Update on the role of pathology and laboratory medicine in diagnosing periprosthetic infection.

Technological and implant design advances have helped reduce the frequency of aseptic total joint arthroplasty failure, but periprosthetic joint infections (PJI) remain a clinical important problem with high patient morbidity. Misinterpreting PJI as aseptic mechanical loosening commonly leads to unsatisfactory revision arthroplasty, persistent infection, and poor long-term results. While there is no single "gold standard" diagnostic test for PJI, recent collaborative efforts by Orthopaedic and Infectious Disease Societies have developed algorithms for diagnosing PJI. However, the efficacy of individual tests as well as diagnostic thresholds are controversial. We review the recommended thresholds for commonly used screening tests as well as tissue histopathology and confirmatory tests to diagnose periprosthetic infection. We also update lesser-known laboratory tests, and we briefly summarize rapidly evolving molecular tests to diagnose periprosthetic infection. Pathologists hold a critical role in assisting with PJI diagnosis, maintaining laboratory test quality and interpreting test results. Collaboration between clinicians and pathologists is essential to provide optimal patient care and reduce the burden of PJI.

Reproducibility of pathologic scoring systems for periprosthetic adverse local tissue reactions: A cross-sectional study.

BACKGROUND: Several previous studies have described broad histologic classifications of peri-prosthetic reactions that likely reflect the underlying mechanism of arthroplasty failure; however, a consensus has not yet been reached about the relative importance of individual observations. QUESTION/PURPOSE: The purpose of this study was to evaluate the inter-examiner repeatability of commonly used histopathologic grading methods, and to determine the utility of assigning a more simple, global categorization in patients undergoing revision THA surgery of implants with a variety of bearing combinations. METHODS: Between March 2013 and February 2020, a total of 2131 patients underwent revision hip arthroplasty surgery at a one center, of which 12% (248 of 2131) of patients were enrolled. Two pathologists independently reviewed microscope slides of periprosthetic tissue from these patients, of which 425 slides (229 hips, 222 subjects) were reviewed by both pathologists. Separate slides were used for a priori training of the pathologists. Slides were evaluated with the Campbell Aseptic Lymphocyte-dominant Vasculitis-Associated Lesion (ALVAL) score, the Oxford ALVAL score as modified by Grammatopolous, the Fujishiro and Natu scores, and a proposed simplified pattern classification, similar to that of Krenn et al., that incorporates individual factors of these existing scoring methods and was previously shown to correspond to Magnetic Resonance Imaging findings. Inter-rater agreement was assessed using Gwet's AC1 and AC2 coefficients and correspondence analysis was used to examine associations between individual factors of prior scoring methods with the proposed major pattern. RESULTS: Almost perfect inter-rater repeatability (Gwet's AC2 > 0.8) was found for 71% (15/21) of the individual factors, and substantial interrater agreement was found for the proposed major overall pattern (Gwet's AC1: 0.80, 95%CI: 0.72-0.85). Correspondence analysis was able to explain 89-91% of data variability and was able to identify individual features not commonly associated with a major pattern, but discriminatory of the major pattern, such as "Lymph Cuff Thickness 0.25-0.5″ with ALVAL. CONCLUSION: In contrast to prior examinations, excellent interrater agreement was found that may be attributable to a priori training of raters with a test set of slides or difficulty of interpreting grading criteria. The proposed simplified major pattern classification may facilitate evaluation of histopathologic tissue samples.

A Brief Overview and Update on Major Molecular Genomic Alterations in Solid, Bone and Soft Tissue Tumors, and Hematopoietic As Well As Lymphoid Malignancies.

CONTEXT.­: Recent advances in comprehensive genomic profiling by next-generation sequencing have uncovered the genomic alterations at the molecular level for many types of tumors; as such, numerous small specific molecules that target these alterations have been developed and widely used in the management of these cancers. OBJECTIVE.­: To provide a concise molecular genomic update in solid, bone and soft tissue tumors, hematopoietic as well as lymphoid malignancies; discuss its clinical applications; and familiarize practicing pathologists with the emerging cancer biomarkers and their diagnostic utilities. DATA SOURCES.­: This review is based on the National Comprehensive Cancer Network guidelines and peer-reviewed English literature. CONCLUSIONS.­: Tumor-specific biomarkers and molecular/genomic alterations, including pan-cancer markers, have been significantly expanded in the past decade thanks to large-scale high-throughput technologies and will continue to emerge in the future. These biomarkers can be of great value in diagnosis, prognosis, and/or targeted therapy/treatment. Familiarization with these emerging and ever-changing tumor biomarkers will undoubtedly aid pathologists in making accurate and state-of-the-art diagnoses and enable them to be more actively involved in the care of cancer patients.

