: NUT midline carcinoma (NMC) is a rare and aggressive subtype of squamous carcinoma that typically arises from midline supradiaphragmatic structures, frequently from the head and neck area. NMC is genetically driven by a chromosomal rearrangement involving the NUT gene, which forms oncoproteins considered major pathogenic drivers of cellular transformation. Diagnosis of NMC has been made remarkably easier with the availability of a commercial antibody against NUT, and can be established through positive nuclear immunohistochemical staining. Although NMC remains an underrecognized malignancy, in recent years there has appeared to be increasing awareness of disease and frequency of diagnosis in adults. To date, a standard treatment for head and neck NMC has not been established and a multimodal approach with systemic chemotherapy, surgery and radiation therapy is currently adopted in clinical practice. Recently, BET inhibitors and histone deacetylase inhibitors have emerged as two promising classes of targeted agents, currently investigated in clinical trials for adults with head and neck NMC. At the same time, combination approaches and novel targeted agents, such as next-generation BET inhibitors and CDK9 inhibitors, have shown preclinical activity. The present review explores the clinical pathological characteristics of NMC of the head and neck and presents the current state of the art on diagnosis, prognosis, and treatment of this rare but lethal disease.

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PurposeEvolving therapies have improved the prognoses of patients with breast cancer; and currently, the number of long-term survivors is continuously increasing. However, these patients are at increased risk of developing a second cancer. Thus, late side effects are becoming an important issue. In this study, we aimed to investigate whether patient and tumor characteristics, and treatment type correlate with secondary tumor risk.MethodsThis case-control study included 305 patients with a diagnosed second malignancy after almost 6 months after the diagnosis of primary breast cancer and 1,525 controls (ratio 1:5 of cases to controls) from a population-based cohort of 6,325 women. The control patients were randomly selected from the cohort and matched to the cases according to age at diagnosis, calendar period of diagnosis, disease stage, and time of follow-up.ResultsBRCA1 or BRCA2 mutation, human epidermal growth factor receptor 2 (HER2)+ status, chemotherapy, and radiotherapy were related to increased risk of developing a second cancer, whereas hormonotherapy showed a protective effect. Chemotherapy, radiotherapy, and estrogenic receptor level <10% increased the risk of controlateral breast cancer. HER2+ status increased the risk of digestive system and thyroid tumors, while BRCA1 or BRCA2 mutation increased the risk of cancer in the genital system.ConclusionBreast cancer survivors are exposed to an excess of risk of developing a second primary cancer. The development of excess of malignancies may be related either to patient and tumor characteristics, such as BRCA1 or BRCA2 mutation and HER2+ status, or to treatments factors.

Objective Head and neck cancer survivors have increased risk of developing second primary tumors compared to overall population. Because second primary represents a major cause of morbidity and mortality in this population, early detection is fundamental. Materials and Methods In this 10‐year single‐institution study, we investigated the following: incidence, clinical‐pathological risk factors, and survival of patients with second primary tumor. We included all patients with diagnosis of squamous cell carcinoma of the head and neck seen at the Modena University Hospital from 2008 to 2018. Results Among 1,177 patients included, 222 (18.9%) developed second primary tumor; its survival probability at 5 years was 40.6%. Alcohol consumption (p = .0055) and index cancer in oropharynx (p = .0029), supraglottic larynx (p = .0000), glottic larynx (p = .0222) were associated with higher risk of second primary. The most common second primary sites were head and neck district and lung (70, 31.5%, and 67, 30.2%, respectively). Head and neck district were more common in oral cavity (18, 43%) and oropharynx index cancer (20, 31%); lung second primary in hypopharynx (4, 40%), supraglottic larynx (17, 43%), and glottic larynx index cancer (23, 35%). Conclusion Head and neck cancer survivors developing a second primary tumor have dismal prognosis. Tailored surveillance is recommended.

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