Two Cases of NUT Carcinoma of the Lung: Same Name With Different Appearance: A Case Report

NUT carcinoma is a poorly differentiated tumor defined by nuclear protein in testis (NUTM1) gene rearrangement. Histologically, it is characterized by a primitive small round cell proliferation with abrupt squamous differentiation, although the extent of squamous differentiation varies among cases. Inconspicuous squamous epithelium may result in misdiagnosis as lymphoma or other small round cell tumors. In this study, we present two cases of NUT carcinoma: (1) a man in his 20s with a right hilar and middle lobe mass, in whom a lymph node biopsy was performed followed by autopsy; and (2) a woman in her 30s with a left lung mass that was surgically resected. Both cases showed primitive small round cell proliferation; however, they differed in both morphological and immunohistochemical features. Morphologically, the appearance and extent of squamous differentiation varied between the two cases. The first case exhibited abrupt squamous epithelium intermingled with the round cell component, whereas the second exhibited tiny foci of squamous epithelium, with the remainder composed of primitive round cells. Regarding immunohistochemistry, the first case showed diffuse keratin positivity, whereas the second showed almost no staining. Based on these results, the first case was considered typical NUT carcinoma, whereas the second was difficult to diagnose due to limited squamous epithelium. Although the key diagnostic feature of NUT carcinoma is reported to be abrupt squamous differentiation, many cases do not exhibit this feature, which may represent a diagnostic pitfall. There are also pitfalls in immunohistochemistry: keratin, which confirms epithelial origin, may be negative; p40, which highlights squamous differentiation, may also be negative; and TTF-1 and neuroendocrine markers may be positive. This report compares these two cases morphologically and immunohistochemically and highlights the diagnostic challenges of NUT carcinoma with scant squamous components. Additionally, related literature is reviewed, and key diagnostic points, including immunohistochemistry, are discussed.