Paraneoplastic Syndrome

Paraneoplastic syndromes encompass a heterogeneous group of conditions characterized by a wide range of signs and symptoms not directly attributable to tumor invasion or compression. Patients with paraneoplastic syndromes are usually challenging because of various aspecific signs (e.g. fever, nocturnal sweat, anorexia and cachexia) as well as the occurrence of complex manifestations involving various organs /systems, such as the skin (e.g., achantosis nigricans), endocrinological (multiple autoimmune endocrinopathy), gastrointestinal (severe dysmotility), hematological (polyglobulia) neurological (encephalomyelitis, limbic encephalitis, subacute cerebellar degeneration), and connective tissue (i.e. an array of rheumatological disorders) (Pelosof and Gerber, 2010). Current knowledge indicates that the best defined paraneoplastic syndromes occur as a result of two major pathophysiological mechanisms: (1) the cellular secretion of bioactive peptides/hormones by the tumor; (2) the immune cross-reactivity between tumor and normal host tissues. Notably, most paraneoplastic syndromes may herald cancer diagnosis which is delayed of months since the onset of symptoms/signs (Sillevis Smitt et al., 2002; Lucchinetti et al., 1998). For this reason, their early recognition is of key importance in order to guide to the detection of an otherwise clinically occult tumor at an early and, hopefully, treatable stage. Overall, about 8% of any (either solid or hematological) cancer may develop a paraneoplastic syndrome. However, no exact data exist on the epidemiology of these conditions (Pelosof and Gerber, 2010) and their incidence is significantly higher in selected neoplasms, such as small cell lung cancer (SCLC) (Kanaji et al., 2014), renal cell carcinoma (Gold et al., 1996), hepatocellular carcinoma (Chang et al., 2013), leukemia/lymphoma (Graus et al., 2014), breast cancer (Fanous and Dillon, 2015), and ovarian cancer (Ashour et al., 1997) (Table 1).