Retrospective application of WHO reporting system for lung cytopathology with assessment of risk of malignancy.

INTRODUCTION: The recently introduced World Health Organization (WHO) Reporting System for Lung Cytopathology presents 5 diagnostic categories with corresponding risk of malignancy (ROM) and management protocols. This study uses the system to categorize our institutional respiratory tract cytology specimens, evaluating ROM and diagnostic accuracy for each category. MATERIALS AND METHODS: In a retrospective analysis (May 2020 to August 2021), the following respiratory cytology specimens were classified based on the WHO categories: bronchoalveolar lavage (BAL), bronchial wash/bronchial brushings (BB/BW), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), fine-needle aspiration cytology (FNAC), sputum, biopsy imprint (BI), and endotracheal wash. Exclusions comprised pleural effusions and EBUS-TBNA from mediastinal and hilar lymph nodes. Correlation of cytologic and histopathologic diagnoses was performed to assess ROM collectively and individually. RESULTS: A total of 1518 respiratory samples (BAL [968], BW/BB [380], EBUS-TBNA [42], FNAC [32], sputum [80], BI [11] and endotracheal wash [5]) of 1410 patients were screened, of which 522 cases (34.3%) had histopathologic correlation. One hundred forty-one cases (9.3%) were Insufficient/Inadequate/Non-Diagnostic (ND), 1221 (80.4%) were Benign (B), 3 (0.2%) were Atypical (A), 32 (2.1%) were Suspicious for malignancy (SM) and 121 (8.0%) were Malignant (M). The estimated ROM for each category was 49.2% for ND, 13.3% for B, 66.6% for A, 81.5% for SM and 92.7% for M. FNAC and EBUS-TBNA exhibited the highest sensitivity (100%) compared with BW/BB (66.3%). Specificity ranged from 96.8% to 100% across the samples, while diagnostic accuracy varied from 58.8% to 100%. CONCLUSIONS: Application of the WHO reporting system enhances standardized terminology, aiding clinicians in informed decision-making and improving patient care through accurate risk assessment of malignancy.

Assessment of Brain Metastasis at Diagnosis in Non-Small-Cell Lung Cancer: A Prospective Observational Study From North India.

PURPOSE: The incidence of symptomatic brain metastasis at diagnosis in non-small-cell lung cancer (NSCLC) is 5%-10%, and up to 40% develop during the disease course. There is a paucity of data supporting the role of brain imaging at diagnosis in asymptomatic cases particularly from resource-constraint settings. Here, we present our experience of mandatory baseline brain imaging with contrast-enhanced computed tomography (CECT) scans of all patients with NSCLC. MATERIALS AND METHODS: This was a prospective observation study of patients with NSCLC with mandatory baseline brain CECT and a CNS examination. All histology proven patients with NSCLC diagnosed between January 2018 and October 2019 were included irrespective of stage. RESULTS: A total of 496 patients were enrolled. The median age was 57 years (range, 23-84) with majority being males (75%) and smokers (66%). The prevalence of epidermal growth factor receptor mutations and anaplastic lymphoma kinase fusions was 33.4% and 12%, respectively. Brain imaging leads to upstaging in 7% cases. The prevalence of brain metastases was 21% (n = 104), with half being asymptomatic (51%). Factors associated with higher proportion of brain metastasis were young age (≤ 40 years), adenocarcinoma histology, poor Eastern Cooperative Oncology Group performance status (3 and 4), and high neutrophil-lymphocyte ratio (NLR) (> 2.5). After a median follow-up of 10.8 months (95% CI, 7.33 to 12.73), the median overall survival was 7.46 versus 12.76 months (hazard ratio 0.67; 95% CI, 0.46 to 0.96; P = .03) in patients with and without brain metastases, respectively. On multivariate analyses, high NLR and molecular graded prognostic assessment affected the overall survival significantly. CONCLUSION: In our study, 21% of patients had brain metastasis at diagnosis detected with a mandatory baseline brain imaging with CECT. NLR and molecular graded prognostic assessment are significant predictors of survival in patients with brain metastasis.

Impact of the COVID-19 pandemic on cytology practice: An international survey in the Asia-Pacific region.

BACKGROUND: The purpose of the current study was to examine the impact of coronavirus disease 2019 (COVID-19) on various aspects of cytology practice in the Asia-Pacific region. METHODS: An online questionnaire was distributed to cytopathology laboratories in 24 Asia-Pacific countries to explore the impact of restrictive measures on access to health care, use of general and personal protective equipment (PPE), and changes in cytology workflow and workload from February to April 2020. RESULTS: A total of 167 cytopathology laboratories from 24 countries responded to the survey; the majority reported that restrictive measures that limited the accessibility of health care services had been implemented in their cities and/or countries (80.8%) and their hospitals (83.8%). The respondents noted that COVID-19 had an impact on the cytologic workflow as well as the workload. Approximately one-half of the participants reported the implementation of new biosafety protocols (54.5%) as well as improvements in laboratory facilities (47.3%). Rearrangement or redeployment of the workforce was reported in 53.3% and 34.1% of laboratories, respectively. The majority of the respondents reported a significant reduction (>10%) in caseload associated with both gynecological (82.0%) and nongynecological specimens (78.4%). Most laboratories reported no significant change in the malignancy rates of both gynecological (67.7%) and nongynecological specimens (58.7%) compared with the same period in 2019. CONCLUSIONS: The results of the survey demonstrated that the COVID-19 pandemic resulted in a significant reduction in the number of cytology specimens examined along with the need to implement new biosafety protocols. These findings underscore the need for the worldwide standardization of biosafety protocols and cytology practice.

