Paraneoplastik Sendromların Mekanizması
Özet
Paraneoplastik sendromlar (PS), bir tümör veya metastazları ile doğrudan ilişkili olmayan, tümör yerleşim yerinden uzak ancak neoplazinin varlığına bağlı olarak ortaya çıkan klinik belirti ve bulgulardır. En sık küçük hücreli akciğer kanseri, meme, jinekolojik ve hematolojik malignitelerle ilişkilendirilen bu sendromlar, bazen kanser tanısından önce kendini göstererek gizli tümörlerin erken saptanmasına yardımcı olur. PS patogenezi temel olarak iki ana mekanizmaya dayanır: tümör tarafından salgılanan hormonlar, aktif peptitler, enzimler ve sitokinler ya da neoplastik ve normal dokular arasında çapraz reaksiyon gösteren antikorların tetiklediği otoimmün süreçler. Bu kapsamda paraneoplastik endokrin sendromlar (SIADH, hiperkalsemi, Cushing sendromu, hipoglisemi) metabolik düzensizliklere yol açarken; paraneoplastik nörolojik sendromlar (PNS) sinir sistemini etkileyen bağışıklık yanıtlarıyla ortaya çıkar. Ayrıca akantozis nigrikans, dermatomiyozit, Sweet sendromu gibi dermatolojik/romatolojik bozukluklar ile eozinofili ve trombositoz gibi hematolojik tablolar da sıkça gözlenir. Sonuç olarak, kanser evresinden bağımsız gelişebilen bu sendromların erken fark edilmesi, malignitelerin etkili tedavisi ile morbidite ve mortalitenin azaltılması açısından kritik öneme sahiptir.
Paraneoplastic syndromes (PS) are clinical signs and symptoms that are not directly related to a tumor or its metastases, occurring distant from the primary tumor site but triggered by the presence of the neoplasm. Most commonly associated with small cell lung cancer, breast, gynecological, and hematological malignancies, these syndromes can precede cancer diagnosis, thereby facilitating the early detection of occult tumors. The pathogenesis of PS fundamentally relies on two main mechanisms: the production of hormones, functional peptides, enzymes, and cytokines by tumor cells, or autoimmune processes mediated by antibodies cross-reacting between neoplastic and normal tissues. In this context, paraneoplastic endocrine syndromes (SIADH, hypercalcemia, Cushing syndrome, hypoglycemia) cause metabolic dysfunction, while paraneoplastic neurological syndromes (PNS) result from immune responses targeting the nervous system. Furthermore, dermatological and rheumatological disorders such as acanthosis nigricans, dermatomyositis, and Sweet syndrome, alongside hematological conditions like eosinophilia and thrombocytosis, are frequently observed. Consequently, early recognition of these syndromes, which can manifest independently of the cancer stage, is critical for timely tumor eradication and reducing associated morbidity and mortality rates.
Referanslar
Darnell RB, Posner JB: Paraneoplastic syndromes. 1. print. New York. Oxford University Press, 2011;3-29.
Pelosof, L. C., & Gerber, D. E. (2010). Paraneoplastic syndromes: an approach to diagnosis and treatment. Mayo Clinic proceedings, 85(9), 838–854.
Spinazzé S, Schrijvers D. Metabolic emergencies. Crit Rev Oncol Hematol. 2006;58(1):79-89.
Raftopoulos H. Diagnosis and management of hyponatremia in cancer patients. Support Care Cancer. 2007;15:1341-1347.
Lumachi F, Brunello A, Roma A, Basso U. Medical treatment of malignancy-associated hypercalcemia. Curr Med Chem. 2008;15:415-421.
Stewart AF. Hypercalcemia associated with cancer. N Engl J Med. 2005;352:373-379.
Barbosa SL, Rodien P, Leboulleux S et al. Ectopic adrenocorticotropic hormone-syndrome in medullary carcinoma of the thyroid: a retrospective analysis and review of the literature. Thyroid. 2005;15:618-623.
