The histological spectrum and immunoprofile of head and neck NUT carcinoma: A multicentre series of 30 cases

Abstract

Background and aim: Head and neck nuclear protein of testis carcinoma (HN-NUT) is a rare form of carcinoma diagnosed by NUT immunohistochemistry positivity and/or NUTM1 translocation. Although the prototype of HN-NUT is a primitive undifferentiated round cell tumour (URC) with immunopositivity for squamous markers, it is our observation that it may assume variant histology or immunoprofile.

Methods: We conducted a detailed clinicopathological review of a large retrospective cohort of 30 HN-NUT, aiming to expand its histological and immunohistochemical spectrum.

Results: The median age of patients with HN-NUT was 39 years (range = 17-86). It affected the sinonasal tract (43%), major salivary glands (20%), thyroid (13%), oral cavity (7%), larynx (7%), neck (7%) and nasopharynx (3%). Although most cases of HN-NUT (63%) contained a component of primitive URC tumour, 53% showed other histological features and 37% lacked a URC component altogether. Variant histological features included basaloid (33%), differentiated squamous/squamoid (37%), clear cell changes (13%), glandular differentiation (7%) and papillary architecture (10%), which could co-exist. While most HN-NUT were positive for keratins, p63 and p40, occasional cases (5-9%) were entirely negative. Immunopositivity for neuroendocrine markers and thyroid transcription factor-1 was observed in 33 and 36% of cases, respectively. The outcome of HN-NUT was dismal, with a 3-year disease specific survival of 38%.

Conclusions: HN-NUT can affect individuals across a wide age range and arise from various head and neck sites. It exhibits a diverse spectrum of histological features and may be positive for neuroendocrine markers, potentially leading to underdiagnosis. A low threshold to perform NUT-specific tests is necessary to accurately diagnose HN-NUT.

Keywords: NUTM1; NUT carcinoma; head and neck.

Figure 1.. Histologic features of head and neck NUT carcinoma.

(A-B) The most common histologic appearance is a primitive undifferentiated round cell tumor. The tumor cells are of medium size with round nuclei, vesicular chromatin, prominent centrally located nucleoli, and abundant eosinophilic to basophilic cytoplasm. Abrupt keratinization/keratin pearls may be seen (B). Other variant histologic features of head and neck NUT carcinoma include basaloid (C), differentiated squamous/squamoid (D-G), clear cell change (D), glandular/mucocytes differentiation (E-F), prominent exophytic papillary architecture (G), and rhabdoid features (H). The basaloid morphology (C) shows prominent peripheral palisading (insert). The tumor cells have hyperchromatic nuclei, high nuclear/cytoplasmic ratio, and scanty cytoplasm. The differentiated squamous/squamoid areas (D/E) are composed of relatively bland tumor cells showing prominent squamous differentiation, sometimes with clear cell changes (D) or exophytic papillary architecture (G and G insert). (E/F) A parotid NUT carcinoma shows exclusive differentiated squamous/squamoid morphology admixed with scattered mucocytes (arrowheads and insert) and extracellular mucin on H&E and mucicarmine stain (M). (H) A thyroid NUT carcinoma shows prominent rhabdoid/plasmacytoid morphology with abundant cytoplasm and eccentrically located nuclei.

Figure 2.. Immunohistochemistry profile of head and neck NUT carcinoma.

(A-F) A NUT carcinoma in the neck region with BRD4::NUTM1 fusion is initially diagnosed as carcinoma with neuroendocrine features. The tumor is positive for synaptophysin (B), chromogranin focally (C), INSM1 (D), and TTF-1 (E). The tumor cells show moderate to strong speckled nuclear immunopositivity for NUT (F). (G-I) A sinonasal NUT carcinoma with BRD4::NUTM1 fusion shows differentiated squamous and papillary features. The tumor is diffusely positive for p40 (H). NUT immunohistochemistry demonstrates weak speckled nuclear positivity.