Neuroendocrine tumors of the thymus: the oncologist point of view

Thymic malignancies represent a heterogeneous group of rare thoracic cancers, which are classified according to the World Health Organization (WHO) histopathologic classification that distinguishes thymomas from thymic carcinomas and neuroendocrine tumors (1,2); neuroendocrine thymic tumors (NETTs) exhibit the same histological spectrum as in other anatomical locations, although with different frequencies. NETTs represent around 2% of all neuroendocrine tumors, and about 5% of all thymic malignancies (3). NETTs are characterized by neuroendocrine morphology and differentiation, and comprise carcinoid tumors, which are classified as well-differentiated neuro-endocrine tumors, large cell neuroendocrine carcinoma (LCNEC) and small cell cancer (SCC), which are high-grade, poorly-differentiated tumors (1). Carcinoids are further subdivided into typical (low-grade) and atypical (intermediate grade) carcinoids, based on mitotic count and presence of necrosis (1,2). Meanwhile, the European Neuroendocrine Tumors Society (ENETS) developed a grading system of three groups: G1 (fewer than 2 mitoses per 10 HPFs and/or Ki-67 index of 2% or less); G2 (2 to 20 mitoses per 10 HPFs and/or Ki-67 index of 3% to 20%); and G3 (more than 20 mitoses per 10 HPFs and Ki-67 index higher than 20%) (4). The ENETS grading was validated as a prognostic variable in NETTs in a series of 28 patients (5). Ultimately, primary location, beyond histology and grade, matters as an independent prognostic variable, as thymic NETTs are more aggressive than primary pulmonary carcinoids, with more frequent invasion and metastatic recurrences (4,6): carcinoid/low- to intermediate grade NETTs present with a 5-year survival of 50–70% and a 10-year survival of only 10–30% (vs. 90% and 85% for lung carcinoids); high-grade NETTs have a 5-year survival of nearly 0% (7-14). Recurrence rates after initial treatment is high, ranging from 40% to 70% at 5-year for non-SCC NETTs (13)