Publications by authors named "Jordan P Reynolds"

57 Publications

Spindle cell neoplasms of the upper gastrointestinal tract, hepatobiliary tract, and pancreas by fine needle aspiration: A single institutional experience of 15 years with follow-up data.

Diagn Cytopathol 2021 May 18. Epub 2021 May 18.

Department of Laboratory Medicine, Robert J Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Background: The diagnosis of spindle cell neoplasms (SCN) of the upper gastrointestinal (GI) tract, hepatobiliary tract, and pancreas detected by fine needle aspiration (FNA) is challenging. We describe a single-center experience of these samples with follow-up data and characterization of the morphologic findings.

Methods: We retrospectively reviewed pathology records for all FNAs diagnostic for or suggestive of SCN on esophagus, stomach, small bowel, liver, and pancreas in a 15 year period. All cases with at least 6 month follow-up were included. Surgical material (biopsy or resection) was the diagnostic gold standard. All FNAs with subsequent surgical specimens were reviewed and assessed for cellularity, architectural features, and nuclear features.

Results: In 15 years, 5101 FNAs of the upper GI tract, hepatobiliary tract, and pancreas were performed. SCN was diagnosed in 98 (2%) patients. Seventy-two patients had definitive pathologic diagnoses: 68 were neoplastic and four were non-neoplastic. Cytomorphologic review in relationship to final diagnosis revealed three statistically significant features: low cellularity favors a benign process (P = .00544), epithelioid nuclear morphology favors malignancy (P = .00278), and identification of perinuclear vacuoles favors a diagnosis of GIST over non-GIST SCN (P = .04236).

Conclusions: Among cases with follow-up, final pathologic diagnoses were SCN in 94% of cases diagnosed as SCN on FNA of upper GI, hepatobiliary tract, and pancreas. Although some cytomorphologic criteria are more suggestive of malignancy, arriving at a specific diagnosis relies on collaboration of clinical, radiologic, cytomorphologic, and immunohistochemical data.
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http://dx.doi.org/10.1002/dc.24801DOI Listing
May 2021

Urine cytology findings in patients with biopsy-confirmed urothelial carcinoma in situ with plasmacytoid features.

Cancer Cytopathol 2021 Apr 26. Epub 2021 Apr 26.

Department of Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.

Background: Urine cytology is an important screening tool in the diagnosis of high-grade urothelial carcinoma. Diagnosis in urine samples follows criteria outlined by The Paris System for Reporting Urinary Cytology (TPS). However, cytologic characteristics of the recently described urothelial carcinoma in situ with plasmacytoid features (P-CIS) have not been described, and it is unknown whether they conform to TPS criteria for high-grade urothelial carcinoma. This study was aimed at better characterizing possibly unique cytologic features of P-CIS.

Methods: The authors collected urine cytology specimens from patients with subsequent bladder biopsy-proven P-CIS. Specimens were re-reviewed according to the TPS criteria. The proposed cytologic features of P-CIS (eccentric, enlarged, and hyperchromatic nuclei) were evaluated; this included the reproducibility of 3 cytopathologists for the proposed cytologic features.

Results: Seventy-four urine specimens from 18 patients with P-CIS-diagnosed bladder biopsies were identified. The TPS diagnoses of the 74 urine cytology specimens were as follows: negative for high-grade urothelial carcinoma (n = 26), atypical urothelial cells (n = 26), suspicious for high-grade urothelial carcinoma (n = 12), and high-grade urothelial carcinoma (n = 10). Only 7 urine specimens met the proposed cytologic criteria for P-CIS, and they had TPS diagnoses of negative for high-grade urothelial carcinoma (n = 1), atypical urothelial cells (n = 3), and high-grade urothelial carcinoma (n = 3). The κ interobserver agreement ranged from poor to fair.

Conclusion: The features of P-CIS on urine cytology are subtle and infrequently reproducible and often do not meet the TPS criteria for diagnosis as high-grade urothelial carcinoma. In specimens that do not meet TPS criteria for high-grade urothelial carcinoma, P-CIS cytology in isolation would be best classified as atypical urothelial cells.
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http://dx.doi.org/10.1002/cncy.22445DOI Listing
April 2021

(TAZ)- gene fusion is sufficient to dysregulate YAP/TAZ signaling and drive epithelioid hemangioendothelioma tumorigenesis.

Genes Dev 2021 Apr 25;35(7-8):512-527. Epub 2021 Mar 25.

Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Epithelioid hemangioendothelioma (EHE) is a genetically homogenous vascular sarcoma that is a paradigm for TAZ dysregulation in cancer. EHE harbors a (TAZ)- gene fusion in >90% of cases, 45% of which have no other genetic alterations. In this study, we used a first of its kind approach to target the gene fusion to the locus, to develop a conditional EHE mouse model whereby is controlled by the endogenous transcriptional regulators upon Cre activation. These mice develop EHE tumors that are indistinguishable from human EHE clinically, histologically, immunohistochemically, and genetically. Overall, these results demonstrate unequivocally that TAZ-CAMTA1 is sufficient to drive EHE formation with exquisite specificity, as no other tumor types were observed. Furthermore, we fully credential this unique EHE mouse model as a valid preclinical model for understanding the role of TAZ dysregulation in cancer formation and for testing therapies directed at TAZ-CAMTA1, TAZ, and YAP/TAZ signaling.
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http://dx.doi.org/10.1101/gad.348220.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015722PMC
April 2021

Endotracheal Tube Obstruction Among Patients Mechanically Ventilated for ARDS Due to COVID-19: A Case Series.

J Intensive Care Med 2021 May 30;36(5):604-611. Epub 2020 Dec 30.

Department of Pulmonary/Critical Care, Respiratory Institute, 2569Cleveland Clinic, OH, USA.

Background: Patients with COVID-19 and ARDS on prolonged mechanical ventilation are at risk for developing endotracheal tube (ETT) obstruction that has not been previously described in patients with ARDS due to other causes. The purpose of this report is to describe a case series of patients with COVID-19 and ARDS in which ETT occlusion resulted in significant clinical consequences and to define the pathology of the obstructing material.

Methods: Incidents of ETT occlusion during mechanical ventilation of COVID-19 patients were reported by clinicians and retrospective chart review was conducted. Statistical analysis was performed comparing event rates between COVID-19 and non-COVID 19 patients on mechanical ventilation over the predefined period. Specimens were collected and submitted for pathological examination.