Histopathologic Assessment of Capsular Invasion in Follicular Thyroid Neoplasms-an Observer Variation Study.

The assessment of capsular invasion is an essential but challenging step in the diagnosis of encapsulated follicular thyroid neoplasms. Therefore, interobserver agreement in the assessment of capsular invasion in these tumors was investigated among 11 thyroid pathologists by using virtual slides of 20 cases in which the original diagnosis considered the differential diagnosis of definite capsular invasion versus questionable capsular invasion. The assessment of capsular invasion was divided into three categories: (1) non-invasive, (2) questionable invasive, and (3) clear-cut invasive. The interobserver agreements for clear-cut invasive and non-invasive categories were fair (Kappa value = 0.578 and 0.404, respectively), whereas agreement for the questionable invasion was poor (Kappa value = 0.186). Disagreements in the assessment of invasion resulted in variable final pathological diagnoses. For example, the agreement for a diagnosis of malignancy was only fair (Kappa value = 0.545). Moreover, pathologists did not have a uniform approach for rendering a final diagnosis in cases with questionable capsular invasion, though nine of 11 pathologists did use the follicular tumor of uncertain malignant potential diagnosis as proposed by the World Health Organization classification of endocrine organs published in 2017. In conclusion, this study revealed considerable interobserver variation in the evaluation of capsular invasion, especially in follicular neoplasms with questionable invasion.

IASLC Multidisciplinary Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy.

Currently, there is no established guidance on how to process and evaluate resected lung cancer specimens after neoadjuvant therapy in the setting of clinical trials and clinical practice. There is also a lack of precise definitions on the degree of pathologic response, including major pathologic response or complete pathologic response. For other cancers such as osteosarcoma and colorectal, breast, and esophageal carcinomas, there have been multiple studies investigating pathologic assessment of the effects of neoadjuvant therapy, including some detailed recommendations on how to handle these specimens. A comprehensive mapping approach to gross and histologic processing of osteosarcomas after induction therapy has been used for over 40 years. The purpose of this article is to outline detailed recommendations on how to process lung cancer resection specimens and to define pathologic response, including major pathologic response or complete pathologic response after neoadjuvant therapy. A standardized approach is recommended to assess the percentages of (1) viable tumor, (2) necrosis, and (3) stroma (including inflammation and fibrosis) with a total adding up to 100%. This is recommended for all systemic therapies, including chemotherapy, chemoradiation, molecular-targeted therapy, immunotherapy, or any future novel therapies yet to be discovered, whether administered alone or in combination. Specific issues may differ for certain therapies such as immunotherapy, but the grossing process should be similar, and the histologic evaluation should contain these basic elements. Standard pathologic response assessment should allow for comparisons between different therapies and correlations with disease-free survival and overall survival in ongoing and future trials. The International Association for the Study of Lung Cancer has an effort to collect such data from existing and future clinical trials. These recommendations are intended as guidance for clinical trials, although it is hoped they can be viewed as suggestion for good clinical practice outside of clinical trials, to improve consistency of pathologic assessment of treatment response.

Immunohistochemical Assessment of BAP1 Protein in Mucoepidermoid Carcinomas.

Mucoepidermoid carcinomas are common malignant salivary gland tumors. Despite recent advances in diagnosis and treatment, there has not been much improvement in outcome of these patients, necessitating identification of novel targeted therapeutic agents. Genomic profiling of mucoepidermoid carcinomas has recently revealed aberrations in BAP1 gene. Therefore, we conducted this study to identify BAP1 loss by immunohistochemistry in these tumors. Mucoepidermoid carcinoma cases were retrieved; hematoxylin-and-eosin stained sections were reviewed. Immunohistochemistry for BAP1 was performed. Forty cases were assessed, including 25 salivary gland and 15 pulmonary mucoepidermoid carcinomas. There were 19 cases in the parotid (76%), two in submandibular gland (8%), and remaining 16% from minor salivary gland locations. Ten (40%) were low grade, nine (36%) were intermediate grade, and six (24%) were high grade mucoepidermoid carcinomas. Thirteen (86.7%) pulmonary mucoepidermoid carcinomas were tracheobronchial, while two (13.3%) were intraparenchymal; all were low grade mucoepidermoid carcinomas. On immunohistochemistry, BAP1 nuclear staining was retained in all cases (100%), irrespective of tumor location or grade. Therapeutic connotations necessitate the identification of readily applicable techniques to detect BAP1 loss in mucoepidermoid carcinomas. Using immunohistochemistry, loss of BAP1 staining was not seen in any of our cases, suggesting insensitivity of BAP1 IHC to detect aberrations at genomic level in these tumors. Analysis of BAP1 alterations by targeted sequencing may therefore be performed prior to excluding the possibility of response to BAP1-targeted therapeutics based on immunohistochemistry alone.

