Publications by authors named "Zahra Maleki"

119 Publications

Fibroblast Growth Factor-2 Levels are Elevated in The Serum of Patients with Multiple Sclerosis

Iran J Immunol 2022 06;19(2):193-198

Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

Background: Various factors contribute to the pathogenesis of Multiple Sclerosis (MS), one of which is Fibroblast Growth Factor 2 (FGF2). The function of FGF2 is pleiotropic. The investigation of the role of this factor in the myelination has produced conflicting results.

Objective: To investigate the serum levels of FGF2 in patients with MS.

Subjects And Methods: Eighty patients with MS and eighty healthy volunteers with no history of inflammation or demyelinating disorders were included, and serum samples were collected to evaluate serum levels of FGF2 using the ELISA technique. Both groups had the same age and gender distribution. For analysis, the Mann-Whitney U test was used.

Results: Patients with MS had considerably greater serum FGF2 levels than the control group (p = 0.005). There was no difference between the FGF2 level in men and women.

Conclusion: Our data indicate that FGF2 levels may be related to the susceptibility of Iranian patients with MS. Further studies are required to analyze the involvement of FGF2 in enhancing the inflammatory process in MS.
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http://dx.doi.org/10.22034/iji.2022.94027.2275DOI Listing
June 2022

Relationships Between Job Satisfaction of Operating Room Nurses and Hospital's Compliance With Protective Guidelines During the Covid-19 Pandemic: A Cross-Sectional Study, Iran.

J Perianesth Nurs 2022 May 2. Epub 2022 May 2.

Associate Professor, Community Based Psychiatric Care Research Center, Department of Nursing, School of Nursing and Midwifery, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Purpose: The Covid-19 pandemic is considered the biggest threat to human health in the recent century. During emergency surgeries, the possibility of infection of members of the surgical team with Covid-19 increases due to the direct contact with patients. The present study has been conducted aimed to investigate the relationships between job satisfaction of operating room nurses and the hospital's compliance with protective guidelines (guidance) during Covid-19 pandemic from the perspective of operating room nurses.

Design: This was a descriptive and cross-sectional study conducted from September 22, 2020 to April 21, 2021.

Methods: This study was conducted on 926 nurses working in operating rooms in 15 metropolises of Iran. The sampling method in this study was multistage clustering. The questionnaire was sent to the target group through social apps (WhatsApp and Telegram). The collected data were analyzed by SPSS software version 26 using descriptive and analytical statistics.

Findings: The mean age and job satisfaction of the participants were 28.81 ± 5.64 years and 51.15 ± 11.45, respectively. Participants (n = 259; 27.97%) reported very good job satisfaction. Also, the mean hospital's compliance with protective guidelines during Covid-19 pandemic from the perspective of operating room nurses was 42.29 ± 7.11. The results of the present study showed a significant relationship between job satisfaction and hospital's compliance with protective guidelines during Covid-19 pandemic (P-value ≤ .001).

Conclusions: Optimization of infrastructure, improvement of management decisions and increasing human resources in a crisis can affect the quality of performance and job satisfaction of operating room nurses. The researchers suggest that health system managers can contribute to the safety and efficiency of the existing human resources by taking measures to increase job satisfaction.
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http://dx.doi.org/10.1016/j.jopan.2022.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058135PMC
May 2022

Head and Neck Cystic Lesions: A Cytology Review of Common and Uncommon Entities.

Acta Cytol 2022 Jun 17:1-12. Epub 2022 Jun 17.

Department of Pathology, The Johns Hopkins University School of Medicine and The Johns Hopkins Hospital, Baltimore, Maryland, USA.

Background: Cystic lesions of the head and neck are a diagnostic challenge since they are seen in the clinical presentation of a wide variety of conditions. Herein, common and uncommon entities that present as cystic lesions in the head and neck are reviewed.

Summary: In this study, peer-reviewed articles were selected using the database PubMed, Google, Google Scholar, and Scopus. Emphasis was placed on peer-reviewed articles that discuss the cytomorphology and differential diagnosis of entities that present as cystic lesions of the head and neck. In the anterior neck, both benign and malignant neoplasms can present, including papillary thyroid carcinoma (PTC), thyroid adenomatoid nodule, parathyroid cysts, and thyroglossal cysts. In the lateral neck, branchial cleft cyst, PTC, ectopic thyroid cyst, and squamous cell carcinomas (human papilloma virus and non- human papilloma virus-related) are common. Age over 40 years raises the possibility of malignancy. In the deep neck, mostly benign cystic entities occur such as a pleomorphic adenoma, paraganglioma, schwannoma, branchial cyst, epidermal inclusion cyst, and lymphoepithelial cyst. Lesions with squamous cell features can pose diagnostic dilemmas.

Conclusion: Cytologic examination of head and neck cysts can provide valuable information regarding the nature of the cystic lesions. Information about anatomic site and clinical history can assist with the differential diagnoses. Ancillary studies can improve the diagnosis in some cases. Each case should be evaluated very carefully since there are a wide variety of congenital conditions, infectious/inflammatory conditions, benign neoplasms, and primary and secondary malignancies presenting as a cystic mass in the head and neck.
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http://dx.doi.org/10.1159/000525144DOI Listing
June 2022

Treatment of EAE mice with Treg, G-MDSC and IL-2: a new insight into cell therapy for multiple sclerosis.

Immunotherapy 2022 Jul 8;14(10):789-798. Epub 2022 Jun 8.

Medical Cellular & Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

This study investigates the therapeutic and protective effects of Tregs, myeloid-derived suppressor cells (MDSCs) and IL-2 on multiple sclerosis (MS) disease model. C57BL/6 mice were immunized to develop an experimental autoimmune encephalomyelitis (EAE) model. We then investigated effects of pre- and post-treatment EAE mice with Tregs, MDSCs and IL-2 on inflammation and demyelination in brain tissue, and on the number of Treg, granulocytic-MDSC and Th-17 cells in spleen. Pre- and post-treatment of EAE mice by Tregs, MDSCs and IL-2 resulted in no weight change, reduced Th-17 cells and suppression of pathological properties. Pre- and post-treatment of immunized mice by Tregs, MDSCs and IL-2 prevent EAE induction.
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http://dx.doi.org/10.2217/imt-2021-0045DOI Listing
July 2022

Case Report: New Onset Lymphadenopathy After Immune Checkpoint Inhibitor Therapy Presents a Clinicopathological and Radiological Challenge.