Findings: Eleven COVID-19 patients experienced endotracheal tube occlusion over a period of 2 months. Average age was 69 (14.3, range 33-85) years. Mean APACHE III score was 73.6 (17.3). All patients had AKI and cytokine storm. Nine exhibited biomarkers for hypercoagulability. Average days on mechanical ventilation before intervention for ETT occlusion was 14 (5.18) days (range of 9 to 23 days). Five patients were discharged from the ICU, and 4 expired. Average documented airway resistance on admission was 14.2 (3.0) cm HO/L/sec. Airway resistance before tube exchange was 28.1 (8.0) cm HO /L/sec. No similar events of endotracheal tube occlusion were identified in non-COVID patients on mechanical ventilation during the same time period. Microscopically, the material consisted of mucin admixed with necrotic cell debris, variable numbers of degenerated inflammatory cells, oral contaminants and red blood cells.

Interpretation: Patients with COVID-19 and ARDS on prolonged mechanical ventilation are at risk for developing ETT obstruction due to deposition of a thick, tenacious material within the tube that consists primarily of mucin and cellular debris. Clinicians should be aware of this dangerous but treatable complication.
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http://dx.doi.org/10.1177/0885066620981891DOI Listing
May 2021

Germline EGFR variants are over-represented in adolescents and young adults (AYA) with adrenocortical carcinoma.

Hum Mol Genet 2021 01;29(22):3679-3690

Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.

Adrenocortical Carcinoma (ACC) is a rare endocrine tumor with poor overall prognosis and 1.5-fold overrepresentation in females. In children, ACC is associated with inherited cancer syndromes with 50-80% of childhood-ACC associated with TP53 germline variants. ACC in adolescents and young adults (AYA) is rarely due to germline TP53, IGF2, PRKAR1A and MEN1 variants. We analyzed exome sequencing data from 21 children (<15y), 32 AYA (15-39y), and 60 adults (>39y) with ACC, and retained all pathogenic, likely pathogenic, and highly prioritized variants of uncertain significance. We engineered a stable lentiviral-mutant ACC cell line, harboring an EGFR variant (p.Asp1080Asn) from a 21-year-old female without germline-TP53-variant and with aggressive ACC. We found that 4.8% of the children (P = 0.004) and 6.2% of AYA (P < 0.0001), all-female participants, harbored germline EGFR variants, compared to only 0.3% of the control group. Expanding our analysis to the RTK-RAS-MAPK pathway, we found that the RTK genes have the highest number of highly prioritized germline variants in these individuals amongst all three arms of this pathway. We showed EGFR mutant cells migrate faster and are characterized by a stem-like phenotype compared to wild type cells. While EGFR inhibitors did not affect the stemness of mutant cells, Sunitinib, a multireceptor tyrosine kinase inhibitor, significantly reduced their stem-like behavior. Our data suggest that EGFR could be a novel underlying germline predisposition factor for ACC, especially in the Childhood-AYA (C-AYA) population. Further clinical validation can improve precision oncology management of this disease, which is known to have limited therapeutic options.
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http://dx.doi.org/10.1093/hmg/ddaa268DOI Listing
January 2021

Reversing Historical Trends.

Am J Clin Pathol 2021 01;155(1):1-3

Department of Pathology and Laboratory Medicine, University of Washington, Seattle.

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http://dx.doi.org/10.1093/ajcp/aqaa192DOI Listing
January 2021

Results from the 2019 American Society of Cytopathology survey on rapid onsite evaluation (ROSE)-part 2: subjective views among the cytopathology community.

J Am Soc Cytopathol 2020 Nov - Dec;9(6):570-578. Epub 2020 Jul 21.

Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.

Introduction: This study aims to improve understanding of the cytopathology community's perspective regarding the value of rapid onsite evaluation (ROSE) in clinical practice.

Materials And Methods: The American Society of Cytopathology membership was surveyed in 2019 to obtain subjective data on the cytopathology community's perceptions regarding ROSE. Comments were categorized by major themes and attitudes and analyzed by respondent's role in laboratory, practice size, and practice setting (Fisher's exact and χ tests).

Results: A total of 541 responses were received from 255 cytopathologists/pathologists, 261 cytotechnologists, 19 trainees, and 6 others (as previously reported). Reasons for which cytopathology personnel provide this service aligned with their perceptions of why clinicians request ROSE. A minority of respondents, disproportionally from high volume centers, felt ROSE is unnecessary. Overall attitude regarding ROSE was generally positive. There were no significant differences in attitude regarding ROSE according to role in laboratory or practice size, but respondents from academic centers provided a significantly higher percentage of positive comments than those in private or community practice. Although survey respondents generally felt that ROSE is valuable to patient care, they also highlighted several challenges, including staffing, time commitment, and inadequate reimbursement. Implementation of telecytology was felt to potentially alleviate some of these challenges.

Conclusions: Survey results show that the cytology community views ROSE favorably, practices vary considerably, and there is a perceived need for improved reimbursement. Data from this study may be used to identify areas that warrant additional research to clarify the clinical value of ROSE.
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http://dx.doi.org/10.1016/j.jasc.2020.06.010DOI Listing
July 2020

Malignant solitary fibrous tumour of the prostate: four cases emphasising significant histological and immunophenotypical overlap with sarcomatoid carcinoma.

Pathology 2020 Oct 2;52(6):643-648. Epub 2020 Aug 2.

Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address:

Solitary fibrous tumour (SFT) is well-described in the urinary tract, but malignant examples are rare. We studied our experience with high grade malignant SFT of the prostate to address the degree of histological and immunophenotypical overlap with sarcomatoid carcinoma and prostatic stromal sarcoma. Four cases were identified from the surgical pathology consultation archives. All available H&E stained sections were reviewed. Immunostains for STAT6, CAM5.2, NKX3.1, PAX-8, GATA3, high molecular weight cytokeratin (34BE12), p40, and p63 were performed on available material. Each case was evaluated by three separate SFT prognostic risk models based on clinicopathological features, and for features of 'dedifferentiated SFT'. The patient's ages were 49, 55, 69, and 73 years. Three presented with symptoms of benign prostatic hyperplasia and one with haematuria. Tumour sizes were 5, 9, 13, and 13 cm. Mitotic rate ranged from 6 to 20 mitoses per 10 high power fields, and two cases showed abrupt transition from conventional SFT to areas with marked nuclear pleomorphism/anaplasia (i.e., 'de-differentiation'). Immunophenotypically, all four cases had strong and diffuse nuclear reactivity for STAT6. For other markers, three of three had both focal PR and GATA3 nuclear expression (up to 30% of cells). One case with 'dedifferentiated' features showed expression of multiple epithelial markers, including EMA (focal), high molecular weight cytokeratin (focal), p63, and p40. In summary, malignant SFT may rarely occur in the prostate and may closely mimic sarcomatoid carcinoma or prostatic stromal sarcoma, both histologically and immunophenotypically. Consideration of the diagnostic possibility of malignant SFT, recognition of unexpected GATA3 and PR expression, and utilisation of monoclonal STAT6 immunohistochemistry facilitate appropriate diagnosis at this unusual anatomical site.
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http://dx.doi.org/10.1016/j.pathol.2020.06.004DOI Listing
October 2020

Cytology and curetting diagnosis of endocervical adenocarcinoma.

