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The World Health Organization (WHO), the International Academy of Cytology, and the International Agency for Research on Cancer, with expert contributors from around the world, present an international approach to standardized reporting of pancreaticobiliary cytopathology. This reporting system is one of the first in a series from various body sites that mirror the WHO Classification of Tumours series and provides an evidence-based terminology system with associated risk of malignancy and diagnostic management recommendation per diagnostic category. The WHO Reporting System for Pancreaticobiliary Cytopathology (WHO system) revises the Papanicolaou Society of Cytopathology (PSC) system for Reporting Pancreaticobiliary Cytology published in 2015 and replaces the six-tiered system with a seven-tiered system: “insufficient/inadequate/nondiagnostic”; “benign (negative for malignancy),” “atypical,” “pancreaticobiliary neoplasm of low risk/low grade,” “pancreatic neoplasm of high risk/high grade,” “suspicious for malignancy,” and “malignant.” The principal differences between the WHO and the PSC systems revolve around the classification of neoplasia. In the PSC system, there was a single category for “neoplastic” lesions that includes two groups, one for “benign neoplasms” [primarily serous cystadenoma] and one named “other,” dominated by premalignant intraductal neoplasms (primarily intraductal papillary mucinous neoplasms) and low-grade malignant neoplasms [pancreatic neuroendocrine tumors (PanNETs) and solid pseudopapillary neoplasms (SPNs)]. In the WHO system, benign neoplasms with virtually no risk of malignancy are included in the “benign” category and low-grade malignancies (PanNET and SPN) are included in the “malignant” category, as per the WHO Classification of Digestive System Tumours, thus leaving in the “neoplasm” category primarily those noninvasive premalignant lesions of the ductal system. These neoplasms are divided by the cytomorphological grade of the epithelium into low risk/low-grade and high risk/high-grade, with distinctly different risks of malignancy. As with the PSC system, the WHO system advocates close correlation with imaging and encourages incorporation of ancillary testing into the final diagnosis, such as biochemical (CEA and amylase) and molecular testing of cyst fluid and bile duct brushings. Key diagnostic cytopathological features of specific lesions or neoplasms, ancillary studies for diagnostic and prognostic evaluation, and implications of diagnosis for patient care and management are discussed. In addition, the WHO system includes reporting and diagnostic management options that recognize the variations in the availability of diagnostic and prognostic ancillary testing modalities in low- and middle-income countries, where cytopathology is particularly useful and is increasingly available in the absence of histopathological services.

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.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.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.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.

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.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.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.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.

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.

BACKGROUND The term "atypical" has had a long history of usage in cytology but has had variable definitions and usage. Most commonly the term was used to indicate a degree of cytomorphologic abnormality greater than that clearly due to reactive or reparative changes but not associated with a high concern on the part of the cytopathologist that a malignancy is present. The Papanicolaou Society of Cytopathology System for Reporting Respiratory Cytology provided a foundation for using the category "Atypical" along with the category "Suspicious for Malignancy" to categorize the spectrum of morphologic changes ranging from those which are clearly benign to those that are clearly malignant. The two intermediate categories of "Atypical" and "Suspicious for Malignancy" have characteristic recommendations resulting in clinical utility for both categories. CONCLUSION The Papanicolaou Society of Cytopathology System for Reporting Respiratory Cytology represents a useful system with defined intermediate categories of Atypical and Suspicious for Malignancy.

A 57-year-old patient developed severe, persistent pain following MR arthrography with iodinated contrast. MRI 1 week later showed synovitis which was new compared to the prior MRI. Arthroscopy showed severe synovitis. Histopathology showed synovitis characterized by lymphocytes, neutrophils, and necrosis. One out of 4 intraoperative cultures was positive, but ultimately believed to be due to contaminants. CRP normalized within 1 month. Repeat MRI 2 years later showed progressive degenerative findings, but no evidence of ongoing infection, or stigmata of previous infection. We believe this to be an unusually severe case of reactive synovitis. The purpose of the report is to add to knowledge of reactions to intra-articular contrast injection.

