Lung cancer is the leading cause of cancer-related mortality worldwide. Screening high-risk populations for lung cancer with low-dose computed tomography (LDCT) reduces lung cancer mortality. Bronchoscopy is a diagnostic procedure used to monitor patients suspected of having lung cancer after LDCT. Rapid on-site evaluation (ROSE) can improve the diagnostic accuracy of endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA), although its diagnostic value remains unclear. In this meta-analysis, the authors evaluated the diagnostic accuracy of ROSE during bronchoscopy.
The PubMed, Embase, and Cochrane Library databases were searched for studies evaluating the diagnostic accuracy of ROSE for lung cancer during bronchoscopy. Studies evaluating the performance of ROSE and articles providing sufficient data for constructing a 2 × 2 table on a per-lesion basis were included. A meta-analysis was conducted using a bivariate random-effects model.
In total, 32 studies involving 8243 lung lesions were included with a pooled sensitivity of 91.8% and a pooled specificity of 94.9%. Subgroup analysis of 12 studies involving 2929 specimens from patients who underwent computed tomography revealed a pooled sensitivity of 93.8% and a pooled specificity of 96%. Further subgroup analysis of seven studies on the diagnostic outcomes of ROSE for intrathoracic or mediastinal lymph nodes through EBUS-TBNA for lung cancer staging revealed a pooled sensitivity of 90.1% and a pooled specificity of 96.9%.
ROSE exhibited high sensitivity and specificity for diagnosing lung cancer during bronchoscopy. It also exhibited high sensitivity in detecting lung cancer in patients undergoing LDCT and higher specificity for nodal staging with EBUS-TBNA.
ThyroSeq offers the opportunity to stratify the risk of malignancy (ROM) in the characterization of indeterminate thyroid nodules, especially those categorized as atypia of undetermined significance (AUS). However, whether ThyroSeq interpretations correlate with cytologic features, management, and surgical outcome remains unclear.
Thyroid fine-needle aspiration specimens categorized as AUS and follicular neoplasm (FN) from 2017 to 2021 were identified from a cytology database search. Patient clinical information and ThyroSeq results were collected and correlated with resection diagnosis if available.
A total of 520 cases were classified as AUS and 111 cases were classified as FN. Within the AUS lesions, 190 cases (36.5%) were subcategorized as cytologic atypia (III-C), 109 cases (21.0%) as architectural atypia (III-A), 138 cases (26.5%) as both cytologic and architectural atypia (III-CA), and 69 cases (13.0%) as oncocytic cell aspirate (III-O). Category III-C showed the highest malignancy rate (16.7%; p = .29), and a higher ThyroSeq-defined probability of cancer or noninvasive follicular thyroid neoplasms with papillary-like nuclear features. Notably, within III-C, intermediate-risk mutations led to a significantly higher malignancy rate (46.7%; p = .0012). Conversely, III-A had the lowest malignancy rate (9.7%) but this was significantly increased by concurrent high-risk mutations (62.5%). BRAFV600E-like mutations were frequently associated with III-C and classical papillary thyroid carcinoma in histology. RAS-like mutations were the most common alterations across all subcategories, and were frequently associated with follicular-patterned lesions.
Atypia subcategories have differential ThyroSeq-defined ROMs and histologic outcomes. Combining atypia subcategory interpretation, ThyroSeq-defined ROMs and molecular results aids in optimal clinical management for indeterminate thyroid lesions.
Trichorhinophalangeal syndrome 1 (TRPS1) expression in primary breast and other solid tumors has been investigated but its role as a marker in metastatic tumors is unclear. The objective of this study was to evaluate the sensitivity and specificity of TRPS1 as a breast cancer immunomarker in metastatic tumors that originated from breast, Müllerian, lung, gastrointestinal (GI), and pancreatic primary tumors with cell blocks from fine-needle aspiration (FNA) and effusion specimens.
Cell blocks were immunostained with anti-TRPS1 monoclonal antibody (clone EPR16171). Histochemical scores (H scores) (proportion × intensity; range, 0–300) were assigned; H scores of ≥10 were considered positive. Overall, 160 specimens were examined, including 127 FNAs (35 breast, 25 Müllerian, 36 lung, and 31 GI and pancreatic carcinomas) and 33 effusion specimens (18 breast, 12 Müllerian, one lung, and two GI carcinomas).
TRPS1 was positive in 51 of 53 (96%) metastatic breast carcinomas and in 28 of 107 (26.2%) nonbreast metastatic tumors. Metastatic breast carcinoma showed the highest mean H score of 247.35, compared to 45.36 in Müllerian, 8.4 in lung, and 5.88 in GI tumors. The sensitivity and specificity of TRPS1 for identifying a breast origin in metastatic tumors was 96.22% and 72.89%, respectively.
