The Critical Value of Telepathology in the COVID-19 Era.

Background: Telepathology, which includes the use of telecommunication links, helps enable transmission of digital pathology images for primary diagnosis, quality assurance, education, research, or second opinion diagnoses. Observations: This review covers all aspects of telepathology implementation, including the selection of platforms, budgets and regulations, validation, implementation, education, quality monitoring, and the potential to improve practice. Considering the long-term trends, the lessons of the COVID-19 pandemic, and the potential for future pandemics or other disasters, the validation and implementation of telepathology remains a reasonable choice for laboratories looking to improve their practice. Conclusions: Though barriers to implementation exist, there are potential benefits, such as the wide spectrum of uses like frozen section, telecytology, primary diagnosis, and second opinions. Telepathology represents an innovation that may transform the future of pathology practice.

Compliance with the Current NCCN Guidelines and Its Critical Role in Pancreatic Adenocarcinoma.

OBJECTIVES: Since 2019, the National Comprehensive Cancer Network (NCCN) has recommended genetic testing for patients diagnosed with pancreatic adenocarcinoma that includes universal germline testing and tumor gene profiling for metastatic, locally advanced, or recurrent disease. However, testing compliance with this guideline has not yet been published in the English literature. METHODS: A quality assurance/quality improvement retrospective review was done to identify patients diagnosed with pancreatic adenocarcinoma from January 2019 to February 2021 to include the patient's clinical status and genetic test results. RESULTS: There were 20 patient cases identified with pancreatic adenocarcinoma. A total of 11 cases had molecular tumor gene profiling and microsatellite instability/mismatch repair (MSI/MMR) testing performed and 1 case had only MSI/MMR testing by immunohistochemistry performed. Only 3 patients of the 20 in total received germline testing. CONCLUSION: There was a significant number of patients for whom tumor gene profiling or germline testing had never been attempted as per recommended NCCN guidelines.

A MUC5B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality.

Rationale: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear. Objectives: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with coronavirus disease (COVID-19) infection among participants in the Million Veteran Program (MVP). Methods: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by transancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (body mass index, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease, and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects. Measurements and Main Results: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations in transancestry meta-analyses within the MVP (Ncases = 4,325; Ncontrols = 507,640; OR = 0.89 [0.82-0.97]; P = 6.86 × 10-3) and joint meta-analyses with the HGI (Ncases = 13,320; Ncontrols = 1,508,841; OR, 0.90 [0.86-0.95]; P = 8.99 × 10-5). The rs35705950-T allele was not associated with reduced COVID-19 positivity in transancestry meta-analysis within the MVP (Ncases = 19,168/Ncontrols = 492,854; OR, 0.98 [0.95-1.01]; P = 0.06) but was nominally significant (P < 0.05) in the joint meta-analysis with the HGI (Ncases = 44,820; Ncontrols = 1,775,827; OR, 0.97 [0.95-1.00]; P = 0.03). Associations were not observed with severe outcomes or mortality. Among individuals of European ancestry in the MVP, rs35705950-T was associated with fewer post-COVID-19 pneumonia events (OR, 0.82 [0.72-0.93]; P = 0.001). Conclusions: The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations.

Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait.

