Skin adnexal carcinoma with BRD3‐NUTM2B fusion

Abstract

NUT carcinomas are genetically defined epithelial neoplasms. Most tumors harbor fusions of NUTM1 with BRD4 or BRD3. Their histopathologic features have been predominantly reported as undifferentiated or poorly differentiated squamous cell carcinoma, and clinically they tend to be aggressive cancers. However, recent studies have revealed a broader spectrum of NUTM1‐rearranged neoplasms with several new fusion partners and associated variable histopathologic phenotypes and clinical behaviors, including benign and malignant cutaneous poroid tumors. We report herein a primary invasive carcinoma of skin adnexal origin with a previously undescribed fusion between BRD3 and NUTM2B. The tumor occurred on the shoulder of a 7‐year‐old girl and was excised with negative margins. A sentinel lymph node was positive. After follow‐up of 23 months, and without systemic treatment, the child remains free of tumor. This case expands the spectrum of NUT carcinomas by including a skin adnexal variant with follicular infundibular differentiation, a novel genomic aberration, and preliminary evidence of a less aggressive clinical course.

Gene fusions in poroma, porocarcinoma and related adnexal skin tumours: An update

“…Interestingly, the evaluation of NUT expression in skin tumours in several independent studies 15–17,47 confirmed the high specificity of NUT expression for the diagnosis of poroma and porocarcinoma, but also allowed identification of a new tumour entity, i.e. NUT adnexal carcinoma, 19–21,99 an extremely rare tumour that will be mentioned as a provisional tumour entity in the 5th WHO classification of cutaneous tumours.…”

“…So far, only four cases with either BRD3::NUTM1 or NSD3::NUTM1 fusions have been published 19,20,99 . One case with BRD3::NUTM2B may belong to the same spectrum 21 . So far no primary cutaneous tumour with BRD4::NUTM1 fusion has been identified.…”

“…Although additional cases are needed to fully characterise this new tumour entity, adnexal NUT carcinoma, together with the metastasis of extracutaneous NUT carcinoma, appears as a new differential diagnosis of porocarcinoma, especially in the case of NUT immunohistochemical positivity. In this setting, recognition of a distinctive architecture with formation of thin strands and isolated tumour cells, a characteristic cytology with fine/clear chromatin and prominent nucleoli, as well as detection of abrupt keratinisation foci, would allow NUT adnexal carcinoma to be distinguished from NUT‐rearranged porocarcinoma 19–21,99 …”

“…Furthermore, immunohistochemical evaluation of YAP1 (C‐terminus part) and NUT has been shown to be a specific diagnostic surrogate for molecular testing 11,15–18 . Interestingly, the systematic examination of large cohorts of cutaneous skin tumours for the expression of YAP1, NUT and their related fusion transcripts has allowed the identification of novel and emerging tumour entities related to NUTM1 fusion 11,19–21 …”

“…11,[15][16][17][18] Interestingly, the systematic examination of large cohorts of cutaneous skin tumours for the expression of YAP1, NUT and their related fusion transcripts has allowed the identification of novel and emerging tumour entities related to NUTM1 fusion. 11,[19][20][21] In this review, we aim to discuss the clinical, morphological and molecular features of poroma, porocarcinoma and related cutaneous tumour entities, with a focus upon emerging differential diagnoses. The contribution of genetic characterisation of these tumours to a more accurate classification will also be discussed.…”