Abrupt Dyskeratotic and Squamoid Cells in Poorly Differentiated Carcinoma: Case Study of Two Thoracic NUT Midline Carcinomas with Cytohistologic Correlation

Abstract

Cytologic diagnosis of nuclear protein in testis (NUT) midline carcinoma (NMC) is important due to its aggressive behavior and miserable prognosis. Early diagnosis of NMC can facilitate proper management, and here we report two rare cases of thoracic NMC with cytohistologic correlation. In aspiration cytology, the tumor presented with mixed cohesive clusters and dispersed single cells, diffuse background necrosis and many neutrophils. Most of the tumor cells had scanty cytoplasm and medium-sized irregular nuclei, which had fine to granular nuclear chromatin. Interestingly, a few dyskeratotic cells or squamoid cell clusters were present in each case. Biopsy specimen histology revealed more frequent squamous differentiation, and additional immunohistochemistry tests showed nuclear expression of NUT. Because this tumor has a notorious progression and has been previously underestimated in terms of its prevalence, awareness of characteristic findings and proper ancillary tests should be considered in all suspicious cases.

Keywords: BRD4-NUT fusion oncogene protein; Cytology; Lung; NUT midline carcinoma.

Fig. 1.

Thoracic nuclear protein in testis (NUT) midline carcinoma and cytohistologic findings. (A–H) Case 1. (A–D) Chest radiograph and computed tomography (CT) shows 3.8-cm-sized mass in the right lower lobe with multiple enlarged lymph nodes (arrows). Positron emission tomography (PET) reveals 18F-fluorodeoxyglucose uptake of the mass and lymph nodes. (E) Mediastinal lymph node aspiration smears are highly cellular with cohesive clusters and dispersed single cells. Scattered dyskeratotic cells and squamous differentiations are noticed (arrows). (F) Tumor cells have scanty cytoplasm, nuclear molding, irregular nuclear contours, and fine to granular nuclear chromatin. Nucleoli are small but occasionally identified. A few dyskeratotic cells are also identified. Background of the smear shows many neutrophils and necrosis. (G, H) Biopsy of a mediastinal lymph node shows monotonous tumor cells and hyperchromatic nuclei. Nuclei have fine to granular chromatin and the occasional small nucleolus, and the cytoplasm is scant and delicately amphophilic. Foci of squamous differentiation are more often identified than in cytology. (I–R) Case 2. (I–L) Chest and abdomen CT show a 5.5-cm-sized mass (white arrow) in the left lower lobe, and multiple metastases in both a lobe of the liver (arrowheads) and the adrenal glands (black arrow). PET highlights multiple hypermetabolic lesions in the whole spine, ribs, pelvic bone and scapulae, in addition to the lung and liver masses. (M–P) In aspiration cytology of a mediastinal lymph node, some tumor cells are medium-sized and poorly differentiated with scanty cytoplasm and hyperchromatic nuclei. However, others have more abundant amphophilic to eosinophilic cytoplasm and a lower nuclear to cytoplasmic ratio, which can be considered squamous differentiation. (Q, R) Histology of a mediastinal lymph node shows two different tumor cell components with extensive necrosis, poorly differentiated cells and squamous cells, which are similar to the findings of aspiration cytology. (S–V) Immunohistochemistry shows nuclear expression of NUT in case 1 (S) and case 2 (U). Tumor cells are positive for p63 (T, case 1) and there is a variable proliferation index of Ki-67 (V, case 2).