Importance: Sickle cell trait (SCT), defined as the presence of 1 hemoglobin beta sickle allele (rs334-T) and 1 normal beta allele, is prevalent in millions of people in the US, particularly in individuals of African and Hispanic ancestry. However, the association of SCT with COVID-19 is unclear. Objective: To assess the association of SCT with the prepandemic health conditions in participants of the Million Veteran Program (MVP) and to assess the severity and sequelae of COVID-19. Design, Setting, and Participants: COVID-19 clinical data include 2729 persons with SCT, of whom 353 had COVID-19, and 129 848 SCT-negative individuals, of whom 13 488 had COVID-19. Associations between SCT and COVID-19 outcomes were examined using firth regression. Analyses were performed by ancestry and adjusted for sex, age, age squared, and ancestral principal components to account for population stratification. Data for the study were collected between March 2020 and February 2021. Exposures: The hemoglobin beta S (HbS) allele (rs334-T). Main Outcomes and Measures: This study evaluated 4 COVID-19 outcomes derived from the World Health Organization severity scale and phenotypes derived from International Classification of Diseases codes in the electronic health records. Results: Of the 132 577 MVP participants with COVID-19 data, mean (SD) age at the index date was 64.8 (13.1) years. Sickle cell trait was present in 7.8% of individuals of African ancestry and associated with a history of chronic kidney disease, diabetic kidney disease, hypertensive kidney disease, pulmonary embolism, and cerebrovascular disease. Among the 4 clinical outcomes of COVID-19, SCT was associated with an increased COVID-19 mortality in individuals of African ancestry (n = 3749; odds ratio, 1.77; 95% CI, 1.13 to 2.77; P = .01). In the 60 days following COVID-19, SCT was associated with an increased incidence of acute kidney failure. A counterfactual mediation framework estimated that on average, 20.7% (95% CI, -3.8% to 56.0%) of the total effect of SCT on COVID-19 fatalities was due to acute kidney failure. Conclusions and Relevance: In this genetic association study, SCT was associated with preexisting kidney comorbidities, increased COVID-19 mortality, and kidney morbidity.

Hospital and Laboratory Practice in an Integrated Medical System for HIV Infection Prevention Interventions at a Veteran Affairs Medical Center.

OBJECTIVE: The impact of sexually transmitted infection (STI) results on prompting clinicians to consider pre-exposure prophylaxis (PrEP) indication is sparse in the literature, particularly for veterans. METHODS: A retrospective search from June 2018 to February 2020 was performed to identify all patients who were HIV-negative at a regional Veteran Affairs Medical Center with a positive STI test result and review the medical chart of these patients. RESULTS: We identified 220 veterans who were HIV-negative with a positive STI test result. Of these 220 veterans, 51 unique patients were identified by the clinicians. In a provider-initiated discussion, PrEP was discussed with all 51 patients. In the end, 27 of these 51 patients started PrEP after discussion with their clinical providers. CONCLUSION: Prior positive STI results successfully helped identify patients who may benefit from PrEP. Quality assurance studies on clinician reactions to test result reporting, particularly regarding highly effective preventive therapies, are important.

Moving Toward a Systematic Approach for Reporting Salivary Gland Cytopathology: An Institutional Experience and Literature Review.

CONTEXT.­: Despite the clinical utility of fine-needle aspiration for the diagnosis of salivary pathologies, salivary lesions remain one of the most challenging areas in cytopathology. This is partially because there is no consensus on how to report salivary gland cytopathology, which has resulted in inconsistent terminology among institutions and individual cytopathologists and in confusion in communication among cytopathologists and ordering providers. OBJECTIVE.­: To summarize our experience with an institutional salivary gland cytopathology reporting system, as an initiative to promote collaborative work toward a consensus on a reporting system. DESIGN.­: We developed an empirical 6-tier classification reporting system. Slides of 107 salivary gland fine-needle aspirations with subsequent histology slides were reviewed and reclassified using the 6-tier system. The performance of the cytology reporting system was evaluated with the histology diagnoses serving as the gold standard. RESULTS.­: Fine-needle aspiration diagnoses made based on the institutional 6-tier classification system were generally consistent with histology diagnoses for the disease spectrum reported in this study. The sensitivity, specificity, positive predictive value, and negative predictive value for diagnosing malignancies with the system were 86% (12 of 14), 93% (40 of 43), 80% (12 of 15), and 95% (40 of 42), respectively. The risk of malignancy increased from 0% (0 of 13) for negative for neoplasm to 7% (2 of 29) for benign neoplasm, 67% (2 of 3) for suspicious for malignancy, and 83% (10 of 12) for positive for malignancy. CONCLUSIONS.­: The institutional 6-tier system provides a succinct, risk-of-malignancy-based system to report salivary gland cytology. Our experience with this system helps to pave the way for the adoption of the Milan System for Reporting Salivary Gland Cytopathology.

Utility of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of colorectal carcinoma.

