Mast cell infiltration and activation in the gallbladder wall: Implications for the pathogenesis of functional gallbladder disorder in adult patients.

BACKGROUND: Functional gallbladder disorder (FGD) is characterized by recurrent biliary colic with a decreased gallbladder ejection fraction on cholescintigraphy but absence of visible gallbladder abnormalities on ultrasonography. FGD is generally regarded as a primary gallbladder motility disturbance, however, the underlying pathophysiology remains largely unknown. In this study, we investigated the potential role of mast cells in the pathogenesis of FGD by examining mast cell density and activation in the gallbladder wall. DESIGN: Twenty adult patients with FGD undergoing cholecystectomy were included in the study. Seven patients with no gallbladder disease were served as controls who were subject to incidental cholecystectomy during abdominal surgery such as partial hepatectomy. The density of mast cells in the gallbladder wall was assessed by immunohistochemistry and by toluidine blue special stain. Mast cell activation was evaluated by calculating the percentage of degranulated mast cells on toluidine blue stain. RESULTS: Compared to the controls, patients with FGD showed a significant increase in mast cell infiltration in the gallbladder walls. Peak mast cell accumulation was predominantly located in the inner muscular layer of the gallbladder wall. Mast cell activation was also markedly increased in the FGD group as evidenced by significantly enhanced mast cell degranulation. CONCLUSIONS: Mast cell infiltration and activation were significantly increased in the muscular wall of gallbladders from FGD patients, suggesting potential involvement of mast cells in the compromised gallbladder motility in adult patients with FGD.

PD-L1 expression in sarcomas: An immunohistochemical study and review of the literature.

BACKGROUND: Immunotherapy is increasingly used for treatment of metastatic melanoma and carcinomas. PD-1 (programmed death 1) and its associated ligand (PD-L1) inhibits the activation of T-lymphocytes. This inhibition can be impacted by a number of drugs. Response to these drugs is predicted by assessment of PD-L1 expression. PD-L1 expression varies between 19% and 92% in melanomas and carcinomas. PD-L1 expression is less well documented for sarcomas. DESIGN: Fifty-six sarcomas of various histopathologic types were immunohistochemically stained (IHC) for PD-L1 using the antibody clone SP263 (Ventana, Tuscan, AZ). Membrane staining of tumor cells was quantitated as a percentage of total tumor cells. Sarcomas were judged as non-expressors (less than 1%) low-expressors (1 to 50%) and high expressors (greater than 50%). The percentage of each type of sarcoma judged as an expressor was determined. RESULTS: Table 1 documents the percentage of each type of sarcoma expressing PD-L1. 14% of sarcomas expressed PD-L1. Percentage of sarcomas expressing PD-L1 varied significantly between types but the majority of sarcomas were non-expressors. CONCLUSION: PD-L1 IHC expression is valuable in predicting response to immune-modulating drugs. Such therapies may be useful for treatment of metastatic sarcomas. Expression of PD-L1 in carcinomas and melanomas is variable ranging from 19% to 92%. In our study, a minority (14%) of sarcomas expressed PD-L1. Other studies have shown similar results with between 1.4 and 59% (average 24%) of sarcomas expressing PD-L1. Expression appears to be sarcoma type specific. These finding suggest that PD-L1 based therapy may be less useful in sarcomas than in other malignancies.

A rare case of plexiform fibromyxoma in stomach: FNA diagnosis with histological correlation and differential diagnoses.

Plexiform angiomyxoma (PF) is a rare benign mesenchymal neoplasm that arises in the antrum and pyloric region of the stomach. To the best of our knowledge, there are only two prior endoscopic ultrasound guided fine needle aspiration cytology examples have been reported. We report a case of PF which was diagnosed via EUS FNA and later confirmed on resection specimen. Differential diagnoses of this tumor are discussed. Although diagnosis of plexiform fibromyxoma on FNA specimen is difficult, a good FNA specimen with subsequent careful morphological evaluation and immunohistochemical staining work-up makes this task possible.