Machine learning integration of scleroderma histology and gene expression identifies fibroblast polarisation as a hallmark of clinical severity and improvement.

OBJECTIVE: We sought to determine histologic and gene expression features of clinical improvement in early diffuse cutaneous systemic sclerosis (dcSSc; scleroderma). METHODS: Fifty-eight forearm biopsies were evaluated from 26 individuals with dcSSc in two clinical trials. Histologic/immunophenotypic assessments of global severity, alpha-smooth muscle actin (aSMA), CD34, collagen, inflammatory infiltrate, follicles and thickness were compared with gene expression and clinical data. Support vector machine learning was performed using scleroderma gene expression subset (normal-like, fibroproliferative, inflammatory) as classifiers and histology scores as inputs. Comparison of w-vector mean absolute weights was used to identify histologic features most predictive of gene expression subset. We then tested for differential gene expression according to histologic severity and compared those with clinical improvement (according to the Combined Response Index in Systemic Sclerosis). RESULTS: aSMA was highest and CD34 lowest in samples with highest local Modified Rodnan Skin Score. CD34 and aSMA changed significantly from baseline to 52 weeks in clinical improvers. CD34 and aSMA were the strongest predictors of gene expression subset, with highest CD34 staining in the normal-like subset (p<0.001) and highest aSMA staining in the inflammatory subset (p=0.016). Analysis of gene expression according to CD34 and aSMA binarised scores identified a 47-gene fibroblast polarisation signature that decreases over time only in improvers (vs non-improvers). Pathway analysis of these genes identified gene expression signatures of inflammatory fibroblasts. CONCLUSION: CD34 and aSMA stains describe distinct fibroblast polarisation states, are associated with gene expression subsets and clinical assessments, and may be useful biomarkers of clinical severity and improvement in dcSSc.

Lymphoid Enhancer Binding Factor 1 (LEF1) and Paired Box Gene 8 (PAX8): A Limited Immunohistochemistry Panel to Distinguish Solid Pseudopapillary Neoplasms and Pancreatic Neuroendocrine Tumors.

Solid pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine tumors (PanNETs) are distinctive entities. However, due to overlapping morphologies, distinguishing them remains a diagnostic challenge. Our study investigates the utility of immunohistochemistry for nuclear lymphoid enhancer binding factor 1 (LEF1) and paired box gene 8 (PAX8) in differentiating these 2 entities. LEF1 and PAX8 immunohistochemistry were performed on fine-needle aspiration cell blocks and surgical resection specimens diagnosed as SPN or PanNET at our institution from January 2007 to August 2016. Eight SPN and 25 PanNET cell blocks and 17 SPN and 34 PanNET surgical resection specimens were examined. On cell blocks, positive staining for LEF1 had high frequency, sensitivity, and specificity for SPN (88%, 88%, and 88%) as did positive staining for PAX8 for PanNET (76%, 76%, and 75%). The findings on surgical resection specimens were consistent with those from cell blocks (LEF1+ in SPN: 100%, 100%, and 97%; PAX8+ in PanNET: 59%, 59%, and 100%). A combined LEF1+/PAX8- phenotype showed high sensitivity and specificity for SPN (cell block: 63% and 100%; surgical specimen: 100% and 98%) as did a LEF1-/PAX8+ phenotype for PanNET (cell block: 64% and 100%; surgical specimen: 59% and 100%). SPN and PanNET exhibit opposite immunophenotypic profiles with LEF1+/PAX8- in SPN and LEF1-/PAX8+ in PanNET. The combination of these 2 stains provides an effective means of distinguishing these 2 entities.

Polyomavirus (BK) cytopathic effect in urine cytology is not associated with high risk of developing high-grade urothelial carcinoma.

