Takeshi Saraya, MD, PhD
Assistant Professor Department of Respiratory Medicine Kyorin University School of Medicine 6-20-2 Shinkawa, Mitaka City Tokyo 181-8611, Japan; Tel. +81 (0)422 44 0671; Fax: +81 (0)422 44 0671; E-mail: sara@yd5.so-net.ne.jp
Pulmonologists often encounter patients with oncologic emergencies (Figure 1) such as metabolic syndrome (tumor lysis syndrome),1 hypercalcemia, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), hematologic (febrile neutropenia and hyperviscosity syndrome) and structural disorders (superior vena cava syndrome,2 spinal cord compression syndrome, malignant pericardial effusion,3 and malignant airway obstruction4), alongwith drug-related adverse eventsin already-known malignancies including liver5 or pulmonary toxicity6,7 and renal disease.8,9 Additionally, pulmonologists occasionally encounter paraneoplastic syndrome (PNS), which partially overlaps with oncologic emergencies (Figure 1). In this regard, pulmonologists should be aware of PNS, involving organ-based classification (Figure 2).
Figure 1: Schema of the Common Oncologic Emergencies.
SIADH: Syndrome of Inappropriate Secretion of Antidiuretic Hormone; SVC: Superior Vena Cava Syndrome.
Figure 2: Organ-based Classification of Paraneoplastic Syndrome.
ACTH: Adrenocorticotropic Hormone; ANNA1: Type I Anti-Neuronal Nuclear Antibody; Anti-SOX1: Anti-Sry-related HMG; AntiTIF1: Anti-transcriptional intermediary factor 1-gamma; Anti-VGCC: Anti-Voltage-Gated Calcium Channel; Anti-VGKC: AntiVoltAge-Gated Potassium Channel, G-CSF: Granulocyte-Colony Stimulating Factor, GHRH/GH: Growth Hormone Releasing Hormone/Glucose Hormone, PTH: Parathyroid Hormone, SCLC: Small Cell Lung Cancer.
PNS has diverse symptoms and signs in neurologic,10,11 muscle/neuromuscular junction/skeletal,10 hematological,12 eye,13 renal,14 metabolic,1 skin,15,16 and endocrine systems,17 which often present as antecedent problems of lung cancer or other malignancies. In some cases, physicians might have difficulty in discriminating PNS from malignant independent conditions due to clinical similarity but they are pathologically different.18 PNS occurs in approximately 10% of patients with lung cancer,19 and the histology of lung cancer influences the type of associated PNS. The most common forms of PNS are hypercalcemia fromsquamous carcinoma and SIADH in small cell lung cancer.
Nowadays, various onconeural antibodies have been detected, and well-characterized autoantibodies such as anti-Hu (ANNA1), anti-Yo (PCA1), anti-CV2 (CRMP5), anti-Ri, anti-Ma2 (Ta), and anti-amphiphysin have been described. Other partially characterized onconeural antibodies and other antibodies were also identified.17 These antibodies seem to be directly involved in cell surface or synaptic proteins or disrupt function of receptors by cross-linking and internalization, which leads to PNS.20
Of note, a high frequency of anti-Hu antibody has been reported in PNS such as limbic encephalitis, cerebellar degeneration, and peripheral neuropathy (Figure 2), which resulted in “anti-Hu syndrome” being considered an independent entity.21 Moreover, although identification of onconeural antibodies can be a useful marker for early diagnosis of PNS and/or malignancies, multidisciplinary assessment for PNS is needed along with long-term observation.