J Am Soc Cytopathol 2020 Nov - Dec;9(6):556-562. Epub 2020 Jun 5.

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Introduction: Papanicolaou testing is effective in identifying squamous intraepithelial lesions of the cervix. Endocervical adenocarcinoma (EAC) and adenocarcinoma in situ (AIS) are far less commonly identified. Endocervical curettings (ECCs) are usually obtained after colposcopic biopsy, sample the endocervical canal, and aid in the detection of endocervical glandular lesions. Here, we examine the utility of Papanicolaou testing and endocervical curetting for detecting AIS and EAC.

Materials And Methods: Cases from 2007 to 2019 with a histologically confirmed diagnosis of AIS and EAC were identified and the clinical data and diagnostic material, including the cytology and surgical specimens, obtained.

Results: A total of 108 cases of AIS and EAC were identified, Papanicolaou tests were performed in 97 of these cases, and ECC in 87. AIS or EAC were detected in 46.4% of Papanicolaou tests; 41.4% of ECC showed AIS or EAC. A total of 92.7% of cases were positive for high-risk human papillomavirus (HPV) and concurrent squamous intraepithelial lesion was present in 53.3% of cases. AIS or EAC were more commonly identified in cases without concurrent squamous intraepithelial lesions.

Conclusions: Papanicolaou testing and endocervical curettings have a low detection rate for AIS and EAC. The majority of AIS and EAC cases test positive for high-risk HPV. Papanicolaou test and ECC show different detection rates and are complementary tools in patients with AIS and EAC. In some settings, an ECC can increase the diagnostic sensitivity and specificity of the pathologic diagnosis.
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http://dx.doi.org/10.1016/j.jasc.2020.05.007DOI Listing
June 2020

A Modern Assessment of Cancer Risk in Adrenal Incidentalomas: Analysis of 2219 Patients.

Ann Surg 2020 Jun 11. Epub 2020 Jun 11.

Department of Endocrine Surgery, Cleveland Clinic, Cleveland, OH.

Objective: The aim of this study was to analyze the incidence of and risk factors for adrenocortical carcinoma (ACC) in adrenal incidentaloma (AI).

Summary Of Background Data: AI guidelines are based on data obtained with old-generation imaging and predominantly use tumor size to stratify risk for ACC. There is a need to analyze the incidence and risk factors from a contemporary series.

Methods: This is a retrospective review of 2219 AIs that were either surgically removed or nonoperatively monitored for ≥12 months between 2000 and 2017. Multivariate logistic regression was performed to define risk factors. ROC curves constructed to determine optimal size and attenuation cut-offs for ACC.

Results: 16.8% of AIs underwent upfront surgery and rest initial nonoperative management. Of conservatively managed patients, an additional 7.7% subsequently required adrenalectomy. Overall, ACC incidence in AI was 1.7%. ACC rates by size were 0.1%, 2.4%, and 19.5% for AIs of <4, 4 to 6, and >6 cm, respectively. The optimal size cut-off for ACC in AI was 4.6 cm. ACC risks by Hounsfield density were 0%, 0.5%, and 6.3% for lesions of <10, 10 to 20, and >20 HU, with an optimal cut-off of 20 HU to diagnose ACC. 15.5% of all AIs and 19.2% of ACCs were hormonally active. Male sex, large tumor size, high Hounsfield density, and >0.6 cm/year growth were independent risk factors for ACC.

Conclusion: This contemporary analysis demonstrates that ACC risk per size in AI is less than previously reported. Given these findings, modern management of AIs should not be based just on size, but a combination of thorough hormonal evaluation and imaging characteristics.
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http://dx.doi.org/10.1097/SLA.0000000000004048DOI Listing
June 2020

Fine needle aspiration of mediastinal germ cell tumors.

Semin Diagn Pathol 2020 Jul 13;37(4):174-178. Epub 2020 May 13.

Department of Pathology and Laboratory Medicine University of Florida-Jacksonville, Jacksonville, FL.

Germ cell tumors in the mediastinum are rare and often occur in young patients but may occur in older patients. Seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma and teratoma have distinct morphologic features with high grade nuclei. They are the primary diagnostic consideration in young males but may be lower on the list in older patients, where they may be misdiagnosed as carcinomas. Review of the history, use of immunohistochemistry stains and recognition of morphologic features will help to make the diagnosis of germ cell tumor of the mediastinum. These tumors have a good to intermediate prognosis, depending on when they are detected.
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http://dx.doi.org/10.1053/j.semdp.2020.04.008DOI Listing
July 2020

Cytopathology milestones: can you get to level 5?

J Am Soc Cytopathol 2020 Jul - Aug;9(4):242-248. Epub 2020 Mar 30.

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio.

Introduction: ACGME Milestones describe 6 areas of proficiency, indicating readiness for practice. Each is divided into 5 levels of mastery; Level 1 (new trainees) through Levels 4 (graduation) and 5 (aspirational). Milestones reporting began Spring 2016. We used Milestones to assess graduated fellows.

Materials And Methods: We conducted phone interviews with previous fellows and collected demographic information including practice setting. We asked graduates if they fulfilled each example of mastery and recorded their answers.

