Long-term control with chemoradiation of initially metastatic mixed adenoneuroendocrine carcinoma of the rectum: a case report

Abstract

Background: Mixed adenoneuroendocrine carcinomas are highly malignant tumors with both adenocarcinomatous and neuroendocrine components. They can originate in any organ but are more common in the rectum. Due to their rarity, current treatment recommendations for mixed adenoneuroendocrine carcinoma are based on limited data and follow general guidelines for the management of adenocarcinomas and neuroendocrine neoplasms. Uncertainty regarding the efficacy of the available local and systemic treatment strategies is a compounding issue. Even those patients with locally limited disease have a relatively short life expectancy. In this report, we describe a case of deep rectal mixed adenoneuroendocrine carcinoma with long survival after chemoradiation.

Case presentation: A 48-year-old Caucasian woman was diagnosed with a grade 3 rectal adenocarcinoma combined with a poorly differentiated large cell neuroendocrine carcinoma component and synchronous metastases (cT3cN1cM1) in both lobes of the liver in 2012. She received concomitant chemoradiotherapy followed by four additional cycles of cisplatin plus irinotecan. Initial treatment induced complete remission of the rectal tumor and liver metastases. Consequently, it was not necessary to surgically resect the primary tumor or any of the metastases. Three months after the end of treatment, one metastasis in the first segment of the liver showed regrowth, and stereotactic body radiotherapy of the metastasis and chemotherapy resulted in a clinical complete response. The patient has been recurrence-free for more than 5 years.

Conclusions: Extended long-term control of a poorly differentiated metastatic (stage IV) mixed adenoneuroendocrine carcinoma is rare. The multimodal first- and second-line regimens of radiotherapy and chemotherapy described in this case report represent a new therapeutic approach. Encouraged by the results in this case, we compiled a review of the literature on mixed adenoneuroendocrine carcinoma.

Keywords: Chemoradiation; MANEC; Rectum; SBRT.

Fig. 1

Deep seated, wall-penetrating rectal carcinoma (a, arrow, magnetic resonance imaging (MRI) with multiple bilateral liver metastases (b, arrow, computed tomography (CT) before treatment in April 2012. The patient reached partial remission after two cycles of cisplatin/irinotecan (c, residual metastasis in segment I with an arrow, CT) in June 2012 and complete remission after six cycles (d, arrow: no evidence of macroscopic metastasis in segment I, CT) in October 2012. View of segment I showing post-treatment recurrence in February 2013 (e, arrow, MRI) and status 5 years after stereotactic body radiotherapy and chemotherapy in February 2018 (f, no evidence of vital tumor: arrow, MRI)

Fig. 2

Findings of histological examination of the rectal tumor specimen. a Tumor with a small glandular component (hematoxylin and eosin stain (H&E stain)), adenocarcinoma (thin arrow), and a dominant neuroendocrine component (thick arrow). The neoplasm was CD56-positive (b) and had a high Ki67 proliferation index > 80% (c). An identical histologic pattern was seen in the liver metastasis (hematoxylin and eosin stain (H&E stain), d)

Fig. 3

Neuron-specific enolase (NSE) tests showed peak levels before treatment and at the time of metastasis recurrence. Low levels were reached after first chemoradiation (CRT) at the time of complete response (CR) and after second chemoradiation of the liver metastasis