Journal of the American Society of Cytopathology · 2026
NKX3.1 in the airways: a diagnostic trap in transbronchial fine needle aspirations.
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Gillam Joseph, McMullen Phillip, Barkan Güliz A
Аннотация
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.
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.