Results: A total of 22 fellows graduated from 2010 to 2017; 15 responded (10 academic, 5 private). Milestones in which nearly all respondents performed well (Level 4+) were: PC1, MK1, SBP2, SBP4, PROF1-4, ICS1-3. Some were more challenging (PC2, MK2, SBP1/3/5, PBL1). For PC2, 2 respondents achieved Level 1 (did not perform fine-needle aspirations). For MK2, 2 respondents achieved Level 1 (did not evaluate Papanicolaou). For SBP1, 80% in private practice achieved Level 5; 50% in academics achieved Level 3. For SBP3, 80% in private practice achieved Level 4+; 100% in academics achieved maximum Level 2. For SBP5, 60% of all respondents achieved maximum Level 3; only 1 achieved Level 5.

Conclusions: Many Milestones are attainable. Eleven of 18 yielded Level 4+ from most respondents. Three (PC2, MK1, MK2) yielded rare Level 1 due to scope of practice. Others (SBP1, SBP3) reflect more of an all-or-nothing phenomenon. For SBP5, most respondents achieved Level 3; only 1 achieved Level 5. Some Milestones are highly dependent on practice setting, and others remain aspirational.
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http://dx.doi.org/10.1016/j.jasc.2020.03.002DOI Listing
July 2021

E-cigarette or vaping product use-associated lung injury: What is the role of cytologic assessment?

Cancer Cytopathol 2020 06 27;128(6):371-380. Epub 2020 Jan 27.

Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.

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http://dx.doi.org/10.1002/cncy.22237DOI Listing
June 2020

Fibrous Extracellular Spheroids in an Endoscopic Ultrasound-Guided Pancreatic Fine Needle Aspiration Correlating to a Gyriform Pancreatic Endocrine Tumor with a Unique Cobblestone Pavement Growth Pattern.

Case Rep Pathol 2019 17;2019:1701072. Epub 2019 Oct 17.

Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.

Pancreatic neuroendocrine neoplasms (PanNENs) are uncommon tumors. Fine needle aspiration (FNA) samples from PanNENs are typically of high cellularity and lack necrosis. In cytology slides from these tumors, dyscohesive cells are usually reported with variably round to oval to plasmacytoid forms exhibiting coarsely granular chromatin and showing immunoreactivity for synaptophysin. We present an unusual, and to our knowledge not previously described, example of an FNA of a PanNEN with large extracellular fibrous spheroids containing intrinsic fibroblasts and rimmed by small to intermediate sized neoplastic epithelial cells with high nuclear cytoplasmic ratios. The cytomorphology of the PanNEN in this case was in some ways reminiscent of that expected in adenoid cystic carcinomas of the salivary glands that most often contain large extracellular globules of basement membrane material and a somewhat biphasic population of lesional cells. The cytomorphology in this case was found to correlate well with the resection specimen histomorphology of an exaggerated gyriform pattern of growth resulting in a unique cobblestone-pavement like microscopic appearance. Knowledge of this potential cytomorphology will aid the cytology community through recognition and reporting of this previously undescribed pattern in an uncommon disease.
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http://dx.doi.org/10.1155/2019/1701072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854169PMC
October 2019

Primary tumor types and origins in positive abdominopelvic washing cytology, a single institution experience.

J Am Soc Cytopathol 2020 Mar - Apr;9(2):89-94. Epub 2019 Oct 14.

Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio.

Introduction: Abdominopelvic washing cytology is a common specimen evaluated for ovarian, fallopian tubal, and peritoneal cancer staging or other nongynecologic malignancies presented as metastases. We reviewed our experience in diagnosing abdominopelvic washing specimens and assessing the primary tumor types and origins of the positive abdominopelvic washings.

Materials And Methods: A pathology archive database search was performed for abdominopelvic washing specimens from 2007 to 2018. The corresponding cytologic diagnoses, results of ancillary studies, clinical histories, and surgical follow-up were reviewed. The primary sites were determined based on the synoptic reports, when available.

Results: A total of 5.8% (350 of 6023) of cases were positive for malignancy or neoplasm. Additionally, 1.3% (78 of 6023) were diagnosed as atypical cells. Of the 350 positive cases, 93.4% were müllerian tumors. The frequency of primary sites for müllerian tumors in descending order were: ovary, uterus, fallopian tube, peritoneum, and uncertain müllerian sites. The common ovarian tumors identified in pelvic washing in descending order were: high-grade serous carcinoma, serous borderline tumor, clear cell carcinoma, low-grade serous carcinoma, and endometrioid carcinoma. Gastrointestinal, breast, bladder, and lymphoma primaries were the 23 nongynecologic tumors identified in pelvic washings.

Conclusions: Positive findings in abdominopelvic washing cytology is rare. The majority of the positive cases were from müllerian origins, with ovary and uterus as the most common sites. Endometrial adenocarcinoma, endometrioid type and ovarian high-grade serous carcinoma were the most common tumor types. Knowing prior history of malignancy, morphologic comparison with concurrent surgical cases, and performing ancillary studies are keys to improve diagnostic accuracy of abdominopelvic washings.
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http://dx.doi.org/10.1016/j.jasc.2019.10.001DOI Listing
June 2021

Results from the 2019 American Society of Cytopathology survey on rapid on-site evaluation-Part 1: objective practice patterns.

J Am Soc Cytopathol 2019 Nov - Dec;8(6):333-341. Epub 2019 Aug 8.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.

Introduction: Rapid on-site evaluation (ROSE) is a service provided by cytologists that helps ensure specimen adequacy and appropriate triage for ancillary testing. However, data on the current usage patterns across different practice settings have been lacking.

Materials And Methods: To obtain an accurate and timely assessment of the current state of practice of ROSE, a 14-question online survey was constructed by the Clinical Practice Committee of the American Society for Cytopathology. The survey was available to the membership of the American Society for Cytopathology for a 3-week period in early 2019.

Results: A total of 541 responses were received, including from 255 cytopathologists/pathologists, 261 cytotechnologists, 19 cytology resident/fellow trainees, and 6 others. ROSE was offered as a clinical service by 95.4% of the respondents, with telecytology for ROSE used in 21.9% of the practices. Endobronchial ultrasound-guided transbronchial needle aspiration was the procedure most frequently reported to use ROSE (mean, 59.1%; median, 70%). Cytotechnologists were involved in ROSE in most practices. The number of daily ROSE procedures correlated with the annual nongynecologic cytology volumes. Approximately 70% of ROSE procedures were reported to require >30 minutes, on average, for the cytologist.

