Acquired Predisposing Diseases Notes

Acquired Predisposing Diseases

There are several precursor lesions, certain benign tumors, some non-neoplastic chronic conditions and immunodeficiency states, which may predispose to the subsequent development of cancer.

Such conditions are important to recognise so as to prevent the subsequent occurrence of an invasive cancer.

During the natural history of these diseases, many of them undergo malignant morphologic changes in the cells which may be possible to detect at an early stage.

These morphologic features are increased nuclear-cytoplasmic ratio, allomorphism of cells and nuclei, increased mitotic activity, poor differentiation etc.

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Groups of these predisposing conditions are as under:

1. Precursor lesions:

As dysplasia or intraepithelial lesion is an abnormality in cytologic features and may be of varying severity (low-grade to high-grade). The biologic behavior of intraepithelial lesions is variable — low grade lesions may regress if detected early and revert back to normal, while high-grade lesions may progress, especially when the stimulus which caused it persists.

The common sites for occurrence of precursor lesions are as under:

1. Squamous metaplasia of uterine cervix at the junction of echo- and endocervix
2. Squamous metaplasia of bronchus
3. Bowen’s disease of the skin
4. Actinic or solar keratitis
5. Oral leukoplakia
6. Barrett’s oesophagus
7. Atypical hyperplasia of the breast.

Progression of a precursor lesion may result in marked cytological atypia confined to the entire thickness of epithelial layers above the basement membrane without invading the basement membrane, called carcinoma in situ.

The area involved in carcinoma in situ may be single and small, or multifocal. In some sites such as in the cervix and bronchus, there are sequential stages in transformation: normal epithelium→ squamous metaplasia→ epithelial aplasia (varying grades) → carcinoma in situ → invasive cancer.

2. Some benign tumors:

Commonly, benign tumors do not become malignant. However, there are some exceptions for examples

• Multiple adenomas of the large intestine (APC) have a high incidence of developing adenocarcinoma.
• Neurofibromatosis (von Recklinghausen’s disease) may develop into sarcoma.
• Pleomorphic adenoid (mixed salivary tumor) may sometimes develop into carcinoma (carcinoma ex-pleomorphic adenoid)
• Uterine leiomyoma may rarely develop into leiomyosarcoma.

3. Chronic conditions:

Certain chronic inflammatory (both infectious and non-infectious) and hyperplastic conditions are prone to development of cancer, for examples

• High-risk HPV-infected chronic cervicitis has a high risk of developing cervical cancer.
• Patients of long-standing ulcerative colitis are predisposed to develop colorectal cancer.
• Cirrhosis of the liver (alcoholic, post-necrotic, and haemochromatosis) has predilection to
  develop hepatocellular carcinoma.
• H. pylori-associated conditions such as gastritis and peptic ulcer has high risk of developing gastric cancer and lymphoma.
• Chronic bronchitis in heavy cigarette smokers may develop cancer of the bronchus.
• Asbestosis of the lung may develop into mesothelioma and oncogenic carcinoma.
• Long-standing chronic cholecystitis may develop into gallbladder cancer.
• Long-standing Hashimoto thyroiditis may develop into lymphoma.
• Draining sinus in chronic osteomyelitis may develop carcinoma.
• Chronic irritation from jagged tooth or ill-fitting dentures may progress to cancer of the oral cavity.
• Squamous cell carcinoma may rarely develop in an old burn scar (Marjolin’s ulcer).
• Chronic cystitis due to schistosomiasis has higher risk of developing squamous cell carcinoma of the urinary bladder.

4. Immunodeficiency:

T-cell deficiency disorders in particular have a high risk of developing lymphomas and carcinomas for example, Various cancers in HIV-AIDS.

Predisposing Hormones

Cancer is more likely to develop in organs and tissues which undergo proliferation under the influence of excessive hormonal stimulation. On cessation of hormonal stimulation, such tissues become atrophic.

Hormone-sensitive tissues developing tumors are the breast, endometrium, myometrium, vagina, thyroid, liver, prostate and testis. Some examples of hormones influencing

Carcinogenesis in experimental animals and humans are given below:

1. Oestrogen:

Examples of estrogen-induced cancers are as under:

• In experimental animals:  Induction of breast cancer in mice by administration of high-dose of oestrogen and reduction of the tumour development following oophorectomy is the most important example.
  • It has been known that associated infection with mouse mammary tumour virus (MMTV or Bittner milk factor) has an added influence on the development of breast cancer in mice.
  • Other cancers which can be experimentally induced in mice by estrogens are squamous cell carcinoma of the cervix, connective tissue tumor of the myometrium,
  • Leydig cell tumour of the testis in male mice, tumour of the kidney in hamsters, and benign as well as malignant tumours of the liver in rats.
• In humans:  Women receiving estrogen therapy and women with oestrogen-secreting granulosa cell tumours of the ovary have an increased risk of developing endometrial carcinoma.
  • Adenocarcinoma of the vagina is seen with increased frequency in adolescent daughters of mothers who had received estrogen therapy during pregnancy.

2. Contraceptive Hormones:

The sequential types of oral contraceptives increase the risk of developing breast cancer. Other tumours showing a slightly increased frequency in women receiving contraceptive pills for long durations are benign tumours of the liver, and a few patients have been reported to have developed hepatocellular carcinoma.

3. Anabolic Steroids:

Consumption of anabolic steroids by athletes to increase muscle mass is not only unethical athletic practice but also increases the risk of developing benign and malignant tumours of the liver.

4. Hormone-Dependent Tumours:

It has been shown in experimental animals that induction of hyperfunction of adenohypophysis is associated with an increased risk of developing neoplasia of the target organs following preceding functional hyperplasia. There is tumor regression on the removal of the stimulus for excessive hormonal secretion.

A few examples of such phenomena are seen in humans:

• Prostatic cancer usually responds to the administration of estrogens.
• Breast cancer may regress with oophorectomy, hypophysectomy or on the administration of male hormones.
• Thyroid cancer may slow down in growth with the administration of thyroxine which suppresses the secretion of TSH by the pituitary.

Epidemiology of Cancer:

In general, the most common cancers in developed countries are lung, breast, prostate and colorectal, and in developing countries are liver, cervix, oral cavity and oesophagus.

Several factors predispose to the occurrence of cancers. These are: constitutional factors (age and gender), familial and genetic factors, racial and geographic factors, and environmental and cultural factors.

High-grade dysplasia and carcinoma in situ of some sites such as the uterine cervix, bronchus, skin, oral cavity, esophagus etc may progress to cancer.

A few benign tumours and polyps may predispose to cancer for example, Colorectal adenomas, neurofibromatosis.

Some long-standing chronic inflammatory (infectious ad non-infectious) and hyperplastic conditions may develop into cancers for example, HPV-induced cervices, H. pylori gastritis, ulcerative colitis, cirrhosis, old burn scar etc.

T-cell immunodeficiency disorders have high risk of the development of various cancers such as in AIDS.

High levels of some hormones have a role in predisposition to cancer for example, Endogenous or exogenous excess of oestrogen associated with higher risk of endometrial cancer, oral contraceptives in breast cancer, testosterone in prostate cancer etc.