Incidence of NUT carcinoma in Western Australia from 1989 to 2014: a review of pediatric and adolescent cases from Perth Children\u2019s Hospital

Tina Carter,Alex H Beesley,Ursula R Kees,Ashleigh Murch,Nick De Klerk,Adrian Charles,Maxine Crook

doi:10.1186/s12885-021-08432-0

Abstract

BackgroundNUT carcinoma (NC), previously known as NUT midline carcinoma, is a rare and very aggressive cancer that occurs in both children and adults. NC is largely chemoresistant, with an overall survival of less than 7 months. Because the carcinoma is not restricted to a particular organ, diagnosis is often a challenge. In the absence of a clearly determined incidence for NC, we sought to study the diagnosis of patients in a well-defined population.MethodsWe systematically reviewed records of all patients that presented to the Oncology Department of the Princess Margaret Hospital for Children from 1989 to 2014. This institution in the geographically isolated state of Western Australia has a catchment population of around 2 million. We then identified all high grade undifferentiated sarcomas or carcinomas in the 0–16 year age group.ResultsOver 26 years, we found 14 patients of 16 years or younger with undifferentiated malignant tumors. Of these, five tumors were positive by immunohistochemistry for the NUT/NUTM1 (Nuclear Protein in Testis) protein and/or the translocation t(15;19). Three patients presented with thoracic tumors, one with a para-spinal tumor, and one had an upper airway nasopharyngeal carcinoma. In all five cases, there was an initial response to therapy and then progression. This 26-year survey was conducted in a geographically isolated state with a well-defined population, and we determined an estimated incidence of NC of around 0.41 per million child years (0–16 yrs. of age) at risk. From three patients it was feasible to derive cell lines for further genetic analyses and drug screening.ConclusionsFor the first time, the incidence of NC could be determined in a well-defined geographic area. The calculated rate of NC incidence is consistent with a history of under-recognition for this malignancy. These findings indicate that improved diagnostic detection of NC would enable better management and counselling of patients. Our findings emphasize the heterogeneity of NC, and they highlight the need to develop personalised therapy options, and to consider a diagnosis of NC in undifferentiated malignant tumors.

Highlights

NUT carcinoma (NC), previously known as NUT midline carcinoma, is a rare and very aggressive cancer that occurs in both children and adults
Patients From 1989 to 2014, fourteen cases presenting to Perth Children’s Hospital (PCH) were identified as undifferentiated sarcoma or carcinoma (Table 1)
The cases were reviewed with respect to karyotype, histopathology and further immunohistochemical staining to determine consistency with NC

Summary

Introduction

NUT carcinoma (NC), previously known as NUT midline carcinoma, is a rare and very aggressive cancer that occurs in both children and adults. Since NC is rare, not restricted to a particular organ and lacks specific clinical and histomorphological features, the diagnosis is often challenging and misdiagnoses occur [2, 5, 6]. The characteristic translocation t(15; 19) results in the fusion of the NUTM1 gene (previously called NUT), located at 15q14, with another gene. The remaining cases show translocations between NUTM1 and non-BRD4 genes, including BRD3 or NSD3, or other genes [1, 2, 10,11,12] These fusions lead to the formation of oncogenic complexes that, in cell lines, prevent squamous cell differentiation, and alter histone acetylation [11, 13,14,15,16]

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