Clinical Aspects Of Neoplasia Notes

Clinical Aspects Of Neoplasia

This section deals with application of knowledge and understanding of neoplasia in clinical settings i.e. clinical effects of cancer on patients, prognostic parameters (grading and staging), and pathological diagnosis.

Clinical Effects Of Tumour On Host

In the battle between immune defence by the host and the growth of cancer, most cancers overwhelm the patient eventually. The natural biology of tumours, however, depends upon several factors, but in general malignant tumours produce more ill effects than the benign tumours.

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The effects may be local, or generalised and more widespread.

Local Effects

• Both benign and malignant tumours cause local effects on the host due to their size or location. Malignant tumours due to rapid and invasive growth potential have more serious effects.
• Some of the local effects of tumours are as under:
• Compression: Many benign tumours pose only a cosmetic problem. Some benign tumours, however, due to their critical location, have more serious consequences for example, Pituitary adenoma may lead to serious endocrinopathy; a small benign tumour in the ampulla of Water may lead to biliary obstruction.
• Mechanical obstruction: Benign and malignant tumours in the gut may produce intestinal obstruction.
• Tissue destruction: Malignant tumours, both primary and metastatic, infiltrate and destroy vital structures.
• Infarction, ulceration, haemorrhage: Cancers have a greater tendency to undergo infarction, surface ulceration and haemorrhage than the benign tumours. Secondary bacterial infection may supervene. Large tumours in mobile organs (for example, Ovarian tumours) may undergo torsion and produce infarction and haemorrhage.

Read And Learn More: General Pathology Notes

Systemic Manifestations

Generalised effects of cancer include

1. Cancer cachexia
2. Fever
3. Tumour lysis syndrome and
4. Paraneoplastic syndromes.

1. Cancer Cachexia:

Patients with advanced and disseminated cancers terminally have asthenia (emaciation), and anorexia, together referred to as cancer cachexia (meaning wasting).

• The exact mechanism of cachexia is not clear, but it does not occur due to the increased nutritional demands of the tumour. Certain cytokines such as tumour necrosis factor α (TNF-α), interleukin- 1 and interferon-γ play a contributory role in cachexia.
• Various other causes of cancer cachexia include necrosis, ulceration, haemorrhage, infection, malabsorption, anxiety, pain, insomnia, hypermetabolism and pyrexia.

2. Fever:

Fever of unexplained origin may be a presenting feature in some malignancies such as Hodgkin’s disease, adenocarcinoma kidney, osteogenic sarcoma and many other tumours. The exact mechanism of tumour-associated fever is not known but probably the tumour cells themselves elaborate pyrogens.

3. Tumour Lysis Syndrome:

This is a condition caused by the extensive destruction of a large number of rapidly proliferating tumour cells.

• The condition is seen more often in cases of lymphomas and leukaemias than solid tumours and may be due to large tumour burden (for example, Burkitt’s lymphoma), chemotherapy, administration of glucocorticoids or certain hormonal agents (for example, Tamoxifen).
• It is characterised by hyperuricaemia, hyperkalaemia, hyperphosphataemia and hypocalcaemia, all of which may result in acidosis and renal failure.

4. Paraneoplastic Syndromes:

Paraneoplastic syndromes (PNS) are a group of conditions developing in patients with advanced cancer which are neither explained by the direct and distant spread of the tumour, nor by the usual hormone elaboration by the tissue of origin of the tumour.

About 10–15% of the patients with advanced cancer develop one or more of the syndromes included in the PNS. Rarely, PNS may be the earliest manifestation of a latent cancer.

The various clinical syndromes included in the PNS are as summarised in the Table and are briefly outlined below.

• Endocrine syndromes: The elaboration of hormones or hormone-like substances by cancer cells of non-endocrine origin is called as ectopic hormone production. Some examples are given below:
  • Hypercalcaemia Symptomatic: Hypercalcaemia unrelated to hyperparathyroidism, called humoral hypercalcaemia of malignancy, is the most common syndrome in PNS.
    • It occurs from elaboration of parathormone-like substance by tumours such as squamous cell carcinoma of the , lung, carcinoma kidney, breast and adult T-cell leukaemia lymphoma.
    • Another cause of humoral hypercalcameia of malignancy is excess production of vitamin D.

Summary of paraneoplastic syndromes.

