NUT Rearrangement in Undifferentiated Carcinomas of the Upper Aerodigestive Tract

Stelow, Edward B.; Bellizzi, Andrew M.; Taneja, Krishan; Mills, Stacey E.; LeGallo, Robin D.; Kutok, Jeffery L.; Aster, Jon C.; French, Christopher A.

doi:10.1097/pas.0b013e31815a3900

Cited by 214 publications

(198 citation statements)

References 22 publications

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“…NUT, p63 immunohistochemistry, and periodic acid-Schiff (PAS) with and without diastase and mucicarmine histochemistry had been performed previously on corresponding surgical pathology material. 14,15 Patient age, sex, primary tumor site, aspirated site, and original cytologic diagnosis were noted; concise clinical follow-up was obtained. Cases were assessed for the following cytologic features: cellularity, architecture, cytoplasm, cell size, nuclear contours, nucleoli, chromatin, anisonucleosis/cytosis, mitotic activity, background, and nuclear crush.…”

Section: Cancer Cytopathologymentioning

confidence: 99%

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The cytologic features of NUT midline carcinoma

Bellizzi

Bruzzi

French

et al. 2009

Cancer Cytopathology

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BACKGROUND:Nuclear protein in testis (NUT) midline carcinoma (NMC) represents an aggressive, high‐grade carcinoma typically involving the upper aerodigestive tract or mediastinum. Although the tumor was originally noted in young persons, we have subsequently identified 5 adult cases. To our knowledge, the cytology of NMC has not been systematically described.METHODS:We recently published a series of NMCs identified by fluorescent in situ hybridization for characteristic NUT rearrangement. Three of these patients had undergone fine‐needle aspiration. Patient age, sex, primary tumor location, and aspiration site were noted. Cases were assessed for the following: cellularity, architecture, cytoplasm, cell size, nuclear contours, nucleoli, chromatin, anisonucleosis/cytosis, mitotic activity, background, and nuclear crush.RESULTS:The 3 cases occurred in 2 women and 1 man, ages 31‐79 years. Primaries involved the sinonasal tract (2) and larynx. Aspirates were of right neck masses (2) and supraclavicular lymph node. Smears were highly cellular and generally noncohesive. Cytoplasm was scant/delicate, although occasional cells with denser cytoplasm were noted in 1 case. Cells were 2‐3 times the diameter of a small lymphocyte with irregular nuclear contours, discrete nucleoli, and fine/granular to vesicular chromatin. Anisonucleosis/cytosis was slight to moderate. Mitotic figures were noted in each case. The background contained naked nuclei and karyorrhectic debris; nuclear crush was noted.CONCLUSIONS:NMCs exhibit cytologic features of a poorly differentiated or undifferentiated carcinoma. Although reports mention squamous differentiation as a histologic feature, it is typically focal, and overt squamous differentiation was not identified in our cases. Given morphologic overlap with other high‐grade carcinomas, diagnosis requires a high index of suspicion. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.

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Section: Cancer Cytopathologymentioning

confidence: 99%

“…14 Although previous screening attempts had been undertaken in pediatric tumors, our patient population was unselected for age. All 5 tumors involved mature adults, ages 31-78 years, including 4 patients older than any previously reported.…”

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confidence: 99%

The cytologic features of NUT midline carcinoma

Bellizzi

Bruzzi

French

et al. 2009

Cancer Cytopathology

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“…Sinonasal tract involvement by NUT carcinoma is much less common than mediastinal disease, but most head and neck cases affect the nasal cavity and paranasal sinuses (65%), with a median presentation in the 20 s, showing a slight female predominance. [67][68][69][70][71][72][73] There is no known etiologic association. Patients present with a rapidlygrowing, extensively destructive mass, often with orbital involvement, and lymph node metastases in about 50% of patients.…”