Histologic diagnosis of a case of anal duct carcinoma with cytological correlation and differential diagnoses.

Anal duct carcinoma is an uncommon malignancy of the glands of the anal duct. This entity poses a diagnostic challenge, both clinically and histologically. This article describes histopathologic findings in a case of anal duct carcinoma, including the initial diagnosis on biopsy and subsequent cytology specimens. Additionally, differential diagnoses of this neoplasm are discussed. With a high index of suspicion, and attention to histological and immunohistochemical features, anal duct carcinoma can be accurately diagnosed both on biopsy and on cytology.

Cytomorphological criteria for separation of pulmonary adenocarcinomas from squamous cell carcinomas: A statistical learning approach.

BACKGROUND: Current therapy requires separation of non-small cell carcinomas into adenocarcinomas (AC) and squamous cell carcinomas (SCC). A meta-analysis has shown a pooled diagnostic sensitivity of 63% and specificity of 95% for the diagnosis of AC. While a number of cytomorphological features have been proposed for separation of AC from SCC, we are unaware of a statistically based analysis of cytomorphological features useful for separation of these two carcinomas. We performed logistic regression analysis of cytological features useful in classifying SCC and AC. DESIGN: Sixty-one Papanicolaou-stained fine needle aspiration specimens (29 AC/32 SCC) were reviewed by two board-certified cytopathologists for nine features (eccentric nucleoli, vesicular chromatin, prominent nucleoli, vacuolated cytoplasm, 3-dimensional cell balls, dark non-transparent chromatin, central nucleoli, single malignant cells and spindle-shaped cells). All cytological specimens had surgical biopsy results. Inter-rater agreement was assessed by Cohen's κ. Association between features and AC was determined using hierarchical logistic regression model where feature scores were nested within reviewers. A model to classify cases as SCC or AC was developed and verified by k-fold verification (k = 5). Classification performance was assessed using the area under the receiver operating characteristic curve. RESULTS: Observed rater agreement for scored features ranged from 49% to 82%. Kappa scores were clustered in three groups. Raters demonstrated good agreement for prominent nucleoli, vesicular chromatin and eccentric nuclei. Fair agreement was seen for 3-dimensional cell balls, dark non-transparent chromatin, and presence of spindle-shaped cells. Association of features with adenocarcinoma showed four statistically significant associations (P < 0.001) with adenocarcinoma. These features were prominent nucleoli, vesicular chromatin, eccentric nuclei and three-dimensional cell balls. Spindle-shaped cells and dark non-transparent chromatin were negatively associated with adenocarcinoma. CONCLUSIONS: Logistic regression analysis demonstrated six features helpful in separation of AC from SCC. Prominent nucleoli, vesicular chromatin, cell balls and eccentric nucleoli were positively associated with AC and demonstrated a P value of 0.001 or less. The presence of dark, non-transparent chromatin and spindle-shaped cells favoured the diagnosis of SCC.

Testis specific Y-like 5: gene expression, methylation and implications for drug sensitivity in prostate carcinoma.

