Virtual biopsies: Proof of concept for a novel quantitative approach to liver biopsy adequacy and pathology education.

OBJECTIVES: To quantitatively measure liver biopsy adequacy requirements and the effect of a teaching intervention that uses a virtual biopsy platform. METHODS: A library of virtual liver biopsies was created using digital whole-slide, trichrome-stained tissue sections from liver resection material and QuPath image analysis software. Blinded participants staged fibrosis on the virtual biopsies before and after a teaching intervention. RESULTS: This platform both modeled adequacy requirements for cirrhosis diagnosis on biopsy material and measured the effect of a teaching intervention on participant performance. Using this platform, diagnostic accuracy for cirrhosis could be modeled according to the function y = λ(1 ‒ e‒x/γ). The platform demonstrated that the relationship between biopsy size and diagnostic accuracy was statistically significant and that biopsies smaller than 6 mm long and 0.8 mm wide were insufficient to diagnosis cirrhosis. The platform also measured improvement in fibrosis staging accuracy among participants following a teaching intervention. CONCLUSIONS: These results provide proof of concept for a virtual biopsy method by which outstanding questions in anatomic pathology can be addressed quantitatively using open source software. Future work is needed to validate these findings in clinical practice.

Neuroendocrine Neoplasms of the Pancreas: Diagnostic Challenges and Practical Approach.

Most pancreatic neuroendocrine neoplasms are slow-growing, and the patients may survive for many years, even after distant metastasis. The tumors usually display characteristic organoid growth patterns with typical neuroendocrine morphology. A smaller portion of the tumors follows a more precipitous clinical course. The classification has evolved from morphologic patterns to the current World Health Organization classification, with better-defined grading and prognostic criteria. Recent advances in molecular pathology have further improved our understanding of the pathogenesis of these tumors. Various issues and challenges remain, including the correct recognition of a neuroendocrine neoplasm, accurate classification and grading of the tumor, and differentiation from mimickers. This review focuses on the practical aspects during the workup of pancreatic neuroendocrine neoplasms and attempts to provide a general framework to help achieve an accurate diagnosis, classification, and grading.

Histological features of Clostridioides difficile colitis in patients with inflammatory bowel disease.

AIMS: Patients with inflammatory bowel disease (IBD) are at increased risk for Clostridioides difficile infection, although clinically important infections can be difficult to recognise. C. difficile infection does not produce pseudomembranes when it occurs in IBD patients. These individuals may also be colonised by the organism, in which case diarrhoeal symptoms are not necessarily attributed to C. difficile. We performed this study to determine whether any features distinguished C. difficile-associated colitis from an IBD flare. METHODS AND RESULTS: We reviewed the clinical, endoscopic and biopsy findings from 50 patients with established IBD and worsening diarrhoea, including 22 with concurrent positive C. difficile stool toxin polymerase chain reaction (PCR) assays and 28 with negative C. difficile assay results. We found that C. difficile-infected patients had symptoms and endoscopic findings that were indistinguishable from active IBD. Although most biopsy samples from patients with C. difficile infection showed chronic active colitis indistinguishable from IBD, some displayed neutrophilic infiltrates unaccompanied by plasma cell-rich inflammation involving superficial (41%) and crypt (18%) epithelium as well as neutrophilic infiltrates within lamina propria distant from foci of cryptitis (32%). All three of these features were significantly more common among infected than uninfected patients (4, 0 and 4%; P = 0.002, P = 0.03 and P = 0.02, respectively). CONCLUSIONS: Although colonic biopsies from IBD patients with C. difficile infection usually lack features that aid distinction from colitic flares, some cases show an acute colitis pattern not seen in IBD alone. When identified in biopsies from symptomatic IBD patients, these changes should alert pathologists to the possibility of this clinically important infection.

Postconvalescent SARS-CoV-2 IgG and Neutralizing Antibodies are Elevated in Individuals with Poor Metabolic Health.