Conclusions: The results from our survey of cytologists have shown that the reported practice patterns for the usage of ROSE vary considerably. The presented data can help inform future guideline recommendations and the implementation of ROSE in different clinical settings.
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http://dx.doi.org/10.1016/j.jasc.2019.07.007DOI Listing
July 2020

Thyroglobulin washout from cervical lymph node fine needle aspiration biopsies in patients with differentiated thyroid cancer: an analysis of different expressions to use in post-total thyroidectomy follow-up.

Surgery 2020 01 6;167(1):34-39. Epub 2019 Sep 6.

Department of Endocrine Surgery, Cleveland Clinic, OH. Electronic address:

Introduction: Although frequently used as an adjunct to cytology in patients with differentiated thyroid cancers, interpretation of thyroglobulin washout remains unclear. We aim to compare the utility of different analytic tools to develop recommendations for use in post-total thyroidectomy follow-up.

Methods: This is an institutional review board-approved retrospective study of patients who underwent lymph node fine needle aspiration biopsy with thyroglobulin washout between 2012 and 2018, during the post-total thyroidectomy follow-up of differentiated thyroid cancer. The utilities of thyroglobulin washout concentration, thyroglobulin washout/serum thyroglobulin ratio, and absolute thyroglobulin content were compared.

Results: Sixty-four patients underwent 79 fine needle aspirations with thyroglobulin washout of cervical lymph nodes. Fifty-two lymph nodes were found to be metastatic and 27 benign. One patient had a pathologically confirmed lymph node metastasis despite a thyroglobulin washout of 0. The optimal cutoffs of thyroglobulin washout, thyroglobulin washout/serum thyroglobulin ratio, and absolute thyroglobulin content to predict metastatic involvement were 2.5 ng/ml (94% sensitive, 100% specific), 0.1 (100% sensitive and specific), and 12.5 (94% sensitive, 100% specific), respectively. The second measure lacked utility in patients with undetectable serum thyroglobulin.

Conclusion: The use of thyroglobulin washout concentration or thyroglobulin washout/serum thyroglobulin ratio has drawbacks based on variations in technique and clinical scenario. Absolute thyroglobulin content is an alternative that may be a more objective expression of thyroglobulin washout.
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http://dx.doi.org/10.1016/j.surg.2019.05.083DOI Listing
January 2020

Fine-needle aspiration of the liver: a 10-year single institution retrospective review.

Hum Pathol 2019 10 24;92:25-31. Epub 2019 Jul 24.

Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.

Fine-needle aspiration (FNA) of liver masses is a minimally invasive means of evaluation, with diagnostic accuracy over 85%. Given that most of the recent literature on sampling hepatic tumors was published by radiologists and gastroenterologists, we herein conduct a 10-year retrospective review of a single institution's cytopathology experience with the diagnosis of liver lesions. Electronic record review of the cytopathology files (CoPathPlus; Cerner Corp) was conducted for the 10-year interval January 2007 through December 2016. All cytology specimens designated as "liver" and "FNA" were included. Associated concurrent and subsequent surgical pathology and cytopathology cases were identified. All FNA cases were organized into four diagnostic categories: positive for malignancy, atypical, negative for malignancy, and non-diagnostic. There were 713 hepatic FNAs that were categorized as follows: positive for malignancy 467 (65.5%), atypical 49 (6.9%), negative 171 (24.0%) and non-diagnostic 26 (3.6%). Metastatic tumors (95.7%) were more common that primary (4.3%). The top two metastatic primary sites were pancreas (30.1%) and colon (12.7%). A total of 166 (23.2%) cases had concurrent core needle biopsies (CNB). 111 (66.9%) were concordant with the FNA diagnosis. Of the 55 discordant cases, 43 (25.9%) had diagnostic material only on CNB and 12 (7.2%) had diagnostic material only on FNA. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 93.4%, 96.7%, 98.2%, 84.3%, and 89.3% respectively. Irrespective of endoscopic versus percutaneous approach, hepatic FNA is a sensitive and specific means of identifying metastatic and primary malignancies of the liver.
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http://dx.doi.org/10.1016/j.humpath.2019.07.007DOI Listing
October 2019

Molecular testing in metastatic colorectal adenocarcinoma cytology cell pellets.

Diagn Cytopathol 2019 Nov 9;47(11):1132-1137. Epub 2019 Jul 9.

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio.

Background: Mutational status for KRAS, NRAS, and BRAF genes should be performed on all colorectal carcinoma (CRC) specimens in order to guide targeted therapy selection for metastatic disease. Mutations are typically assessed via polymerase chain reaction and/or next generation sequencing (NGS) on formalin-fixed paraffin-embedded tissues. With minimally invasive diagnostic methodologies, the cytology cell pellet obtained by fine-needle aspiration (FNA) can serve as an alternative source of tumor deoxyribonucleic acid.

Methods: An electronic record review of the cytopathology files (CoPathPlus, Cerner Corp., North Kansas City, Missouri) from September 1, 2015 through December 31, 2018 was conducted. All cytology specimens obtained via FNA and diagnosed as metastatic CRC on which NGS was performed were included. NGS for KRAS, NRAS, and BRAF mutations using the AmpliSeq Cancer Hotspot Panel v2.0 kit (Thermo Fisher Scientific, Waltham, Massachusetts) was performed on cytology cell pellets.

Results: Forty-eight cases were identified. Forty-six of 48 specimens (96%) were adequate for molecular testing. Of those adequate specimens, proportion of malignant cells in the sample ranged from 5% to 95% (mean 46%). Twenty-seven of 48 cases (56%) were positive for clinically relevant mutations. Twenty-four of 27 cases (89%) were positive for KRAS mutations, with exon 2 most frequently involved (22/24 cases, 92%). Two of 27 cases (7%) were positive for NRAS mutations and one case (1/27, 4%) was positive for a BRAF mutation involving codon 594.

Conclusion: Mutational analysis performed on cytology cell pellets serves as a useful means of gathering clinically actionable information on tumor mutation status in metastatic CRC.
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http://dx.doi.org/10.1002/dc.24275DOI Listing
November 2019

Fine-needle aspiration of adrenal lesions: A 20-year single institution experience with comparison of percutaneous and endoscopic ultrasound guided approaches.

Diagn Cytopathol 2019 Oct 21;47(10):986-992. Epub 2019 Jun 21.

Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio.

Background: Historically, sampling of adrenal lesions has been performed by percutaneous image-guided fine-needle aspiration (FNA) biopsy. Endoscopic ultrasound guided (EUS)-FNA of the adrenals was first employed at Cleveland Clinic ~10 years ago. We report a two-decade experience of adrenal FNA in our institution.