BACKGROUND: TSPYL5, a putative tumor suppressor gene, belongs to the nucleosome assembly protein family. The chromosomal location of the TSPYL5 gene is 8Q22.1, and its exact role in prostate cancer etiology remains unclear. Further TSPYL5 gene and protein expression in prostate carcinoma cells and diseased tissues including its susceptibility for epigenetic silencing is unknown. Also, not known is the variation in TSPYL5 protein expression with regards to progression of prostatic carcinoma and its possible role in drug sensitivity. METHODS: TSPYL5, DNMT-1 and DNMT-B gene expression in DU145, LNCaP and RWPE-1 cells and prostate tumor tissues was analyzed by qRT-PCR and RT-PCR. Demethylation experiments were done by treating DU145 and LNCaP cells with 5-aza-2'-deoxycytidine in vitro. Methylation analysis of TSPYL5 gene was performed by methylation specific PCR and pyrosequencing. TSPYL5 protein expression in benign and diseased prostate tumor tissues was performed by immunohistochemistry and in the cells by Western blotting. RESULTS: TSPYL5 was differentially expressed in non-tumorigenic prostate epithelial cells (RWPE-1), androgen independent (DU145), dependent (LNCaP) prostate carcinoma cells and tissues. Methylation-specific PCR and pyrosequencing analysis identified an inverse relationship between DNA methylation and expression leading to the silencing of TSPYL5 gene. Treatment of prostate carcinoma cells in which TSPYL5 was absent or low (DU145 and LNCaP) with the demethylating agent 5-aza-2'-deoxycytidine upregulated its expression in these cells. Immunohistochemical studies clearly identified TSPYL5 protein in benign tissue and in tumors with Gleason score (GS) of 6 and 7. TSPYL5 protein levels were very low in tumors of GS ≥ 8. TSPYL5 overexpression in LNCaP cells increased the cell sensitivity to chemotherapy drugs such as docetaxel and paclitaxel, as measured by the cellular viability. Furthermore, the cells also exhibited reduced CDKN1A expression with only marginal reduction in pAKT. CONCLUSIONS: Decrease in TSPYL5 protein in advanced tumors might possibly function as an indicator of prostate tumor progression. Its absence due to methylation-induced silencing can lead to reduced drug sensitivity in prostate carcinoma.

The role of mast cells in histologically "normal" appendices following emergency appendectomy in pediatric patients.

Fifteen percent to 25% of appendices resected for a preoperative diagnosis of acute appendicitis have no neutrophilic infiltration, thus histologically "normal." The discrepancy between clinical presentation and the lack of definite morphologic changes is confounding. It has been indicated that mast cells may play a role in the pathogenesis of the appendicitis-like pain in patients with histologically negative appendices (HNAs). To investigate whether mast cell density (MCD) is increased in pediatric HNAs, we retrieved 50 appendectomy cases (30 HNA and 20 control, ages 2 days-18 years) in our institute in the last 10 years. All cases were stained with mast cell tryptase by immunohistochemistry, and MCD (count/high-power field) was measured in mucosa, submucosa, muscularis, and serosa. Mast cells had the greatest density in the mucosa, followed by the submucosa, in all appendices. MCDs in all 4 layers were significantly higher in HNAs than in the normal controls (mucosa: 46±9 vs 26±11, P<.01; submucosa: 18±5 vs 11±5, P<.01; muscularis: 6±3 vs 4±2, P<.01; serosa: 6±2 vs 4±2, P<.01). This result suggests that mast cells play an important role in pathogenesis of HNA cases. In clinical practice, pathologists may order immunohistochemical stains for mast cells in cases with no classic histologic findings of acute appendicitis following emergency appendectomy. If increased MCD is noted, the case may be reported as "appendicitis with increased mast cells." This assures surgeons that the appendectomy is the correct treatment and it is not necessary to look for other causes of acute abdomen. This is especially important in children.

Molecular testing of cytology specimens: Issues in specimen adequacy and clinical utility.

BACKGROUND: Next generation sequencing (NGS) is standard of care for workup of many neoplasms including adenocarcinomas of the lung. Molecular testing of cytology samples is used for many types of neoplasms but the value of such testing for the selection of "first"- and "second-line" treatment protocols is incompletely understood. METHODS: Fifty-six sequentially performed cytology specimens (49 fine needle aspirates and 7 fluids) submitted for molecular analysis were reviewed by a medical oncologist to determine specimen adequacy and utility of results for therapy selection. Chart review was performed to determine availability of microsatellite instability status, tumor mutational burden, and presence of driver mutations treatable with targeted therapy in a "first"- or "second-line" application. RESULTS: Forty of 56 cases were successfully sequenced and 34% (19/56) had targetable mutations detected by NGS. Ten of these 19 cases (53%) received targeted therapy for their tumor type with five of 10 patients receiving "first-line" therapy and five (50%) "second-line" therapy. Twenty-two mutations were detected where no targeted therapy for the patient's tumor type existed but targeted therapies were available for other tumor types. Of these specimens, only one patient received treatment using protocols associated with a second tumor type. Total mutation burden and microsatellite instability status results were obtained in 29 of 56 cases (52%). CONCLUSIONS: 71% (40/56) of cytologic specimens were adequate for sequencing with 34% (19/56) demonstrating a targetable mutation and 53% of these patients receiving therapy targeted to the driver mutation of their tumor type.