INTRODUCTION: Polyomavirus cytopathic effect (BK-CPE) is classified as "negative for high-grade urothelial carcinoma" (NHGUC) in the Paris System for Reporting Urinary Cytology. However, polyomaviruses have been historically associated with tumor development and have been recently reported as an independent risk factor for renourinary carcinoma in transplant patients. The aim of the present study was to investigate the relationship between polyomavirus infection in the urinary tract and the subsequent risk of developing high-grade urothelial carcinoma (HGUC) in the general population. MATERIALS AND METHODS: A retrospective case-control study was conducted to assess BK-CPE in all urinary cytology examinations performed from 2009 to 2011 for cases with an interpretation of NHGUC, NHGUC with BK, atypical urothelial cells (AUCs), or AUCs with BK. The endpoint of the present study was a diagnosis of HGUC on either bladder biopsy or urine cytology for those patients with subsequent follow-up data. RESULTS: A total of 252 cases with a urinary cytology interpretation of NHGUC, 234 with NHGUC + BK, 255 with AUCs, and 64 with AUCs + BK were identified. The surgical and cytological follow-up data showed that the overall risk of the development of HGUC for those with NHGUC, NHGUC + BK, AUCs, and AUCs + BK was 6.0%, 6.8%, 23.5%, and 12.5%, respectively. No statistically significant differences were found between the patients with NHGUC and those with NHGUC + BK. A statistically significant difference was found for patients with AUCs compared with patients with NHGUC + BK and those with AUCs + BK (P < 0.001). CONCLUSIONS: The presence of BK-CPE in urine cytology samples does not increase the overall risk of the development of HGUC. Our results support the recommendation from the Paris System for Reporting Urinary Cytology to place urine samples with BK-CPE in the NHGUC category.

Significance of atypical endometrial cells in women younger than 40 years of age.

INTRODUCTION: The presence of atypical endometrial cells in the Papanicolaou (Pap) test has been associated with an increased rate of endometrial malignancy, with reported rates ranging from 14% to 47%. However, most reported studies have focused on patients who were aged >40 years. The purpose of the present study was to investigate the clinical significance of identifying atypical endometrial cells in Pap test samples in women aged <40 years of age. MATERIALS AND METHODS: A search of the cytology Pap test database was performed from 2000 to 2014 using the keywords "atypical endometrial cells" or "atypical glandular cells favor endometrial origin" in women aged <40 years. The available ThinPrep slides were reviewed. The patients' clinical presentation, follow-up endometrial biopsy findings, treatment, and clinical follow-up data were recorded. Endometrial carcinoma tissue sections were screened for Lynch syndrome. RESULTS: The database search yielded 63 study cases. Of these 63 patients, 52 had subsequently undergone endometrial biopsy. Of the 52 patients with follow-up biopsy findings available, 9 (17.3%) had premalignant (5 with atypical hyperplasia) or malignant (4 with endometrioid adenocarcinoma) lesions. In addition, 16 patients (30.8%) had other endometrial pathologic features. The 9 patients with premalignant or malignant endometrial lesions (8 white, 1 black) were overweight or obese; 3 of the patients did not have any clinical symptoms. All 4 patients with endometrioid adenocarcinoma had negative Lynch syndrome screening findings. CONCLUSIONS: Our results suggest that it is important to recognize the presence of atypical endometrial cells in the Pap tests from young patients, given its association with the finding of premalignant and malignant pathologic features in subsequent endometrial biopsies.

Case 272: Decubital Ischemic Fasciitis.

HistoryA 92-year-old bedridden woman presented to the emergency department from an assisted living facility with fever, cough, and swelling over the right lateral hip. She had baseline dementia and frailty and had been bedridden for 4 years. She did not have any recent falls or history of trauma at the site of swelling. She had a history of diffuse large B-cell lymphoma that had been diagnosed and treated 7 years ago, and thoracoabdominal CT at last follow-up 3 years ago did not show any recurrence. Physical examination findings were unremarkable except for a painful hard and fixed mass measuring approximately 5 × 5 × 10 cm (in the transverse, anteroposterior, and craniocaudal directions, respectively) located at the right lateral superior thigh. The overlying skin was intact, without any color changes. Pertinent blood test results showed an increased white blood cell count of 13,000/µL (13 × 109/L) (normal range, 3700-11,000/µL [3.7-11 × 109/L]). The remaining hematologic and biochemical test results were normal. Abdominal and pelvic CT performed at presentation did not show any abnormal lymph nodes. Because chest radiography showed consolidation in addition to typical clinical picture, the patient was diagnosed with pneumonia and underwent antibiotic treatment for 3 weeks. US and Doppler US of the mass were performed. MRI was not performed because the patient had a pacemaker; instead, CT of the lower extremity was performed.