Front Oncol 2022 20;12:876797. Epub 2022 May 20.

Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.

The use of immune-checkpoint inhibitor (ICI) therapy has significantly improved patient outcomes in a wide variety of cancers and has become a cornerstone in the treatment of renal cell carcinoma. However, ICI treatment has the potential to cause a variety of immune-related adverse events (irAEs) that can affect any tissue or organ. This report describes the diagnostic dilemma of a patient with both RCC and diffuse large B-cell lymphoma who developed acute onset of fever and diffuse lymphadenopathy following treatment with combined ipilimumab and nivolumab. While diagnostic considerations included worsening lymphoma, hyperprogression of RCC, sarcoid-like reaction from immunotherapy, and fungal infection, his lymphadenopathy eventually resolved with treatment for histoplasmosis and discontinuation of immunotherapy. Despite only receiving two doses of immunotherapy, he has not required additional systemic therapy for RCC. This case demonstrates both the effectiveness of ICI therapy and the need for multidisciplinary approach to potential irAEs.
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http://dx.doi.org/10.3389/fonc.2022.876797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165714PMC
May 2022

Salivary gland neoplasms with basaloid features in the era of the Milan system for reporting salivary gland cytology: Classification and interobserver agreement.

Diagn Cytopathol 2022 Jul 23;50(7):341-349. Epub 2022 Apr 23.

Department of Pathology, University of Utah Health Care and ARUP Laboratories, Salt Lake City, Utah, USA.

Background: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has been shown to have moderate to good reproducibility for categorization of salivary gland fine-needle aspiration (FNA) specimens. Less is known of its accuracy and interobserver reproducibility for categorization of the diagnostically difficult group of basaloid neoplasms.

Methods: Forty-five salivary gland specimens with a basaloid morphology (pleomorphic and monomorphic adenomas and adenoid cystic carcinomas) were independently assigned by seven cytopathologists to one of the MSRSGC categories. Interobserver agreement was assessed for average agreement, chance expected agreement and by Cohen's κ and diagnostic accuracy. Correlation of the salivary gland neoplasm of unknown malignant potential (SUMP) category with histologic diagnosis and benign or malignant designation along with interobserver reproducibility were calculated.

Results: Average observed agreement for assignment to the MSRSGC was 46% and Cohen's κ = 0.2%. The SUMP category did not correlate with tumor type or with the benign or malignant nature of the neoplasm. Diagnostic specificity and sensitivity were 92% and 100% for consensus diagnosis, but were 76% and 77% for individual diagnoses.

Conclusion: The interobserver agreement in categorizing basaloid neoplasms by the MSRSGC is poorer than for salivary gland lesions overall. This reflects the difficulty in diagnosing basaloid neoplasms. Nonetheless, diagnostic accuracy appears similar to that of salivary gland neoplasms as a whole.
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http://dx.doi.org/10.1002/dc.24962DOI Listing
July 2022

Secretory carcinoma of the salivary gland, a rare entity: An international multi-institutional study.

Cancer Cytopathol 2022 Apr 6. Epub 2022 Apr 6.

Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland.

Background: Secretory carcinoma (SC) of the salivary gland is a rare entity with limited published literature on cytomorphology. The authors present the largest cohort to date of SC fine-needle aspiration (FNA) cases.

Methods: FNA cases of histologically confirmed SC were retrospectively retrieved from 12 academic institutions in the United States, Italy, Finland, and Brazil. The collated data included patient demographics, imaging findings, cytopathologic diagnoses according to the Milan System for Reporting Salivary Gland Cytopathology, cytomorphologic characteristics, and immunohistochemical/molecular profiles.

Results: In total, 40 SCs were identified (male-to-female ratio, 14:26) in patients with a mean age of 52 years (age range, 13-80 years). Ultrasound imagining revealed a hypoechoic, ovoid, poorly defined, or lobulated mass. The most common primary site was the parotid gland (30 of 40 tumors). Regional lymph node metastasis (9 patients) and distant metastasis (4 patients; brain, liver, lungs, and mediastinum) were noted. Two patients died of disease. FNA smears were cellular and demonstrated mainly large, round cells with intracytoplasmic vacuoles or granules and round-to-oval nuclei with smooth nuclear contour, minimal irregularities, and prominent nucleoli arranged predominantly in clusters, papillary formations, and single cells. The background was variable and contained inflammatory cells, mucin, or proteinaceous material. The diagnoses were malignant (19 of 38 tumors; 50%), suspicious for malignancy (10 of 38 tumors; 26%), salivary gland neoplasm of uncertain malignant potential (7 of 38 tumors; 18%), and atypia of undetermined significance (2 of 38 tumors; 6%) according to the Milan System for Reporting Salivary Gland Cytopathology. Two malignant cases (2 of 40 tumors; 5%) were metastases. The neoplastic cells were immunoreactive for S100 (23 of 24 tumors), mammaglobin (18 of 18 tumors), GATA-3 (13 of 13 tumors), AE1/AE3 (7 of 7 tumors), and vimentin (6 of 6 tumors). ETV6-NTRK3 fusion was detected in 32 of 33 tumors by fluorescence in situ hybridization (n = 32) and next-generation sequencing (n = 1).

Conclusions: Familiarity with cytomorphologic features and the immunohistochemical/molecular profile of SC can enhance diagnostic accuracy.
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http://dx.doi.org/10.1002/cncy.22574DOI Listing
April 2022

Adrenal gland cytology reporting: a multi-institutional proposal for a standardized reporting system.

Cancer Cytopathol 2022 06 4;130(6):423-432. Epub 2022 Mar 4.

Department of Pathology and Laboratory Medicine, Loyola University Medical Center, Maywood, Illinois.

Background: With the development of new technologies and the changing patient profiles, cytopathology departments receive increasing numbers of adrenal gland cytology specimens. In this study, the authors analyzed archival adrenal gland cytology cases and attempted to implement a diagnostic reporting system.