Osimertinib Resistance via Histologic Transformation From Non-small Cell Lung Carcinoma to Carcinosarcoma.

Resistance to tyrosine kinase inhibitors (TKIs) in non-small cell lung carcinoma (NSCLC) remains a significant clinical challenge. Osimertinib, a third-generation TKI, has demonstrated efficacy in overcoming resistance, but novel resistance mechanisms continue to emerge. This case report presents a unique instance of histologic transformation from NSCLC to carcinosarcoma, representing a previously unreported manifestation of osimertinib resistance. We describe the clinical course of a 63-year-old female with epidermal growth factor receptor (EGFR)-mutant NSCLC who initially responded to osimertinib but eventually developed carcinosarcoma. The transformation was associated with additional EGFR mutations and alterations in RB and TP53. Despite aggressive treatment, the patient's condition deteriorated, emphasizing the limited therapeutic options for carcinosarcoma. This case underscores the need for further research to elucidate the molecular mechanisms behind histologic transformation and explore novel therapeutic strategies to address osimertinib resistance in NSCLC. Understanding and addressing these mechanisms are crucial for improving outcomes in patients facing this challenging form of resistance.

World Health Organization Reporting System for Soft Tissue Cytopathology: Risk of malignancy and reproducibility of categories among observers.

INTRODUCTION: In 2024, the World Health Organization (WHO) is scheduled to publish the WHO Reporting System for Soft Tissue Cytopathology (WHORSSTC). This system establishes categories with well-defined definitions, criteria, and estimated risks of malignancy (ROMs) for soft tissue tumors. The estimates of ROM are based on a relatively small number of published studies. Interobserver reproducibility is not addressed in the reporting system even though reproducibility of a reporting system is highly important. METHODS: A manual search of one authors personal consultation files and teaching set (L.J.L.) was conducted for all cytologic specimens of soft tissue tumors accessioned between January 1, 1985 and December 31, 2022. Only cases with documented surgical pathology follow-up were included in the study. Slides from each case were evaluated independently by three cytopathologists with each case assigned to one of the WHORSSTC categories. A ROM for each of the WHORSSTC categories was calculated. Interobserver agreement was evaluated by the kappa and weighted kappa statistics. RESULTS: Risk for malignancy by category were: Category 1: 0%, Category 2: 28%, Category 3: 57%, Category 4: 47%, Category 5: 63%, and Category 6: 88%. Kappa statistics for agreement between raters varied from 0.2183 to 0.3465 and weighted kappa varied from 0.3778 to 0.5217. CONCLUSIONS: The WHORSSTC showed a progression of malignancy risk from the category "benign" (28%) to the category "malignant" (88%). Interobserver agreement was only fair.

Molecular testing in cytology.

In the era of personalized medicine, molecular testing plays a critical role in patient care. The rapid advance of molecular techniques, especially next-generation sequencing, makes molecular diagnosis feasible in daily practice. Molecular testing can be used as a valuable ancillary test to increase diagnostic sensitivity and specificity, especially in small biopsy or cytology samples. In addition, molecular testing plays an important role in selecting patients for appropriate treatment by detecting therapeutic and predictive biomarkers in tissue or cytology samples. Molecular studies can be applied in all cytology samples, sometimes with better results than histology. As molecular testing has become essential for patient care and is often requested to be performed in cytology samples, it is critical for cytopathologists to understand the basics of molecular diagnostic methods, indications for molecular testing, and how to best utilize different cytologic samples for this purpose. In this special issue, experts in various areas of cytopathology and molecular pathology review the literature and discuss the basics of molecular techniques and the application of molecular testing in various types of cytology samples. It is our hope that after reading the articles in this special issue, the readers can know better about the possibilities of molecular cytology, a very exciting field of pathology.

