Rectal neuroendocrine carcinoma: case report of a rare entity and perspective review of promising agents

Abstract

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of tumours, which can be classified into neuroendocrine tumours (NETs), neuroendocrine carcinomas (NECs) and mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs). To date, there is no consensus regarding the optimal therapy, which usually depends on the primary location and classification, according to morphological features of differentiation and proliferation rates. Nevertheless, multidisciplinary strategies combining medical treatments and locoregional strategies have yielded better efficacy results. Here, we report the case of a patient diagnosed with a nonfunctional rectal NECs with metastatic widespread to pelvic lymph nodes and bilateral lung metastases. The patient received three cycles of platinum-etoposide, concomitantly with palliative radiotherapy. Although CT scan after three cycles showed a significant partial response, there was an early fatal progression only 3 months after having stopped systemic therapy. As formerly described in the literature, this case highlights the aggressive behaviour of NECs, rare tumours that often present in advanced stages at diagnosis. Lately, new insights into the molecular biology of NECs have unveiled the possibility of using novel drugs, such as targeted agents or immunotherapy, in molecularly selected subgroups of patients. In this review, we discuss the current management of this rare entity and provide an overview of the most relevant molecular findings, whilst illustrating the potential value that prescreening panels can offer, searching for actionable targets (MSI/dMMR, PD-L1, BRAF^v600E) to guide therapy with promising agents that could fill a void in this disease.

Keywords: chemotherapy; epigenetic; gastro-entero-pancreatic neuroendocrine neoplasms; immunotherapy; molecular alterations; neuroendocrine carcinomas; radiotherapy; targeted agents.

Figure 1

Diagnostic algorithm for rectal neoplasms. The differential diagnosis of a rectal tumour includes considering epithelial and neuroendocrine neoplasms. Epithelial tumours comprise adenocarcinomas (ADCs), squamous carcinomas (SCCs) or mixed adeno-squamous carcinomas (ADSCCs). Neuroendocrine neoplasms (NENs) are currently subdivided in three different categories, comprising neuroendocrine tumours (NETs), neuroendocrine carcinomas (NECs) and mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs). NETs include G1, G2 and G3 tumours, depending on their proliferation rates (mitosis rate and Ki-67 index), grade (low, intermediate and high) and morphology differentiation (well or poorly) characteristics. NEC tumours can morphologically include large cell (LCNEC) and small cell carcinomas (SCNEC). MiNEN tumours display variable grades of all the possible histopathological characteristics.

Figure 2

Pathology findings of a rectal NEC. Rectal NEC pathological findings showed undifferentiated small cells with haematoxylin and eosin staining (A). Immunohistochemistry staining was positive for epithelial markers, such as cytokeratin CAM 5.2 (B), and neuroendocrine markers as synaptophysin (C). In this case, Ki-67 index >80% confirmed a high-grade poorly differentiated SCNEC subtype (D).

Figure 3

Pelvic MRI and dosimetry volumes for planned radiotherapy treatment. (A). Pelvic MRI sagittal view shows the primary tumour, a 9-cm rectal mass (red arrow) infiltrating the posterior vaginal wall. (B). In the radiotherapy dosimetric view, 95% of the doses covering the involved locoregional lymph nodes are highlighted in red. (C). Pelvic CT image 2 months after radiotherapy treatment, showing a local partial response within the primary rectal tumour (red arrow).