Supplementary Material for: Mixed neuroendocrine-non-neuroendocrine neoplasms of the rectum: a case report

Introduction
Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms (MiNEN) represent roughly 1-2% of all colorectal malignancies. Given the rareness and heterogeneity of these mixed tumors, recognition and accurate diagnosis remain a challenge. In the absence of established guidelines, they are treated according to the standard of care for pure neuroendocrine carcinomas or adenocarcinomas from similar sites of origin.
Case presentation
We herein report a case of a rectal MiNEN in a 55-year-old male. He underwent colonoscopy for rectal bleeding and mucus emission, which revealed a vegetating lesion located approximately 8 cm from the anal verge, corresponding to a moderately differentiated low-grade adenocarcinoma of the rectum. Computed Tomography scan and Magnetic Resonance Imaging uncovered the presence of lung, lymph node and subcutaneous implants metastases. The biopsy of the cutaneous implant showed Neuroendocrine Carcinoma Ki-67 90%. The patient underwent systemic Chemotherapy.
Conclusion
High grade MiNEN tumors are the most commonly encountered in clinical practice and have an aggressive biological behavior. Little is known about the genetic drivers of this neoplasm and its pathogenesis remains controversial. Clinical and pathological awareness of this rare entity is a key step to design future targeted therapies and improve treatment options.
The aim of this case report is to further our understanding regarding the clinical presentation, radiological features, pathology, management and prognosis of MiNEN.