Neurological Paraneoplastic Syndromes in Lung Cancer Patients

Stefens-Stawna, Patrycja; Piorunek, Tomasz; Gabryel-Batura, H; Kozubski, Wojciech; Michalak, Sławomir

doi:10.1007/978-94-007-4549-0_40

Cited by 12 publications

(6 citation statements)

References 26 publications

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“…Laboratory analyzes may reveal the presence of onconeuronal antibodies. They are detected by means of an indirect immunofluorescence and confirmatory Western or line blot (Monstad et al 2008 ; Stefens-Stawna et al 2013 ). The most common type of antibody found in PCD is anti-cdr2 (cerebellar degeneration protein-2 antibody) (also known as anti-Yo) (Anderson et al 1988 ; Peterson et al 1992 ).…”

Section: Diagnosismentioning

confidence: 99%

Paraneoplastic neurological syndromes associated with ovarian tumors

Zaborowski

Spaczyński

Nowak‐Markwitz

et al. 2014

J Cancer Res Clin Oncol

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IntroductionParaneoplastic neurological syndromes (PNS) are neurologic deficits triggered by an underlying remote tumor. PNS can antedate clinical manifestation of ovarian malignancy and enable its diagnosis at an early stage. Interestingly, neoplasms associated with PNS are less advanced and metastasize less commonly than those without PNS. This suggests that PNS may be associated with a naturally occurring antitumor response.MethodsWe review the literature on the diagnosis, pathogenesis and management of PNS associated with ovarian tumors: paraneoplastic cerebellar degeneration (PCD) and anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. An approach to the diagnostic workup of underlying tumors is discussed.ResultsPCD can precede the manifestation of ovarian carcinoma. Anti-NMDAR encephalitis in young women appears often as a result of ovarian teratoma. Since ovarian tumors and nervous tissue share common antigens (e.g., cdr2, NMDAR), autoimmune etiology is a probable mechanism of these neurologic disorders. The concept of cross-presentation, however, seems insufficient to explain entirely the emergence of PNS. Early resection of ovarian tumors is a significant part of PNS management and improves the outcome.ConclusionsThe diagnosis of PNS potentially associated with ovarian tumor indicates a need for a thorough diagnostic procedure in search of the neoplasm. In some patients, explorative laparoscopy/laparotomy can be considered.

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Section: Diagnosismentioning

confidence: 99%

Paraneoplastic neurological syndromes associated with ovarian tumors

Zaborowski

Spaczyński

Nowak‐Markwitz

et al. 2014

J Cancer Res Clin Oncol

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“…One of the most common PNS, Hu-syndrome, may coexist with small cell lung carcinoma (SCLC). It often manifests as a subacute sensory neuronopathy associated with anti-Hu antigen antibodies detected in serum [8]. Ovarian cancer, in turn, may be complicated by subacute cerebellar degeneration that is often related to anti-Yo antibodies [9].…”

Section: Introductionmentioning

confidence: 99%

Granzyme B in peripheral blood mononuclear cells as a measure of cell-mediated immune response in paraneoplastic neurological syndromes and malignancy

Zaborowski

Stefens-Stawna

Osztynowicz

et al. 2020

Cancer Immunol Immunother

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Background Paraneoplastic neurological syndromes (PNS) may coexist with ovarian or lung cancers. Some tumors coexisting with PNS are smaller and have a better prognosis than tumors without PNS. PNS may constitute an opportunity to observe a natural immune antitumor response. We aimed to investigate a cytotoxic immune response by measuring granzyme B (GrB) in peripheral blood mononuclear cells (PBMC) in patients affected with ovarian or lung malignancy, with and without accompanying PNS. Methods We enrolled patients with: nonmalignant lesions (n = 21), ovarian cancer (n = 19), lung cancer (n = 57), and PNS (n = 30). PBMC were isolated by density gradient centrifugation with Ficoll–Paque. We evaluated the expression of GrB in PBMC lysates by ELISA and normalized to protein content as measured by the Lowry method. Results GrB levels in PBMC in the group with malignant tumors—median 1650 pg/mg protein (interquartile range 663–3260 pg/mg) and in patients with PNS—median 1890 pg/mg protein (range 1290–2640 pg/mg) was lower than in control group with nonmalignant lesions—median 5240 pg/mg protein (range 2160–7440 pg/mg), p = 0.0003 and p = 0.0038, respectively. The differences in GrB levels in PBMC between these groups were independent of epidemiological factors—age, sex, body mass index (BMI), and the number of immune cells, as confirmed by multiple regression analysis. Within the group of patients with malignancy and PNS, GrB levels in PBMC were elevated if onconeural antibodies were detected (2610; 2390–3700 pg/mg protein) as compared to patients without antibodies (1680; 970–1880 pg/mg protein, p = 0.035). GrB in PBMC was higher if the malignancy was diagnosed at the low (3060; 2120–5220 pg/mg protein) as compared to the high stage (1330; 348–2140, p = 0.00048). In patients with lung cancer, the expression of GrB in PBMC was lower (1430; 635–2660 pg/mg protein) than in the group with ovarian cancer (2580; 1730–3730, p = 0.02). Conclusion The cytotoxic response measured in peripheral blood by GrB in PBMC is impaired both in the course of malignancy and PNS. Levels of GrB in PBMC were higher if onconeural antibodies were detected. Tracking reactive immune responses, such as GrB in PBMC may have diagnostic and monitoring value in malignancy and PNS.

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“…This phenomenon may be related to the immune response mediated by cytotoxic T cells ( 8 ). Thus HuAb positivity represents an important marker in the early diagnosis of SCLC ( 9 ). However, positivity for HuAb may falsely flag patients who do not have SCLC ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

Neurological paraneoplastic syndrome caused by small cell lung cancer: a case report

Yan¹,

Wang²,

Wang³

et al. 2020

Transl Cancer Res TCR

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Paraneoplastic syndrome (PNS) is a term used to describe pathological changes in organ function among patients with malignancy that does not metastasize. Clinical manifestations affect nerve, digestive, hematopoietic, endocrine, bone, joint, and urinary function. Here we present the case of a 59-year-old male with PNS as the initial symptom of SCLC. PNS symptoms manifested as repeated attacks after surgery and chemotherapy. The severity of the patient’s symptoms has rarely been reported. The tumor type involved most frequently is small-cell lung cancer (SCLC). Symptoms caused by PNS typically manifest earlier than those caused by the tumor. Immunohistochemical staining was positive for Syn, CgA, CD56, TTF-1, CK (AE1/AE3), Hu antibodies, and Ki67 (90%). Treatment remains challenging. A case of severe Neurological PNS caused by early small cell carcinoma was reported. Although the patient accepted surgery and postoperative radiotherapy and chemotherapy, symptoms persist. In this case report, treatment with pregabalin and antidepressant agents improved the patient’s numbness. Currently, the patient has been followed-up for >3 years without any signs of recurrence and PNS. This case may inform future treatment of patients with PNS.

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Neurological Paraneoplastic Syndromes in Lung Cancer Patients

Cited by 12 publications

References 26 publications

Paraneoplastic neurological syndromes associated with ovarian tumors

Paraneoplastic neurological syndromes associated with ovarian tumors

Granzyme B in peripheral blood mononuclear cells as a measure of cell-mediated immune response in paraneoplastic neurological syndromes and malignancy

Neurological paraneoplastic syndrome caused by small cell lung cancer: a case report

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