Despite high overall sensitivity, TRPS1 showed lower specificity as a breast immunomarker because of its expression in nonbreast tumors. The mean H score in nonbreast tumors was significantly lower than in metastatic breast tumors. It is important to recognize the broad range of expression of TRPS1 in metastatic breast and nonbreast tumors to avoid an incorrect determination of a metastatic tumor’s organ of origin.
Thyroid cytopathology cases with suspicious for malignancy (SFM) diagnosis often result in resection. However, molecular testing offers details that may provide additional insights. In this study, the molecular profiles of SFM cases from two institutions that routinely used ThyroSeq v3 (TSV3) were examined.
Following institutional review board approval, SFM thyroid cytopathology cases with TSV3 results were retrieved from the databases of two institutions. Molecular information including molecular-derived risk of malignancy (MDROM), cytologic-histologic correlation data, and other related parameters were calculated. Statistical comparisons were made with a p <.05 considered significant.
The core data set comprised 114 SFM cases that passed TSV3 quality assurance. All TSV3 results were reported as positive or negative for genomic alterations and all except five cases provided a probability of malignancy estimate. The overall combined baseline MDROM of 75.7% (95% CI, 70.0–81.4) was comparable to the risk of malignancy (74%) published in the Bethesda System. There was a statistically significant difference between the combined MDROMs of resected and unresected cohorts (79.0% vs 58.6%; p = .0153). Interestingly, the MDROMs of the resected cohorts from the two institutions were statistically different (75.0% vs 85.3%; p = .020). Cytologic–histologic correlation revealed malignant outcome in 88.5% of resected cases.
Molecular analyses of SFM cases demonstrated higher risk genomic alterations that were associated with histologically overt neoplasms, resulting in increased malignancy outcome compared to baseline. MDROM analysis revealed differences in the cytopathologic practice patterns regarding follicular-patterned neoplasms at the two institutions.
Papillary renal neoplasm with reverse polarity is a recently recognized low-grade neoplasm with a favorable prognosis. To date, its cytologic features have not been well documented.
Two patients with papillary renal neoplasm with reverse polarity sampled by fine needle aspiration and core needle biopsy are described, one of whom is under active surveillance without clinical progression and the other is alive and well 16 years after partial nephrectomy.
The cytologic features included a mix of papillae and dispersed cells with abundant oncocytic cytoplasm and round, bland nuclei apically displaced away from the papillary core. Immunohistochemistry showed positive staining for GATA3 in both cases. Molecular studies on one of the cases showed a KRAS p.G12V mutation.
The cytologic features of this distinctive, indolent neoplasm are important to recognize because patients with papillary renal neoplasm with reverse polarity may be excellent candidates for partial nephrectomy or even active surveillance.
Recently, a new World Health Organization Reporting System for Soft Tissue Cytopathology (WHO System) was introduced. To analyze the value of this system, routine fine-needle aspiration soft tissue tumor (STT) cases were reviewed.
Cytology samples of STTs collected between 1954 and 2022 at the Institut Curie were used (2214 cases, including 1376 primary tumors). All specimens were classified according to the predominant cytomorphological pattern and the WHO System. The diagnostic accuracy and risk of malignancy (ROM) in each category were calculated.
Final diagnoses revealed 1236 malignancies and 978 benign or low-risk tumors. The original cytological evaluation led to 21 false-negative results (0.85%) and 29 false-positive results (1.17%). Sensitivity, specificity, positive predictive value, and negative predictive value were 98.3%, 92.1%, 97.5%, and 94.2%, respectively. Overall diagnostic accuracy was 94.2%. The ROM calculated according to the WHO System was 29.87%, 2.49%, 39.62%, 51.43%, 68.42%, and 97.69% in the nondiagnostic, benign, atypical, soft tissue neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant categories, respectively; however, it varied broadly depending on the morphological pattern (62.78% in spindle cell tumors, 84.58% in myxoid tumors, 3.00% in lipomatous tumors, 78.15% in epithelioid tumors, 94.26% in pleomorphic tumors, and 100% in round cell tumors).
Cytology of STTs is a powerful diagnostic method. Some cytological patterns overlap in different morphological groups, and the possibility of false-negative and false-positive diagnoses may persist. This analysis evidenced utility of the WHO System, especially when combined with morphological pattern assessment. Subclassification in particular diagnostic categories allowed for calculation of the ROM, which is crucial for optimal patient management.
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