Challenging Diagnosis in NUT Carcinoma

Abstract

Nuclear protein in testis (NUT) carcinoma represents a highly aggressive, poorly differentiated carcinoma that is genetically defined by rearrangement of NUT gene. The histomorphological appearance ranges from entirely undifferentiated carcinoma to carcinoma with prominent squamous differentiation. NUT carcinoma can display neuroendocrine features. Although it is typically distributed along the midline axis, it may manifest in nonmidline locations. The majority of patients develop rapidly disseminated disease. We illustrate 2 cases of NUT carcinoma, one located in the lung, which closely resembled a neuroendocrine carcinoma, and the other one with assumed lung origin demonstrating metastatic dissemination with diffuse bone involvement, which was clinically first suspected to be a hematological malignancy. Due to its undifferentiated nature, NUT carcinoma may be confused with many entities. NUT immunohistochemistry is considered to be sufficient for the diagnosis. Fluorescence in-situ hybridization analysis and next-generation sequencing are currently used to confirm the diagnosis.

Keywords: fluorescence in-situ hybridization; next-generation sequencing; nuclear protein in testis.

Figure 1.

(A and B) Transbronchial lung biopsy showing infiltrates by primitive-appearing monotonous cells (hematoxylin and eosin) with nuclear molding, speckled chromatin, and crush artifacts. (C) Synaptophysin ( + ), (D) punctate NUT expression in the tumor cell nuclei ( + ), (E) expression of CK5/6 ( + ), and (F) uniform expression of p40 ( + ). (G) FNA specimen and (H) NUTM1 dual-color break-apart fluorescence in-situ hybridization showing fused signals and single orange/green signals in the majority of tumor cells.

Figure 2.

(A and B) Bone marrow biopsy showing diffuse infiltration by blastoid cells (hematoxylin and eosin). (C) CD45 ( − ) (scattered leukocytes positive), (D) CD99 ( + ), (E) NUT ( + ), (F) p63 ( + ), (G) pancytokeratin ( − ), and (H) NUTM1-FISH ( + ).