Background In 2016, the Papanicolaou Society of Cytopathology (PSC) proposed a classification scheme for reporting cytologic specimens obtained from the respiratory system. Diagnostic sensitivity, specificity, and risk of malignancy were reported for endobronchial ultrasound guided fine needle aspiration but data for other sampling techniques has been poorly documented. Methods In 2016, a modified version of the PSC guidelines was adopted at the University of Missouri for classification of sputum, bronchial washing, bronchial brushing, and fine-needle aspiration specimens. Specimens assigned to the negative category included all specimens containing evaluatable inflammatory or epithelial cells including benign appearing respiratory epithelium. Only specimens with marked artifactual distortion or obscuring blood or mucus were placed in the non-diagnostic category. Results 672 bronchial washing specimens (479 with histology) and 511 bronchial brushings specimens (324 with histology) were reviewed. Washing specimens were classified as non-diagnostic (3%), benign (73%), atypical (10%), suspicious (4%), and malignant (10%). Bronchial brushing specimens were classified non-diagnostic (0.4%) benign (73%), atypical (6%), suspicious (3%), and malignant (17%). Malignancy risks for bronchial washings were insufficient (50%), benign (38%), atypical (62%), suspicious (83%), and malignant (98%). Risks of malignancy for bronchial brushings were insufficient (0%), benign (32%), atypical (79%), suspicious (75%), and malignant (94%). Conclusion Malignancy risks associated with bronchial washings and bronchial brushings are different than those reported for EBUS FNA. When the benign category includes specimens with "normal" appearing cellular elements, the risk of malignancy is substantial (between 32% and 38%).

Appendiceal mucinous neoplasms are rare findings defined by an accumulation of mucus within the vermiform appendix, and can be caused by a variety of conditions. Appendiceal mucinous neoplasms are important to consider because they can develop into pseudomyxoma peritonei as a consequence of perforation. We report a case of a 55-year-old man who initially presented with increasing abdominal girth, constipation, anorexia, and unintentional weight loss. Computed tomography examination of the abdomen and pelvis demonstrated a huge thin-walled cystic mass causing significant displacement of the surrounding abdominal and pelvic structures. The mass was amenable to resection and removed without perforation. Gross pathologic examination demonstrated a 44.0 × 40.0 × 23.0 cm unilocular cystic mass with a section of attached bowel. Microscopic examination revealed high-grade appendiceal mucinous neoplasm arising in a background of low-grade appendiceal mucinous neoplasm. This case report provides an evidence to include appendiceal mucinous neoplasms in the differential diagnosis of large abdominal cystic masses.

OBJECTIVE. The purpose of this study was to assess the utility of radiography in diagnosing osteonecrosis of the femoral head with pathologic examination as the reference standard. MATERIALS AND ME...

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.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.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.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.

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.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.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.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.

To determine the frequency with which MRI of tenosynovial giant cell tumor demonstrates hemosiderin, visible intralesional fat signal, and proximity to synovial tissue. This is a retrospective study of 31 cases of tenosynovial giant cell tumors which had concomitant MRI. Images were examined for lesion size, morphology, origin, bone erosions, MRI signal characteristics, contrast enhancement, and blooming artifact, comparing prospective and retrospective reports. Histology was reviewed for the presence of hemosiderin and xanthoma cells. Eight lesions were diffuse and 23 were localized nodules. Three lesions were located in subcutaneous tissue and 4 adjacent to tendons beyond the extent of their tendon sheath. All lesions exhibited areas of low T1- and T2-weighted signal. Blooming artifact on gradient echo imaging was present in 86% of diffuse and only 27% of nodular disease. There was interobserver variability of 40% in assessing blooming. Iron was visible on H&E or iron stain in 97% of cases. Fat signal intensity was seen in only 3% of cases, although xanthoma cells were present on in 48%. The correct diagnosis was included in the prospective radiology differential diagnosis in 86% of diffuse cases and 62% of nodular cases. Blooming on GRE MRI has low sensitivity for nodular tenosynovial giant cell tumors and is not universal in diffuse tumors. There was high interobserver variability in assessment of blooming. Intralesional fat signal is not a useful sign and may occur adjacent to tendons which lack a tendon sheath and may occur in a subcutaneous location.

BACKGROUND Pembrolizumab is an anti-programmed death receptor 1 (PD-1) that was shown to have a tolerable safety profile with 17% of grade 3-4 drug-related adverse events, notable response rate of 16% with median duration of response of 8 mo, and median overall survival of 8 mo. Severe mucositis is a very rare complication with only two cases of grade 4 mucositis reported, and both cases had good response to intravenous methylprednisolone and subsequent oral prednisone tapering. We report the first case of pembrolizumab-induced severe mucositis that was refractory to steroid treatment. CASE SUMMARY An 80-year-old woman with a past medical history of recurrent right cheek nodular melanoma status post resection and new right lung metastatic melanoma on immunotherapy presented with dysphagia and odynophagia for 2 mo. She initially received 2 doses of ipilimumab 1 year ago with good outcome, but treatment was discontinued after developing severe diarrhea and rash. Pembrolizumab was then initiated 4 mo after disease progression. Significant improvement was noted after 3 doses. However, after 6 cycles of pembrolizumab, patient developed odynophagia and malnutrition. Improvement of symptoms was noted after discontinuation of pembrolizumab and initiation of steroids. 3 mo later, patient developed pharyngeal swelling with hoarseness and new oxygen requirement due to impending airway obstruction while being on prednisone tapering regimen, finally ended up with intubation and tracheostomy. Histologic analysis of left laryngeal and epiglottis tissue showed granulation tissue with acute on chronic inflammation, negative for malignancy and infection. Patient achieved marked improvement after 2 doses of infliximab of 5 mg/kg every 2 wk while continuing on prednisone tapering course. CONCLUSION We report the first case of pembrolizumab-induced grade 4 mucositis that had limited recovery with prolonged steroid course but had rapid response with addition of infliximab. The patient had recurrent mucositis symptoms whenever steroids was tapered but achieved complete response after receiving two doses of infliximab while continuing to be on tapering steroids. The success of infliximab in this patient with pembrolizumab-induced severe mucositis presents a potentially safe approach to reduce prolonged steroid course and accelerate recovery in managing this rare complication.