• • • Cushing’s syndrome: About 10-20% patients of with Cushing’s syndrome have ectopic production of ACTH or ACTH-like substance. Most common cause is small cell lung carcinoma; others are carcinoid tumours and islet cell tumour of the pancreas.
    • Ectopic ADH: Inappropriate secretion of vasopressin or ADH may occur in certain tumours such as small cell lung carcinoma and carcinoid tumour.
    • Hypoglycaemia Ectopic: Production of insulin-like growth factor II (IGF-II) causing hypoglycaemia occurs in fibrosarcomas, haemangiopericytoma and hepatocellular carcinoma.
    • Human chorionic: Gonadotropin (hCG)-Ectopic production of hCG occurs in embryonal carcinoma testis and extragonadal germinomas.
  • Haematologic syndrome: Frequently, there is pancytosis (erythrocytosis, leukocytosis, thrombocytosis) and eosinophilia in many solid tumours and may parallel the course of a malignant process.
    • Erythrocytosis Ectopic:P production of erythropoietin by malignant cells stimulates the bone marrow to produce excess red blood cells and raised haematocrit for example, Renal cell carcinoma,
      hepatocellular carcinoma, CNS tumours.
    • Leukocytosis: Mainly agranulocytosis, is seen in one-third of cases of solid tumours due to the secretion of granulocyte colony stimulation factor (G-CSF). Advanced cases may develop a leukemoid reaction.
    • Thrombocytosis:  Thrombocytosis is due to the elaboration of IL-6 or thrombopoietin by tumour cells such as in lung cancer, cancer of the GI tract etc.
    • Eosinophilia is seen in lymphomas and leukaemias due to the secretion of IL-5.
    • Advanced cancers may develop disseminated intravascular coagulation (DIC)
    • Anaemia Autoimmune haemolytic anaemia may be associated with B-cell malignancies. Advanced cancers develop anaemia of chronic disease (normocytic normochromic anaemia).
  • Vascular syndrome: The most common thrombotic complications in cases of cancer are deep vein thrombosis (DVT), pulmonary embolism and non-bacterial thrombotic endocarditis (NBTE).
    • The coexistence of venous thrombosis (thrombophlebitis) with visceral cancers (in particular pancreatic and lung cancer) is called Trousseau’s syndrome.
    • The predisposition of cancer patients to thrombosis is due to various factors—bed-ridden or immobilised state, and obstruction or compression by the tumour.
  • Effects on osseous, joints and soft tissue: Hypertrophic pulmonary osteoarthropathy and clubbing of fingers in cases of bronchogenic carcinoma, by unknown mechanism but is probably due to increased blood flow to the limb. Oncogenic osteomalacia is seen in certain benign mesenchymal tumours.
  • Neuromuscular syndromes: About 5% of cancers are associated with progressive destruction of neurons throughout the nervous system without evidence of metastasis in the brain and spinal cord.
    • This is probably mediated by immunologic mechanisms.
    • The changes in the neurons may affect the muscles as well. The changes are Peripheral neuropathy, Cortical cerebellar degeneration, Myasthenia gravis syndrome, and Polymyositis.
  • Cutaneous syndromes: Acanthosis nigricans characterised by the appearance of black warty lesions in the axillae and the groins may appear in the course of cancer in the stomach, large bowel and lungs.
    • Other cutaneous lesions in PNS include seborrheic dermatitis in advanced malignant tumours and exfoliative dermatitis in lymphomas and Hodgkin’s disease.
  • Renal syndromes:  Renal vein thrombosis or systemic amyloidosis may produce nephrotic syndrome in patients with cancer.
  • Malabsorption syndrome:  Malabsorption of various dietary components as well as hypoalbuminaemia may be associated with a variety of cancers which do not directly involve the small bowel.
  • Amyloidosis: Primary amyloid deposits may occur in multiple myeloma whereas renal cell carcinoma and other solid tumours may be associated with secondary systemic amyloidosis.

Clinical Effects of Tumour on Host:

The natural history of a neoplasm depends upon the host’s response against the tumour (or cancer immunology) and the effect of the tumour on the host. Malignant tumours produce more ill effects on the host than benign tumours and these may be local, or generalised and more widespread.

Local effects of the tumour depend upon the site. These effects are due to mechanical compression, obstruction, tissue destruction and infarction, ulceration and haemorrhage.

Systemic effects are in the form of cancer cachexia, fever, tumour lysis syndrome, and paraneoplastic syndrome.

Paraneoplastic syndromes have several presentations with widespread manifestations.

Some of the important features are:

• Ectopic hormone elaboration (Hypercalcaemia, Cushing’s, ADH, hypoglycaemia, hCG)
• Haematologic (pinocytosis, Eosinophilia, DIC, anaemia)
• Vascular (thrombophlebitis, NBTE)
• Osseous (hypertrophic arthropathy, clubbing of fingers, osteomalacia)
• Neuromuscular (myasthenia gravis, neuropathy)
• Cutaneous (acanthosis nigricans, seborrheic and exfoliative dermatitis)
• Renal (nephrotic syndrome)
• Gastrointestinal (malabsorption), and
• Amyloidosis.