PURPOSE: Comorbidities making up metabolic syndrome (MetS), such as obesity, type 2 diabetes, and chronic cardiovascular disease can lead to increased risk of coronavirus disease-2019 (COVID-19) with a higher morbidity and mortality. SARS-CoV-2 antibodies are higher in severely or critically ill COVID-19 patients, but studies have not focused on levels in convalescent patients with MetS, which this study aimed to assess. METHODS: This retrospective study focused on adult convalescent outpatients with SARS-CoV-2 positive serology during the COVID-19 pandemic at NewYork Presbyterian/Weill Cornell. Data collected for descriptive and correlative analysis included SARS-COV-2 immunoglobin G (IgG) levels and history of MetS comorbidities from April 17, 2020 to May 20, 2020. Additional data, including SARS-CoV-2 IgG levels, body mass index (BMI), hemoglobin A1c (HbA1c) and lipid levels were collected and analyzed for a second cohort from May 21, 2020 to June 21, 2020. SARS-CoV-2 neutralizing antibodies were measured in a subset of the study cohort. RESULTS: SARS-CoV-2 IgG levels were significantly higher in convalescent individuals with MetS comorbidities. When adjusted for age, sex, race, and time duration from symptom onset to testing, increased SARS-CoV-2 IgG levels remained significantly associated with obesity (P < 0.0001). SARS-CoV-2 IgG levels were significantly higher in patients with HbA1c ≥6.5% compared to those with HbA1c <5.7% (P = 0.0197) and remained significant on multivariable analysis (P = 0.0104). A positive correlation was noted between BMI and antibody levels [95% confidence interval: 0.37 (0.20-0.52) P < 0.0001]. Neutralizing antibody titers were higher in COVID-19 individuals with BMI ≥ 30 (P = 0.0055). CONCLUSION: Postconvalescent SARS-CoV-2 IgG and neutralizing antibodies are elevated in obese patients, and a positive correlation exists between BMI and antibody levels.

Diagnostic and management considerations in the modern patient with AIDS: a case of concurrent disseminated Kaposi sarcoma and colesional Cryptococcus neoformans.

In the era of highly active antiretroviral therapy (HAART), disseminated Kaposi sarcoma (KS) has become much rarer in the USA. We report a case of a 34-year-old man with KS of the skin, oropharynx, lung and rectum. Within the same lung nodule, we discovered significant burden of colesional Cryptococcus neoformans, in the context of a positive asymptomatic cryptococcal antigenemia, which was a previously unreported occurrence. The gold standard of treatment for KS continues to be HAART. The role of chemotherapy is still controversial. In addition, a cryptococcal antigen screen-and-treat approach with fluconazole is still not routinely recommended in the USA to prevent serious meningeal disease despite recent studies showing efficacy and applicability. We discuss both issues here and the outcome of our patient. We also present the patient's own unique perspective in dealing with the ramifications of these diagnoses.

Endoscopic ultrasound-guided tissue acquisition of solid mass lesions of the pancreas: A retrospective comparison study of fine-needle aspiration and fine-needle biopsy.

BACKGROUND: Although endoscopic ultrasound guided fine-needle biopsy (EUS-FNB) has emerged as an alternative to fine-needle aspiration (FNA) for the sampling of solid pancreatic mass lesions, it remains unclear which method is more effective. We compared the diagnostic yields of FNA, FNB, and combined FNA/FNB at a tertiary care institution. METHODS: Specimens from EUS-FNA (04/2014-08/2017) and EUS-FNB (10/2015-08/2017) with SharkCore needle of pancreatic solid mass lesions were retrieved. Clinical, radiologic, and pathologic data was recorded. Pathology results of malignancy/neoplasms with uncertain malignant potential were considered as true positive. The "negative" cases included were with ≥6 months of follow-up. Nondiagnostic cases showed unremarkable pancreatic tissue, nonpancreatic elements, atypia, or features suspicious for malignancy. Diagnostic yield was defined as percentage of lesions sampled in which a benign or malignant tissue diagnosis, as defined above, was obtained. Statistical comparisons were performed using Fisher's exact test and univariable and multivariable logistic regression analysis. RESULTS: The study cohort included 76 FNA only cases, 88 FNB only cases, and 40 combined FNA/FNB cases. Diagnostic yields were 70% (FNA), 70% (FNB), and 83% (FNA/FNB), which were not statistically different. Increase in lesion size and presence of ROSE were significantly associated with a diagnostic outcome on both univariable and multivariable analysis, unlike the number of passes. CONCLUSION: Our results demonstrate that for solid pancreatic lesions, the diagnostic yields of FNA, FNB, and combined FNA and FNB are comparable. Presence of ROSE and increasing lesion size increased the diagnostic yield while the number of passes had no significant impact.

Digital image analysis supports a nuclear-to-cytoplasmic ratio cutoff value below 0.7 for positive for high-grade urothelial carcinoma and suspicious for high-grade urothelial carcinoma in urine cytology specimens.