Context.— The need for appropriate specimen use for ancillary testing has become more commonplace in the practice of pathology. This, coupled with improvements in technology, often provides less invasive methods of testing, but presents new challenges to appropriate specimen collection and handling of these small specimens, including thoracic small biopsy and cytology samples. Objective.— To develop a clinical practice guideline including recommendations on how to obtain, handle, and process thoracic small biopsy and cytology tissue specimens for diagnostic testing and ancillary studies. Methods.— The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Core needle biopsy, touch preparation, fine-needle aspiration, and effusion specimens with thoracic diseases including malignancy, granulomatous process/sarcoidosis, and infection (eg, tuberculosis) were deemed within scope. Ancillary studies included immunohistochemistry and immunocytochemistry, fluorescence in situ hybridization, mutational analysis, flow cytometry, cytogenetics, and microbiologic studies routinely performed in the clinical pathology laboratory. The use of rapid on-site evaluation was also covered. Results.— Sixteen guideline statements were developed to assist clinicians and pathologists in collecting and processing thoracic small biopsy and cytology tissue samples. Conclusions.— Based on the systematic review and expert panel consensus, thoracic small specimens can be handled and processed to perform downstream testing (eg, molecular markers, immunohistochemical biomarkers), core needle and fine-needle techniques can provide appropriate cytologic and histologic specimens for ancillary studies, and rapid on-site cytologic evaluation remains helpful in appropriate triage, handling, and processing of specimens.

BACKGROUND Sebaceous lymphadenomas and sebaceous lymphadenocarcinomas are uncommon neoplasms occurring predominately within the parotid gland. Cytomorphology of these neoplasms is rarely reported. Occasional reports have discussed the cytomorphological features of these neoplasms but criteria distinguishing sebaceous lymphadenomas from lymphadenocarcinomas have not been described. METHODS The senior authors' consultation files and records of the University of Missouri were searched for all cases with a diagnosis of sebaceous adenoma, lymphadenoma, lymphadenocarcinoma, and adenocarcinoma. Slides from these cases were reviewed by the authors for cytologic features characteristic of these neoplasms. These features were compared with other salivary gland lesions in the differential diagnosis and for utility in separating benign from malignant sebaceous neoplasms. RESULTS Three sebaceous lymphadenomas and one sebaceous lymphadenocarcinoma were found. Smears contained large numbers of mature lymphocytes dispersed in a watery or bloody background. Scattered among the lymphoid cells were small nests of epithelial cells characterized by a finely to coarsely vacuolated cytoplasm. The majority of cells contained bland nuclei with finely granular chromatin and conspicuous nucleoli. A second population of small basaloid cells was present. The single sebaceous lymphadenocarcinoma had a similar cytomorphology. CONCLUSIONS Sebaceous lymphadenomas can be distinguished from other neoplasms within the differential diagnosis due to their prominent lymphoid background and population of epithelial cells with a finely to coarsely vacuolated cytoplasm. The nuclei are bland but have conspicuous nucleoli. Based on our small series, cytomorphologic features are inadequate to definitively separate sebaceous lymphadenomas from lymphadenocarcinomas.