Section: Nut Carcinoma (Squamous Cell Carcinoma)mentioning

confidence: 99%

“…The neoplastic cells will be positive with pancytokeratin (AE1/AE3), along with CK5/6, p63 and p40, 69,70,75 frequently with CD34 (55%) 76 , and uncommonly with neuroendocrine markers, p16 and TTF-1. By definition, NUTM1 rearrangement must be documented, which can be achieved by strong, diffuse (450%) nuclear staining with the NUT monoclonal antibody (C52, Cell Signaling Technologies, Inc.; Figure 7), 75,77 or by other methodologies (FISH, reverse-transcriptase PCR, targeted next-generation sequencing).…”

Section: Nut Carcinoma (Squamous Cell Carcinoma)mentioning

confidence: 99%

Small round blue cell tumors of the sinonasal tract: a differential diagnosis approach

Thompson

2017

Modern Pathology

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One of the most challenging diagnostic categories within tumors of the sinonasal tract is the small round blue cell tumors. Biopsies are usually small and limited, resulting in considerable diagnostic difficulty for practicing surgical pathologists. These tumors share several overlapping histologic and immunophenotypic findings while also showing considerable variation within and between cases. Specific tumor site of origin, imaging findings, and clinical findings must be combined with the histology and pertinent ancillary studies if the correct diagnosis is to be reached. Discrimination between neoplasms is critical as there are significant differences in therapy and overall outcome. It is important to have a well developed differential diagnosis for this category of tumors, where each of the diagnoses is considered, evaluated, and either confirmed or excluded from further consideration. In an undifferentiated tumor, showing a small round blue cell morphology, using the mnemonic 'MR SLEEP' helps to highlight tumors to consider: melanoma, mesenchymal chondrosarcoma, rhabdomyosarcoma, sinonasal undifferentiated carcinoma, squamous cell carcinoma (including NUT carcinoma), small cell osteosarcoma, lymphoma, esthesioneuroblastoma (olfactory neuroblastoma), Ewing sarcoma/primitive neuroectodermal tumor, pituitary adenoma, and plasmacytoma. A panel of pertinent immunohistochemistry studies, histochemistries and/or molecular tests should aid in reaching a diagnosis, especially when taking the pattern and intensity of reactions into consideration.

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“…Subsequent studies have revealed NC to constitute 18 % of Epstein-Barr Virus (EBV) negative undifferentiated carcinomas of the upper aerodigestive tract, making it a likely under diagnosed tumor entity of the head and neck [7]. Histopathologically, NC is an epithelial neoplasm composed of poorly differentiated basaloid cells with focal squamous differentiation and immunohistochemically positive for cytokeratin 7 (CK7) and p63 [8].…”

Section: Introductionmentioning

confidence: 99%

NUT Carcinoma of the Sublingual Gland

Andreasen

French

Josiassen

et al. 2015

Head and Neck Pathol

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NUT carcinoma (NC) is a recently described, rare and extremely aggressive cancer primarily located to supradiaphragmatic structures and affecting young individuals. NC is characterized by translocations involving the NUT gene on 15q14 with the most common translocation partner gene being BRD4 on 19p13, resulting in the t(15;19)(q14;p13) karyotype. NC is poorly differentiated and is likely to be overlooked and misdiagnosed as poorly differentiated squamous cell carcinoma (SCC) when immunohistochemical evaluation of NUT protein expression is omitted. Previously, NC has been found in the parotid and submandibular glands and we present the first case in the sublingual gland arising in a 40-year-old woman. We discuss the diagnostic considerations for poorly differentiated carcinomas of the salivary glands and advocate the inclusion of NUT immunohistochemistry in this setting. Not only does the NC diagnosis confer a grave prognosis when treated as SCC as illustrated by the present case, but is important for the inclusion of patients in ongoing clinical trials.

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NUT Rearrangement in Undifferentiated Carcinomas of the Upper Aerodigestive Tract

Cited by 214 publications

References 22 publications

The cytologic features of NUT midline carcinoma

The cytologic features of NUT midline carcinoma

Small round blue cell tumors of the sinonasal tract: a differential diagnosis approach

NUT Carcinoma of the Sublingual Gland

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