Shioto Suzuki1, Nobuya Kurabe2, Hiroshi Minato3, Aki Ohkubo4, Ippei Ohnishi5, Fumihiko Tanioka5, Haruhiko Sugimura2. 1. Division of Pathology, Iwata City Hospital, Japan. Electronic address: shiosuzuki-path@umin.net. 2. Department of Tumor Pathology, Hamamatsu University School of Medicine, Japan. 3. Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Japan. 4. Division of Otolaryngology, Iwata City Hospital, Japan. 5. Division of Pathology, Iwata City Hospital, Japan.
Abstract
BACKGROUND: NUT (nuclear protein in testis) midline carcinoma (NMC) is a recently described aggressive malignancy that is genetically defined by rearrangements of the NUT locus at 15q14. In approximately two-thirds of cases, the characteristic t(15;19) results in the fusion oncogene BRD4-NUT. Only 10 sinonasal NMCs have been documented, none of which were Japanese cases. CASE PRESENTATION: An 18-year-old woman was admitted because of a rapidly progressing tumor in the nasal cavity. A biopsy revealed an undifferentiated neoplasm without squamous differentiation. The tumor cells had round to oval nuclei with vesicular chromatin, prominent nucleoli, and scant cytoplasm. Immunohistochemical staining demonstrated a strong positivity for vimentin and NUT, with focal CD138 and only spotty EMA and cytokeratin AE1/AE3 staining. Cytogenetic and fluorescence in situ hybridization analyses revealed a t(15;19) and BRD4-NUT gene rearrangement. Direct sequencing identified the in-frame fusion of exon11 of BRD4 with exon2 of NUT. The patient was transferred to another hospital for chemoradiotherapy. CONCLUSION: We herein describe the first Japanese case with an NMC of the sinonasal cavity, providing detailed and unambiguous cyto- and molecular genetic information on BRD4-NUT-rearrangement. The accumulation of cases with well-documented genetic data should provide clues to the treatment of this tumor entity.
BACKGROUND:NUT (nuclear protein in testis) midline carcinoma (NMC) is a recently described aggressive malignancy that is genetically defined by rearrangements of the NUT locus at 15q14. In approximately two-thirds of cases, the characteristic t(15;19) results in the fusion oncogene BRD4-NUT. Only 10 sinonasal NMCs have been documented, none of which were Japanese cases. CASE PRESENTATION: An 18-year-old woman was admitted because of a rapidly progressing tumor in the nasal cavity. A biopsy revealed an undifferentiated neoplasm without squamous differentiation. The tumor cells had round to oval nuclei with vesicular chromatin, prominent nucleoli, and scant cytoplasm. Immunohistochemical staining demonstrated a strong positivity for vimentin and NUT, with focal CD138 and only spotty EMA and cytokeratin AE1/AE3 staining. Cytogenetic and fluorescence in situ hybridization analyses revealed a t(15;19) and BRD4-NUT gene rearrangement. Direct sequencing identified the in-frame fusion of exon11 of BRD4 with exon2 of NUT. The patient was transferred to another hospital for chemoradiotherapy. CONCLUSION: We herein describe the first Japanese case with an NMC of the sinonasal cavity, providing detailed and unambiguous cyto- and molecular genetic information on BRD4-NUT-rearrangement. The accumulation of cases with well-documented genetic data should provide clues to the treatment of this tumor entity.
Authors: Nicole G Chau; Shelley Hurwitz; Chelsey M Mitchell; Alexandra Aserlind; Noam Grunfeld; Leah Kaplan; Peter Hsi; Daniel E Bauer; Christopher S Lathan; Carlos Rodriguez-Galindo; Roy B Tishler; Robert I Haddad; Stephen E Sallan; James E Bradner; Christopher A French Journal: Cancer Date: 2016-08-10 Impact factor: 6.860
Authors: Valentina Gonzalez-Pecchi; Albert K Kwan; Sean Doyle; Andrey A Ivanov; Yuhong Du; Haian Fu Journal: J Mol Cell Biol Date: 2020-07-03 Impact factor: 6.216