Serous fluids are excessive accumulation of fluids in a serous cavity as effusion. However, traditionally this area also covers cytopathologic evaluation of washings of these cavities including pelvic/peritoneal washing. This is the introductory review article in series on this topic with the application of simplified algorithmic approaches. The series would be compiled finally as a book after minor modifications of individual review articles to accommodate the book layout on the topic as second edition of ‘Diagnostic Cytopathology of Serous Fluids’ book. The approach is primarily directed towards detection of neoplastic cells based on morphology alone or with the help of various ancillary tests, including commonly applied immunocytochemistry to be interpreted as second foreign population with application of SCIP (subtractive coordinate immunoreactivity pattern) approach in effusion fluid tapings. As the role of molecular pathology tests is increasing, this component as ancillary testing will also be covered as applicable. Because a picture and sketches are worth a thousand words, illustrations and figures are included generously even at the risk of moderate repetition. The clinically important serous cavities include peritoneal cavity, pericardial cavity, and two pleural cavities. The primary topic of this series is specimens from these cavities as effusion fluids and washings including cytopathologic evaluation of peritoneal/pelvic washing. It is expected that some readers may not read the entire series or the final book from beginning to end, but refer to the individual review articles and chapters sporadically during their clinical practice. Considering this practical limitation, some brief repetition may be observed throughout the book. Some of the important themes will be highlighted as italicized and bolded text for quick reference. Dedicated articles/chapters are assigned for technical and other reference material as appendices. Tables, algorithms, sketches, and combination of pictures are included generously for quick reference. Most of the illustrations are attempted to be labeled appropriately with arrows and other indicators to avoid equivocation, especially for beginners in the field. This introductory review article describes general details under the following three broad headings: Histology and general cytology of serous cavity lining Effusion (general considerations) Ancillary techniques in brief.

Collection of most serous fluids from various effusions is a relatively simple procedure. Because of this, serous fluids are commonly submitted for pathologic examination including cytopathologic evaluation by various clinical institutions. As a consequence, even a general pathology laboratory which may not have expertise with highly trained cytopathologist would be confronted with serous fluids for cytologic evaluation. However, cytopathologic evaluation of serous fluids is complex as compared to evaluation of fine needle aspiration cytology. This signifies the fact that all pathologists, irrespective of subspeciality cytopathology training and level of subspeciality expertise, should be conversant with the diagnostic challenges and pitfalls of effusion fluid cytology. Although, majority of effusions are due to reactive and non-neoplastic etiologies, cancer is one of the causes of an effusion as a manifestation of advanced cancer. Detecting neoplastic cells in effusion specimens in most of clinical settings is related to the advanced status of the disease, which usually is equivalent to incurable stage. Thus, interpretation of cytopathology as positive for cancer cell is highly critical in planning the trajectory of the clinical management with an obvious negative impact of false positive interpretation. Apart from cancer, effusions may be secondary to hemodynamic pathologies such as heart failure, hypoalbuminemia, cirrhosis etc. in addition to the different inflammatory conditions including parasitic infestations, bacterial, fungal, or viral infections, and other non-neoplastic etiologies including collagen diseases. Due to the cytomorphologic overlap of reactive mesothelial cells with malignant cells, general cytologic criteria for diagnosis of malignancy in single cells cannot be applied in most of the effusion specimens. This challenge is further amplified because of surface tension related phenomenon which ‘round up’ the cells after exfoliation in serous fluids. As a result, the native shapes of cancer cells cannot be a guiding feature. Thus the cytomorphologic features of cancer cells in serous fluids may not be same as seen in routine cytopathology of exfoliative, brushing, and fine-needle aspiration specimens. The cancer cells may continue to proliferate after exfoliation in the nutrient rich effusion fluids and may form proliferation spheres. It is crucial to consider these factors when interpreting effusion cytology. Amongst malignant effusions, adenocarcinomas are the most common cause of metastatic cancers, but almost any type of malignancy including melanomas, hematopoietic neoplasms, sarcomas, and mesotheliomas may involve serous cavities. The interpreter must be aware of the wide range of the cytomorphologic appearances of reactive mesothelial cells in effusion fluids. It is essential to understand these and other nuances related to effusion fluid cytology. Understanding potential pitfalls during various stages from processing to application of ancillary studies would increase the diagnostic accuracy and minimize atypical interpretations and false positivity.

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.

We report a case of a 70-year-old woman with a BMI of 58 who developed cellulitis refractory to treatment, within an area of massive localized lymphedema. Biopsy showed angiosarcoma. MRI showed multiple lobulated, low T1, high T2 masses within a background of prominent soft tissue septal stranding, dilated lymphatic channels, and skin thickening. CT also showed the mass well, within the background lymphedema. Massive localized lymphedema is increasing in prevalence due to the worsening obesity epidemic. Radiologists should be aware that the presence of a nodule within an area of massive localized lymphedema is suspicious for sarcoma.