Design: Retrospective electronic medical record search was performed for adrenal gland cytology specimens in seven tertiary care centers. The cytology diagnoses were grouped in 7 categories: nondiagnostic, nonneoplastic, benign adrenal cortical elements (BACE), primary neoplasm of noncortical origin (NONC), atypia of undetermined significance (AUS), suspicious for malignancy (SM), and malignant (MAL). If available, histopathology results of concurrent and/or follow-up biopsies and/or resections were documented.

Results: A total of 473 adrenal gland cytology cases were included. BACE cases comprised 21.8%, whereas MAL cases were 57.5% of all cases. For BACE and MAL categories, there were 100% and 98.9% correlation, respectively, in the cases with histopathology follow-up. Six of 10 NONC cases had histopathology diagnoses and there were 3 pheochromocytomas and 3 schwannomas. Twenty-one AUS cases had histology follow-up and 10 (47.6%) of them were malignant. Six cases of SM had histopathology follow-up, and all of them were malignant on the follow-up.

Conclusions: The authors propose a 7-tier diagnostic scheme for adrenal gland cytology. The risk of malignancy was 98.9% in MAL cases (87/88) in the cohort. The only case with discordance was reported as "adrenal cortical adenoma with marked atypia"' on resection. There was no difference between endoscopic ultrasound-guided and percutaneous methods. Further studies are needed to validate and make this approach universal.
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http://dx.doi.org/10.1002/cncy.22564DOI Listing
June 2022

Ancillary studies on cell blocks from fine needle aspiration specimens of salivary gland lesions: A multi-institutional study.

Diagn Cytopathol 2022 May 29;50(5):235-252. Epub 2022 Jan 29.

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: Ancillary studies are commonly performed on cell blocks prepared from fine-needle aspiration (FNA) specimens. There are limited studies in application of ancillary studies on cell blocks from salivary gland (SG) FNAs. This multi-institutional study evaluates the role of ancillary studies performed on cell blocks in the diagnosis of SG lesions, and their impact on clinical management.

Method: The electronic pathology archives of three large academic institutions were searched for SG FNAs with ancillary studies performed on cell blocks. The patient demographics, FNA site, cytologic diagnosis, ancillary studies, and surgical follow-up were recorded. If needed, the cytologic diagnoses were reclassified as per the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC).

Results: 117 SG FNA cases were identified including 3, 10, 11, 6, 23, 4, and 60 cases in MSRSGC categories I, II, III, IVa, IVb, V, VI, respectively with surgical follow-up available ranging from 27% to 100% within each category. Ancillary studies including histochemistry, immunocytochemistry (IHC), and in situ hybridization (ISH) were beneficial in 60%-100% of cases in each category. Risk of malignancy was 100% in both the suspicious for malignancy (V) and malignant (VI) categories. Ancillary studies improved diagnosis in 60% of non-neoplastic cases (II, 6/10), 100% of benign neoplasm cases (IVa, 6/6), and 98.3% of malignant cases (VI, 59/60).

Conclusion: Judicious and case-based ancillary studies performed on SG FNA cell blocks with sufficient material can improve the diagnostic yield by further characterization of the atypical/neoplastic cells, particularly in MSRSGC categories IVa-VI.
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http://dx.doi.org/10.1002/dc.24939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303557PMC
May 2022

Application of the Milan System for Reporting Salivary Gland Cytopathology in pediatric patients: An international, multi-institutional study.

Cancer Cytopathol 2022 05 26;130(5):370-380. Epub 2022 Jan 26.

Department of Pathology, Catholic University of Sacred Heart University, Rome, Italy.

Background: Pediatric salivary gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a small proportion of malignancies. This international, multi-institutional cohort evaluated the application of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and the risk of malignancy (ROM) for each diagnostic category.

Methods: Pediatric (0- to 21-year-old) salivary gland FNA specimens from 22 international institutions of 7 countries, including the United States, England, Italy, Greece, Finland, Brazil, and France, were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. Cytology-histology correlation was performed where available, and the ROM was calculated for each MSRSGC diagnostic category.

Results: The cohort of 477 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 10.3%; nonneoplastic, 34.6%; AUS, 5.2%; benign neoplasm, 27.5%; SUMP, 7.5%; SM, 2.5%; and malignant, 12.4%. Histopathologic follow-up was available for 237 cases (49.7%). The ROMs were as follows: nondiagnostic, 5.9%; nonneoplastic, 9.1%; AUS, 35.7%; benign neoplasm, 3.3%; SUMP, 31.8%; SM, 100%; and malignant, 100%. Mucoepidermoid carcinoma was the most common malignancy (18 of 237; 7.6%), and it was followed by acinic cell carcinoma (16 of 237; 6.8%). Pleomorphic adenoma was the most common benign neoplasm (95 of 237; 40.1%).

Conclusions: The MSRSGC can be reliably applied to pediatric salivary gland FNA. The ROM of each MSRSGC category in pediatric salivary gland FNA is relatively similar to the ROM of each category in adult salivary gland FNA, although the reported rates for the different MSRSGC categories are variable across institutions.
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http://dx.doi.org/10.1002/cncy.22556DOI Listing
May 2022

COVID-19 pandemic impact on cytopathology practice in the post-lockdown period: An international, multicenter study.

Cancer Cytopathol 2022 05 10;130(5):344-351. Epub 2022 Jan 10.

Department of Pathology, Izumi City General Hospital, Izumi, Japan.

Background: In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 "lockdown" period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020).

Methods: Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses.

Results: A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001).

Conclusions: The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality.
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http://dx.doi.org/10.1002/cncy.22547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9015399PMC
May 2022

Psychometric properties of the childhood executive functioning inventory (CHEXI): A confirmatory factor analysis and measurement invariance by sex and age in Iranian children.

Neuropsychol Rehabil 2022 Jan 6:1-19. Epub 2022 Jan 6.

MSc of Psychometrics, Mashhad, Iran.

