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

Paraneoplastic syndrome refers to any sign or symptom which occurs due to hormone or cytokine production by tumour cells, or by the immune response to the malignancy. Generally, it's defined as any syndrome due to non-metastatic effects of the malignancy. Paraneoplastic syndromes are rare, occuring in somewhere from 2-20% of malignancies. They often develop before the cancer diagnosis.

It’s important to recognise these diseases because they can give earlier diagnosis of the tumour and because their prognosis is better the earlier the treatment is initiated.

Pathomechanism

There may be many underlying mechanisms. Tumour cells may produce hormones or cytokines which cause systemic or distant effects. Another mechanism is molecular mimicry, where the immune system T cells or antibodies directed against the tumour cells may mistakenly attack healthy cells.

Dermatology

Many dermatological paraneoplastic syndromes exist, but they are rare.

Acanthosis nigricans is normally a genetic disorder characterized by formation of grey-black patches on the skin, an asymmetric velvety thickening and hyperpigmentation of skin folds. Pruritus may also occur. In may occur often before the malignancy itself becomes symptomatic. It's most common in elderly

Leser-Trélat sign refers to the sudden appearance of many seborrheic keratoses, a form of common benign skin tumour. This is associated with solid cancers, especially GI malignancies.

Other possible dermatological paraneoplastic syndromes include:

• Dermatological disorders only seen as paraneoplastic syndromes (obligate paraneoplastic disorders)
  • Erythema gyratum repens
    • Adenocarcinoma
  • Acrodermatitis psoriasiformis
    • Upper airway cancer
  • Hypertrichosis acquisita
  • Acrokeratosis bazex/acrokeratosis paraneoplastica
    • Psoriasiform lesions
    • Upper airway or GI cancer
  • Paraneoplastic pemphigus
• Dermatological orders also seen without malignancies (facultative paraneoplastic disorders)
  • Pyoderma gangrenosum
    • Painful, rapidly progressive ulcerated lesions
    • Also in Crohn disease
  • Bullous pemphigoid
  • Dermatomyositis
  • Sweet syndrome
    • Painful erythematous papules, plaques, nodules
  • Generalised herpes zoster (due to immune system depression)
  • Generalized acquired ichthyosis

Tumour markers

A tumour marker, also called a cancer biomarker, is a substance found in the body which concentration in the blood or other body fluid increases when cancer is present. The tumour marker may be produced by the cancer cells themselves or by healthy cells in response to the cancer. Tumour markers are usually proteins and are often produced in small amounts even in people without cancer. The term tumour marker may also be used to mean typical molecular changes in cancers, like ALK rearrangement and overexpression in NSCLC.

Tumour markers are not used for diagnosis of cancer, as they are not specific (can be elevated even without cancer) and are not sensitive (not all cancers cause tumour marker elevation). Some are used for screening, the prototypical example being PSA for prostate cancer, but because of the low specificity and sensitivity, this is controversial.

One of the main uses tumour markers is to monitor an already diagnosed cancer, often after treatment Following successfull cancer treatment, one expects the tumour marker level to drop or even normalise. If this does not occur, one can often assume that treatment was unsuccessfull. Following treatment, one can monitor the tumour marker regularly. A sudden increase in tumor marker is a sign of cancer recurrence.

However, as already mentioned, tumour markers are not sensitive, meaning that some cancer do not produce tumour markers. In these cases, tumour markers cannot be used to evaluate treatment response or monitor for recurrence.

Another main use of tumour markers is to evaluate the prognosis of a newly diagnosed cancer. If a cancer is diagnosed (or highly suspected), a significantly elevated tumour marker confers a worse prognosis than a non-elevated or only slightly elevated tumour marker, and may be a sign of locally advanced or metastatic disease.

Table of most important tumour markers

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

Those which are bolded are the most important.