Paraneoplastic neurological syndromes in patients with carcinoid

Tschernatsch, Marlene; Dierkes, Christian; Gerriets, Tibo; Hosch, J.; Stolz, Erwin; Kaps, Manfred; Krasenbrink, I.; Claus, D.; Blaes, Franz

doi:10.1111/j.1468-1331.2008.02328.x

Cited by 22 publications

(17 citation statements)

References 27 publications

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“…Few studies have correlated paraneoplastic syndrome to patients with midgut carcinoids and lung carcinoids as well [15], [25]. Our finding that Ma2 was consistently detected in primary SI-NET specimens and in a variety of metastasis made it interesting to investigate whether antibodies against Ma2 are present in the blood of SI-NET patients.…”

Section: Discussionmentioning

confidence: 87%

Paraneoplastic Antigen Ma2 Autoantibodies as Specific Blood Biomarkers for Detection of Early Recurrence of Small Intestine Neuroendocrine Tumors

et al. 2010

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BackgroundSmall intestine neuroendocrine tumors (SI-NETs) belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2) as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs.Methodology/Principal FindingsA novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC), to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples.ConclusionHere we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA) for the risk of recurrence after radical operation of these tumors.

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Section: Discussionmentioning

confidence: 87%

Paraneoplastic Antigen Ma2 Autoantibodies as Specific Blood Biomarkers for Detection of Early Recurrence of Small Intestine Neuroendocrine Tumors

et al. 2010

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“…Carcinoid-related paraneoplastic neurological syndromes have occasionally been described in isolated case reports. 9 These include Lambert Eaton myasthenic syndrome, cerebellar degeneration, limbic encephalitis, sensory neuropathy, autonomic dysfunction, and myelopathy with brain stem encephalitis. 9,10 Our patient was diagnosed with NMO-SD, and was found to have gastric carcinoid tumor.…”

Section: Discussionmentioning

confidence: 99%

“…9 These include Lambert Eaton myasthenic syndrome, cerebellar degeneration, limbic encephalitis, sensory neuropathy, autonomic dysfunction, and myelopathy with brain stem encephalitis. 9,10 Our patient was diagnosed with NMO-SD, and was found to have gastric carcinoid tumor. While this occurrence could be incidental, it may represent a possible paraneoplastic effect of the cancer.…”

Section: Discussionmentioning

confidence: 99%

“…5 Carcinoids are neuroendocrine tumors that originate from the enterochromaffin cells of the gastrointestinal tract (74%), bronchial system (25%), and other less frequent organs. 8,9 These tumors cause symptoms by local mass effect, fibrosis, metastasis, or secretion of bioactive substances, including various hormones, cytokines and growth factors. As a result, patients may present with a carcinoid syndrome, causing cutaneous flushing, diarrhea, abdominal pain, cardiopulmonary effects, and various endocrinological syndromes.…”

Section: Discussionmentioning

confidence: 99%

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Paraneoplastic neuromyelitis optica spectrum disorder associated with stomach carcinoid tumor

Al-Harbi

Al-Sarawi

Binfalah³

et al. 2014

Hematology/Oncology and Stem Cell Therapy

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Neuromyelitis optica (NMO), or Devic's syndrome, is an autoimmune central nervous system demyelinating disorder primarily affecting the spinal cord and the optic nerves. It is characterized by the presence of NMO antibodies, alongside clinical and radiological findings. NMO and NMO-spectrum disorders (NMO-SD) have been reported in autoimmune disorders, and are infrequently described as a paraneoplastic syndrome with cancers of lung, breast, and carcinoid tumors of the thyroid. We report a patient who presented with severe vomiting, blurring of vision, vertigo, diplopia, left hemiparesis and hemisensory loss and ataxia. She was found to have a longitudinally-extensive demyelinating lesion extending from the medulla to the upper cervical spinal cord on MRI. Her gastric endoscopy revealed carcinoid tumor of the stomach, and classic paraneoplastic antibodies in the serum were negative. She had extremely high serum gastrin level and high titer of NMO IgG autoantibody. The patient made an excellent recovery with tumor resection and immunotherapy, with both clinical and radiological improvement. On rare instances, NMO or NMO-SD may present as a paraneoplastic neurological syndrome associated with carcinoid tumor of the stomach.

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“…The neuronal auto-antibodies have diagnostic and possibly pathogenic roles [47]. Most of these clinically defined PNSs in adults are associated with lung cancer of neuroendocrine origins (i.e., SCLC and carcinoid tumors [48]). The overlap of syndromes and the overlap of highly specific autoantibodies directed against onconeuronal antigens strongly support an autoimmune pathogenesis.…”

Section: Paraneoplastic Neurological Syndromesmentioning

confidence: 99%

Lung cancer-induced paraneoplastic syndromes

Yeung

Habra

Thosani

2011

Current Opinion in Pulmonary Medicine

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Paraneoplastic neurological syndromes in patients with carcinoid

Abstract: This study demonstrates that carcinoids can also be associated with classical antineuronal antibody-associated PNS.

Cited by 22 publications

References 27 publications

Paraneoplastic Antigen Ma2 Autoantibodies as Specific Blood Biomarkers for Detection of Early Recurrence of Small Intestine Neuroendocrine Tumors

Paraneoplastic Antigen Ma2 Autoantibodies as Specific Blood Biomarkers for Detection of Early Recurrence of Small Intestine Neuroendocrine Tumors

Paraneoplastic neuromyelitis optica spectrum disorder associated with stomach carcinoid tumor

Lung cancer-induced paraneoplastic syndromes

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