Background: A number of guidelines have been developed to improve standardization of the terminology and criteria for cytologic specimens obtained from the thyroid, pancreas, lung, and salivary glands. A major goal of these guidelines is to improve reproducibility and understanding of the reporting of diagnostic results among cytopathologists and between cytopathologists and clinicians. The International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy Cytopathology (IAC YSRB) is the most recent of these guidelines. The value of this system is, in part, dependent upon interobserver reproducibility. Design: Ninety consecutive fine-needle aspiration biopsies (FNAB) of the breast, performed over a 6-year period, were independently evaluated by 4 board-certified pathologists blinded to the original diagnoses. The 5 diagnostic categories used were those of the IAC YSRB according to published criteria for these categories. Observed agreement and chance corrected agreement (Fliess κ) were calculated. Differences in κ values were evaluated using the T statistic of Gwent. Statistical calculations were performed using STATA v16.0 (STATA Corp., College Station, TX, USA). Results: Overall agreement between observers was good. Observed unweighted agreement was 69% and weighted agreement was 91%. The majority of diagnoses were concordant (68.6%). Conclusions: Interobserver agreement of 4 cytopathologists was good using the 5 categories of the IAC YRSB (69%). Agreement was greater among pathologists with more years of experience. The IAC YSRB system appears to provide greater agreement among viewers than guidelines for cytologic specimens obtained from some other body sites (salivary gland and lung). Most discrepancies were only by a single category, with only 22/113 (19%) differing by more than one category.

Tissue diagnosis of a soft tissue neoplasm is of paramount importance for the development of an appropriate treatment plan. Biopsy technique including approach and biopsy method is important to the success of diagnosis and subsequent treatment. Histologic and cytologic diagnoses are difficult and complicated by the large number of soft tissue lesions described, distinctly different biopotential for morphologically similar lesions, often small biopsy specimen size, and the generally limited experience many pathologists have in the diagnosis of soft tissue neoplasms. While utilized less frequently than core-needle biopsies, fine-needle aspiration is a valuable initial approach for the classification of soft tissue neoplasms. The combination of pattern based morphologic analysis, immunohistochemistry, and molecular diagnostics represents a utilitarian and generally successful approach for the diagnosis of soft tissue lesions.

Background We evaluated the diagnostic accuracy (DA), risk of neoplasm (RON), and risk of malignancy (ROM) for the commonly encountered malignant salivary gland tumors mucoepidermoid carcinoma (MECa), acinic cell carcinoma (ACCa), and adenoid cystic carcinoma (ADCa) applying The Milan System for Reporting Salivary Gland Cytology (MSRSGC). Materials and methods The cytology archives from 2007 to 2017 of 9 academic institutions were searched for salivary gland FNAs for the following key words mentioned either in the principal and/or differential diagnosis: MEC, ACCa, and ADCa. The original cytology diagnosis was retrospectively classified according to the MSRSGC. Patient demographics, biopsy site, and available surgical follow-up were recorded. The final analysis included only cases with surgical follow-up. Results A total of 212 salivary gland FNAs were included. Based on retrospective reclassification according to MSRSGC, 97 of 212 (46%) FNA cases carried a diagnosis of malignancy specific for either MECa, ACCa, or ADCa. In the remaining 115 cases, 24 of 212 (11%) were reclassified as suspicious for malignancy (SM) and 91 of 212 (43%) as salivary gland neoplasm of uncertain malignant potential (SUMP). The DA for MECa, ACCa, and ADCa was 78.7%, 75% and 89%, respectively. The RON was 100% for all 3 tumors and the ROM was 93.6% for MECa, 96.8% for ACCa, and 94.4% for ADCa. Conclusions The DA of 78.7% for MECa, 75% for ACCa, and 89% for ADCa is reasonable in FNA specimens. Although the management of definitive cases of malignancy remains unchanged, the MSRSGC provides a ROM for SM and SUMP categories, which can improve patient management.

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.

Background Cytopathologists reviewing pulmonary specimens are expected to classify samples into clinically useful categories. Clinicians prefer reports to convey a definitively benign or definitively malignant diagnosis. Cytopathologists recognize a spectrum of morphologic features with increasing degrees of atypia between clearly benign and clearly malignant. A variety of terms are used to convey to clinicians how concerned a cytologist is that a malignancy maybe present. These terms include "atypia", "atypical" and "suspicious for malignancy", but have had variable meanings among cytopathologists and clinicians. Categorization schemes have been proffered to include standardization of terminology with many of these systems containing one or more intermediate categories. Methods An electronic search of the University of Missouri cytology reporting system was made for all bronchial brushings specimens diagnosed using the Papanicolaou Society of Cytopathology System for Reporting Respiratory Cytology (PSCSR) between January 2019 and December 2019. Slides were reviewed to determine adequate cellularity and preparation quality. From those found to be adequately cellular and of good quality, four bronchial brushing specimens from each PSCSR category were randomly selected. For each case a slide was digitized and at least 70 of the most "atypical" cells were analyzed by the Aperio System for nuclear area and nuclear/cytoplasmic ratio. Distribution of measured parameters among categories was analyzed by the Kruskal-Wallis test. Results During the study period, only the PSCSR categories "benign", "atypical" and "malignant" were recorded. A significant difference in distribution of nuclear/cytoplasmic ratio was seen between the "benign" and "atypical" categories but not between the "atypical" and "malignant" categories. The "atypical" category appeared to be bi-modal indicating that it could be divided into two categories, "atypical" and "suspicious for malignancy". Conclusions The categories "atypical" and "suspicious for malignancy" served to divide the spectrum of cytomorphologic changes between "benign" and "malignant" into clinically useful groups. The use of these categories is supported by cytomorphometric analysis of bronchial brushing specimens.