1. Honda K, Saraya T, Tamura M, Yokoyama T, Fujiwara M, Goto H. Tumor lysis syndrome and acquired ichthyosis occurring after chemotherapy for lung adenocarcinoma. J Clin Oncol. 2011; 29(35): e859-e860. doi: 10.1200/jco.2011.36.8175
2. Saraya T, Shimura C, Mikura S, et al. Huge mediastinal mass with SVC syndrome accompanying numerous chest wall collateral vessels. Intern Med. 2008; 47(19): 1719-1722. doi: 10.2169/internalmedicine.47.1076
3. Saraya T, Takata S, Fujiwara M. The role of vital signs in predicting cardiac tamponade in asymptomatic patients with malignancy-associated pericardial effusion. Pulm Res Respir Med Open J. 2016; SE(1): S3-S7. doi: 10.17140/PRRMOJ-SE-1-102
4. Nakajima A, Saraya T, Takata S, et al. The saw-tooth sign as a clinical clue for intrathoracic central airway obstruction. BMC Res Notes. 2012; 5: 388. doi: 10.1186/1756-0500-5-388
5. Hirukawa I, Saraya T, Wada S, Takizawa H. Marked enlargement of liver over a short period of time illustration. Pulm Res Respir Med Open J. 2016; 3(1): 1. doi: 10.17140/PRRMOJ-3-123
6. Tamura M, Saraya T, Fujiwara M, et al. High-resolution computed tomography findings for patients with drug-induced pulmonary toxicity, with special reference to hypersensitivity pneumonitis-like patterns in gemcitabine-induced cases. Oncologist. 2013; 18(4): 454-459. doi: 10.1634/theoncologist.2012-0248
7. Koide T, Saraya T, Nakamoto K, et al. A case of imatinib mesylate-induced pneumonitis based on the detection of epithelioid granulomas by video-assisted thoracoscopic surgery biopsy in a patient with chronic myeloid leukemia. Nihon Kokyuki Gakkai Zasshi. 2011; 49(6): 465-471.
8. Yao X, Panichpisal K, Kurtzman N, Nugent K. Cisplatin nephrotoxicity: A review. Am J Med Sci. 2007; 334(2): 115-124. doi: 10.1097/MAJ.0b013e31812dfe1e
9. Toriumi S, Sara-ya T, Tsujimoto N. Renal salt wasting syndrome due to carboplatin in a patient with lung cancer. Pulm Res Respir Med Open J. 2014; 1(1): 9-12. doi: 10.17140/PRRMOJ-1-102
10. Graus F, Dalmau J. Paraneoplastic neurological syndromes. Curr Opin Neurol. 2012; 25(6): 795-801. doi: 10.1186/1750-1172- 2-22
11. Higaki M, Kurai D, Ito A, Saraya T. Evidence for hypohydrosis as clinical clue to diagnosis of Horner’s syndrome. BMJ Case Rep. 2013; 2013. doi: 10.1136/bcr-2013-009732
12. Nishizawa T, Saraya T, Kurai D, et al. Good syndrome occurred in a patient a prolonged time after thymectomy: A case report and literature review of cases in Japan. Journal of General and Family Medicine. 2016; 17(3): 238-243. doi: 10.14442/jgfm.17.3_238
13. Sakamori Y, Kim YH, Okuda C, et al. Two cases of cancer-associated retinopathy combined with small-cell lung cancer. Jpn J Clin Oncol. 2011; 41(5): 669-673. doi: 10.1093/jjco/hyr025
14. Bacchetta J, Juillard L, Cochat P, Droz JP. Paraneoplastic glomerular diseases and malignancies. Crit Rev Oncol Hematol. 2009; 70(1): 39-58. doi: 10.1016/j.critrevonc.2008.08.003
15. Owen CE. Cutaneous manifestations of lung cancer. Semin Oncol. 2016; 43(3): 366-369. doi: 10.1053/j.seminoncol.2016.02.025
16. Higaki M, Ishida M, Nakamoto Y, Saraya T. Horner’s syndrome with a sensation of warmth due to hypohidrosis. Intern Med. 2013; 52(15): 1757-1758. doi: 10.2169/internalmedicine.52.0660
17. Kanaji N, Watanabe N, Kita N, et al. Paraneoplastic syndromes associated with lung cancer. World J Clin Oncol. 2014; 5(3): 197-223. doi: 10.5306/wjco.v5.i3.197
18. Saraya T, Fujiwara M, Shimura C, Goto H. Not paraneoplastic pemphigus but pemphigus vulgaris in a patient with thymoma. BMJ Case Rep. 2015; 2015. doi: 10.1136/bcr-2015-210433
19. Spiro SG, Gould MK, Colice GL, American College of Chest P. Initial evaluation of the patient with lung cancer: Symptoms, signs, laboratory tests, and paraneoplastic syndromes: ACCP evidenced-based clinical practice guidelines (2nd ed). Chest. 2007; 132(Suppl 3): 149S-160S. doi: 10.1378/chest.07-1358
20. Lancaster E, Dalmau J. Neuronal autoantigens–pathogenesis, associated disorders and antibody testing. Nat Rev Neurol. 2012; 8(7): 380390. doi: 10.1038/nrneurol.2012.99
21. Ost DE, Jim Yeung SC, Tanoue LT, Gould MK. Clinical and organizational factors in the initial evaluation of patients with lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013; 143(Suppl 5): e121S-e41S. doi: 10.1378/chest.12-2352
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