Paraneoplastic syndromes

● Occur in 10% of persons with cancer.

● They may be the earliest manifestation of an occult neoplasm. 

● They may mimic metastatic disease and therefore confound treatment.

● Classification wise MC PNS =Endocrinopathies

● MC Endocrinopathy in cancers =Cushing syndrome.

● 50% of pts with Paraneoplastic Cushing syndrome have carcinoma of the lung, chiefly the small-cell type.

● It is caused by ↑↑ production of corticotropin or corticotropin-like peptides.

● Here Precursor of corticotropin is = Pro-opiomelanocortin.

● Lung cancer pts with Cushing syndrome have elevated serum levels of both pro-opiomelanocortin and corticotropin.

● ↑pro-opiomelanocortin is not found in serum of ptss with excess corticotropin produced by the pituitary = point of difference.

● MC PNS = Hypercalcemia

● Symptomatic hypercalcemia is
more commonly related to some form of cancer > hyperparathyroidism.

● Cancer Osteolysis in multiple myeloma = Not a PNS.

● Production of calcemic humoral substances by extraosseous neoplasms = Only mechanism considered PNS

● Hypercalcemia d/t 1° or 2° involvement of the skeleton by tumor =not a PNS.

● Most imp. factor for hypercalcemia of malignancy = PTHRP.      

● Normal tissues which can produce PTHRP = keratinocytes, muscles, bone, and ovary.

● Function of PTHRP = regulates Calcium transport in the lactating breast and across the placenta,modulates pulmonary development and remodeling.

● MC Tumor asso. with paraneoplastic hypercalcemia =  Ca Breast, f/b lung, kidney, and ovary.

● MC lung Cancer asso. with hypercalcemia = Squamous Cell Ca.

● In addition to PTHRP, other factors, such as IL-1, TGF-α, TNF, and dihydroxyvitamin D also implicated in the hypercalcemia of malignancy.

● Hypertrophic osteoarthropathy is seen in = 1% to 10% of Lung Ca.

● Migratory thrombophlebitis (Trousseau syndrome) MC seen in = deep-seated cancers Ca. Pancreas > Lung.

● DIC MC asso. with = Acute Promyelocytic Leukemia > prostatic adenocarcinoma.