Methods: An electronic retrieval identified adrenal FNAs from 1997 to 2017. Data points from each case (diagnosis, method of FNA, age, sex, laterality, needle gauge, size of lesion, adequacy of sample, and histologic follow up) were analyzed.

Results: Our retrieval confirmed 198 adrenal FNAs performed over 20 years. Of these, 90% (179/198) were percutaneous, and the remaining 10% (19/198) were collected by EUS. Of the 179 CT guided FNAs, 93% (162/179) yielded an adequate specimen as compared with an adequacy rate of 89% (17/19) for EUS-FNAs, with no significant difference in adequacy rates by collection method, P = .64 (Fisher's exact). Of all adrenal FNAs, 53% (105/198) confirmed metastases, 33% (65/198) showed adrenal cells or primary adrenal neoplasms (85% cortical cells, 14% cortical neoplasia, 1% pheochromocytoma), 8% were inadequate (15/198), 3% were atypical (7/198), and 2% were suspicious for malignancy (5/198).

Conclusion: FNA of the adrenal glands can be useful in the diagnosis and staging of metastatic neoplasms, as well as in distinguishing primary adrenal cortical from medullary neoplasms and characterizing hematolymphoid and mesenchymal neoplasms. Overall adequacy rates for adrenal cytology are high (92%) with no statistically significant difference between CT-guided (93%) and EUS-FNA adequacy (89%). The majority of our procedures confirmed metastases, sparing patients unnecessary surgery.
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http://dx.doi.org/10.1002/dc.24261DOI Listing
October 2019

Atypical intraductal proliferation detected in prostate needle biopsy is a marker of unsampled intraductal carcinoma and other adverse pathological features: a prospective clinicopathological study of 62 cases with emphasis on pathological outcomes.

Histopathology 2019 Sep 2;75(3):346-353. Epub 2019 Jul 2.

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland, OH, USA.

Aims: Intraductal proliferations of the prostate with more complexity and/or cytological atypia than high-grade prostate intra-epithelial neoplasia (HGPIN), but falling short of intraductal carcinoma (IDC-P), are described as 'atypical intraductal proliferation' (AIP). When present in needle biopsy (NBX) without IDC-P, the clinical significance is not known.

Methods And Results: Sixty-two NBX cases were diagnosed as AIP over 7 years with estimated incidence of 1%. AIP was characterised by loose cribriform architecture (90%) or non-cribriform architecture exhibiting significant nuclear atypia that fell short of IDC-P. Fifty patients had concomitant PCa (20% grade group (GG) 1, 48% GG2, 14% GG3, 8% GG4 and 10% GG 5), and 12 had AIP alone. Of 40 patients who were candidates for no therapy (AIP alone) or active surveillance (AIP with GG1 or GG2 PCa without cribriform pattern 4), 20 had subsequent follow-up pathology [seven NBXs and 13 radical prostatectomy (RP)]. Of the 12 AIP only patients, six had a subsequent biopsy diagnosis of: benign prostate (two), IDC-P with PCa (one) and PCa (three). One or more adverse pathological features at subsequent RP were present in 93% of patients with AIP and GG1 or GG2 PCa, defined as: GG ≥ 3 (15%), IDC-P (77%), cribriform Gleason pattern 4 (69%), pT3a (77%) or pT3b (8%).

Conclusions: AIP in NBX may be a marker of unsampled IDC-P and/or other adverse pathological features in suspected low- to intermediate-risk PCa. AIP should be considered distinct from HGPIN for risk assessment and warrant consideration for further work-up to detect unsampled high-risk PCa.
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http://dx.doi.org/10.1111/his.13878DOI Listing
September 2019

Clinical significance and EZH2, ERG and SPINK1 protein expression in pure and mixed ductal adenocarcinoma of the prostate.

Histol Histopathol 2019 Apr 24;34(4):381-390. Epub 2018 Sep 24.

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Background: Although ERG and SPINK1 molecular alterations have been studied in acinar and ductal adenocarcinoma of the prostate, EZH2 expression has not been previously evaluated in ductal adenocarcinoma.

Methods: We collected cases of pure and mixed ductal adenocarcinoma of the prostate and evaluated clinical significance and EZH2, ERG, and SPINK1 protein expression.

Results: We investigated 61 ductal adenocarcinomas, 22 pure and 39 mixed ductal/acinar. Except for tumor growth pattern, none of the clinical parameters studied significantly differed between pure and mixed tumors. Thirty-five percent of ductal adenocarcinomas were organ confined, 15% displayed seminal vesicle invasion. Lymph node and distal metastasis occurred in 13% and 24% of cases, respectively; 34% of patients experienced biochemical failure, 7% died of disease. Ninety-eight percent of tumors expressed EZH2; in 80% of cases >50% of tumor cells were positive. ERG and SPINK1 were expressed in 20% and 36% of cases, respectively. There was no difference in protein expression between pure and mixed ductal adenocarcinomas. ERG expression tended to be lower, and SPINK1 higher than reported for acinar tumors. Biochemical failure, metastasis and death did not differ between EZH2, ERG, and SPINK1 positive and negative patients, nor between <50% versus >50% expression of SPINK1 and EZH2, respectively.

Conclusions: Pure and mixed ductal adenocarcinomas have similar clinical behavior and molecular alterations. Higher EZH2 and SPINK1 protein expression, compared to acinar prostatic adenocarcinoma, might account for the more aggressive clinical course of ductal adenocarcinoma.
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http://dx.doi.org/10.14670/HH-18-046DOI Listing
April 2019

Diagnostic Advances in Urine Cytology.

Surg Pathol Clin 2018 Sep 13;11(3):601-610. Epub 2018 Jul 13.

Cleveland Clinic Foundation, Pathology and Laboratory Medicine Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Electronic address:

The utility of urine cytology has shifted from the identification of red blood cells, crystals, or parasites to its currently used role of detection of cancer cells exfoliated in urine samples. A variety of ancillary tests have been developed to complement the diagnostic ability of urine cytology. Furthermore, urine testing will continue to evolve as the pathogenesis of genitourinary tract diseases in depth is understood. This article focuses on the diagnostic advances in urine cytology from the cytomorphological perspective, past and current reporting schemes, and the application of ancillary testing in urine samples.
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http://dx.doi.org/10.1016/j.path.2018.06.001DOI Listing
September 2018

Postmenopausal Squamous Atypia: Cytologic Features, Hybrid Capture 2 Tests and Contribution to the ASCUS Pool.

