Clinical Syndromes Major Forms of Underlying Cancer Causal Mechanism

Endocrinopathies

Cushing syndrome Small cell carcinoma of lung ACTH or ACTH-like substance

Pancreatic carcinoma

Neural tumors

Syndrome of inappropriate antidiuretic hormone

secretion

Small cell carcinoma of lung; intracranial neoplasms Antidiuretic hormone or atrial natriuretic hormones

Hypercalcemia Squamous cell carcinoma of lung Parathyroid hormone-related protein (PTHRP), TGF-, TNF, IL-1

Breast carcinoma

Renal carcinoma

Adult T-cell leukemia/lymphoma

Ovarian carcinoma

Hypoglycemia Fibrosarcoma Insulin or insulin-like substance

Other mesenchymal sarcomas

Hepatocellular carcinoma

Carcinoid syndrome Bronchial adenoma (carcinoid) Serotonin, bradykinin

Pancreatic carcinoma

Gastric carcinoma

Polycythemia Renal carcinoma Erythropoietin

Cerebellar hemangioma

Hepatocellular carcinoma

Nerve and Muscle Syndromes

Myasthenia Bronchogenic carcinoma Immunologic

Disorders of the central and peripheral nervous systems Breast carcinoma

Dermatologic Disorders

Acanthosis nigricans Gastric carcinoma Immunologic; secretion of epidermal growth factor

Lung carcinoma

Uterine carcinoma

Dermatomyositis Bronchogenic, breast carcinoma Immunologic

Osseous, Articular, and Soft Tissue Changes

Hypertrophic osteoarthropathy and clubbing of the

fingers

Bronchogenic carcinoma Unknown

Vascular and Hematologic Changes

Venous thrombosis (Trousseau phenomenon) Pancreatic carcinoma Tumor products (mucins that activate clotting)

Bronchogenic carcinoma

Other cancers

Nonbacterial thrombotic endocarditis Advanced cancers Hypercoagulability

Anemia Thymic neoplasms Unknown

Others

Nephrotic syndrome Various cancers Tumor antigens, immune complexes

ACTH, adrenocorticotropic hormone; TGF, transforming growth factor; TNF, tumor necrosis factor; IL, interleukin.

The E6-p53 interaction may also offer some clues regarding risk factors for cervical cancer development in infected persons. Human p53 is polymorphic at amino acid 72, encoding either a proline or arginine residue at that position. It turns out that the arginine-containing p53 at position 72 is much more susceptible to degradation by E6. The arginine form is found more frequently in infected individuals with cervical are small. It is thought that PTHRP regulates calcium transport in the lactating breast and across the placenta. Tumors most often associated with paraneoplastic hypercalcemia are carcinomas of the breast, lung, kidney, and ovary. In breast cancers, PTHRP production is associated with osteolytic bone disease, bone metastasis, and humoral hypercalcemia. The most common lung neoplasm associated with hypercalcemia is the squamous cell bronchogenic carcinoma, rather than small cell cancer of the lung (more often associated with endocrinopathies). In addition to PTHRP, several other factors, such as IL-1, TGF-, TNF, and dihydroxyvitamin D, have also been implicated in causing the hypercalcemia of malignancy. The neuromyopathic paraneoplastic syndromes take diverse forms, such as peripheral neuropathies, cortical cerebellar degeneration, a polymyopathy resembling polymyositis, and a myasthenic syndrome similar to myasthenia gravis. The cause of these syndromes is poorly understood. In some cases, antibodies, presumably induced against tumor cells that cross-react with neuronal cells, have been detected. It is postulated that some neural antigens are ectopically expressed by visceral cancers. For some unknown reason, the immune system recognizes these antigens as foreign and mounts an immune response.

Acanthosis nigricans is characterized by gray-black patches of verrucous hyperkeratosis on the skin. This disorder occurs rarely as a genetically determined disease in juveniles or adults ( Chapter 25 ). In addition, in about 50% of the cases, particularly in those over age 40, the appearance of such lesions is associated with some form of cancer. Sometimes the skin changes appear before discovery of the cancer.

Hypertrophic osteoarthropathy is encountered in 1% to 10% of patients with bronchogenic carcinomas. Rarely, other forms of cancer are involved. This disorder is characterized by (1) periosteal new bone formation, primarily at the distal ends of long bones, metatarsals, metacarpals, and proximal phalanges; (2) arthritis of the adjacent joints; and (3) clubbing of the digits. Although the osteoarthropathy is seldom seen in non-cancer patients, clubbing of the fingertips may be encountered in liver diseases, diffuse lung disease, congenital cyanotic heart disease, ulcerative colitis, and other disorders. The cause of hypertrophic osteoarthropathy is unknown.

Several vascular and hematologic manifestations may appear in association with a variety of forms of cancer. As mentioned in the discussion of thrombosis ( Chapter 4 ), migratory thrombophlebitis (Trousseau syndrome) may be encountered in association with deep-seated cancers, most often carcinomas of the pancreas or lung. Disseminated intravascular coagulation may complicate a diversity of clinical disorders ( Chapter 13 ). Acute disseminated intravascular coagulation is most commonly associated with acute promyelocytic leukaemia and prostatic adenocarcinoma. Bland, small, nonbacterial fibrinous vegetations sometimes form on the cardiac valve leaflets (more often on left-sided valves), particularly in patients with advanced mucin-secreting adenocarcinomas. These lesions, called nonbacterial thrombotic endocarditis, are described further in Chapter 12 . The vegetations are potential sources of emboli that can further complicate the course of cancer.

Date: 2016-04-22; view: 740