Paraneoplastic Gastrointestinal Motor Dysfunction: Clinical and Laboratory Characteristics

Abstract

The diagnosis of paraneoplastic GI motor dysfunction requires a high index of clinical suspicion. A panel of serological tests for paraneoplastic autoantibodies, scintigraphic gastric emptying, and esophageal manometry are useful as first-line screening tests. Seropositivity for ANNA-1, PCA-1, or N-type calcium channel-binding antibodies should prompt further evaluation for an underlying malignancy even when routine imaging studies are negative.

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

“…Seropositivity for anti-neuronal autoantibodies (ANAs) is a diagnostic marker of occult malignancy in the presentation of paraneoplastic CIPO, which usually precedes the diagnosis of a tumour Lucchinetti et al 1998;Lee et al 2001). To confirm the absence of such autoantibodies in our cohort of patients, all those with SID were screened for ANAs.…”

“…These include lymphocytic and plasmacellular infiltration, enteroglial cell proliferation and neuronal degeneration and loss, progressing to aganglionosis in the most severe cases (Schuffler et al 1983;Chinn et al 1988;Schobinger-Clement et al 1999;Lee et al 2001); (2) patients with SCLC and GI dysmotility often have co-existing neurological disorders including peripheral neuropathies, cerebellar degeneration and limbic encephalitis, which are thought to have an autoimmune origin (Chinn et al 1988;Lucchinetti et al 1998;Vernino et al 1998); (3) several potentially pathogenic 'paraneoplastic autoantibodies' reactive against antigens expressed by tumour cells and neurons have been identified, which in combination with neurological disorders, including GI symptoms, strongly suggest the presence of an underlying malignancy (Lucchinetti et al 1998;Pande et al 1999;Schobinger-Clement et al 1999;Lee et al 2001). …”

“…Most common in this context are type 1 anti-neuronal nuclear autoantibodies (ANNA-1, also known as anti-Hu), which recognise neuron-specific RNA binding proteins expressed by central and peripheral neurons, including enteric neurons, and SCLC tumour cells (Bell et al 1976;Lucchinetti et al 1998;Lee et al 2001). Antibodies targeting cell-surface channels have been detected in smaller numbers of cases, including anti-N-type VGCCs with SCLC, retroperitoneal Bcell lymphoma, ovarian and breast carcinoma Dhamija et al 2008), anti-P/Q-type VGCCs with SCLC (Pardi et al 2002), anti-VGKCs with thymoma (Viallard et al 2005) and anti-ganglionic α3 nAChR antibodies with SCLC, thymoma, bladder and rectal carcinoma (Vernino et al 2000).…”

Enteric Autoantibodies and Gut Motility Disorders

“…Lee et al published a series of 12 cases of which esophageal dysmotility was seen in 4 patients with small cell lung cancer. Two patients had pseudoachalasia, one had a non specific esophageal motility disorder and one patient had abnormal manometry but no esophageal symptoms [21].…”

“…In vitro, its Cdr antigen, a prominent cytoplasmic component of large neurons in the central and autonomic/ enteric nervous systems [19], has been shown to promote neuronal apoptosis and degeneration by inhibiting c-myc transcriptional activity [20]. Paraneoplastic gastrointestinal dysmotility has been documented in a minority of PCA-1 seropositive patients (with and without cerebellar ataxia) in association with gynecological or breast carcinoma [21].…”