This study aimed to examine the psychometric properties, factor structure, and measurement invariance of the Persian version of the Childhood Executive functioning Inventory (CHEXI). Participants were 1076 typically developing children, 6- to 12-years old (M =  9.2 years, SD =  1.96); females (52.1%) recruited from 17 provinces and 30 children with attention-deficit/ hyperactivity disorder (ADHD) (females, % 36) and 30 children with specific learning disability (SLD) (females, % 40). Children's parents completed CHEXI and the Barkley Deficits in Executive Functioning Scale-Children and Adolescents (BDEFS-CA). Confirmatory factor analysis (CFA) supported the two-factor structure, including (1) working memory and (2) inhibition, which had been identified previously. The Results showed that the CHEXI had high internal consistency and adequate test-retest reliability. The CHEXI was found to be invariant by sex (female vs. male) and age (7 age groups) across all factors. Lastly, the CHEXI demonstrated adequate convergent validity with the BDEFS-CA and known-group validity. We highlighted the implications of these findings for using CHEXI in typically developing children and clinical samples, along with directions for future research.
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http://dx.doi.org/10.1080/09602011.2021.2021952DOI Listing
January 2022

Atypia of undetermined significance in the Milan System for Reporting Salivary Gland Cytopathology: Cystic versus non-cystic masses.

Diagn Cytopathol 2022 Apr 5;50(4):154-161. Epub 2022 Jan 5.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

The term "Atypia" has been employed to describe a wide spectrum of cytomorphologic features associated with reactive/inflammatory processes as well as those suspicious for neoplasms in cytology. Similar to other cytopathology reporting systems, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has reserved the atypical category for cytology specimens lacking quantitative and/or qualitative cytomorphologic features to be diagnosed with confidence as either non-neoplastic or neoplastic. In MSRSGC, the atypical category is associated with a risk of malignancy and recommendation for clinical management. In this review, we discuss the value of atypical diagnostic category of MSRSGC in both cystic and non-cystic salivary gland lesions by evaluating our institutional case cohort.
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http://dx.doi.org/10.1002/dc.24913DOI Listing
April 2022

INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists' View.

Diagnostics (Basel) 2021 Nov 23;11(12). Epub 2021 Nov 23.

Department of Pathology, Fimlab Laboratories, Tampere, Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland.

Background: Insulinoma-associated protein 1 (INSM1) has been considered as a novel immunostain for neuroendocrine tumors (NETs) and is hypothesized to be more reliable than first-generation NET biomarkers, such as CGA (chromogranin A), SYP (synaptophysin) and CD56 (neural cell adhesion molecule). In this review, we summarize existing literature on INSM1's reliability as an immunostain for detection of various NETs, its results in comparison to first-generation NET biomarkers, and its expression in both non-NETs and benign tissues/cells on cytology specimens (cell blocks/smears).
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http://dx.doi.org/10.3390/diagnostics11122172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700458PMC
November 2021

The Value of Second-Opinion Consultation in Nongynecologic Cytopathology.

Am J Clin Pathol 2022 05;157(5):724-730

Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.

Objectives: The value of consultation in pathology has been well documented in surgical pathology, but there are few comprehensive studies of consultation cases in cytopathology. Here we report our experience with cytopathology consultation cases at a large academic center.

Methods: A review of consultation cases at our institution was performed by searching our laboratory information system. The contributing institution's diagnosis was compared with that rendered by the reviewing cytopathologist to assess major and/or minor diagnostic discrepancies.

Results: In total, 928 cases were reviewed with the following distribution: fine-needle aspiration (FNA, 79.4%), exfoliative nongynecologic cytology (18.3%), and cases with both FNA and nongynecologic cytology (2.3%). There were 379 (40.8%) true consults and 549 (59.2%) confirming consults. A total of 586 (63.1%) cases were in agreement with the outside pathologist, 78 (8.4%) cases had major discrepancies, and 264 (28.4%) cases had minor discrepancies. Major discrepancies were most common for pancreas (38.5%), lymph node (11.5%), and soft tissue sites (9.0%).

Conclusions: Of the cases, 8.4% had major diagnostic discrepancies between the original diagnosis and the consultation diagnosis, which is consistent with reported values in surgical pathology consultation studies. The findings support the importance of second-opinion consultation in cytopathology to guide patient care.
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http://dx.doi.org/10.1093/ajcp/aqab182DOI Listing
May 2022

Bronchoalveolar Lavage in a Pediatric Population.

Am J Clin Pathol 2022 05;157(5):678-684

Department of Pathology, The Johns Hopkins University School of Medicine and The Johns Hopkins Hospital, Baltimore, MD, USA.

Objectives: The cytomorphologic findings of bronchoalveolar lavage (BAL) in pediatrics were correlated with clinical symptoms.

Methods: Patient demographics, clinical symptoms/history, cytomorphologic findings, and oil red O (ORO) staining of 100 pediatric patients who underwent BAL between 2014 and 2016 were reviewed at a large academic institution.

Results: Of the 100 patients (males/females, 62:38), the most common conditions for BAL included cough (46/100), reflux (39/100), pneumonia (30/100), dysphagia (22/100), asthma (19/100), and cystic fibrosis (15/100). Sixteen of 100 patients were admitted with pulmonary symptoms from the emergency department. Cytomorphologic findings showed acute inflammation in 37 BALs and chronic inflammation in 9. Abundant thick mucin was present in 3 cytology cases from patients with cystic fibrosis. Fungal elements were detected in 3 cases (Candida, Aspergillus, and Pneumocystis jirovecii) and viral effects (rhinovirus) in one. Thirty-seven of 100 had rare ORO-positive lipid-laden macrophages (LLMs), 7 of 100 had moderate LLMs, 11 of 100 had numerous LLMs, 18 of 100 had positive staining without the degree of staining, 25 of 100 had negative ORO staining, and 2 of 100 had noncontributory ORO staining. An iron stain was done on 15 BALs (2 positive, 9 negative, and 4 noncontributory).

Conclusions: BAL cytology is a useful tool in pediatrics to discriminate underlying causes of aerodigestive system conditions, while ORO staining may occasionally help.
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http://dx.doi.org/10.1093/ajcp/aqab177DOI Listing
May 2022

Comparison of Cervical Cancer Screen Results on Female-to-Male Transgender Patients With Female Patients.