Nayar MK, Lombard MG, Furlong NJ, et al. Diagnosis and management of nonislet cell tumor hypoglycemia: case series and review of the literature. Endocrinologist. 2006;16(4):227-230.
Dalmau JO, Posner JB. Paraneoplastic syndromes affecting the nervous system. Semin Oncol. 1997;24:318–328.
Honnorat J, Antoine JC. Paraneoplastic neurological syndromes. Orphanet J Rare Dis. 2007;2:22.
Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol. 2008;7:327-340.
Graus F, Delattre J, Antoine J, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. 2004;75:1135-1140.
Devine MF, Kothapalli N, Elkhooly M, Dubey D. Paraneoplastic neurological syndromes: clinical presentations and management. Ther Adv Neurol Disord. 2021;;14:1756286420985323
Anderson SH, Hudson-Peacock M, Muller AF. Malignant acanthosis nigricans: potential role of chemotherapy. Br J Dermatol. 1999;141(4):714-716.
Fain O, Hamidou M, Cacoub P, et al. Vasculitides associated with malignancies: analysis of sixty patients. Arthritis Rheum. 2007;57:1473–1480.
Solans-Laqué R, Bosch-Gil JA, Pérez-Bocanegra C, et al. Paraneoplastic vasculitis in patients with solid tumors: report of 15 cases. J Rheumatol. 2008;35:294–304.
Chung VQ, Moschella SL, Zembowicz A, Liu V. Clinical and pathologic findings of paraneoplastic dermatoses. J Am Acad Dermatol. 2006;54:745-762.
Kaji K, Fujimoto M, Hasegawa M, et al. Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis: an association with malignancy. Rheumatology. 2007;46:25-28.
Atkinson S,Fox SB, Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) play a central role in the pathogenesis of digital clubbing. J Pathol. 2004;203:721-728.
Thiers BH, Sahn RE, Callen JP, Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59:73-98.
Arima K, Origuchi T, Tamai M, et al. RS3PE syndrome presenting as vascular endothelial growth factor associated disorder. Ann Rheum Dis. 2005;64:1653–1655.
Raza S, Kirkland RS, Patel AA, et al. Insight into Sweet's syndrome and associated-malignancy: a review of the current literature. Int J Oncol. 2013;42:1516–1522.
Sweet RD. An acute febrile neutrophilic dermatosis. Br J Dermatol. 1964;76:349–356.
Paydas S. Sweet's syndrome: a revisit for hematologists and oncologists. Crit Rev Oncol/Hematol. 2013;85-95.
Anagnostopoulos GK, Sakorafas GH, Kostopoulos P. Disseminated colon cancer with severe peripheral blood eosinophilia and elevated serum levels of interleukine-2, interleukine-3, interleukine-5, and GM-CSF.J Surg Oncol. 2005;89:273-275.
Holland SM, Gallin JI. Disorders of granulocytes and monocytes. Harrison's Principles of Internal Medicine. 17th ed. McGraw Hill Medical, New York, NY2008: 375-384.
Ahn HJ, Park YH, Chang YH. A case of uterine cervical cancer presenting with granulocytosis. Korean J Intern Med. 2005;20:247-250.
Araki K, Kishihara F, Takahashi K. Hepatocellular carcinoma producing a granulocyte colony-stimulating factor: report of a resected case with a literature review. Liver Int. 2007;27:716-721.
Sawada K, Hirokawa M, Fujishima N. Diagnosis and management of acquired pure red cell aplasia. Hematol Oncol Clin North Am. 2009;23: 249-259.
Schafer AI. Thyrombocytosis. N Engl J Med. 2004;350(12):1211–1219.
Buergy D, Wenz F, Groden C, Brockmann MA. Tumor-platelet interaction in solid tumors. Int J Cancer. 2012;130(12):2747–2760.
Kaser A, Brandacher G, Steurer W, et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis. Blood. 2001;98(9):2720–2722.