Acta Cytol 2018 25;62(5-6):418-422. Epub 2018 Jul 25.

Department of Pathology, Ohio State University Wexner Medical Center, Columbus, Ohio,

Objective: Postmenopausal squamous atypia (PSA) mimics squamous intraepithelial lesion (SIL). We investigate the PSA contribution to the atypical squamous cells of undetermined significance (ASCUS) pool, its cytologic features and Hybrid Capture 2 (HC2) relative light unit/cutoff (RLU/CO) values.

Study Design: 658 ASCUS Pap tests in women ≥55 years were reviewed to select those with koilocyte-like cells and/or atypical parakeratosis. Follow-up was positive when a biopsy showed SIL or carcinoma or a later HC2 test was positive.

Results: Sixty-nine cases (10.5%) were selected. Forty-two (60.9%) were HC2 negative, and 27 (39.1%) were HC2 positive. Follow-up was available for 23 (54.7%) HC2-negative and 19 (70.3%) HC2-positive cases. No HC2-negative (0%) and 8 HC2-positive (42.1%) cases were positive on follow-up. Within cases negative on follow-up, 3 were PSA on biopsy. PSA was characterized by perinuclear halos, mild nuclear enlargement, smooth nuclear contours, and smooth chromatin. PSA-associated RLU/CO values were 0.25-2.95. Cases with SIL or carcinoma had RLU/CO values from 3.78 to 1,241.59.

Conclusions: PSA contributes 0.5-2.3% to the ASCUS pool in women ≥55 years old. HC2 testing with RLU/CO of ≥1 may result in PSA occasionally testing positive. A different cutoff is not recommended but awareness of this caveat is important.
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http://dx.doi.org/10.1159/000490691DOI Listing
January 2019

Sampling Utility of the Convex Probe Endobronchial Ultrasound Visible Intrapulmonary Lesion.

J Bronchology Interv Pulmonol 2018 Oct;25(4):290-299

Pathology and Laboratory Institute, Cleveland Clinic, Cleveland, OH.

Background: The value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the mediastinal staging of lung cancer has been well established. However, data regarding its utility in the diagnosis of intrapulmonary lesions has been sparse. This study assesses the sampling utility of convex probe EBUS-visible intrapulmonary lesions not visualized by the white-light bronchoscopy.

Methods: A retrospective analysis of EBUS-TBNA of EBUS-visible intrapulmonary lesions was performed between January 2010 and March 2015. Patients with visible endobronchial lesions by white-light bronchoscopy were excluded from analysis.

Results: Among 108 procedures, the diagnostic yield of EBUS-TBNA for EBUS-visible intrapulmonary lesions was 87%. Following diagnoses were established: lung cancer (73/67.6%), lung metastases (10/9.2%), infection (5/4.6%), lymphoma (1/<1%), sarcoma/spindle cell sarcoma or neoplasm (3/2.8%), unspecified malignancy (1<1%), and hamartoma (1/<1%). EBUS-TBNA was nondiagnostic in 14 (13%); among these, 9 turned out to have benign disease based on additional bronchoscopy samples or other testing and/or follow-up imaging. Five were ultimately diagnosed with a malignant condition: lymphoma (1), epithelioid hemangioendothelioma (1), and non-small cell lung cancer (3). The sensitivity and the negative predicted value of EBUS-TBNA for differentiating malignancy from benign disease was 94.7% and 75%, respectively, while the accuracy for diagnosing the neoplastic disease was 95.3%. There was one major bleeding requiring bronchial artery embolization and 1 pneumothorax requiring chest tube drainage.

Conclusion: EBUS-TBNA is safe and effective in the diagnosis of EBUS-visible intrapulmonary lesions. It should be considered as the diagnostic test of choice in patients with these lesions undergoing EBUS-TBNA for the staging of suspected lung cancer.
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http://dx.doi.org/10.1097/LBR.0000000000000509DOI Listing
October 2018

Acquired Cystic Disease-associated Renal Cell Carcinoma (ACD-RCC): A Multiinstitutional Study of 40 Cases With Clinical Follow-up.

Am J Surg Pathol 2018 09;42(9):1156-1165

Robert J Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic.

The incidence of renal cell carcinoma (RCC) is known to be higher in patients with end-stage renal disease, including those with acquired cystic kidney disease due to dialysis. Acquired cystic disease (ACD)-associated RCC was recently incorporated into the 2016 WHO Classification of Tumors of the Urinary System and Male Genital Tract as a distinct entity and is reportedly the most common RCC arising in end-stage renal disease. In this study, we sought to further describe clinicopathologic findings in a large series of ACD-RCC, emphasizing histologic features, immunophenotype, clinical outcome, and patterns of disease spread. We collected 40 previously unpublished cases of ACD-RCC with mean clinical follow-up of 27 months (median, 19 mo; range, 1 to 126 mo). Mean tumor size was 2.7 cm (median, 2.4 cm), and 32 tumors (80%) were confined to the kidney (pT stage less than pT3a). International Society of Urological Pathology grade was 3 in 37 cases (92.5%), grade 2 in 1 case (2.5%), and grade 4 in 2 cases (5%). Architectural variability among ACD-RCC was common, as 39 cases (98%) showed varying combinations of tubular, cystic, solid, and/or papillary growth. ACD-RCC frequently occurred in association with other renal tumor subtypes within the same kidney, including papillary RCC (14 patients), papillary adenomas (7 cases), clear cell papillary RCC (5 cases), clear cell RCC (1 case), and RCC, unclassified type (1 case). A previously undescribed pattern of perinephric and renal sinus adipose tissue involvement by dilated epithelial cysts with minimal or absent intervening capsule or renal parenchyma was identified in 20 cases (50%); these cysts were part of the tumor itself in 5 cases (25%) and were part of the non-neoplastic acquired cystic change in the background kidney in the remaining 15 cases (75%). Of the 24 cases (60%) with tissue available for immunohistochemical stains, 19 (79%) were positive for PAX8, 20 (83%) showed negative to patchy expression of cytokeratin 7, and 24 (100%) were both positive for AMACR and negative for CD117. Fumarate hydratase expression was retained in all tumors, including those with nuclear features resembling fumarate hydratase-deficient RCCs. Of the 36 patients (90%) with available follow-up information, 4 (11%) experienced adverse events: 2 patients developed a local recurrence, 1 patient experienced multiple visceral metastases and subsequently died of disease, and 1 patient developed metastases to regional lymph nodes only. One local recurrence and the lymph node only metastasis both had an unusual, exclusively cystic pattern of growth. In summary, we present the largest clinicopathologic series of ACD-RCC to date and describe previously unreported cystic patterns of local soft tissue involvement and recurrence/metastases.
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http://dx.doi.org/10.1097/PAS.0000000000001091DOI Listing
September 2018

Cytologic parameters predicting neoplasia in Papanicolaou smears with atypical glandular cells and histologic follow-up: a single-institution experience.

