Search

Background: The microphthalmia-associated transcription factor gene (MITF) belongs to the MYC supergene family and plays an important role in melanocytes' homeostasis. Individuals harboring MITF germline pathogenic variants are at increased risk of developing cancer, most notably melanoma and renal cell carcinoma., Case Presentation: We describe a cohort of ten individuals who harbor the same MITF c.952G > A (p.Glu 318Lys), or p.E318K, germline pathogenic variant. Six carriers developed at least one malignancy (4 cases of breast cancer; 1 cervical cancer; 1 colon cancer; 1 melanoma; 1 ovarian/fallopian tube cancer). A significant phenotypic heterogeneity was found among these individuals and their relatives. Breast cancer was, overall, the most frequent malignancy observed in this case series, with 13 occurrences of 60 (21.67 %) total cancer cases described among the probands and their relatives., Conclusions: Our retrospective analysis data raise the hypothesis of a possible association of the MITF p.E318K pathogenic variant with an increased risk of breast cancer., (© 2021. The Author(s).)

Background: NUT midline carcinoma is a rare and aggressive subset of squamous cell carcinoma, which is characterized by the translocation of nuclear protein in testis gene that is mostly fused with bromodomain and extraterminal family proteins. We describe here the first Brazilian case of NUT midline carcinoma with BRD4-NUT fusion detected in a next-generation sequencing panel and we present the clinical evolution of this patient., Case Presentation: A 42-year-old Caucasian man was diagnosed with poorly differentiated squamous cell carcinoma of the left maxillary sinus, with negative in situ hybridization for Epstein-Barr encoding region and human papillomavirus genotyping. He received induction therapy, chemoradiotherapy with weekly systemic chemotherapy, and, concurrently, weekly intra-arterial chemotherapy. New imaging evaluation, 1 month after the end of the last treatment, revealed a good partial response in the primary lesion. However, positron emission tomography-computed tomography showed multiple suspicious lesions in his bones and lungs, which were histologically confirmed. He died exactly 2 months after metastatic disease was diagnosed., Conclusions: NUT midline carcinoma is usually very aggressive. Currently, there is no standard of care for treatment of NUT midline carcinoma. The definitive diagnosis must be by demonstration of NUTM1 rearrangement. Immunohistochemical staining of greater than 50% of tumor nuclei on formalin-fixed paraffin-embedded tissue using the monoclonal rabbit antibody to NUT (clone C52B1), has a specificity of 100%, and sensitivity of 87% for the diagnosis of NUT midline carcinoma. Our case is the first Brazilian case of NUT midline carcinoma with BRD4-NUT fusion.