with final histopathology. Among samples with malignancy on surgical resection, nodules were stratified by size. Results A total of 2531 thyroid FNAs were identified; 587 samples had histologic correlation, and 259 malignancies were reported. They were separated into nodules >1 cm (n = 144, 56%) and ≤1 cm (n = 115, 44%). Microcarcinoma was further subdivided into incidental (size ≤0.5 cm, n = 55, 48%) and non-incidental (size >0.5 cm and ≤1 cm, n = 60, 52%). The preoperative cytologic diagnoses for incidental microcarcinoma were: benign (B, n = 11, 20%), follicular lesion of undetermined significance (FLUS, n = 15, 27%), follicular neoplasm (FN, n = 11, 20%), suspicious for malignancy (SM, n = 7, 13%), malignant (M, n = 8, 15%), and nondiagnostic (ND, n = 3, 5%). The FNA categories for non-incidental microcarcinoma were: B (n = 13, 22%), FLUS (n = 3, 5%), FN (n = 3, 5%), SM (n = 10, 17%), M (n = 29, 48%), and ND (n = 2, 3%). Conclusions Incidental microcarcinoma is not an uncommon entity, making up 21% (55 of 259) of malignant nodules on thyroidectomy. Indeterminate diagnoses (FLUS + FN + SM) accounted for the majority (60%) of preoperative FNAs for incidental microcarcinoma, compared with 27% for those of non-incidental microcarcinoma (P < 0.05, χ2 test).
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    Fine-Needle Aspiration Cytology of Noninvasive Follicular Variant of Papillary Thyroid Carcinoma Is Cytomorphologically Distinct From the Invasive Counterpart
    (Oxford, 2016-09) Ibrahim, Ashley A.; Wu, Howard H.; Pathology and Laboratory Medicine, School of Medicine
    Objectives: To review a series of noninvasive encapsulated follicular variant of papillary thyroid carcinomas (FVPTCs) in an attempt to further define the role of cytopathology in the diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features and invasive FVPTC. Methods: Surgical pathology cases diagnosed as FVPTC with correlating thyroid fine-needle aspiration (FNA) were identified and divided into two FVPTC groups: noninvasive and invasive. Cytologic diagnoses were compared between them. Results: We identified 23 cases that met the criteria for noninvasive FVPTC and 27 cases that were typical infiltrative FVPTC (n = 16) or encapsulated FVPTC with either capsular and/or lymphovascular invasion (n = 11). Of the noninvasive FVPTC cases, there were four benign lesions, 14 follicular lesions of undetermined significance (FLUS), four follicular neoplasms (FNs), one suspicious case, and no papillary thyroid carcinomas (PTCs). In the invasive FVPTC group, there were no benign cases, four FLUS, three FNs, 12 suspicious cases, and eight PTCs. Conclusions: There is a distinction in the cytologic diagnosis between noninvasive and invasive FVPTC. The invasive subtype was diagnosed by FNA as suspicious for PTC or PTC in nearly 75% of cases, while only one (4%) case for the noninvasive subtype was diagnosed as suspicious for PTC ( P  < .05).
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    Fine‐needle aspiration cytology of metastatic spindle cell follicular thyroid carcinoma: A case report
    (Wiley, 2019-06) Chen, Yu-Hsin; Perrino, Carmen M.; Cheng, Liang; Wu, Howard H.; Pathology and Laboratory Medicine, School of Medicine
    Follicular thyroid carcinoma, spindle cell variant is extremely rare. The tumor is predominantly composed of spindle cells with a fusiform appearance that are arranged in intersecting fascicles. Fine‐needle aspiration biopsy of this entity has not been previously described. We report a case of a 58‐year‐old woman who presented with metastasis to a left neck lymph node 15 years after the original diagnosis. Fine‐needle aspiration cytology showed numerous bland, spindled to epithelioid cells with thin, elongated, and plump nuclei with finely granular chromatin and inconspicuous nucleoli. The tumor cells had a moderate amount of cytoplasm with occasional elongated cytoplasmic tails. The cells were arranged in irregular aggregates with a fascicular pattern or singly dispersed. The tumor cells demonstrated positive staining for pan‐keratin, PAX8, thyroid transcription factor‐1, and thyroglobulin, which confirmed thyroid primary origin.