Cytomorphology of primary pulmonary NUT carcinoma in different cytology preparations

Abstract

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.

Immunotherapy and Targeting the Tumor Microenvironment: Current Place and New Insights in Primary Pulmonary NUT Carcinoma

“…The nuclei were large and hyperchromatic, which could be round, ovoid or irregular ( 45 – 47 ) ( Figures 3A, B ). Scattered bare nuclei were also observed ( 46 , 47 ). The nucleoli was prominent and nuclear chromatin was fine to granular ( 45 , 47 , 48 ).…”

“…The nucleoli was prominent and nuclear chromatin was fine to granular ( 45 , 47 , 48 ). Mitoses and apoptotic nuclei were frequent ( 46 , 47 ).…”

“…Both primary pulmonary NUT carcinoma and small cell lung cancer (SCLC) show scarce cytoplasm and high Ki-67 proliferation index, but the latter has no obvious nucleoli and no focal squamous cell differentiation. Immunohistochemical staining is positive for chromogranin and synaptophysin, negative for NUT ( 46 , 63 ). Differentiation of poorly differentiated lung adenocarcinoma and primary pulmonary NUT carcinoma mainly relies on immunohistochemistry.…”

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

“…The size of the nucleus is about twice that of the nucleus of a lymphocyte [298]. The cytological images are often rather similar to those described for small-cell lung carcinomas or poorly differentiated carcinomas [298,299]. Another differential diagnosis must be considered for an exceptional primitive lung Ewing sarcoma, too [298].…”

“…Diagnosis of NUT carcinoma can be performed with cytological material [298] (Figure 2). In this situation, the sample often contains many poorly cohesive tumor cells or, conversely, more cohesive tumor cells with small-or intermediate-sized nuclei with a single nucleolus within fine or fragmented granular chromatin [298,299] (Figure 2). The size of the nucleus is about twice that of the nucleus of a lymphocyte [298].…”