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The Conceptual and Clinical Problems of Paraneoplastic Syndrome in Oncology and Internal Medicine B.T

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The Conceptual and Clinical Problems of Paraneoplastic Syndrome in Oncology and Internal Medicine B.T 82 Experimental Oncology 37, 82–88, 2015 (June) Exp Oncol 2015 REVIEWS 37, 2, 82–88 THE CONCEPTUAL AND CLINICAL PROBLEMS OF PARANEOPLASTIC SYNDROME IN ONCOLOGY AND INTERNAL MEDICINE B.T. Bilynsky1,*, M.B. Dzhus2, R.I. Litvinyak3 1Danylo Halytsky Lviv National Medical University, Lviv 79010, Ukraine 2O.O. Bogomolets National Medical University, Kyiv 01601, Ukraine 3Lviv State Oncological Regional Treatment and Diagnostic Center, Lviv 79031, Ukraine Symptomatology of oncological diseases consists not only of local symptoms caused by the primary malignancy or its metastases, but also by general systemic signs that are not directly connected with the tumor. These symptoms are mostly associated with auto- immunity or endocrine influences. In many cases, the source of paraneoplastic syndromes (PNS) is unknown. Nearly 15% of on- cological patients demonstrate these syndromes but it is diagnosed much more rarely. The survey of the numerous PNS is offered. The significance of the PNS differs for oncologists and other physicians who encounter it in their practice. The reason of those differences, as well as the connection between PNS and cancer toxicity is discussed. The experience of antitoxic therapy (hemo- sorption, lymphosorption, enterosorption) used in our clinic in the previous years is overviewed. Key Words: cancer, diagnosis, paraneoplastic syndromes, tumor toxicosis. Tumors usually produce symptoms by invasion, ences of the tumor. Over 600 PNS have already been obstruction and bulk mass on the primary localization described so far (Table). of neoplasm and their regional or distant metastases. Table1. Most common PNS In addition, tumors can produce signs at a distance Syndrome Clinical signs from their localization. These are the so-called para- group neoplastic syndromes (PNS) [1, 2]. Cutane- Acanthosis nigricans maligna These syndromes are not a direct effect of the tu- ous Erythema gyratum repens Bazex paraneoplastic acrocheratosis mor or its metastases. They are caused by substances Acquired hypertrichosis lanuginose produced by tumor and distributed by circulation. Necrolytic migratory erythema These substances act on the target organs and result Leser-Trélat Sign Paraneoplastic pemphigus in clinical picture named PNS. Most of these substan- Dermatomyositis ces are polypeptide hormones, autoantibodies, growth Sweet syndrome factors, cytokines, hormones and their precursors. Palmoplantar keratoderma Pyoderma gangrenosum The ethiology and pathogenesis of a number of PNS Neurolo- Limbic encephalitis are unknown till now (e.g. acanthosis nigricans) and gical Subacute cerebellar degeneration require additional investigations [3]. Opsoclonus-myoclonus Over the last years, many of these tumor-se- Optic neuritis Cancer associated retinopathy creted proteins have been described. The PNS may Subacute sensory neuronopathy be the first sign of a malignancy and we can use it for Guillain — Barre’ syndrome early cancer detection. PNS does not predict the result Chronic gastrointestinal pseudo-obstruction Myasthenia gravis of treatment of the underlying malignancy [4]. Lambert — Eaton myasthenic syndrome Thus, proteins secreted in PNS may be used as tu- Necrotising myelopathy mor markers. Different PNS caused by diverse reasons Endocrine SIADH Hypercalcemia (hormonal, immunological etc.) demonstrate various Cushing syndrome treatment results. A successful treatment of the tumor Hypoglycemia usually leads to disappearance of the PNS. In many Hemato- Eosinophilia logic Granulocytosis cases, the underlying tumor cannot be treated, but Pure red cell aplasia symptoms and complications of the PNS can be suc- Thrombocytosis cessfully managed by nonspecific means which were Thrombocytopenia tried in our institution (Lviv Oncological Center) several Anemia Coagulopathies (thrombophlebitis, thromboembolism, disse- years ago [5]. minated intravascular coagulation — DIC) It is believed that appearance of PNS is connected Rheuma- Paraneoplastic polyarthritis with endocrine, immunological or metabolic influ- tologic Remitting seronegative symmetrical synovitis with pitting edema Polymyalgia rheumatica Palmar fasciitis Submitted: March 5, 2015. Multicentric reticulohistiocytosis *Correspondence: E-mail: [email protected] Tumor-induced osteomalacia Abbreviations used: aPL — antiphospholipid antibodies; CLL — Vasculitis chronic lymphocytic leukemia; DIC — disseminated intravascular Renal Glomerulonephritis coagulation; PNS — paraneoplastic syndromes. Nephrotic syndrome Experimental Oncology 37, 82–88, 2015 (June) 83 Syndrome gastrointestinal abnormalities. I (here — B. Bilyn- Clinical signs group sky) remember a