Am J Clin Pathol 2022 04;157(4):540-545

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objectives: There are limited data on cervical screen results from female-to-male (FTM) transgender patients. Herein, we compiled demographic information and cervical screen testing on FTM transgender patients and compared with age-appropriate controls.

Methods: A search of our previous and current databases was performed for Papanicolaou (Pap) tests from patients taking testosterone and/or with a diagnosis of gender dysphoria, transsexualism, or transvestism. Patient data were reviewed. Relative risks of abnormal Pap smear and human papillomavirus (HPV) infection were calculated against age-matched controls.

Results: Eighty-nine Pap tests from FTM transgender individuals were identified, with a mean age of 31.3 years (range, 21-60 years). The Pap test diagnoses were distributed as follows: negative for intraepithelial lesion (n = 84, 94.4%), atypical squamous cells of undetermined significance (n = 0), low-grade intraepithelial lesion (n = 4, 4.5%), and high-grade squamous intraepithelial lesion (n = 1, 1.1%). Fifty (56.2%) patients had concurrent high-risk HPV testing with four (8%) positive results. Relative risk was 0.625 (95% confidence interval [CI], 0.25-1.59; P = .32) for an abnormal Pap test and 0.55 (95% CI, 0.19-1.52; P = .24) for HPV compared with 267 age-matched controls. Of note, 13.5% of patients older than 21 years had documentation of never having a prior Pap test in our medical record.

Conclusions: In our study, FTM transgender individuals were not at a higher or lower risk of HPV infection or abnormal Pap test result compared with women. However, larger studies are needed to support our findings.
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http://dx.doi.org/10.1093/ajcp/aqab158DOI Listing
April 2022

Cytomorphologic features of intraductal salivary gland carcinoma: A multi-institutional study of 13 FNA cases with histologic, molecular, and clinical correlations.

Cancer Cytopathol 2021 12 1;129(12):928-946. Epub 2021 Oct 1.

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Background: Intraductal carcinoma of the salivary gland (IDC) is a rare cancer with potential actionable targets, including RET fusions. Histologic and molecular features of IDC were recently reported, but cytomorphologic data are limited. In the largest multi-institutional fine-needle aspiration (FNA) series, the authors describe the cytomorphologic features of 13 IDC cases with available clinical, radiologic, histopathologic, and molecular data.

Methods: The cases included 13 FNAs for 9 low-grade (LG) IDCs and 4 high-grade (HG) IDCs with corresponding histopathology and available molecular, imaging, and clinical data. Smears and liquid-based preparations available for 12 FNAs were semiquantitatively scored for key cytomorphologic findings and correlated with the corresponding resection.

Results: LG IDC FNAs showed a cellular, biphasic population of large, atypical ductal cells with mildly pleomorphic nuclei in a clean background and a minor population of small, uniform myoepithelial cells. In contrast, all HG IDC FNAs showed predominantly ductal cells with marked nuclear pleomorphism, coarse chromatin, and necrosis. With the Milan system, most LG and HG IDC FNAs were classified as either salivary gland neoplasms of uncertain malignant potential (54%) or malignant (31%). Immunohistochemistry showed ductal epithelial reactivity with mammaglobin, androgen receptor, and S100, whereas myoepithelial cells were positive for p63 and/or calponin. Among cases with next-generation sequencing, 4 LG IDCs showed NCOA4-RET gene fusions, whereas an HG IDC showed HRAS and PIK3CA mutations.

Conclusions: The cytomorphology of IDC overlaps with other benign and malignant salivary gland neoplasms. Immunohistochemistry limits the differential diagnosis, but definitive classification requires molecular analysis. A diagnosis of IDC has potential implications for patient management.
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http://dx.doi.org/10.1002/cncy.22504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328448PMC
December 2021

Risk Assessment of Human Papillomavirus-Positive Cytology-Negative Cervical Cancer Screening in Black and White Women.

Am J Clin Pathol 2022 Mar;157(3):399-405

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objectives: As we move toward human papillomavirus (HPV) only as the preferred cervical cancer screening method, we performed a retrospective analysis of Black and White women with negative cytology (Papanicolaou negative [PAPneg]) and positive high-risk HPV (hrHPV) (HPVpos) results and determined follow-up.

Methods: We searched our pathology data system for patients with PAPneg/HPVpos results (2017-2019). Follow-up data were reviewed (39 months), and a comparison among race was performed.

Results: In total, 1,728 patients were identified (Black, 53%; White, 47%). Twenty-nine percent of the patients had no follow-up with no difference among the races. HPV 16 was more common among Whites (P < .01), while non-16/18 hrHPV was more common among Black patients (P = .01). A total of 30 (3.3%) Black and 26 (3.2%) White patients were diagnosed with cervical intraepithelial neoplasia grade 2/3 (CIN 2/3). More White women were diagnosed on biopsy alone (negative endocervical curettage) compared with Black women (20 vs 9, P < .01). Meanwhile, there were 21 Black and 6 White women with CIN 2/3 on endocervical curettage (P = .01).

Conclusions: Follow-up of women with PAPneg/HPVpos remains a challenge. There was no disparity in follow-up when cohorts were compared. However, Black women had higher numbers of high-grade intraepithelial lesions on endocervical curettage.
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http://dx.doi.org/10.1093/ajcp/aqab129DOI Listing
March 2022

NR4A3 Immunostain Is a Highly Sensitive and Specific Marker for Acinic Cell Carcinoma in Cytologic and Surgical Specimens.

Am J Clin Pathol 2022 Jan;157(1):98-108

Department of Pathology and Laboratory Medicine, New York Presbyterian-Weill Cornell Medicine, New York, NY, USA.

Objectives: Salivary gland acinic cell carcinoma (AciCC) has recognizable cytomorphologic features that can overlap with benign and malignant entities, creating a diagnostic challenge. AciCC harbors a t(4;9) translocation increasing nuclear receptor subfamily 4 group A member 3 (NR4A3) expression, detectable by immunohistochemistry (IHC) on surgical resection (SR). NR4A3 IHC cytology data are limited. Here, we examine NR4A3 IHC on smears, cell blocks (CBs), and SRs of AciCC and its mimickers.