Objectives Destructive arthropathy of the hip refers to noninfectious arthropathy causing extensive femoral head bone destruction. It has been described in the surgical literature using a variety of diagnostic criteria, but it remains a poorly defined entity. Methods Cases of destructive arthropathy diagnosed at our institution between July 1, 2015, and December 31, 2019, were identified by a free text search of the radiology database. The medical record of each case was reviewed for possible causes of femoral head destruction, clinical presentation, laboratory values, imaging studies, and pathologic diagnoses. Imaging studies and pathology specimens were retrospectively reviewed. Results Twenty femoral heads were identified in which there was 25% or greater destruction of the femoral head in the absence of infections, congenital disease, or inflammatory arthritis. Destructive arthropathy was characterized pathologically by fibromyxoid change of the marrow, aggregates of necrotic bone fragments, increased numbers of osteoclasts, increased trabecular destruction, and granuloma-like aggregates. Conclusions The histologic findings were distinctive. We postulate that a variety of preexisting conditions set in motion a cascade of tissue factors that led to bone destruction.

A 57-year-old patient developed severe, persistent pain following MR arthrography with iodinated contrast. MRI 1 week later showed synovitis which was new compared to the prior MRI. Arthroscopy showed severe synovitis. Histopathology showed synovitis characterized by lymphocytes, neutrophils, and necrosis. One out of 4 intraoperative cultures was positive, but ultimately believed to be due to contaminants. CRP normalized within 1 month. Repeat MRI 2 years later showed progressive degenerative findings, but no evidence of ongoing infection, or stigmata of previous infection. We believe this to be an unusually severe case of reactive synovitis. The purpose of the report is to add to knowledge of reactions to intra-articular contrast injection.

To determine the frequency with which MRI of tenosynovial giant cell tumor demonstrates hemosiderin, visible intralesional fat signal, and proximity to synovial tissue.This is a retrospective study of 31 cases of tenosynovial giant cell tumors which had concomitant MRI. Images were examined for lesion size, morphology, origin, bone erosions, MRI signal characteristics, contrast enhancement, and blooming artifact, comparing prospective and retrospective reports. Histology was reviewed for the presence of hemosiderin and xanthoma cells.Eight lesions were diffuse and 23 were localized nodules. Three lesions were located in subcutaneous tissue and 4 adjacent to tendons beyond the extent of their tendon sheath. All lesions exhibited areas of low T1- and T2-weighted signal. Blooming artifact on gradient echo imaging was present in 86% of diffuse and only 27% of nodular disease. There was interobserver variability of 40% in assessing blooming. Iron was visible on HE or iron stain in 97% of cases. Fat signal intensity was seen in only 3% of cases, although xanthoma cells were present on in 48%. The correct diagnosis was included in the prospective radiology differential diagnosis in 86% of diffuse cases and 62% of nodular cases.Blooming on GRE MRI has low sensitivity for nodular tenosynovial giant cell tumors and is not universal in diffuse tumors. There was high interobserver variability in assessment of blooming. Intralesional fat signal is not a useful sign and may occur adjacent to tendons which lack a tendon sheath and may occur in a subcutaneous location.

Introduction The accurate diagnosis of musculoskeletal neoplasms is difficult but a pattern-based approach combined with ancillary testing has been shown to improve diagnostic accuracy. The pattern-based approach is particularly appropriate for myxoid lesions. Materials and methods The authors reviewed their personal experience of over 3 decades of diagnosing myxoid neoplasms of musculoskeletal lesions. Results The authors found that myxoid lesions can be accurately classified based on cell type, nuclear atypia, presence of blood vessel fragments, as well as the results of immunohistochemical and molecular testing. Conclusions Musculoskeletal lesions with a prominence of myxoid or chondroid material in the background can be accurately diagnosed using pattern analysis and ancillary testing.