Molecular features of pancreaticobiliary neoplasms: Implications for diagnosis, prognostication, and therapy selection.

BACKGROUND: Molecular diagnostics has impacted the diagnosis, prediction of prognosis, and selection of targeted therapy for many tumor types. While pulmonary adenocarcinomas and melanomas are among the neoplasms most associated with molecular diagnostics and targeted therapy, malignancies of the pancreaticobiliary system have also been impacted by precision medicine. METHODS: We undertook an electronic search using PubMed and Embase to review the published literature to determine what forms of molecular testing, mutations and oncogenetic pathways are associated with neoplasms of the pancreaticobiliary system. Keywords utilized were pancreas, bile duct, mutations, ERCP, FNA, KRAS, SMAD4, TP53, next-generation sequencing, serous cystadenoma, pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm, cystic mucinous neoplasm, solid pseudo-papillary neoplasm. RESULTS: A search between 1999 and 2022 yielded 6874 manuscripts. Screening of these yielded 302 more focused manuscripts of which 55 were used for the study. Ductal adenocarcinoma of the pancreas is associated with a progression of mutations beginning wit KRAS mutations and ending with a set of mutations in the TP53, SMAD4, and DPC4 genes. Similar mutations are found in neoplastic mucinous cysts. Specific mutations characterize serous cystadenomas, solid, and pseudo papillary neoplasms and adenocarcinomas of the bile ducts. CONCLUSIONS: Mutational analysis of cytologic specimens obtained by fine-needle aspiration, and duct brushings and washings are helpful in the diagnosis of pancreaticobiliary neoplasms and may supply prognostic information.

PD-L1 immunohistochemical testing: A review with reference to cytology specimens.

BACKGROUND: Immunotherapy based on disruption of the PD-1/PD-L1 axis is standard of care for many high stage malignancies including melanomas, non-small cell carcinomas of the lung, triple negative breast carcinomas, and squamous cell carcinomas of the head and neck. Eligibility for immunotherapy requires immunohistochemical assessment of PD-L1 expression. Currently, many high stage malignancies are diagnosed by cytology and cytologic material is the only specimen available for ancillary testing. Formal guidelines do not currently exist defining the optimal specimen type, antibody to be used or the best scoring system for cytologic material. Significant information has been published for PD-L1 testing of pulmonary specimens but much less data exists for the reproducibility, accuracy and best practices for material obtained from other body sites and types of malignancy. METHODS: We searched the PubMed data base for manuscripts relating to PD-L1 testing of cytologic specimens. The search period was between 2016 and 2022. The search terms used were PD-L1, cytology, FNA, immunotherapy, immunohistochemistry, immunocytochemistry, cytology-histology correlation. Cross referencing techniques were used to screen for the most relevant manuscripts. The abstracts of these were then reviewed for final data collection and analysis. RESULTS: A total of 86 studies were identified conforming to study relevancy. These were reviewed in their entirety by two authors (LJL, TZ) for extraction of data. The majority of studies involved pulmonary specimens (79) with three relating to PD-L1 testing of head and neck cytologic specimens and one each for PD-L1 testing of cytology specimens from melanomas, pancreas, pleural fluids, and triple negative breast carcinomas. While smears could be used, most studies found cell blocks optimal for testing. SUMMARY: Currently, four drugs are approved for immunotherapy based on PD-L1 status. These drugs require specific antibody clones as well as scoring systems. Scoring systems and cut points vary with the type of neoplasm being treated. Cytology specimens from the lung, head and neck and melanomas can all be used for PD-L1 testing with good agreement with corresponding histology specimens.

