Coexisting tubular adenoma with a neuroendocrine carcinoma of colon allowing early surgical intervention and implicating a shared stem cell origin

Abstract

High-grade colonic neuroendocrine carcinomas (NECs) are uncommon but extremely aggressive. Their co-existence with tubular adenoma (TA) has rarely been reported. We present a 68-year-old man who was found on routine colonoscopy to have multiple colorectal TAs and an ulcerated lesion in the ascending colon. Microscopically, a poorly-differentiated invasive carcinoma juxtaposed with a TA was identified. Differential diagnosis included a poorly-differentiated adenocarcinoma, medullary carcinoma, high-grade NEC and lymphoma. The immunohistochemical profile showed positive staining for keratins, synaptophysin and chromogranin but negative for LCA, CDX2, CK7, CK20, TTF-1 and PSA, supporting the NEC diagnosis. Upon subsequent laparoscopic right hemicolectomy, the tumor was identified as a 3.0 cm umbilicated and ulcerated mass with an adjacent TA. Both TA and NEC showed positive staining for β-catenin indicating a shared colonic origin. The mitotic counts (77/10 high power fields) and a high proliferation rate (75% by Ki-67) corroborated a high-grade stratification. Mutational analysis indicated a wild-type BRAF and KRAS with mismatch repair proficiency. The AJCC (7th edition) pathologic stage is pT3, pN0, pMx. The patient received adjuvant chemotherapy with cisplatin/etoposides for three cycles and will be followed up for a year to detect recurrence. In conclusion, the co-existence of TA with high grade-NEC in our case allowed early identification and intervention of the otherwise asymptomatic but aggressive tumor. In addition, the finding of a highgrade NEC within a large TA in this case suggests a link between the two lesions and could represent a shared stem cell origin.