Case 272.

History A 92-year-old bedridden woman presented to the emergency department from an assisted living facility with fever, cough, and swelling over the right lateral hip. She had baseline dementia and frailty and had been bedridden for 4 years. She did not have any recent falls or history of trauma at the site of swelling. She had a history of diffuse large B-cell lymphoma that had been diagnosed and treated 7 years ago, and thoracoabdominal CT at last follow-up 3 years ago did not show any recurrence. Physical examination findings were unremarkable except for a painful hard and fixed mass measuring approximately 5 × 5 × 10 cm (in the transverse, anteroposterior, and craniocaudal directions, respectively) located at the right lateral superior thigh. The overlying skin was intact, without any color changes. Pertinent blood test results showed an increased white blood cell count of 13 000/µL (13 ×109/L) (normal range, 3700-11 000/µL [3.7-11 ×109/L]). The remaining hematologic and biochemical test results were normal. Abdominal and pelvic CT performed at presentation did not show any abnormal lymph nodes. Because chest radiography showed consolidation in addition to typical clinical picture, the patient was diagnosed with pneumonia and underwent antibiotic treatment for 3 weeks. US ( Fig 1 ) and Doppler US ( Fig 2 ) of the mass were performed. MRI was not performed because the patient had a pacemaker; instead, CT of the lower extremity was performed ( Fig 3a , 3b ). Figure 1: US image of the mass at the level of the greater trochanter. Figure 2: Doppler US image of the caudal portion of the mass. Figure 3a: (a) Axial unenhanced CT image of the lesion at the level of the greater trochanter. (b) Coronal unenhanced CT image of the mass at the level of the greater trochanter. Figure 3b: (a) Axial unenhanced CT image of the lesion at the level of the greater trochanter. (b) Coronal unenhanced CT image of the mass at the level of the greater trochanter.

Primary salivary gland-type tumors of the tracheobronchial tree diagnosed by transbronchial fine needle aspiration: Clinical and cytomorphologic features with histopathologic correlation.

BACKGROUND: Primary salivary gland-type tumors of the tracheobronchial tree are rare; their cytologic features have been seldom reported. We aim to describe the clinical and cytomorphologic features of tracheobronchial salivary gland-type tumors diagnosed by transbronchial fine needle aspiration (TBNA) at our institution, and correlate the findings with a corresponding surgical specimen. METHODS: We searched our laboratory information system to identify patients with a primary salivary gland-type neoplasm of the tracheobronchial tree diagnosed by TBNA and with a corresponding surgical pathology specimen, over 10 years. RESULTS: The study cohort consisted of 11 patients (7F/4M; mean age 58 years, range 41-78). Presenting symptoms included hemoptysis (4), cough (3), dyspnea (1), stridor (1), and shoulder pain (1). Most had a tracheal mass (5), while 3 had mainstem bronchi masses and 3 had lung masses. Radiographically, the masses were lobulated, rounded, or polypoid in six patients. All underwent TBNA with a 21- or 22-gauge needle and endobronchial biopsy. The most frequent diagnosis was adenoid cystic carcinoma (4/11, 36%), followed by mucoepidermoid carcinoma (3/11, 27%), epithelial-myoepithelial carcinoma (2/11, 18%), oncocytoma (1/11, 9%), and hyalinizing clear cell carcinoma, salivary gland type (1/11, 9%). The surgical pathology specimens confirmed the diagnosis in all cases. CONCLUSIONS: To our knowledge, this is one of the largest cytomorphologic studies of primary salivary gland tumors of the tracheobronchial tree in the literature. Salivary gland tumors of the tracheobronchial tree are rare, and recognizing cytomorphologic changes that occur in salivary gland-type tumors is important for establishing a definitive diagnosis.

Molecular Testing of Non-Small Cell Lung Carcinoma Diagnosed by Endobronchial Ultrasound-Guided Transbronchial Fine-Needle Aspiration: The Cleveland Clinic Experience.

