Paraneoplastic syndromes: Definitions, classification, pathophysiology and principles of treatment

Paraneoplastic syndromes (PNS) are rare clinical syndromes due to the systemic effects of tumours; they are unrelated to tumour size, invasiveness or metastases. Recent years have seen considerable advances leading to improved understanding of their pathophysiology and increased recognition of new PNS entities and PNS associated tumours. While of paramount importance, diagnosis is still frequently missed or delayed. Diverse organs and systems are affected by the associated tumours- which may be benign or malignant. PNS can occur concurrently with tumour diagnosis, before tumour is diagnosed and even after tumours have been resected. Also, there are autoimmune diseases later progressing to PNS when occult tumours are identified. Another confounding factor is that many PNS clinically resemble non-neoplastic diseases. PNS are largely due to two main causes: those due to tumour secretions of hormones, functionally active peptides, enzymes cytokines or to tumours operating through auto-immune/immunological mechanisms with cross-reacting antibodies between neoplastic and normal tissues. Remission of symptoms often follows resection of humoral secretory tumours but not always of tumours due to immunological mechanisms. Classifications schemes vary but most currently place PNS in one of five groups: endocrine, neurological, musculocutaneous, haematological and other. Due to advances both in diagnostic techniques in identifying tumours as well as in therapy, early diagnosis not only results in improved prognosis of both PNS and associated tumours but also enables monitoring response to treatment and early detection of recurrence. This article covers definition, general principals of classification, diagnosis, pathophysiology and treatment, with emphasis on tumour related PNS serving as an introduction to the following articles.