Cytomorphology of primary pulmonary NUT carcinoma in different cytology preparations

Background: NUT carcinoma (NC) is an aggressive neoplasm that often presents with alarge tumor burden and metastases; cytology is frequently one of the primary diagnostic modalities. Primary pulmonary NCs are very rare and cytology descriptions are limited. The current study was performed to analyze the cytomorphological features of primary pulmonary NCs in different cytology samples and preparations. Methods: A total of 15 cytology specimens from 10 patients with primary pulmonary NCs diagnosed primarily on histology were retrieved and reviewed. Results: Fifteen cytology samples, including aspirates from primary (5 samples) and metastatic (5 samples) sites, sputum (1 sample), and effusions (4 samples), that were prepared as direct smears, centrifuged smears, and cell blocks were reviewed. Aspirate smears from all cases were cellular and demonstrated fragments and cohesive clusters of primitive tumor cells with scant cytoplasm, ovoid nuclei with coarse granular chromatin, and consistently conspicuous single nucleoli in a frequently neutrophil-rich necrotic background with dispersed bare tumor nuclei. In fluid cytology, tight, 3-dimensional tumor clusters and singly lying tumor cells were observed. Squamous differentiation in the form of sheets and singly lying polygonal tumor cells with abundant dense cytoplasm was noted focally in rare cases. The diagnoses during original sign-outs were poorly differentiated carcinoma, poorly differentiated squamous cell carcinoma, and malignant small round cell tumor. NUT-1 (NUT family member 1 protein) immunocytochemistry performed on cell blocks demonstrated characteristic speckled nuclear staining in tumor cells. Conclusions: Pulmonary NC presents as a poorly differentiated carcinoma with focal to absent squamous differentiation on cytology. Cellular fragments of primitive tumor cells with conspicuous nucleoli should raise suspicion of NUT carcinoma and prompt ancillary testing.