SMARCB1 (INI1)-deficient sinonasal carcinoma: a series of 13 cases with assessment of histologic patterns.

A significant proportion of sinonasal malignancies comprise poorly differentiated/undifferentiated carcinomas that defy accurate histologic classification and behave aggressively. Recent years have seen a refinement of this spectrum by inclusion of novel entities harboring specific genetic alterations, including SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC), characterized by inactivating alterations in SMARCB1 gene, as demonstrated by loss of INI1 immunoexpression. Cyclin D1 is a cell-cycle regulatory protein downstream of INI1. Loss of INI1 leads to derepression of cyclin D1 transcription, suggesting its role as a putative therapeutic target. However, cyclin D1 expression has not been assessed in SDSCs. We retrieved all sinonasal carcinomas, including sinonasal undifferentiated carcinoma, undifferentiated carcinoma, poorly differentiated squamous cell carcinoma, and adenocarcinoma. Histopathologic features were reviewed. INI1 immunohistochemistry was performed. Cyclin D1 was performed in cases showing INI1 loss. Loss of INI1 staining was seen in 13 cases (5.8%), including 11 males and 2 females (age range, 11-65 years). Original diagnoses included SDSC (3/13), sinonasal undifferentiated carcinoma (3/13), adenocarcinoma (3/13), poorly differentiated squamous cell carcinoma (2/13), and poorly differentiated carcinoma (2/13). Tumors were predominantly basaloid in 6 cases and plasmacytoid/rhabdoid in 5 cases. We identified 2 cases having oncocytoid cells arranged in a gland-like pattern. Significant cyclin D1 immunoexpression was absent. SDSC is a rare, emerging entity that resembles a poorly differentiated carcinoma. Histomorphologic spectrum of these tumors is evolving. In addition to basaloid and plasmacytoid/rhabdoid cells, oncocytoid/adenocarcinoma-like pattern can also be seen in SDSC and predicts INI1 loss. These histologic patterns can further be subjected to INI1 immunohistochemistry for correct diagnosis.

Factors associated with poor seizure control and increased side effects after switching to generic antiepileptic drugs.

OBJECTIVE: To determine those factors associated with increased seizures and side effects after switching from brand name to generic antiepileptic drugs (AEDs). METHODS: We surveyed adult epilepsy patients and obtained demographic, clinical, and psychosocial data. We inquired whether they switched from brand name to generic AEDs, and whether they experienced poorer seizure control and increased side effects. Using univariate analysis, we determined those variables significantly associated with increased seizures and side effects. We applied binary logistic regression to determine those independently associated with these target variables. RESULTS: One hundred and twenty-one subjects completed the questionnaire. Seventy-one switched to generic AEDs. Of these, 18 subjects (25.7%) reported increased seizure frequency. This was associated with high seizure count (p=0.03) and scores on the Beliefs About Medicines-General (BMQ-G) questionnaire (p=0.04). On multivariate analysis, these variables were not independently significant. Fourteen subjects (20.6%) reported increased side effects. This was associated with being African-American (p=0.04), and high scores on the BMQ-G (p=0.01). On multivariate analysis, BMQ-G scores were independently associated with increased adverse effects. INTERPRETATION: High baseline seizure count is associated with increased seizure frequency while high BMQ-G scores are associated with increased seizure frequency and adverse effects when patients switch from brand name to generic AEDs.

Demyelinating disease simulating brain tumours: a histopathologic assessment of seven cases.

BACKGROUND: Demyelinating diseases can present as space occupying lesions with in the brain. It is clinically and radiologically difficult to differentiate them from primary neoplasms. Histopathologically they mimic astrocytic neoplasms closely and identifying these lesions correctly has a profound impact in treatment and prognosis of these patients. AIMS AND OBJECTIVES: The objective was to determine the histopathologic features of such acute focal demyelinating disease that clinically presented as brain tumors. MATERIAL AND METHODS: Seven cases were included for the study. Detailed histopathological examination including stains for myelin and axon were performed. The histopathological keys in arriving at the right diagnoses included a well demarcated lesion that contains uniform distribution of foamy macrophages in the absence of any associated coagulative necrosis, sheets of gemistocytic astrocytes in the white matter that show well-formed processes, perivascular chronic inflammatory cell infiltration and total absence of myelin with relative preservation of axons within these areas. CONCLUSION: The degree of suspicion (clinical, radiological and histopathological) should be high to diagnose these group of lesions. The above-mentioned diagnostic keys should help in arriving at the correct histopathological diagnoses of such cases.