CONTEXT.­: Given the increasing demand for molecular testing of non-small cell lung carcinoma specimens to guide therapeutic decision-making and the trend toward minimally invasive techniques for obtaining diagnostic tissue, cytopathology laboratories must devise strategies to maximize DNA yield for necessary molecular testing. OBJECTIVE.­: To describe our experience at Cleveland Clinic with epidermal growth factor receptor (EGFR) mutation testing by next-generation sequencing and anaplastic lymphoma kinase (ALK) gene rearrangement testing by fluorescence in situ hybridization of non-small cell lung carcinomas diagnosed by cytology, with an emphasis on specimens obtained by endobronchial ultrasound-guided transbronchial fine-needle aspiration. DATA SOURCES.­: Data sources include a review of the current literature, including published articles from our institution. CONCLUSIONS.­: At our institution, liquid-based cytology specimens are the primary resource used for molecular testing of non-small cell lung carcinomas; in most instances, adequate DNA can be extracted from the residual cell pellet for next-generation sequencing, and ThinPrep slides can be used reliably for fluorescence in situ hybridization testing for ALK gene rearrangements. In occasional cases where the cell pellet material is not adequate for molecular testing, cell blocks and/or surgical pathology specimens are secondary options. The cytopathologist's role in specimen handling and triage is essential to ensure that molecular testing can be carried out successfully.

Sensitivity of Cerebrospinal Fluid Cytology for the Diagnosis of Cryptococcal Infections: A 21-Year Single-Institution Retrospective Review.

Objectives: Cryptococcal meningoencephalitis is the most common fungal infection of the central nervous system diagnosed by cerebrospinal fluid cytology (CSF) studies. Existing literature suggests that routine CSF cytomorphologic evaluations are exquisitely specific; however, less is known about their sensitivity. Methods: An electronic record review of the cytopathology and microbiology files was conducted for the 21-year interval from January 1, 1995, through December 31, 2015. Results: In 21 years, 12,584 CSF samples were processed in the laboratory. Of these, 24 (0.2%) were reported positive for cryptococcal organisms by light microscopy, and 129 CSF fungal cultures were positive for Cryptococcus species. All cotested specimens with positive cytology results were positive on culture (15 specimens, 100% specificity). Twenty-four samples with positive culture results were negative by CSF cytology (sensitivity 39%). Conclusions: When culture is used as a gold standard, CSF cytology is 100% specific and 39% sensitive, with a positive predictive value of 100% and a negative predictive value of 99.8%.

Expression of MDM2 and p16 in angiomyolipoma.

Angiomyolipoma (AML) arises primarily from the kidney but may grow into the retroperitoneal space mimicking a primary retroperitoneal tumor. Fine needle aspiration (FNA) and core needle biopsy of AML, particularly the fat-predominant variant, may be difficult to distinguish from retroperitoneal well-differentiated liposarcoma (WDLS) or lipoma. Commonly used immunomarkers, MDM2 and p16, have proven useful in diagnosing WDLS and dedifferentiated liposarcoma (DDLS), while HMB45 and Melan-A are melanocyte-related markers characteristically expressed in AML. In this study, we investigated the utility of MDM2 and p16 along with HMB45 and Melan-A immunohistochemical analysis in distinguishing AML from WDL/DDLS or lipoma. Immunohistochemically, AMLs demonstrated focal MDM2 expression (40% of cases) and focal/diffuse expression of p16 (60%). AMLs marked focally or diffusely with HMB45 (76% of cases) and Melan-A (96%). These latter two immunomarkers were not expressed in any of the WDLS/DDLSs or lipomas tested. WDLS/DDLSs showed focal/diffuse expression of MDM2 (91% of cases) and p16 (97%). While focal expression of MDM2 and p16 was observed in 14% and 67% of lipomas, respectively, no lipoma exhibited diffuse MDM2 positivity. In our hands, MDM2 expression by itself cannot exclude the diagnosis of AML or lipoma, and p16 alone is not helpful in separating AML and conventional lipoma from WDLS/DDLS. However, along with morphology, an immunohistochemical battery including HMB45, Melan-A, MDM2 and p16 are useful in distinguishing AML from WDLS/DDLS or lipoma. For equivocal cases, fluorescence in situ hybridization for MDM2 should be performed.

