Overview of the pathology of thymic neuroendocrine tumors

Luca Bertero, Jasna Metovic, Federico Vittone, Paola Cassoni, Mauro Papotti


In the last edition of WHO classification of tumors of the lung, pleura, thymus and heart, lung and thymic neuroendocrine tumors (NETs) have been incorporated into a separate new category of neuroendocrine neoplasms. Similarly, they were classified into low-grade typical carcinoids (TCs), intermediate-grade atypical carcinoids (ACs) and high-grade poorly differentiated neuroendocrine carcinomas (HGNECs) of the large and small cell types (LCNEC and SCLC), but contrary to lung, most thymic carcinoids are atypical. Different histotypes are distinguished based on morphological features; Ki67, however, can help to differentiate low and intermediate grade tumors from high grade neoplasms, especially on small biopsies. Although available data are limited, genomic profiles of thymic NETs seem similar to corresponding NETs of other locations, but MEN1 alterations are more frequent in thymic carcinoids. RB1, TP53 and PTEN mutations are frequent in HGNEC, as expected. Predictive biomarkers have not been extensively investigated in thymic NETs, but reported evidence suggests possible efficacy of targeted therapies against receptor tyrosine kinases and mTOR pathway. A better integration of lung, thymic, gastrointestinal and pancreatic NETs classifications, in terms of terminology and histological categories, is warranted.