BACKGROUND Fine-needle aspiration (FNA) is commonly used to investigate lymphadenopathy of suspected metastatic origin. While diagnostic accuracy of FNA for lymph node disease is well described, the relationship between node size, percent tumor replacement, and size of metastatic deposit with diagnostic accuracy is less well documented. METHODS All axillary lymph nodes undergoing ultrasound-guided FNA for suspected breast metastases were correlated with subsequent surgical excision specimens. FNAs were judged as positive or negative for malignancy and the percent of false negative FNAs was correlated with node size, percent tumor replacement and size of metastatic deposit RESULTS: Sensitivities were calculated for nodes greater than 15 mm (92%), nodes 11 to 14.9 mm (83%), nodes 7 to 10.9 mm (61%), and for nodes less than 7 mm (60%). Sensitivity increases with increasing node size (P = .001). Percent tumor replacement correlated with sensitivity: 90% or greater replacement (85%) 60% to 89.9% replacement (75%), 40% to 59.9% replacement (75%) and less than 39.9% replacement (64%)(P

Solitary fibrous tumors are rare mesenchymal neoplasms of fibroblastic or myofibroblastic origin. Primary solitary fibrous tumors arising in bone are extremely rare and rarely metastasize. We present a case of solitary fibrous tumor where the diagnosis was delayed due to a failure to recognize the subtle, lytic lesion underlying a fracture of the left humerus. The patient underwent proximal humeral replacement and was followed closely with imaging of humerus and chest. A small lung metastasis was found on CT scan 38 months later and was resected. Two additional small metastases were found and resected 62 months after initial tumor resection. The purpose of this case report is both to highlight the radiologic challenges which can lead to overlooking a lytic lesion underlying a fracture and to show the importance of long-term follow-up in patients with solitary fibrous tumor.

Background Ancillary testing including immunohistochemistry and molecular diagnostics has become an increasingly important component for the evaluation of cytologic specimens. Ancillary testing is important not only for diagnosis but also for predictive and prognostic evaluation. While a number of substrates are appropriate for ancillary testing, cell block specimens are commonly utilized and the success of ancillary testing depends on cell-block cellularity. Methods Forty-six pairs of cases each fixed in both formalin and CytoLyt were each analyzed by two evaluators for overall cellularity. Linear regression was used to assess inter-rater reliability of cell counts for each method. Cellularity scores for each case were obtained by averaging the scores for each rater and cellularity was compared between the methods. Results Inter-rater agreement was very good for both methods. The coefficient of determination was 1.0 and 0.99 for the CytoLyt and formalin methods respectively. Cell blocks using the CytoLyt method have lower levels of cellularity than cell blocks performed by the formalin method. Conclusions Cell blocks prepared using a formalin fixative yield significantly greater cellularity than those produced by the CytoLyt method. Formalin fixation appears to optimize cellularity of cell blocks useful for ancillary testing.

Background Rapid on-site evaluation (ROSE) can increase adequacy and reduce needle passes in fine-needle aspiration cytology (FNAC) procedures. However, ROSE increases the cost of FNAC. Costs may be reduced if ROSE is performed by an alternate evaluator (AE), such as a cytotechnologist (CT), endoscopist, or pulmonologist, rather than a cytopathologist (CP). Studies have shown that AEs can perform ROSE with high accuracy but are generally not as accurate as CPs. The objective of this study was to evaluate the impact of AEs on the cost-effectiveness of ROSE. Methods A cost model, based on a mathematical sampling model, was developed. The cost model was used to compare the impact of the evaluator type on overall costs. Results CTs were likely to be cost-effective for simple procedures and were unlikely to be cost-effective for only the most complex procedures. The model demonstrated the tradeoff in cost savings from using AEs and the potential costs associated with repeated procedures due to the lower accuracy of AEs. Conclusions The cost-effectiveness of AEs is context-dependent. AEs can be cost-effective even if they are less accurate than CPs. AEs are likely to be cost-effective in most contexts.

Solitary fibrous tumors are primary mesenchymal tumors, which may occur in any part of the body. Overall, these tumors are considered to have intermediate malignant potential with 5- and 10-year metastasis-free and overall disease-specific survival rates of 74% and 55%, and 89% and 73%, respectively (Demicco et al, 2012). Herein we present an unusual case of solitary fibrous tumors involving the ischioanal fossa in a 19-year-old woman with radiologic-pathologic correlation. This case was complicated by extensive tumor vascularity and was thus managed with preoperative embolization followed by en bloc surgical resection. Keywords: Solitary fibrous tumor, Embolization, Ischioanal, Hemangiopericytoma

Solitary fibrous tumors (SFTs) are rare fibroblastic mesenchymal tumors that are usually benign with variable malignant potential. They can develop in any organ due to their spindle cell origin. The exact etiology of solitary fibrous tumors is unknown. The majority of SFTs are benign with 10% to 30% of them exhibiting aggressive and malignant features. The aggressiveness of this type of tumor is not associated with its histological features, which makes surgical resection the treatment of choice. We will review the clinical and radiological features and possible differential diagnoses of SFTs according to their anatomical sites following the World Health Organization 2020 classification.