BACKGROUND: Urinary cytology is sensitive and specific for diagnosing and screening high-grade urothelial carcinomas (HGUC). The Paris System (TPS) for urinary cytology was introduced in 2016 to standardize reporting. According to TPS diagnostic categories of HGUC and suspicious for HGUC (SHGUC), the average nuclear-to-cytoplasm (N:C) ratio of atypical cells should be ≥0.7. The objective of the current study was to measure the N:C ratio of urine cytology specimens with HGUC and SHGUC diagnoses and biopsy-proven HGUC follow-up. METHODS: A cohort of 64 cases (HGUC, 49 cases; SHGUC, 15 cases) from 57 patients was constructed. Urine cytology slides were scanned into whole-slide digital images. The nuclear and cytoplasmic areas were enumerated by digital image analysis (DIA), and the N:C ratios were measured. RESULTS: In total, 640 cells were analyzed by DIA (HGUC, 490 cells; SHGUC, 150 cells). For HGUC and SHGUC, the average N:C ratios were 0.57 and 0.53, respectively. The maximum average N:C ratio was 0.73 for HGUC and 0.68 for SHGUC. HGUC had higher average N:C ratio (P < .001), higher average nuclear area (P < .001), higher average maximum N:C ratio (P = .005), and higher average maximum nuclear area (P = .006) compared with SHGUC. CONCLUSIONS: The N:C ratios for the HGUC (0.57) and SHGUC (0.53) categories are lower than those previously suggested in TPS. The authors advocate reducing the N:C ratio below the current threshold of 0.7.

Tumor Grade Is Prognostically Relevant Among Mismatch Repair Deficient Colorectal Carcinomas.

Intestinal-type colorectal adenocarcinomas are graded based on extent of glandular differentiation, although mucinous, signet-ring cell, and solid cancers are, by convention, classified as high grade. Mismatch repair-deficient tumors frequently show high-grade histologic features, yet the World Health Organization classifies them as low grade to reflect their favorable prognosis compared with mismatch repair-proficient cancers. Although some mismatch repair-deficient colorectal cancers behave aggressively, few authors have identified features that predict their behavior. We performed this study to determine which histologic features, if any, predicted outcome among mismatch repair-deficient colorectal carcinomas. We identified 116 mismatch repair-deficient colorectal carcinomas, including 77 localized (stage I to II) and 39 advanced (stage III to IV) tumors, and evaluated them for extent of gland formation, extracellular mucin, signet-ring cell differentiation, solid growth, nuclear grade, tumor-infiltrating lymphocytes and tumor budding. Relationships between these features, pathologic stage, and disease-free survival were assessed. We found that high-grade mismatch repair-deficient tumors were more often of advanced stage than low-grade tumors (46% vs. 23%, P=0.01). Disease-free survival was inversely associated with the presence of a dominant high-grade component and tumor budding (P=0.01 and 0.04, respectively). Predominantly solid tumors, in particular, were significantly associated with decreased disease-free survival compared with low-grade tumors (P=0.001). Nuclear grade and tumor-infiltrating lymphocytes were not associated with pathologic stage or outcome. We conclude that low-grade mismatch repair-deficient carcinomas present at an earlier stage and pursue a more favorable course than those mostly composed of high-grade elements. These findings suggest that mismatch repair status should not supplant histologic grade in the assessment of colorectal carcinomas.

Immunohistochemical staining for S100P, SMAD4, and IMP3 on cell block preparations is sensitive and highly specific for pancreatic ductal adenocarcinoma.

INTRODUCTION: The diagnosis of pancreatic ductal adenocarcinoma (PDA) on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) material is often challenging. An immunohistochemical (IHC) panel may help establish the diagnosis of PDA in cases limited by sample size or ambiguous cytology. S100P, IMP3, and SMAD4 are 3 IHC markers that have shown promise as individual markers for PDA that have never been tested together as a panel. In this study, we evaluated the individual and combined efficacy of S100P, IMP3, and SMAD4 for the detection of PDA. MATERIALS AND METHODS: S100P, IMP3, and SMAD4 IHC staining was performed on cell blocks (CBs) procured from pancreatic EUS-FNA procedures. The cohort included CBs that were diagnostic for PDA (n = 35), suspicious but nondiagnostic for PDA (n = 2), as well as CBs with benign pancreatic ductal epithelium (n = 12) and benign reactive pancreatic ductal epithelium (n = 18). A positive result for IMP3 and S100P was defined as moderate or strong staining of >10% of ductal cells. Complete lack of SMAD4 nuclear staining was considered a positive result-any nuclear SMAD4 staining was considered a negative result. RESULTS: Two and 3 IHC marker panels were almost always more specific than individual IHC markers. Positivity for at least 2 of 3 IHC markers was a sensitive (91.89%) and highly specific (100%) marker of PDA. CONCLUSIONS: The 3 IHC marker panel composed of S100P, IMP3, and SMAD4 is highly specific for PDA. Future studies should evaluate efficacy in a cohort with more atypical and suspicious cases.