Diagnostic Utility of Histological Analysis for Detecting Ongoing Infection During Two-Stage Revision Arthroplasty in Patients With Inflammatory Arthritis.

BACKGROUND: Surgeons often rely on intra-operative histology (frozen sections [FS]) to determine the next step in surgical management during the second stage (re-implantation surgery) of 2-stage revision arthroplasty. The purpose of the study is to assess the accuracy of permanent sections (PS) and FS in the diagnosis of persistent infection during re-implantation in patients with an inflammatory arthritis. METHODS: From 2001 to 2016, 47 planned second-stage revision total hip arthroplasty and total knee arthroplasty in patients with inflammatory arthritis were identified. Revisions were classified as having persistent infection if they were Musculoskeletal Infection Society positive at the time of second stage. PS or FS was considered to be positive for infection when at least one of the specimens demonstrated an acute inflammation. Receiver operating characteristic analysis was performed to obtain the diagnostic parameters. RESULTS: There were 9 (19%) persistent infections. Both PS and FS had very high specificity (PS = FS = 94.7%). Sensitivity of PS was higher than FS, although not statistically significant (PS = 88.9%, FS = 55.6%, P = .083). Overall, PS had a better diagnostic utility than FS (area under the curve: PS vs FS = 0.92 vs 0.75, P = .045). Four specimens had discrepancies between PS and FS histology. In all 4 instances, the specimens were read as positive (infected) by PS, but negative by FS. CONCLUSION: Histological analysis is recommended at the time of re-implantation surgery even in patients with inflammatory arthritis. PS had a better diagnostic utility than FS suggesting that areas of acute inflammation may be scattered and may not always be captured in the specimens taken for FS.

Importance of identification of prostatic adenocarcinoma in urine cytology.

BACKGROUND: Prostate carcinoma (PCa) occasionally involves the urethra and/or bladder. In these cases, PCa cells may be detected in urine. The purpose of this study was to describe the salient cytomorphologic, immunocytochemical, and epidemiologic features of PCa cells detected in urine cytology slides via a retrospective case series review. MATERIALS AND METHODS: We retrospectively identified 28 cases with urine cytology either suspicious or positive for PCa. Clinical and histopathologic data were reviewed. RESULTS: We identified 23 prostatic acinar adenocarcinomas (PAAs) and 5 prostatic adenocarcinomas with ductal features (PDAs). Urine cytology was the first evidence of disease in 6 (26%) patients with PAA and in 4 (80%) of the patients with PDA. In patients with PAA, 17 had a previous history of PAA, with positive urine cytology in the setting of disease recurrence or persistence within the bladder or urethra. The PAA in urine presented as single or small clusters of atypical cuboidal glandular cells with large, eccentric, round, or oval uniform nuclei containing conspicuous nucleoli, and scant to moderate delicate or granular cytoplasm, whereas the PDA presented as atypical columnar glandular cells in flat nests or 3-dimensional clusters, and with prominent nucleoli. CONCLUSIONS: Using standard urine cytology, we were able to detect PCa cells in the urine. Although rare, PCa was first diagnosed by urine cytology in select cases, with a higher frequency in patients with PDA. Clinicians should be aware that PCa cells can be identified by urine cytology as this can lead to an earlier diagnosis and treatment.

Comparison of ß-Catenin and LEF1 Immunohistochemical Stains in Desmoid-type Fibromatosis and its Selected Mimickers, With Unexpected Finding of LEF1 Positivity in Scars.