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.

Testing for SARS-CoV-2 has become a critical component for the management of the COVID-19 pandemic. Reverse transcriptase polymerase chain reaction (RT-PCR) assays are currently the predominate method for testing. Quality control (QC) measures utilize known positive and known negative controls to ensure the adequacy of extraction and RT-PCR steps but do not evaluate all components of testing. We have conducted a quality assurance review of our RT-PCR testing for COVID-19 to determine the rate of false positive results in asymptomatic patients and causes for these errors. Design We have developed a quality control procedure in which all specimens from asymptomatic unexposed persons with SARS-CoV-2 positive tests were retested. When a second test was “non-detected” a third test was performed and a root cause analysis of the erroneous result undertaken. Results In the study period, 24,717 samples were tested and 6251 were from asymptomatic patients. Of the 288 initial positive tests, 20 (6.9%) were negative on retesting. Review of cycle threshold curves, technologists’ records, location of specimen on testing plates and relationships with high viral load specimens was undertaken. Analysis revealed technologists’ errors (misplacement of specimen in testing plate or contamination) and cross contamination from high viral load specimens in adjacent wells of testing plates were common causes for false positive results. Discussion SARS-CoV-2 RT-PCR testing is associated with a small number of false positive results, most easily recognized in asymptomatic non-exposed patients. Implementation of a limited retesting protocol identifies clinically significant testing errors and allows review and improvement of laboratory procedures.

Currently, there is no uniform classification scheme available for reporting of salivary gland fine-needle aspiration (FNA) specimens. Recently, an International group of pathologists has recommended a tiered classification scheme for reporting of salivary gland FNA results known as the "Milan System for Reporting Salivary Gland Cytopathology (MSRSGC)." We performed a comprehensive review of the published literature on FNA of salivary gland lesions by employing the diagnostic categories of the MSRSGC to evaluate their reliability in the management of salivary gland lesions. A comprehensive review of the literature was carried out through PubMed from 1987 to 2015 to identify studies which categorized the cytologic diagnoses and included surgical follow-up. Only cases with histopathologic follow-up were included in the analysis. Twenty-nine studies comprising 4514 cases of salivary gland FNAs with surgical follow-up were included in this study. The cytologic diagnoses were categorized into the following categories proposed by MSRSGC. The number of cases in each diagnostic category and the risk of malignancy (ROM) were as follows: Non-Diagnostic-100 cases (ROM- 25.0% ± 16.7%), Non-Neoplastic-587 cases (ROM: 10.2% ± 5.5%), Benign Neoplasm -2673 cases (ROM: 3.4% ± 1.3%), Salivary Gland Neoplasm of Undetermined Malignant Potential (SUMP)-64 cases(ROM: 37.5% ± 24.7%), Suspicious for Malignant neoplasm-70 cases(ROM: 58.6% ± 19.5%), and Malignant-1012 cases(ROM: 91.9% ± 3.5%). A tiered classification scheme as proposed by MSRSGC may prove helpful in effectively guiding clinical management of patients with salivary gland lesions.

Background and purpose In patients with squamous cell carcinoma of the head and neck (HNSCC), extracapsular spread (ECS) of metastases in cervical lymph nodes affects prognosis and therapy. We assessed the accuracy of intravenous contrast-enhanced computed tomography (CT) and the utility of imaging criteria for preoperative detection of ECS in metastatic cervical lymph nodes in patients with HNSCC. Materials and methods Preoperative intravenous contrast-enhanced neck CT images of 93 patients with histopathological HNSCC metastatic nodes were retrospectively assessed by two neuroradiologists for ECS status and ECS imaging criteria. Radiological assessments were compared with histopathological assessments of neck dissection specimens, and interobserver agreement of ECS status and ECS imaging criteria were measured. Results Sensitivity, specificity, positive predictive value, and accuracy for overall ECS assessment were 57%, 81%, 82% and 67% for observer 1, and 66%, 76%, 80% and 70% for observer 2, respectively. Correlating three or more ECS imaging criteria with histopathological ECS increased specificity and positive predictive value, but decreased sensitivity and accuracy. Interobserver agreement for overall ECS assessment demonstrated a kappa of 0.59. Central necrosis had the highest kappa of 0.74. Conclusion CT has moderate specificity for ECS assessment in HNSCC metastatic cervical nodes. Identifying three or more ECS imaging criteria raises specificity and positive predictive value, therefore preoperative identification of multiple criteria may be clinically useful. Interobserver agreement is moderate for overall ECS assessment, substantial for central necrosis. Other ECS CT criteria had moderate agreement at best and therefore should not be used individually as criteria for detecting ECS by CT.