J Am Soc Cytopathol 2018 Jan - Feb;7(1):7-15. Epub 2017 Aug 24.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida. Electronic address:

Introduction: Studies investigating histologic follow-up of The 2001 Bethesda System diagnosis of atypical glandular cells (AGC) have focused on various screening methods, patient populations, and Papanicolaou preparations. Our aim was to report the histologic follow-up of AGC diagnoses from ThinPrep slides and evaluate specific cytologic features predicting benign or malignant follow-up results.

Materials And Methods: A retrospective search identified liquid-based cervical cytology results interpreted as AGC. AGC diagnoses were stratified into four groups: atypical endometrial cells (AGC-EM); atypical endocervical cells (AGC-EC); AGC, favor neoplastic (AGC-FN); and AGC not otherwise specified (AGC-NOS). Evidence of disease was based on histologic follow-up (biopsy or resection specimen) with a diagnosis of cancer, complex endometrial hyperplasia, or high-grade squamous dysplasia. Available slides were blindly reviewed for specific cytologic features. Statistical analysis compared cytologic factors that would predict benign or malignant follow-up.

Results: We interpreted 264 samples as AGC from 2005 through 2009. Of the 246 (93.2%) with follow-up histologic material, 60 (24.4%) were AGC-EM; 36 (14.6%) were AGC-EC; 28 (11.4%) were AGC-FN; and 122 (49.6%) were AGC-NOS. Neoplasia was diagnosed in 80 (32.5%). Neoplastic cases showed significantly increased numbers of single cells, cells in 3-dimensional clusters, engulfed neutrophils, nuclear enlargement, increased nuclear-to-cytoplasmic ratio, irregular nuclear borders, reniform nuclei, loss of polarity, and macronucleoli.

Conclusions: Cytologic parameters can be used to predict benign from neoplastic glandular lesions. Biopsy follow-up is necessary to correlate cytologic findings when AGC is diagnosed on a Papanicolaou smear.
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http://dx.doi.org/10.1016/j.jasc.2017.08.001DOI Listing
August 2017

Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study).

Am J Surg Pathol 2018 Jan;42(1):39-52

Miraca Life Sciences, Irving, TX.

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, -0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types.
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http://dx.doi.org/10.1097/PAS.0000000000000948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737464PMC
January 2018

Atypical Histiocytoid Cells in Metastatic Papillary Thyroid Carcinoma: An Underrecognized Cytologic Pattern.

Am J Clin Pathol 2017 Jul;148(1):58-63

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH.

Objectives: Fine-needle aspiration (FNA) of head and neck lymph nodes (LNs) is useful in diagnosing metastatic papillary thyroid carcinoma (PTC) and most commonly shows classic cytologic features of PTC. Metastatic PTC, however, may occasionally present with a pattern unfamiliar to most pathologists: atypical histiocytoid cells (AHCs).

Methods: All PTC thyroidectomy specimens with associated FNA of LNs were retrieved from our files for 2007 to 2013. We aimed to assess cytologic features of metastatic PTC, as well as the presence of AHCs and their morphology.

Results: Fifty-six FNAs from LNs with metastatic PTC were reviewed. AHCs were identified in 38 (68%) cases, while only PTC with classic cytologic features was seen in 18 (32%) cases. AHCs did not show diagnostic nuclear features of PTC and presented as large cells with abundant cytoplasm either vacuolated or dense. Nuclei varied from vesicular with prominent nucleoli to dark and smudgy. Thirty-one cases showed mixed AHCs and classic PTC, but seven cases (13% of all metastatic PTCs in LNs) consisted only of AHCs.

Conclusions: AHCs are an often unrecognized metastatic morphologic pattern of cystic PTC, as it does not show diagnostic classic nuclear features of PTC. AHCs are the predominant cytologic finding in approximately 13% of metastatic PTCs to neck LNs.
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http://dx.doi.org/10.1093/ajcp/aqx049DOI Listing
July 2017

Next-generation sequencing of liquid-based cytology non-small cell lung cancer samples.

Cancer Cytopathol 2017 Mar 13;125(3):178-187. Epub 2017 Jan 13.

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio.

Background: The detection of mutated epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) with residual cell pellets derived from liquid-based cytology (LBC) samples (eg, endoscopic ultrasound-guided fine-needle aspiration) has been validated with allele-specific polymerase chain reaction. The aim of this study was to validate next-generation sequencing (NGS) technology for detecting gene mutations with residual cell pellets from LBC.

Methods: Archived DNA extracted from LBC samples of adenocarcinoma stored in PreservCyt with a known EGFR mutation status was retrieved. Genomic DNA was multiplex-amplified and enriched with Ion AmpliSeq Cancer Hotspot Panel v2 chemistry and the OneTouch 2 instrument; this was followed by semiconductor sequencing on the Ion Personal Genome Machine platform. The mutation hotspots of 6 NSCLC-related genes (BRAF, EGFR, ERBB2, KRAS, MET, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α [PIK3CA]) were analyzed with NextGENe and Torrent Suite bioinformatics tools.

Results: The commonly identified EGFR sequence changes, including 4 L858R mutations, 3 exon 19 deletions, and 1 exon 20 insertion, were in 100% concordance between the assay platforms. Less common NSCLC variants were also found in the mutation hotspots of ERBB2, KRAS, MET, and PIK3CA genes.

Conclusions: NSCLC mutation analysis using NGS can be successfully performed on residual cell pellets derived from LBC samples. This approach allows the simultaneous examination of multiple mutation hotspots in a timely manner to improve patient care. Cancer Cytopathol 2017;125:178-187. © 2016 American Cancer Society.
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http://dx.doi.org/10.1002/cncy.21812DOI Listing
March 2017
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