49. Clinical aspects of neoplasm. Paraneoplastic syndromes, tumour markers

Clinical aspects of neoplasia

Neoplasms, even benign ones, have clinical consequences, like:

• Compression of surrounding tissues
• Produce hormones
• Erosion, ulceration
• Rupture or necrosis of tumour
• Cachexia
  • TNF-α
• Paraneoplastic syndromes

Compression of surrounding tissues is a common problem for neoplasms. Neoplasms in endocrine organs can disrupt the organs ability to produce the hormone. A neoplasm in the pituitary for example could compress and destroy the rest of the gland, causing panhypopituitarism. Neoplasms in or close to the gastrointestinal tract can cause obstructive ileus.

tumours in endocrine organs could also originate from the hormone producing cells, causing the tumour to produce hormones. This occurs only in benign or well-differentiated malignant tumours, like insulinomas.

tumours can may ulcerate through surfaces, causing erosion or ulceration of mucous membranes, causing melena, haematuria, haemoptysis or blood aspiration, depending on the localization of the tumour.

Rupture and/or necrosis of the tumour can expose to body to the necrotic debris inside the tumour, which can cause sepsis.

Cachexia is the extensive loss of lean body mass and fat that occurs in people with cancer. However, it doesn’t occur due to the nutritional demands of the tumour but rather due to the prolonged presence of TNF-α in the body, that is produced by macrophages in response to the tumour cells. This cytokine mobilizes fat from stores and reduces appetite. It reduces protein synthesis and stimulates protein metabolism. 1/3 of cancer-related deaths are actually due to cachexia and not the tumour itself!

Another name for TNF-α is cachexin.

Paraneoplastic syndrome

Any symptoms that are caused by a neoplasm but cannot be explained by the spread of the tumour, the local presence of the tumour or hormone production by the tumour (except for primary hormone-producing tumours) is called paraneoplastic syndrome. We have six common paraneoplastic syndromes:

• Ectopic hormone production, where tumours produce hormones that are not characteristic for the tissue the tumour originates from. For example do many small-cell lung carcinomas produce ACTH, and some hepatocellular or pancreatic carcinomas produce serotonin and bradykinin, leading to carcinoid syndrome.
• Hypercalcaemia. Normal tissues produce parathyroid hormone-related protein (PTHRP) in small amounts. Squamous cell carcinomas of the lung may produce large enough amounts to cause hypercalcaemia.
• Neuromyopathies, like peripheral neuropathy, cortical cerebellar degeneration, polymyopathy or myasthenic (muscle weakness) syndrome may develop. The pathomechanism is poorly understood, but may involve immune reaction with molecular mimicry.
• Acanthosis nigricans is normally a genetic disorder characterized by grey-black patches on the skin. In older patients can it appear as a paraneoplastic symptom, often earlier than the disease itself.
• Hypertrophic osteoarthropathy is a condition where there is new bone formation on the distal ends of long tube-like bones like the phalanges. Arthritis and digital clubbing are also common. It occurs in non-small cell lung cancers.
• Vascular/haematological manifestations
  • Migratory thrombophlebitis is a condition where blood clots move around in the body and cause symptoms. It occurs in carcinomas of pancreas and lung.
  • DIC occurs in acute promyelocytic leukaemia and prostatic adenocarcinoma
  • DVT
  • Nonbacterial thrombotic endocarditis occurs in mucin-secreting adenocarcinomas

Tumour markers

Many tumours produce enzymes, hormones or other molecules that can be detected in the blood with biochemical assays. They can contribute to detection of cancer, are useful in screening and can be used to determine the effectiveness of therapy. It’s important to note that the absence of a tumour marker doesn’t rule out the tumours presence, and the presence of a tumour marker isn’t always indicative of a tumour.

The important tumour markers are:

Marker	Associated cancers
Human chorionic gonadotropin (hCG)	Trophoblastic tumours, nonseminomatous testicular tumours
Calcitonin	Medullary carcinoma of thyroid
Catecholamine and catecholamine metabolites	Pheochromocytoma
Ectopic hormones	Small-cell lung carcinoma, hepatocellular and pancreatic carcinomas
α-foetoprotein (AFP)	Liver cell cancer, nonseminomatous testicular tumours
Carcinoembryonic antigen (CEA)	Carcinomas of colon, pancreas, lung, stomach, heart
Prostatic acid phosphatase	Prostate cancer
Neuron-specific enolase	Small-cell lung cancer, neuroblastoma
Immunoglobulins	Multiple myeloma
Prostate specific antigen (PSA)	Prostate cancer
CA-125	Ovarian cancer
CA-19-9	Colon cancer, pancreatic cancer
CA-15-3	Breast cancer

I think the bolded ones are the most important