clinical case when during a clinical Others Cachexia patient round I, being a young docent, diagnosed Fatigue Fever gastric cancer due to the presence of black spots Lactic acidosis on the patient’s face (acanthosis nigricans), which Hypouricemia was evaluated by my colleagues as melanoma [8, 10]. Their number is constantly increasing, but Vascular abnormalities belong to dermatological it is disputable whether all of them can be evaluated appearances. Episodic reddening of the face and neck as PNS. True PNS satisfy two main criteria: strong as- lasting a few minutes is associated with the carcinoid sociation of suspected PNS with malignancy and their syndrome, leukemia, medullary carcinoma of the thy- parallel course [3]. roid, renal cell carcinoma, systemic mastocytosis, and pheochromocytoma. Multifocal migratory thrombo- PARANEOPLASTIC CUTANEOUS phlebitis (antiphospholipid syndrome) is associated SYNDROMES with numerous malignancies, most commonly with For clinicians these syndromes can be of diagnostic gastrointestinal, but also lung, prostate, ovary tumors, value. The attitude of different medical experts to this leukemias and lymphomas. It is related to hyperco- phenomenon differs: dermatologists observe PNS agulable state accompanying the advanced cancer. or similar syndromes in skin diseases. Most important A cordlike thrombophlebitis on the thoracic wall for is to establish a differential diagnosis between der- (Mondor’s disease) may be associated with breast mal PNS and plural dermatosis. Cutaneous manifesta- cancer. Pruritus may be the initial feature of an occult tions of distant cancer are more frequent than other malignancy or a clinical manifestation of a previously similar appearances, and an especially wide variety diagnosed tumor. There are other numerous additional of skin syndromes is associated with malignancies [6]. hereditary disorders associated with cutaneous mani- These are first of all keratinization disorders. The most festations of malignancy [3, 6]. important PNS of this kind is acanthosis nigricans. Dermatologic PNS include also a number of en- It is characterized by grey-brown hyperpigmented docrine and metabolic lesions (systematic modular velvety plaques that often affect the neck, flexor are- panniculitis or subcutaneous fat necrosis, hyperpig- as, and anogenital region. It is typically associated mentation by Addison syndrome), telangiectasia, and with ade nocarcinomas of the gastrointestinal tract, scleroderma-like changes in carcinoid syndrome, and predominantly with gastric cancer, but can be as- others [7, 8]. sociated with other adenocarcinomas (lung, breast, Bullous disorders, mostly paraneoplastic pemphi- ovarian, and even hematologic malignancies) [7]. gus usually occur in the presence of B-cell lympho- In addition, keratinization disorders are represented proliferative disorders — lymphomas, chronic lympho- by tripe palms, usually associated with lung or gastric cytic leukemia (CLL), Castleman’s disease, thymoma, cancers, acquired ichtiosis (associated with Hodg- Waldenstöm’s macroglobulinemia, and spindle cell kin’s and ot her lymphomas, multiple myeloma, Ka- neoplasms. Dermatologic PNS can be represented posi’s sarcoma). Palmar hyperkeratosis is associated by colagen-vascular diseases, disorders of hair, and with esophageal, breast, and ovarian carcinomas [8]. some skin neoplasms associated with internal malig- It is relevant to name several other cutaneous nancy. To the latter belong such autosomal-dominant PNS connected with different tumors: acrokeratosis syndromes as Muir — Torre syndrome (numerous paraneoplastica (Bazex’ syndrome), associated with sebaceous gland neoplasms), Cowden’s syndrome squamous cell carcinoma of the esophagus, head and (multiple hamartomas), Gardner’s syndrome (hun- neck or lung tumors. It precedes the tumor in 60% dreds of adenomatous colorectal polyps and nume- of cases. Exfoliative dermatitis may be associated rous epidermal cysts and soft tissue tumors), and with lymphomas and rarely with solid tumors (lung, Gorlin-Goltz syndrome (multiple basal cell carcinomas liver, prostate) [9]. with numerous bony abnormalities and a strong pre- Disorders of cutaneous discolonation and de- disposition for malignancy) [3, 9, 10]. positation (melanosis, plain xantomas, vitiligo, and leucoderma) are also considered to be PNS associated PARANEOPLASTIC NEUROLOGICAL with different malignancies. Neuroplastic dermatoses SYNDROMES constitute an interesting group. Sweet’s syndrome Neurologic manifestations of PNS are close presents with acute onset: fever, neutrophilia and to the dermatologic ones, and often have some com- appearance of cutaneous plaques on the face, neck, mon signs and etiological display with the skin syn- and upper extremities. Association with malignancies dromes [11]. occurs in 20% of cases. The other dermatologic PNS Neurological symptoms that are not related is
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