Intraoperative cytology of low-grade fetal adenocarcinoma: Critical morphological features for distinction from...

Low-grade fetal adenocarcinoma (L-FLAC) is an exceedingly rare subtype of lung adenocarcinoma, accounting for merely 0.3% of all pulmonary adenocarcinomas. Its accurate intraoperative cytological diagnosis poses substantial challenges, particularly in distinguishing it from carcinoid tumors, which have overlapping morphological features but different therapeutic approaches. We present the case of a 47-year-old female non-smoker with an incidental 21-mm pulmonary nodule spanning the right upper and middle lobes. Intraoperative fine-needle aspiration cytology demonstrated features suggestive of an atypical carcinoid tumor, primarily due to the presence of planar atypical cells with neuroendocrine-like characteristics. Comprehensive cytological assessment revealed two distinct cellular patterns: loosely cohesive planar cells alongside densely nucleated, three-dimensional cohesive clusters with cribriform architecture resembling endometrial tissue. Most importantly, focal cell aggregates with ground-glass nuclei and intranuclear inclusions, corresponding to morule-like structures - a pathognomonic feature of L-FLAC - were identified during detailed examination. Histopathological evaluation confirmed L-FLAC, characterized by atypical glandular proliferation with clear cytoplasm, subnuclear vacuolation, and distinctive morule-like structures demonstrating strong nuclear b-catenin positivity. The patient underwent lobectomy with lymph node dissection and remained recurrence-free at the 2-year follow-up. This case highlights four critical cytomorphological features essential for accurate intraoperative diagnosis of L-FLAC: (1) recognition of dual cell populations (loose planar cells versus cohesive endometrial-like clusters), which contrasts with the monomorphic presentation of carcinoid tumors; (2) identification of ground-glass nuclei and intranuclear inclusions in morule-like structures, features absent in carcinoid tumors; (3) presence of cribriform patterns within cohesive clusters; and (4) awareness that neuroendocrine-like features can dominate the cytological presentation. Accurate distinction between these entities is crucial, as carcinoid tumors may be amenable to limited resection in selected cases, whereas adenocarcinomas generally warrant lobectomy with lymph node dissection. Cytopathologists should remain vigilant for the subtle but diagnostic features of L-FLAC, particularly ground-glass nuclei and intranuclear inclusions, which provide definitive evidence for differentiating this entity from carcinoid tumors in challenging intraoperative settings.