Paraneoplastic brainstem encephalitis in a patient with exceptionally long course of a metastasized neuroendocrine rectum neoplasm

Abstract

Background: Paraneoplastic neurological syndromes (PNS) have frequently been described in patients with lung or breast cancer. However, some reports also described a correlation to carcinoid tumors, probably triggered via the excessive release of hormones.

Case presentation: We report the case of a 40-year-old woman that was diagnosed with a neuroendocrine neoplasm (NEN) of the rectum and multiple synchronous liver metastases ten years ago. She initially responded well to transarterial chemoembolization (TACE), resulting in prolonged disease stabilization. However, ten years after initial diagnosis the patient developed unspecific neurological symptoms that could not be classified by standard neurological diagnostic work-up. Special laboratory analysis revealed a high titer of anti-Ri (ANNA-2), a well-characterized antibody that is associated with paraneoplastic neurologic syndromes. The patient's symptoms improved markedly after a 5-day-course of high-dose glucocorticoid therapy. To our knowledge, this is the first report of a Ri-positive PNS in a patient with hormone-negative rectal NEN.

Conclusion: PNS can complicate the patient's clinical course, response to treatment, impact prognosis and even be interpreted as metastatic spread. However, owing to their rarity, the knowledge of these syndromes is very helpful in order to be able to provide evidence-based diagnostic and therapeutic approaches.

Figure 1

Immunohistochemical characteristics of primary and liver metastases. The initial liver biopsy shows the characteristic cell formation pattern of neuroendocrine tumor cells of solid nests of regular cells with broad eosinophilic cytoplasm and small inconspicuous nuclei. Mitotic cells are absent (a). The proliferation rate is very low, Ki67 marks less than 1% of the tumor cell nuclei (b). Furthermore, the strong immunohistochemical reaction for chromogranin A and synaptophysin is a solid proof for neuroendocrine differentiation (c and d). Likewise the rectum polyp exhibits the same histological (e) and immunohistochemical features including low proliferation (f) and marked reaction for the neuroendocrine markers chromogranin A and synaptophysin (g and h).

Figure 2

Validation of Ri-antibodies via IIFT and immunoblot assay. Characteristic granular fluorescence staining of all neurone nuclei of the grey matter of primate cerebellum (upper left). (SM = stratum moleculare; SG = stratum granulosum; PZ = Purkinje cells). Peripheral neurons of the plexus myentericus (PM) revealed no binding of Ri-antibodies (upper right). High positive reaction with the recombinant Ri-antigen (Nova1) in Lineblot (lower panel) confirmed the IIFT result. No reactivity was observed for anti-Hu, anti-Yo, anti-Ma2/Ta, anti-CV2 and anti-amphiphysin.