Journal of the American Society of Cytopathology最新文献

Introduction: Primary lung mucinous adenocarcinoma (PLMAC) frequently harbors KRAS mutations; however, the distribution of KRAS variants in PLMAC remains under-characterized. This study aimed to investigate the KRAS mutational profile in PLMAC.

Methods: Cases of PLMAC (2018-2022) and primary lung nonmucinous adenocarcinomas (PLNMAC) (Oct-Dec 2022) were identified from pathology archives. Molecular testing was performed using a next-generation sequencing lung cancer hotspot gene panel. Specimen types, molecular results, demographic data, and smoking status were recorded. Statistical significance was assessed using an online Z-score calculator.

Results: A total of 117 PLMAC and 185 PLNMAC cases were identified. KRAS mutations were more common in PLMAC (62/86, 72%) compared to PLNMAC (61/154, 40%). In PLMAC, the most common KRAS variants were G12V (39%), followed by G12D (32%), while G12C was found in 19%. In PLNMAC, G12C was the predominant variant (47%). Among 27 (23%) never-smoking PLMAC patients, 17 were tested, and 12 (71%) harbored KRAS mutations-all non-G12C. Among 26 (14%) never-smoking PLNMAC patients, 20 were tested, and only one had a KRAS mutation, which was G12C.

Conclusions: In our cohort, KRAS mutations were more prevalent in PLMAC than PLNMAC (72% vs. 40%, P < 0.05). However, the KRAS G12C variant was significantly less frequent in PLMAC compared to PLNMAC (19% vs. 47%, P < 0.05), suggesting that patients with PLMAC are less likely to benefit from KRAS G12C-targeted therapy. These findings underscore the importance of comprehensive KRAS genotyping and highlight the need for developing additional KRAS variant-targeted therapy for patients with PLMAC.

Introduction: This study retrospectively assessed the ultrasound parameters in Bethesda category III thyroid nodules accompanied by a diagnostic Afirma genomic sequencing classifier (GSC) testing result and surgical/clinical follow-up, and investigated whether combining ultrasound and GSC classifications could improve risk stratification of the atypia of undetermined significance (AUS) nodules.

Materials and methods: Data including radiologic Thyroid Imaging Report and Data System (TIRADS) score, concurrent GSC test results, and surgical/clinical follow-up were collected from patients with thyroid nodules meeting the study criteria. The distribution of TIRADS scores was compared between GSC-suspicious versus GSC-benign cohorts, as well as between malignant and benign nodules. The diagnostic performance of the GSC was compared between TIRADS 5 and TIRADS < 5 cohorts.

Results: The study consisted of 322 AUS nodules. Compared to the GSC-benign cohort, the GSC-suspicious cohort had a greater proportion of TIRADS 5 nodules (34% vs. 24%, P = 0.045), a lower proportion of TIRADS 1-3 nodules (20% vs. 30%, P = 0.048), and a higher average TIRADS score (4.12 vs. 3.92, P = 0.03). Compared to the benign cohort (histologically and/or clinically benign), the malignant cohort (histologically malignant) showed a higher proportion of TIRADS 5 nodules (52% vs. 24%, P = 0.004). The mean TIRADS score was also significantly higher in the malignant cohort compared to the benign cohort (4.36 vs. 3.92, P = 0.015). GSC testing demonstrated a significantly higher positive predictive value in the TIRADS 5 AUS nodules than that of TIRADS< 5 nodules (39% vs. 17%, P = 0.016).

Conclusions: A GSC-suspicious result combined with TIRADS 5 significantly improved the positive predictive value, thereby enhancing risk stratification in AUS thyroid nodules, while other diagnostic parameters remained unchanged.

Introduction: NKX3.1, a sensitive and specific immunohistochemical marker for prostatic adenocarcinoma, is widely used to identify metastatic prostate cancer. However, its diagnostic utility may be complicated by bronchial epithelial cells (BECs) and seromucinous glands (SMGs) which often appear in transbronchial fine-needle aspiration (FNA) specimens. This study examines FNA biopsies for NKX3.1 nuclear positivity in benign BECs and SMGs in patients without prostate cancer.

Materials and methods: Transbronchial lung mass (TBLM) and lymph node (TBLN) FNA and biopsy specimens from patients without suspicion for prostate cancer were randomly selected from January 2024 to April 2025. Specimens were formalin-fixed, paraffin-embedded, and reviewed for SMGs and BECs. Immunohistochemical staining for NKX3.1 was performed using the EP356 rabbit monoclonal antibody (Roche Diagnostics) on the Ventana Benchmark Ultra platform. Nuclear staining in SMGs and BECs was recorded. For purposes of quality control, peribronchiolar lung sections from recent autopsies were selected for comparative staining patterns.

Results: Seventeen of 18 (94.4%) autopsy lung sections showed nuclear NKX3.1 staining, ranging from weak and scattered in BECs to strong and diffuse in SMGs. Fifty-seven biopsies from 39 patients (22 males, 17 females) were evaluated: 2 TBLM forceps biopsies, 23 TBLM FNA biopsies, and 32 TBLN FNA biopsies. NKX3.1 nuclear staining was present in 77.1%, including 60.8% TBLM FNAs and 87.5% TBLN FNAs. SMGs showed diffuse nuclear positivity, while BECs exhibited focal, variably intense staining.

Conclusions: Given the frequency of NKX3.1 expression in benign bronchial elements, pathologists should interpret NKX3.1 staining in transbronchial FNAs with caution to avoid misdiagnosing metastatic prostatic adenocarcinoma.

In the current landscape of staffing shortages for both cytologists and cytopathologists, telepathology offers a solution for rapid on-site evaluation for a wide scope of practice settings. There are various technologies available to aid both the cytologists on-site and pathologists receiving the telepathology images to create customizable workflows based on the needs of the laboratory. Ultimately, there remains a need for expert guidance regarding the creation of and execution of a quality telecytology system. This review offers a synopsis based on decades worth of combined knowledge of telecytology implementation and practices at 4 large US institutions.

Introduction: The diagnostic accuracy of lymph node fine-needle aspiration cytology (LN-FNAC) relies on proper management of the diagnostic material and on ancillary techniques (AT). Despite the recognized utility of AT in LN-FNAC, their specific role on diagnostic accuracy remains underexplored. This study aims to analyze the impact of AT on the diagnostic accuracy of LN-FNAC.

Materials and methods: A retrospective review of 452 LN-FNAC samples (2021-2024; University Hospital of Salerno) was performed, identifying 187 cases in which AT were applied. Each case was classified according to the Sydney/WHO system. The impact of AT was assessed both on the first diagnostic level (L1 = inadequate/nondiagnostic, L2 = benign, L3 = atypical, L4 = suspicious for malignancy, and L5 = malignant) and on the second diagnostic level (specific diagnostic entity).

Results: Regarding the first level, the number of L3 and L4 diagnoses was reduced by the application of AT: n = 67/71 (94%) L3 cases were reclassified as L2 or L5; n = 26/26 (100%) L4 cases were reclassified as L5. Regarding the second level, it was reached only in 32/187 (17%) cases without AT and in 125/187 (67%) cases with AT. Finally, AT supported 19.8% of diagnoses, enhanced 36.4%, enabled 38.0%, and was noncontributory in only 5.9% of cases.

Conclusions: This study shows that AT impacted on both the first and second level of the Sydney/WHO system and it had a positive impact on diagnoses in a significant proportion of cases. These findings highlight not only the importance of AT for LN-FNAC, but also the impact of strategic material management and the appropriate AT selection in achieving accurate diagnoses.