Epidemiology of Undifferentiated Carcinomas

Undifferentiated carcinomas are rare cancers that lack differentiation, such that they cannot be classified into any conventional histological subtype. These cancers are uniquely codified and are contrasted to carcinomas with an ascertained histology that are grade classified as poorly differentiated, undifferentiated, or anaplastic. Given their rarity, there are no standardized overviews of undifferentiated carcinomas in the literature, and it is unknown if their classification indicates a unique prognosis profile. In this study, we summarize the clinicodemographic and mortality outcomes of undifferentiated carcinomas in twelve primary sites and for unknown primaries, comprising 92.8% of all undifferentiated carcinomas diagnosed from 1975-2017 in the Surveillance, Epidemiology, and End Results Program (SEER). Incidence has decreased to 4 per 1 million cancer diagnoses since 1980. Relative to the most common undifferentiated cancers with a defined histology, undifferentiated carcinomas have overall worse prognosis, except in nasopharyngeal and salivary gland cancers (hazard ratio (HR) 0.7-1.3). After correction for age, sex, race, detection stage, and treatment (surgery, chemotherapy, and radiotherapy), the mortality HR averages 1.3-1.4 for these cancers relative to histologically ascertainable undifferentiated cancers. However, there is a wide variance depending on site, signifying that survival outcomes for undifferentiated carcinomas depend on factors related to site tumor biology.