The objective of this study is to assess the utility of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the diagnosis and staging of colorectal cancer. The study includes patients who underwent EUS-FNA at our institution for staging of colorectal carcinoma or for evaluation peri-rectal masses or distal metastases from August 2000 to November 2010. We assessed the frequency with which EUS-FNA procedure confirms the diagnosis of malignancy and the percent of cases in which it modifies staging of colorectal carcinoma. Using histology as a reference standard, we also assessed the diagnostic performance. We identified 79 cases of EUS-FNA from 77 patients, mean (SD) age of 60 (12.5), 44 males. Twenty-seven (34%) aspirates were from patients with primary rectal/peri-rectal masses, 15 (19%) were from patients with suspected regional lymph node metastasis, and 37 (47%) were cases of suspected of distal metastasis. All lesions were clinically suspicious for primary or metastatic colorectal carcinoma. On cytologic examinations, 43 (54%) cases were confirmed as malignant, 6 (8%) were benign neoplasms, 4 (5%) were suspicious for malignant neoplasm, 2 (3%) showed atypical cells, and the rest 24 (30%) were negative for neoplasms. Fourteen of 27 (52%) of the local rectal masses were confirmed as colorectal carcinoma. Eleven of 15 (73%) regional lymph nodes were positive for metastasis-all, but two of these metastases, were of colorectal origin. Twenty of 37(54%) distal lesions were metastatic neoplasms and 15 of those were colorectal in origin. Diagnosis of primary colorectal carcinoma was confirmed in 52% of the clinically suspicious primary lesions and in 42% regional or distal metastatic lesions. Using histology as a reference standard in 27 of 79 (29%) cases, we calculated an overall sensitivity, specificity, and positive and negative predictive values (C.I) of EUS-FNA of 89% (74-100%), 79% (50-100%) 89% (74-100%), and 79% (51-100%). EUS-FNA is useful for assessing primary and metastatic colorectal lesion. This technique improves staging of suspected nodal or distant metastases.

Endoscopic ultrasound and endobronchial ultrasound-guided fine-needle aspiration of deep-seated lymphadenopathy: Analysis of 1338 cases.

BACKGROUND: We retrospectively studied 1338 samples of lymph nodes obtained by endoscopic and endobronchial ultrasound-guided fine needle aspiration biopsy (EUS and EBUS-FNAB) with an objective of characterizing the utility of this diagnostic modality in the assessment of deep-seated lymphadenopathy. The secondary aims were to establish the utility in the diagnosis of lymphoma and to determine the number of passes required to obtain adequate cellularity for flow cytometric analysis. MATERIALS AND METHODS: On-site assessment was performed by a cytopathologist using Diff-Quik (American Scientific Products, McGraw Park, IL) stain. In addition, Papanicolaou and immunohistochemical stains were performed and additional samples were sent for flow cytometric analyses (n = 145). The final cytologic diagnosis was correlated with surgical pathology diagnosis and/or clinical follow-up. In select cases, fluorescence in situ hybridization analysis with specific probes was performed on Diff-Quik smears. RESULTS: Both morphology as well as ancillary studies (flow cytometry or immunohistochemical stain and/or fluorescence in situ hybridization) show that EUS and EBUS-FNA are effective techniques to detect and stage intrathoracic and intra-abdominal tumors. Operating characteristics show that these are highly sensitive (89%) and specific (100%) techniques for the diagnosis of lymphoma. At least two passes provided an average of 5.66 million cells (range, 0.12-62.32 million) for lymphoma cases. CONCLUSIONS: EUS and EBUS-FNA are powerful modalities to stage malignancies and at least two passes can provide adequate cells for flow cytometric analysis. We also demonstrate that fluorescence in situ hybridization analysis can be performed on Diff-Quik-stained and mounted smears.

Multinational comparison of diagnostic clues for uterine cervical lesions among cytotechnologists in Asian countries.

