Club (Clara) cells in human prostate: A survival guide for conventional histologists/histopathologists

Broncho-pulmonary club (Clara) cells (Cc) play a protective role in the lung due to the secretion of the CC16 protein. Their normal and pathological morphology and function have long been well characterized by histologists and histopathologists. In recent years, human prostatic Cc have become the focus of intensified research. A three-dimensional cellular atlas of normal and pathologic human and experimental prostates has been developed using the most advanced research methods (single-cell RNA sequencing, RNA in situ). This review provides a comprehensive synthesis of current knowledge regarding prostatic Cc and Cc-phenotype conversion across prostate disease. Prostatic Cc possesses anti-inflammatory, regenerative, and immunoregulatory potential, and exhibits features like those of their pulmonary counterparts. Their ontogenesis, localization across different prostatic zones, gene expression profile, and histo-functional morphology are discussed and illustrated immunohistochemically using original material from the authors. Pathophysiological and morphogenetic considerations are also presented.