Methods: Our cohort comprised AciCC (including high-grade transformation), secretory carcinoma, mucoepidermoid carcinoma (MEC), Warthin tumor, pleomorphic adenoma (PA), cellular PA, carcinoma ex-PA, oncocytic carcinoma, oncocytoma, and nodular oncocytosis. NR4A3 IHC (Santa Cruz Biotechnology and Origene antibodies) was positive if more than 5% tumor cells showed nuclear staining.

Results: Among CBs, 90% of AciCC cases and none of the mimickers expressed NR4A3. Among SRs, 100% of AciCC cases showed diffuse NR4A3, whereas one high-grade MEC expressed focal NR4A3. Concordance was 95% with two antibody clones. Sensitivity, specificity, positive predictive value, and negative predictive value were 90%, 100%, 100%, and 94.7% for CBs and 100%, 98.8%, 92.3%, and 100% for SRs, respectively. NR4A3 immunostaining was demonstrable on smears from an AciCC case.

Conclusions: NR4A3 IHC can be a robust diagnostic tool to identify AciCC, especially for cytology specimens.
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http://dx.doi.org/10.1093/ajcp/aqab099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742980PMC
January 2022

Effect of meteorological factors and Air Quality Index on the COVID-19 epidemiological characteristics: an ecological study among 210 countries.

Environ Sci Pollut Res Int 2021 Oct 22;28(38):53116-53126. Epub 2021 May 22.

Research Center for Health Sciences, Institute of Health, Department of Epidemiology, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran.

The survival of COVID-19 in different environments may be affected by a variety of weather, pollution, and seasonal parameters. Therefore, the present study aims to conduct an ecological investigation on COVID-19 average growth rate of daily cases and deaths influenced by environmental factors (temperature, humidity, and air pollution) using a sample size of adjusted cumulative incidence of daily cases and deaths based on five 60-day periods. Research data was gathered on official websites, including information on COVID-19, meteorological data, and air pollution indicators from December 31, 2019, to October 12, 2020, from 210 countries. Spearman correlation and generalized additive model (GAM) were used to analyze the data. During the observed period, the COVID-19 average growth rate of daily cases (r = -0.08, P =0.151) and deaths (r= -0.09, P = 0.207) were not correlated with humidity. Also, there was a negative relationship between the COVID-19 average growth rate of new cases and deaths with the Air Quality Index (AQI) and wind (new cases and wind: r=-0.25, P= 0.04). Furthermore, the data related to the first and second 60 day of the adjusted cumulative incidence of COVID-19 daily cases and deaths were not associated with humidity and Air Quality Index (AQI). The result of GAM showed the effect of AQI on the average growth rate of COVID-19 new cases and deaths. This study provides evidence for a positive relationship between COVID-19 daily cases, deaths, and AQI.
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http://dx.doi.org/10.1007/s11356-021-14322-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140752PMC
October 2021

Intraductal papillary mucinous neoplasm of the pancreas: Cytomorphology, imaging, molecular profile, and prognosis.

Cytopathology 2021 07 1;32(4):397-406. Epub 2021 Apr 1.

Division of Cytopathology, Department of Pathology, The Johns-Hopkins Hospital, Baltimore, MD, USA.

Background: Intraductal papillary mucinous neoplasm (IPMN) constitutes up to 20% of all pancreatic resections, and has been increasing in recent years. Histomorphological findings of IPMN are well established; however, there are not many published papers regarding the cytological findings of IPMN on fine needle aspiration (FNA) specimens. We review the cytomorphological features, molecular profile, imaging findings, and prognosis of IPMN.

Methods: The English literature was thoroughly searched with key phrases containing IPMN.

Observations: IPMN is a rare entity, affecting men and women equally and is usually diagnosed at the age of 60-70 years. The characteristic imaging features include a cystic lesion with associated dilatation of the main or branch pancreatic duct, and atrophy of surrounding pancreatic parenchyma. Cytomorphological features of IPMN include papillary fragments of mucinous epithelium in a background of abundant thick extracellular mucin, a hallmark feature. IPMNs should be evaluated for high-grade dysplasia, which manifests with nuclear atypia, nuclear moulding, prominent nucleoli, nuclear irregularity, and cellular crowding. Molecular profiling of IPMN along with carcinoembryonic antigen and amylase levels is useful in predicting malignancy or high-grade dysplasia arising in IPMN. Overall, the prognosis of IPMN is excellent except in those cases with high-grade dysplasia and malignant transformation. Postoperative surveillance is required for resected IPMNs.

Conclusion: IPMN requires a multidisciplinary approach for management. Cytomorphological findings of IPMN on FNA, in conjunction with tumour markers in pancreatic fluid cytology and imaging findings, are of paramount importance in clinical decision-making for IPMN.
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http://dx.doi.org/10.1111/cyt.12973DOI Listing
July 2021

p16 immunostaining in cytology specimens: its application, expression, interpretation, and challenges.

J Am Soc Cytopathol 2021 Jul-Aug;10(4):414-422. Epub 2020 Dec 15.

Department of Pathology, The Johns Hopkins University School of Medicine and The Johns Hopkins Hospital, Baltimore, Maryland. Electronic address:

Introduction: p16 immunostaining is considered as a surrogate marker for human papillomavirus (HPV)-related head and neck squamous cell carcinomas (HNSCC). Herein, the utility of p16 is evaluated in cytology specimens.

Material And Methods: The electronic data of a large academic institution was searched for cytology cases accompanied by p16 (2014-2018). Cases were categorized based on body sites. P16 staining was quantified (negative [0%], focal/patchy, or diffusely positive [>70%]). HPV testing was correlated where available.

Results: A total of 372 cases were included (male:female, 239:133). The largest differences in application of p16 between men and women were in head/neck cases (209 versus 59) and the abdominal cases (1 versus 33), respectively. p16 diffuse staining is seen in most squamous cell carcinomas, small cell carcinomas, and gynecologic serous carcinomas. p16 expression was patchy or negative in most adenocarcinoma, neuroendocrine carcinoma, spindle cell neoplasms, and benign conditions. HPV testing was done on 217 cases including 138 cases with strong p16 (127 HPV+/11 HPV-), 20 cases with focal/patchy P16 staining (6 HPV+/14 HPV-) and 59 cases with negative p16 staining (3 HPV+/56 HPV-).

