PMC8026310_01
(a) Initial diagnostic CT scan shows an ileocecal mass of approx. 7 cm of diameter, with no clear radiologic signs of bowel distention or obstruction. (b) Initial PET/CT scan shows a 7 cm FDG-avid paramediastinal lesion in stretch contact with the aortic arch. (c) Initial PET/CT scan shows a metastatic lesion at the hepatic segment V. (d) Control PET/CT scan after 2 cycles of carboplatin/etoposide shows complete resolution of the hepatic lesions. (e) Control CT scan after 2 cycles of carboplatin/etoposide and 3 cycles of carboplatin/paclitaxel shows tumor progression (left image) of the paramediastinal mass, further compromising the aortic arch.
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fig1
At the abdominal level, it showed a hypervascular lesion of neoplastic appearance of approximately 7 cm in the ileocecal junction, along with adenopathies in the ileocolic, subcarinal, mediastinal, and pulmonary hilum territories (Figure 1(a)). The latter showed an abnormal FDG-avid activity of the left parahilar mass (6 cm x 6 cm x 4 cm) with soft tissue density, well-defined margins, and in stretch contact with the aortic arch (SUV max 24.18); newly evidenced centimetric lesions in hepatic segments IV, V, and VI (with SUVs of 6.06, 8.15, and 4.66, respectively) (Figures 1(b) and 1(c)); and para-aortic mediastinal lymphadenopathies with an SUV max of up to 16.8 for the largest one. Radiologic control after 2 cycles showed resolution of the hepatic lesions (Figure 1(d)) and no recurrence at the colonic level; however, it showed tumor progression at the pulmonary mass. SQ-NSCLC, without neglecting that of the digestive MiNEN, the ChT regimen was switched to carboplatin+paclitaxel, showing stability of the SQ-NSCLC after 3 cycles, but later progression with increasing size and metabolic activity at the lung mass (Figure 1(e)). Second-line monotherapy treatment with pembrolizumab directed to the SQ-NSCLC was initiated (PD-L1 greater or equal to 1%) with immune-mediated toxicities (e.g., G3 thyroiditis and cytopenias) developing, forcing to completely stop the immunotherapy treatment after only one cycle and progress to a third-line chemotherapy scheme with carboplatin+gemcitabine.
(a) Ileocolic high-grade MiNEN showing both the adenocarcinoma (mucinous glands at the bottom left) and neuroendocrine carcinoma (numerous solid irregular cords and nests, without lumen or mucin production) components. (b) High-power field of the neuroendocrine carcinoma: irregular nuclei with hyperchromasia, high nuclear/cytoplasmic ratio, no prominent nucleoli, and abundant mitotic figures. (c) Ki-67 immunostain shows a very high proliferating index (about 80%) in a NEC metastatic lymph node. (d) Strong and diffuse synaptophysin positivity in a lymph node sample, correspondent with NEC.
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Histopathological results of the resected colonic mass were compatible with a mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN): moderately differentiated colorectal adenocarcinoma+poorly differentiated small cell neuroendocrine carcinoma (NEC) (the neuroendocrine component (NE) comprised 30-35% of the total, with high-grade characteristics and intense positivity for synaptophysin, CD56, and chromogranin A) at the ileocolic level (Figures 2(a)-2(d)), which infiltrated the muscular layer and perivisceral fat focally, also extending to the muscular layer of the appendix and its mucosa but with no serosa perforation.