ß-catenin immunohistochemical stain can be useful in the diagnosis of many tumors including desmoid-type fibromatosis (DTF). Lymphoid enhancer-factor 1 (LEF1), a recently emerged marker, is part of the Wnt pathway with ß-catenin but has not been studied in DTF. We performed LEF1 and ß-catenin immunohistochemistry in DTF (n=26), superficial fibromatosis (n=19), sclerosing mesenteritis (n=12), gastrointestinal stromal tumor (n=17), and cutaneous scar (n=14) using tissue microarray and whole sections. The staining intensity was scored as strong (visible at ×2 objective, value of 3), moderate (visible at ×4, value of 2), weak (visible at ×10, value of 1), and negative (not visible at ×10, value of 0). The percentage of positive nuclei was recorded in 10% increment. Histologic scores were generated by multiplying numerical value of intensity and percentage of positive nuclei. A score of at least 10 was defined as positive. Eighteen of the 25 DTF were positive for LEF1 while 12 of 25 were positive for ß-catenin (1 excluded due to loss of tissue). Gastrointestinal stromal tumor cases were negative for both markers. All superficial fibromatoses were negative except 2 cases with weak positivity for LEF1 but not ß-catenin. Only 2 case of sclerosing mesenteritis were weakly positive for LEF1 but negative for ß-catenin. Ten of 14 scars were positive for LEF1 but only 1 of them was weakly positive for ß-catenin. In conclusion, this study demonstrated that LEF1 may be a useful marker in the differential diagnosis of DTF in certain contexts. However, caution should be exercised since LEF1 positivity can also be seen in scars.

Increased detection of Barrett's esophagus-associated neoplasia using wide-area trans-epithelial sampling: a multicenter, prospective, randomized trial.

BACKGROUND AND AIMS: Wide-area transepithelial sampling (WATS) with computer-assisted 3-dimensional analysis is a sampling technique that combines abrasive brushing of the Barrett's esophagus (BE) mucosa followed by neural network analysis to highlight abnormal-appearing cells. METHODS: We performed a randomized trial of referred BE patients undergoing surveillance at 16 medical centers. Subjects received either biopsy sampling followed by WATS or WATS followed by biopsy sampling. The primary outcome was rate of detection of high-grade dysplasia/esophageal adenocarcinoma (HGD/EAC) using WATS in conjunction with biopsy sampling compared with biopsy sampling alone using standard histopathologic criteria. Secondary aims included evaluating neoplasia detection rates based on the procedure order (WATS vs biopsy sampling first), of each procedure separately, and the additional time required for WATS. RESULTS: One hundred sixty patients (mean age, 63.4 years; 76% men; 95% white) completed the trial. The median circumferential and maximal BE extents were 1.0 cm (interquartile range: .0-5.0) and 4.0 cm (interquartile range, 2.0-8.0), respectively. The diagnostic yield for biopsy sampling alone was as follows: HGD/EAC, 7 (4.4%); low-grade dysplasia (LGD), 28 (17.5%); nondysplastic BE (NDBE), 106 (66.25%); and no BE, 19 (11.9%). The addition of WATS to biopsy sampling yielded an additional 23 cases of HGD/EAC (absolute increase, 14.4%; 95% confidence interval, 7.5%-21.2%). Among these 23 patients, 11 were classified by biopsy sampling as NDBE and 12 as LGD/indefinite for dysplasia (IND); 14 received biopsy sampling first and 9 WATS first (not significant) and most (n = 21; 91.7%) had a prior dysplasia history. WATS added an average of 4.5 minutes to the procedure. CONCLUSION: Results of this multicenter, prospective, randomized trial demonstrate that the use of WATS in a referral BE population increases the detection of HGD/EAC. (Clinical trial registration number: NCT03008980.).

Bone-Forming Tumors.

Bone-forming tumors are defined by neoplastic cells that differentiate along the lines of osteoblasts that deposit neoplastic bone. The morphology and biological spectrum of bone-forming tumors is broad, and their accurate diagnosis requires the careful correlation of their clinical, morphologic, and radiologic characteristics. Immunohistochemical and molecular analyses have an important role in select instances. At present, the identification of neoplastic bone largely depends on histologic analysis, which can be subjective. The major types of osteosarcoma are defined according to their morphology, origin within or on the surface of the bone, and their histologic grade.

Radiation-induced focal cortical necrosis of the femur presenting as a lytic lesion.

Management of soft tissue sarcomas is often complicated, requiring radiation before and in some cases after limb-sparing surgery. Radiation necrosis is a severe complication after radiation treatment and is typically dose related and involves medullary bone. We report on two cases of hitherto unreported focal circumscribed intra-cortical lytic lesions within the radiation portal, which appeared 19 months and 31 months, respectively, after the conclusion of radiation treatment. Both patients had a history of soft tissue sarcoma treated with radiation (66 Gy) and surgical resection. Biopsy of these lesions showed necrotic bone attributed to radiation.