Conclusions: Diffuse p16 staining aids in the diagnosis of HPV-related carcinomas, particularly HPV-related HNSCC, across the body and according to sex. In contrast, focal/patchy p16 staining does not correlate with HPV status across various body sites. In conclusion, intensity of p16 matters and should be correlated with cytomorphology, clinical history, and ancillary studies (eg, p40 immunostaining) for an accurate diagnosis and preventing diagnostic pitfalls.
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http://dx.doi.org/10.1016/j.jasc.2020.12.003DOI Listing
January 2022

Thyroid paraganglioma: A diagnostic pitfall in thyroid FNA.

Cancer Cytopathol 2021 06 24;129(6):439-449. Epub 2020 Nov 24.

Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.

Background: Thyroid paragangliomas are extremely rare and often are misdiagnosed by preoperative fine-needle aspiration (FNA) because their cytologic features overlap with those of other thyroid neoplasms. The objective of this study was to review the cytomorphology in a series of thyroid paragangliomas and correlate the findings with histopathology.

Methods: Five thyroid paraganglioma cases that underwent FNA were reviewed. Their clinical presentation, radiology features, cytomorphology, ancillary tests, and histopathology were analyzed.

Results: All patients were women with an average age of 49 years (age range, 35-61 years) and presented with an asymptomatic, solitary thyroid nodule. Radiologically, these nodules (size range, 1.8-3.0 cm) were well circumscribed, hypoechoic, and hypervascular. FNA smears showed clusters of loosely cohesive, medium-to-large epithelioid cells with clear-to-eosinophilic and occasionally foamy cytoplasm that had indistinct cytoplasmic borders. The nuclei were round to oval with focal nuclear membrane irregularities, inconspicuous nucleoli, focal marked anisonucleosis, and occasional intranuclear pseudoinclusions. Naked nuclei, variable numbers of plasmacytoid cells, multinucleated giant cells, and sustentacular cells were present in the background along with blood vessels and lymphocytes. Cytology diagnoses were incorrect and included follicular neoplasm (n = 4) and follicular lesion of undetermined significance (n = 1). Final histopathology with immunohistochemistry revealed conventional paraganglioma (n = 3) or sclerosing paraganglioma with invasive features (n = 2).

Conclusions: All thyroid paragangliomas were misdiagnosed on FNA as follicular neoplasms, in part because of the rarity of these tumors in this location and cytomorphology mimicking follicles. The absence of colloid, the presence of naked nuclei, focal marked anisonucleosis, and the presence of sustentacular cells are important cytology clues.
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http://dx.doi.org/10.1002/cncy.22390DOI Listing
June 2021

Global impact of the COVID-19 pandemic on cytopathology practice: Results from an international survey of laboratories in 23 countries.

Cancer Cytopathol 2020 Dec 27;128(12):885-894. Epub 2020 Oct 27.

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: To the authors' knowledge, the impact of the coronavirus disease 2019 (COVID-19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported.

Methods: Data regarding the activity of each cytopathology laboratory during 4 weeks of COVID-19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine-needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta-analytical approach.

Results: Overall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%-98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conversely, the percentage of samples from the urinary tract, serous cavities, breast, lymph nodes, respiratory tract, salivary glands, central nervous system, gastrointestinal tract, pancreas, liver, and biliary tract increased (P < .05). An overall increase of 5.56% (95% CI, 3.77%-7.35%) in the malignancy rate in nongynecological samples during the COVID-19 pandemic was observed. When the suspicious category was included, the overall increase was 6.95% (95% CI, 4.63%-9.27%).

Conclusions: The COVID-19 pandemic resulted in a drastic reduction in the total number of cytology specimens regardless of anatomic site or specimen type. The rate of malignancy increased, reflecting the prioritization of patients with cancer who were considered to be at high risk. Prospective monitoring of the effect of delays in access to health services during the lockdown period is warranted.
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http://dx.doi.org/10.1002/cncy.22373DOI Listing
December 2020

Survival Rate of Colorectal Cancer in Eastern Mediterranean Region Countries: A Systematic Review and Meta-Analysis.

Cancer Control 2020 Jan-Dec;27(1):1073274820964146

Nutrition Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths worldwide. Survival rates are among the most important factors in quality control and assessment of treatment protocols. This study was aimed to assess the survival rate of colorectal cancer in Eastern Mediterranean Region Countries. In the present study we comprehensively searched 6 international databases including PubMed/Medline, ProQuest, Scopus, Embase, Web of Knowledge and Google Scholar for published articles until November 2018. The Newcastle-Ottawa Quality Assessment Form for Cohort Studies was applied to evaluate the quality of included studies. The heterogeneity of papers was assessed with the Cochran Test and I-Square statistics. Meta-regression test was performed based on publication year, sample size and Human Development Index (HDI) of each study. Among the total of 1023 titles found in the systematic search, 43 studies were eligible to be included in the present meta-analysis. According to the results, the 1-year, 3-year and 5-year survival rate of patients with Colorectal Cancer was 88.07% (95% CI, 83.22-92.92), 70.67% (95% CI, 66.40-74.93) and, 57.26% (95% CI, 50.43-64.10); respectively. Furthermore, Meta-regressions did not show significant correlations between survival rate and year, sample size or Human Development Index. Survival rates, especially the 5-year survival rate in the EMRO were less than European countries and the USA. Documented and comprehensive evidence-based findings of the present meta-analysis can be used to enhance policies and outcomes of different medical areas including prophylaxis, treatment and health related objectives in colorectal cancer.
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http://dx.doi.org/10.1177/1073274820964146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791530PMC
June 2021

Application of the Milan System for Reporting Salivary Gland Cytopathology to cystic salivary gland lesions.

Cancer Cytopathol 2021 03 1;129(3):214-225. Epub 2020 Oct 1.

Department of Pathology, University of Michigan, Ann Arbor, Michigan.

Background: Cystic salivary gland lesions present diagnostic challenges on fine-needle aspiration (FNA) specimens that are related to sampling limitations and a broad differential diagnosis. This study evaluated the benefit of applying the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) to a series of cystic salivary gland lesions.