Vaccination has been underway in several countries for sexually inactive young girls or women against HPV 16 and 18 to prevent them from infection of these HPV types and concurrent cancer development. However, uterine cervical cancers may remain uncontrolled among some Asian countries, where other types of HPV infection are more frequent. A sensitive cancer screening system would remain important for detection of the earlier stage cervical cancers in Asian countries. In this study, 130 cytotechnologists (CTs) in Asian countries (Taiwan 80, Japan 18, Korea 15, Thailand 11, Singapore 3, Bhutan 2, and Mongolia 1) participated in the vote. Selected 10 cervical Pap smears that would be adequate to identify the diagnostic clues especially for atypical squamous cells (ASC) with two or three representative pictures for each case were displayed on the website. The percentages of consistent diagnosis voted by certified CTs with ≥5 years of experience were compared among 10 cervical cases or among Asian countries enrolled. As results, low consistency for ASC cases and high consistency for squamous intraepithelial lesion (SIL) were observed. Examining specimens for the diagnostic clues of ASC in TBS is crucial to maintain the high sensitivity and positive predictive value of SIL in Asian countries.

Diagnosis of deep-seated lymphoma and leukemia by endoscopic ultrasound-guided fine-needle aspiration biopsy.

We retrospectively studied the use of endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) as a tool for the diagnosis of deep-seated lymphoma. An on-site assessment at the time of EUS-FNAB was performed by a cytopathologist using Diff-Quik (American Scientific Products, McGraw Park, IL) stain. In addition, Papanicolaou stains were performed on EUS-FNAB smears, immunohistochemical stains were performed on cell blocks, and additional samples were sent for flow cytometric analysis. Final cytologic diagnosis was correlated with surgical pathology and/or clinical follow-up. We evaluated EUS-FNAB specimens of deep-seated lymph nodes, spleen, stomach, and pancreas, and 1 EUS-guided needle core biopsy specimen of a lymph node. Thirteen cases of deep-seated lymphoma were diagnosed, including non-Hodgkin lymphomas and Hodgkin lymphoma. One case of hairy cell leukemia was diagnosed. EUS-FNAB is a minimally invasive, cost-effective, and useful tool for the primary diagnosis or staging of deep-seated lymphomas.

Non-Hodgkin's lymphoma of the breast: a review of 18 primary and secondary cases.

We evaluated the clinical features, morphology, and incidence of 18 cases of breast lymphoma over 10 years at the University of Alabama at Birmingham. Fine needle aspiration was performed in 7 of 18 patients, and tissue biopsy/resection was available for all 18 cases. Patients were 33 to 91 years old (median, 61); 17 were women and 1 was a man. Fine needle aspiration was consistent with the tissue diagnosis in 6 of the 7 cases (86%). One case was diagnosed by fine needle aspiration as atypical cells, favor benign; the biopsy revealed diffuse large B-cell lymphoma. Tissue diagnoses revealed that 11 cases (61%) represented diffuse large B-cell lymphoma and 3 (17%) were follicular lymphomas. The remaining 4 cases (22%) were plasma cell neoplasm, T-cell neoplasm, Burkitt's lymphoma, and precursor B-cell lymphoblastic lymphoma. Flow cytometry and/or gene rearrangement supported the diagnosis of lymphoma in 8 cases. Although rare, lymphoma should be considered in the differential diagnosis of a breast mass. Fine needle aspiration can facilitate appropriate triage of patients for further management.

Preoperative diagnosis of a mediastinal granular cell tumor by EUS-FNA: a case report and review of the literature.

We report the first case of a posterior mediastinal granular cell tumor initially diagnosed on cytologic material obtained via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in a 51-year-old male with a prior history of colon cancer. Aspirates obtained were cellular and composed of polygonal cells with abundant granular cytoplasm and small, round dark nuclei. An immunoperoxidase stain performed on the cell block for antibodies to S-100 protein showed strong, diffuse staining of the cytoplasmic granules. Electron microscopy performed on the cell block revealed numerous cytoplasmic lysosomes. This is the first case report in the English literature of a definitive preoperative diagnosis of a mediastinal granular cell tumor utilizing material obtained via EUS-FNA.

Osteosarcoma in a patient with McCune-Albright syndrome and Mazabraud's syndrome: a case report emphasizing the cytological and cytogenetic findings.

