NUT Midline Carcinoma: A Series of Five Cases, Including One with Unusual Clinical Course

Abstract

NUT midline carcinomas (NMCs) are rare, poorly differentiated tumors with aggressive biological behavior and a characteristic molecular signature. Availability of NUT antibody has facilitated diagnosis of NMC without molecular testing. We report a series of head and neck NMCs diagnosed using NUT IHC at our institute, including one case with an unusual course. Immunohistochemistry for NUT was performed in nasal and sinonasal tumors with diagnoses of undifferentiated carcinoma, poorly differentiated squamous cell carcinoma and malignant neoplasm, not otherwise specified, to identify cases of NMC. Clinicopathological features were reviewed. Five cases of NMC were identified, accounting for 9.6% of poorly differentiated/undifferentiated carcinomas of the sinonasal region. These patients had a sex ratio of 2:3, and ranged in age from of 10 to 31 years (mean: 25.2 years). Patient 4 had previously been diagnosed with basal cell carcinoma arising in left nasolacrimal duct, and inverted papilloma of nasal cavity. She presented to us with a left lacrimal fossa mass extending into nasal cavity, which was diagnosed as NMC. NMC is a rare neoplasm, the awareness of which is imperative for pathologists to identify cases in which NUT IHC should be ordered. NUT IHC should be performed in all cases of a poorly differentiated carcinoma, particularly those with foci of squamous differentiation, irrespective of patient age and unusual tumor location, as seen in one of our cases. Although considered a highly aggressive and lethal neoplasm, NMC can have a more prolonged clinical course on occasion.

SMARCB1 (INI‐1) and NUT immunoexpression in a large series of head and neck carcinomas in a Brazilian reference center

“…Thus, the presence of sudden squamous differentiation without gradual differentiation on microscopy, in addition to midline location, should raise the strong suspicion of NUT carcinoma. 27 In the current series, it is relevant the overall survival rate when comparing the SMARCB1 (INI-1)-deficient carcinoma (mean, 29 months) and NUT carcinoma (mean, 15.5 months) cases (Table 1). In this latter, the nasal cavity and paranasal sinuses are commonly involved; however, there are also cases described in the orbital region, nasopharynx, larynx, epiglottis, major salivary glands, and oropharynx.…”

“…In this latter, the nasal cavity and paranasal sinuses are commonly involved; however, there are also cases described in the orbital region, nasopharynx, larynx, epiglottis, major salivary glands, and oropharynx. 11,12,[26][27][28] To date, the most comprehensive reviews involved 63 NUT carcinomas establishing a clinical database, 29 as well as a meta-analysis of 32 NUT carcinomas. 30 A recent study showed that NUT carcinoma represents about 10% of poorly differentiated/undifferentiated carcinomas in the sinonasal region.…”

“…30 A recent study showed that NUT carcinoma represents about 10% of poorly differentiated/undifferentiated carcinomas in the sinonasal region. 27 In the current series, it is relevant the overall survival rate when comparing the SMARCB1 (INI-1)-deficient carcinoma (mean, 29 months) and NUT carcinoma (mean, 15.5 months) cases ( Table 1). All NUT carcinomas were midline, located in the oropharynx, being that an abrupt keratinization on histology was only observed in one case previously diagnosed as hybrid SCC.…”

Prevalence of NUT carcinoma in head and neck: Analysis of 362 cases with literature review

“…Since initial report in 1991, total 105 cases were described. 5,11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] The sinonasal tract accounted for 73.4% of initial presenting site and followed by salivary gland (11%), larynx (7.3%), pharynx (4,6%), and oral cavity (3.7%) ( Table 3). Regarding the overall frequency of NUT carcinoma in head and neck, previous studies reported different results according to the study subjects (1.9-17.9%).…”

Overview and different perspectives on possible treatments related to NUT carcinoma: a systematic review

“…Data on mediastinal NUT midline carcinoma with extensive cardiac invasion have been reported in two cases and in one case it was possible to demonstrate extensive coronary involvement that causes a fatal myocardial infarction 5 . Another study reports the second case that appears in the lacrimal fossa 6 .…”