Diagnosis of salivary gland tumors: Does the triple diagnosis method have value?

BACKGROUND: Appropriate clinical management of salivary gland lesions requires a determination as to whether a salivary gland nodule is benign or malignant. Approximately three-quarters of all salivary gland nodules represent benign neoplasms. Separation of salivary gland carcinomas from benign lesions can be diagnostically challenging. The Milan System for Reporting Salivary Gland Cytopathology recommends the correlation of cytologic diagnoses with imaging and clinical findings creating a diagnostic triplet. How often the "Triple Diagnosis" method is used and its accuracy in separating salivary gland nodules into benign and malignant groups are unknown. METHODS: An electronic records search of cytology files at the University of Missouri was performed for fine needle aspirates of the salivary gland obtained between September 2018 and August 2022. Chart review was performed for preoperative clinical and imaging diagnoses. Diagnostic "Triplets" constructed from cytologic, clinical, and imaging diagnoses were correlated with final surgical pathology diagnosis. RESULTS: One hundred and thirty-six FNAs were identified. Eighty-seven cases had preoperative imaging with 52 of these cases having clinical diagnoses. Due to the lack of a definitive clinical or imaging diagnosis for a nodule as benign or malignant, only 12 (23%) cases had definitive "Triplets." Nine (17%) "Triplets" were benign and three (6%) were malignant. Accuracy of concordant triplets was 100% for the prediction of malignancy and 89% for the prediction of a benign result as determined by final histologic diagnoses. CONCLUSION: While highly accurate in predicting the benign or malignant nature of a salivary gland nodule, concordant triplets made up only 23% of cases limiting their clinical utility.

Core needle biopsy for the diagnosis of primary soft tissue lesions: Accuracy and diagnostic challenges.

BACKGROUND: Core needle biopsy (CNB) and fine needle aspiration (FNA) are currently the most common biopsy methods for investigation of soft tissue lesions. Selection of the method to be used depends on a number of factors including diagnostic accuracy, local expertise with the techniques and the need for ancillary testing. We investigated the diagnostic accuracy of CNB and factors influencing the selection of CNB or FNA. METHODS: An electronic search of the surgical pathology records for all core needle biopsies of soft tissue lesions with subsequent incisional biopsies or excisions between January 1, 2015 and December 31, 2021 was performed. Searches of the literature for publications documenting diagnostic accuracy of core biopsy and FNA were performed using the Pub Med literature data base. RESULTS: The electronic search yielded 177 CNBs with appropriate follow-up. Six cases were non-diagnostic. The remaining 171 cases showed an accuracy of 90% for separation of benign from malignant with two false-positive and 17 false-negative diagnoses. The literature search revealed 11 series of CNBs with a diagnostic accuracy of 74% to 97%. The literature search revealed 20 series of FNAs with an accuracy of 84.8% to 100% for separation of benign from malignant. CONCLUSIONS: Core needle biopsy is a highly accurate diagnostic technique with an accuracy of 90% for separation of benign from malignant lesions. The percentage of non-diagnostic cases is low (3.4%). No significant biopsy related complications were seen in this study.

Performance of Afirma Gene Sequencing Classifier versus Gene Expression Classifier in thyroid nodules with indeterminate cytology.