Osteosarcomatous transformation in fibrous dysplasia is unusual. The incidence is increased in patients with concomitant Mazabraud's syndrome and McCune-Albright syndrome. We report the cytological, histological, and cytogenetic findings of this rare entity arising from a mass in the right elbow of a 44-year-old African-American woman. The fine-needle aspiration (FNA) findings were diagnostic of malignancy, with markedly atypical spindle and polygonal cells admixed with osteoid. The diagnosis of osteosarcoma by FNA was subsequently further confirmed by histological evaluation of an above-elbow amputation specimen. Fluorescence in situ hybridization and comparative genomic hybridization demonstrated trisomies of chromosomes 5 and 7 in the fibrous dysplasia and osteosarcoma. In addition, multiple chromosomal abnormalities were also noted in the osteosarcoma. We are unaware of any previous reports of the cytogenetic findings in the tissue of this rare condition, and argue for the value of FNA in the evaluation of such patients under selected conditions.

Endoscopic ultrasound-guided fine-needle aspiration. A cytopathologist's perspective.

Endoscopic ultrasound (EUS) is used to detect and delineate the extent of lesions in the gastrointestinal tract, periluminal lymph nodes, pancreas and hepatobiliary tree, left kidney, spleen, and adrenal glands. EUS-guided fine-needle aspiration (FNA) has added a new dimension to the capabilities of EUS because it permits characterization of the lesion, thereby enabling triage of patients for more efficient and effective management. This review focuses on the advantages and limitations of EUS-FNA, including a discussion of potential pitfalls in the diagnosis of commonly aspirated deep-seated lesions, such as those of the pancreas and lymph nodes. It also addresses the practical considerations associated with establishing an effective service and the importance of an integrated approach in which the cytopathologist undertakes a key role, interacting extensively with the endoscopist and the patient management team. EUS-FNA is a sensitive modality that enables specific and accurate diagnosis of deep-seated lesions. Samples can be obtained effectively from small lesions (< 25 mm), irrespective of the organ site. On-site assessment permits a highly accurate preliminary diagnosis of malignancy for samples obtained by EUS-FNA and provides an opportunity to increase the diagnostic yield of samples.

Infiltration of Helicobacter pylori in the gastric mucosa.

It is our hypothesis that if Helicobacter pylori could be demonstrated conclusively to have transgressed the mucosal surface into the lamina propria, this would help explain how H pylori recruits inflammatory cells. We report our immunohistochemical and electron microscopic findings that demonstrate that H pylori can be detected in the lamina propria of the stomach, offering evidence of its invasive potential. We stained 67 endoscopic gastric biopsy specimens with Warthin-Starry silver and immunoperoxidase stains for H pylori. In addition, transmission electron microscopy was performed on 1 case. The presence of surface H pylori was associated significantly with active (P < .0001) and chronic (P < .0001) inflammation. H pylori could not be identified in the lamina propria using the Warthin-Starry silver stain alone. Immunoreactivity for H pylori in the lamina propria was detected in 20 (30%) of 67 gastric biopsy specimens. Transmission electron microscopy confirmed the immunohistochemical findings. H pylori can infiltrate the lamina propria of the gastric mucosa, thereby proving morphologic evidence of its invasive capability.

Fine-needle aspiration biopsy of nonteratomatous germ cell tumors of the mediastinum.

We assessed the usefulness of fine-needle aspiration biopsy (FNAB) in the diagnosis of mediastinal germ cell tumors (GCTs). In the archives of 3 pathology departments, we found records of 7 patients with mediastinal GCTs who underwent mediastinal FNAB as part of the diagnostic workup. The FNAB smears, results of the immunocytochemical analysis, the corresponding histologic findings, and the clinical charts were reviewed. All patients were men (age range, 24-44 years; mean, 32 years). One patient had a history of testicular mixed GCT 10 years earlier. The 6 primary mediastinal GCTs consisted of 3 seminomas and 3 yolk sac tumors. Based on the cytologic features and immunocytochemicalfindings, a cytologic diagnosis of GCT was made in 5 cases, including the case of metastatic GCT In 2 cases, the differential diagnosis was between poorly differentiated carcinoma and GCT Results of ancillary studies were noncontributory in 1 case, and the aspirate of the second case demonstrated extensive necrosis. Our findings demonstrate that a diagnosis of mediastinal GCT, primary or secondary, can be established with a high degree of accuracy on the basis of FNAB. Immunocytochemical analysis helps confirm the diagnosis.