Methods: The pathology archives at the Johns Hopkins Hospital were searched to identify cystic salivary gland FNA specimens over a 19-year period (2000-2018). Patient demographics, cytomorphologic features, and clinical and surgical follow-up were recorded. The MSRSGC was applied to the cases. The risk of malignancy (ROM) and the risk of neoplasia (RON) were calculated for each category.

Results: One hundred seventy-eight cases were identified (96 males and 82 females) with a mean age of 53 years (range, 4-90 years). After the MSRSGC was applied, there were 52 nondiagnostic cases (29.2%), 80 nonneoplastic cases (44.9%), 35 cases of atypia of undetermined significance (AUS; 19.7%), 3 benign neoplasms (1.7%), 3 salivary gland neoplasms of uncertain malignant potential (SUMP; 1.7%), 4 cases suspicious for malignancy (SFM; 2.2%), and 1 malignant case (0.6%). One hundred fifty-six of the 178 patients (87.6%) had follow-up data available. The RON and ROM values for cases with surgical follow-up were 33.3% (3 of 9) and 22.2% (2 of 9) for the nondiagnostic category, 42.9% (9 of 21) and 19% (4 of 21) for the nonneoplastic category, 76.5% (13 of 17) and 29.4% (5 of 17) for the AUS category, 100.0% (2 of 2) and 50.0% (1 of 2) for the SUMP category, and 100% (2 of 2) and 100% (2 of 2) for the SFM category, respectively.

Conclusions: Applying the MSRSGC to cystic salivary gland lesions improves patient management by preventing unnecessary surgery for nonneoplastic conditions. The ROM was highest in the SFM category (100%), which was followed by the SUMP, AUS, nondiagnostic, and nonneoplastic categories. Less than adequate specimens may increase the diagnosis of AUS.
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http://dx.doi.org/10.1002/cncy.22363DOI Listing
March 2021

Risk stratification and clinical outcome in the atypia of undetermined significance category in the Milan System for Reporting Salivary Gland Cytopathology.

Cancer Cytopathol 2021 02 16;129(2):132-139. Epub 2020 Sep 16.

Division of Cytopathology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Background: Atypia of undetermined significance (AUS) is a category of the Milan System for Reporting Salivary Gland Cytopathology that refers to salivary gland fine-needle aspiration (FNA) specimens that cannot be definitively diagnosed as neoplastic or nonneoplastic.

Methods: The AUS FNA samples were selected from a large academic institution from 2008 through 2018. The AUS cases were divided into 6 subgroups. The risk of malignancy (ROM), risk of neoplasm (RON), and clinical outcomes for each subgroup were evaluated.

Results: A total of 123 cases were found (76 males and 47 females with a mean age of 62 years [range, 6-94 years]). The parotid gland was the most common FNA site (103 cases), followed by the submandibular gland (9 cases). The overall RON and ROM were 63% and 47%, respectively. Among the subgroups, salivary gland lymph nodes or lymphoid lesions was the most common diagnosis (42%), whereas mucinous cystic lesions with no or a scant epithelial component was the least common (2%). The specimens with preparation artifacts category had the highest RON and ROM (100% for both), whereas the reactive and reparative atypia indefinite for a neoplasm category had the lowest RON and ROM (7% for both). The salivary gland lymph nodes or lymphoid lesions indefinite for a lymphoproliferative disorder category had the second highest RON and ROM at 77% and 74%, respectively.

Conclusions: The overall RON and ROM for the AUS category were 63% and 47%, respectively. The RON and ROM varied among the different AUS subgroups, being highest in the specimens with preparation artifacts category and lowest in the reactive and reparative atypia category, thereby demonstrating the importance of subgrouping in the AUS specimens.
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http://dx.doi.org/10.1002/cncy.22352DOI Listing
February 2021

Cytomorphology and diagnostic pitfalls of sebaceous and nonsebaceous salivary gland lymphadenoma: A multi-institutional study.

Diagn Cytopathol 2021 Jan 14;49(1):83-95. Epub 2020 Sep 14.

Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Background: Salivary gland lymphadenoma (LAD) is a rare benign neoplasm comprising sebaceous (SLAD) and nonsebaceous (NSLAD) types. Despite established histologic criteria, limited data on cytomorphology, tumor heterogeneity, and overlap with other entities make the diagnosis of LAD by fine needle aspiration (FNA) challenging. We describe a multi-institutional cohort of 14 LADs with cytology, clinical, radiologic, and histopathologic data.

Methods: Our cohort included nine SLAD and five NSLAD with corresponding histopathology. Mean patient age and M:F ratio were 60.4 years (range 45-86 years) and 1:2 for SLADs and 57.4 years (range 42-80 years) and 1:1.5 for NSLADs, respectively. One NSLAD patient had a germline predisposition for Cowden syndrome. Glass slides and whole slide images of air-dried Diff-Quik (DQ), alcohol-stained Papanicolaou smears (Pap) and cellblocks were reviewed for key cytomorphologic findings.

Results: FNAs from SLAD and NSLADs demonstrated vacuolated and basaloid epithelial clusters within a lymphoid background. Vacuolated cells from SLAD showed sebaceous cells with microvesicular cytoplasm indenting a central nucleus. Vacuolated cells from NSLAD were columnar with eccentric nuclei, corresponding to abluminal glandular cells. SLADs were classified using the Milan System for Reporting Salivary Gland Cytopathology as nondiagnostic (11.1%), nonneoplastic (44.4%), atypia of uncertain significance (AUS) (22.2%), and salivary gland neoplasm of uncertain malignant potential (SUMP) (22.2%). NSLADs were classified as AUS (40%), SUMP (40%) and Benign Neoplasm (20%).

Conclusion: Although rare, knowing the cytologic features of salivary LAD is important to avoid diagnostic pitfalls. Vacuolated cells can be prominent in both SLAD and NSLAD aspirates. Diagnostic issues arise from insufficient sampling of all tumor components leading to marked variation in diagnostic classification of LAD.
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http://dx.doi.org/10.1002/dc.24602DOI Listing
January 2021
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