INTRODUCTION: About 15% to 30% of thyroid fine-needle aspiration (FNA) nodules have indeterminate cytology. The Afirma (Veracyte Inc, South San Francisco, CA) Gene Expression Classifier (GEC)/Gene Sequencing Classifier (GSC) tests were designed to improve risk stratification of the indeterminate thyroid nodules. This study aimed to evaluate and compare the performance of the Afirma GEC and GSC tests in the indeterminate thyroid lesions. METHODS: Thyroid FNA cases with indeterminate cytology were searched in the pathology database and only those with available Afirma results were selected for this study. Each patient's demographic, sonographic, cytologic, molecular, and subsequent surgical follow-up results were collected and analyzed. RESULTS: There were 100 cases with indeterminate thyroid FNA results, including 49 cases tested by GEC and 51 cases by GSC. In the GEC group, benign call rate (BCR) was 53% (26 of 49) and the calculated negative predictive value (NPV) and positive predictive value (PPV) were 88% and 47% respectively. In the GSC group, the BCR was 63% (32 of 51) and the calculated NPV and PPV were 100% and 64%, respectively. Whereas only 17% (1 of 6) of benign oncocytic lesions were tested benign by the GEC, 60% (3 of 5) of benign oncocytic nodules were tested benign by the GSC. CONCLUSION: We demonstrated in this study that a little more than half of the indeterminate thyroid nodules had negative Afirma GEC/GSC results and the BCR using the Afirma GSC test was higher than GEC. The Afirma GSC showed higher NPV and PPV than GEC. In addition, the Afirma GSC appeared to be superior for differentiating benign and malignant oncocytic thyroid lesions.

Diagnostic sensitivity and risk of malignancy for bile duct brushings categorized by the Papanicolaou Society of Cytopathology System for reporting pancreaticobiliary cytopathology.

BACKGROUND: The Papanicolaou Society of cytopathology developed a six-category system for pancreaticobiliary cytology specimens. Each category is associated with a definition, diagnostic criteria, estimated risk of malignancy and management recommendations. Risks of malignancy are well defined for specimens obtained by fine-needle aspiration but are less well defined for brushing specimens. METHODS: Diagnoses of 232 brushing specimens of the pancreatic and bile ducts were correlated with diagnoses from subsequent surgical or cytologic specimens. Sensitivity for the brushing technique was calculated. Risk of malignancy was calculated for each category using the original definitions for nondiagnostic and negative categories and for those of a modified system. RESULTS: Diagnostic sensitivity was 60%-64%. Risk of malignancy for the nondiagnostic, negative, atypical, suspicious for malignancy, and malignant categories was 28%, 28%, 61%, 91%, and 91%, respectively, when the original category definitions were used. CONCLUSIONS: Diagnostic sensitivity for duct brushings is low in comparison to fine-needle aspiration. Risk of malignancy is comparable to that of needle aspiration for the negative, atypical and suspicious categories but lower for the malignant category. There is a stepwise increase in malignancy risk as one moves from the negative to the atypical to the suspicious for malignancy categories.

The international system for serous fluid cytopathology: Interobserver agreement.

BACKGROUND: A number of categorization systems had been developed for the reporting of cytology specimens with the aim of providing uniform definitions, criteria, and diagnostic terminology. The intention of these systems is to improve reproducibility of diagnostic categorization with standardized estimates of malignancy risk. Required for the success of these systems is a high level of interobserver reproducibility for category assignment. Recently, the international system for serous fluid cytopathology (TIS) was proposed using the categories nondiagnostic, negative for malignancy, atypia of undetermined significance (AUS), suspicious for malignancy, and malignant. Little data exists documenting the interobserver agreement for these categories. DESIGN: A search of the cytology records at the University of Missouri was performed for all pleural fluid specimens obtained between January 2014 and December 2019. A total of 200 specimens were reviewed independently by three board-certified cytopathologists. Specimens were characterized as nondiagnostic, negative, AUS, suspicious for malignancy, and malignant. Interobserver agreement was analyzed using Cohen's kappa. RESULTS: Overall observer agreement was 68% and chance-corrected weighted agreement (weighted kappa) was 0.63. Agreement was good for categories negative and malignant, but poor for categories atypia of uncertain significance, and suspicious for malignancy. CONCLUSIONS: The TIS has performance characteristics similar to other cytologic classification schemes. Interobserver agreement is best for the negative (76%) and malignant (81%) categories. Interobserver agreement is poor for the category's AUS, and suspicious for malignancy. This is similar to interobserver agreement associated with other published categorization systems.

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

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.