Precancerous conditions that portend cancer
The vast majority of cancers are preceded by a precancerous condition (90% of cancers), but the process is often very long. The malignant evolution of precancerous conditions is not mandatory nor can specify an exact time for a malignant transformation. The duration of the evolution is variable from an organ to another, from a few years to tens of years.
Since about 90% of cancers appear as a result of the development of precancerous conditions, it is extremely important to recognize them and the associated etiological factors and to remove them.
Once discovered, the precancerous lesion should be treated accordingly, given the fact that it is considered a major risk factor for cancer.
The recognition and correct treatment of premalignant conditions
– Allows clinical cancer prevention,
– The costs involved are much lower than for invasive cancers,
– Allows healing the patients.
WHO Classification divides the precancerous conditions into 2 groups: precancerous conditions and precancerous lesions.
Precancerous conditions: are biological statuses, histological and clinical, with a high tendency not to develop into cancer, but whose exogenous carcinogen factors are not known.
They are represented by:
a) Chromosomal or genetic anomalies;
b) Hereditary disorders with risk of cancer;
c) Various dystrophies and benign diseases (adenomas, polyps).
Oncogenes can cause certain medical conditions and biological precursors or some cancers: the direct transmission of BRCA2 gene cause gynecomastia with unilateral channeling in men, followed by malignant swelling.
Chromosomal abnormalities: trisomy 21, Klinefelter syndrome (XXY syndrome), the syndrome caused by the deletion of chromosome 13. Trisomy 21 is associated with a higher risk of developing acute leukemia and solid tumors (10-20 x). Chromosome 13 deletion syndrome is associated with high risk of bilateral retinoblastoma.
Polyposis syndromes of hereditary colon (Turcot, Gardner) are associated with a high risk of malignancy.
Peutz-Jeghers syndrome predisposes to cancer of the colon, breast cancer with the phenotypic markers: hyper pigmented spots in the oral region, oral mucosa, and extremities.
Xeroderma pigmentosum (rare inherited disorder characterized by defective transmitted recessive DNA repair) causes multiple skin cancers in people exposed to UV radiation during childhood. Originally, there are some blisters at birth, small erythematous bumps, then they become hyper or hypo pigmented. At 3-4 years, benign cutaneous tumors appear, which turn into melanomas, cancers of the eyelids, cancer of the cornea associated with mental retardation, epilepsy.
Fanconi Anemia (hereditary transmission, with phenotypic markers like anemia, microcephaly, low height, horseshoe kidney, skin pigmentation, eye abnormalities) predisposes to acute myeloid leukemia, cancers of the mucocutaneous junctions, liver cancer.
Vincent Plummer syndrome – young women with iron deficiency anemia due to esophageal dysphagia caused by a diaphragm. This disease requires endoscopic surveillance because it is associated with an increased risk of esophageal cancer.
Ataxia syndrome (hereditary transmission, consisting of: progressive cerebellar ataxia, ocular and cutaneous teleangectasy, immune deficiency) predisposes to the appearance of lymphomas.
Recklinghausen Neurofibromatosis (autosomal dominant transmission) – neurofibromas, brown pigmented spots, molluscum – frequently evolves into sarcomas and predisposes to the occurrence of cerebral gliomas.
Multiple hereditary cancers: Li-Fraumeni syndrome (defect in the p53) is associated with an increased risk of breast or colon cancer, brain cancer, sarcoma, leukemia. Cowden disease can determine, in addition to the skin hamartomas, breast cancer in 30-50% of the cases or thyroid cancer.
Crohn’s disease shows an increased risk for colon cancer.
Chronic atrophic gastritis shows risk of malignancy.
Testicular dysgenesis associated with cryptorchidism is malign in 70% of the cases. Cryptorchidism has a major risk of malignant transformation. Orhidopexia does not prevent testicular cancer if performed late.
Senile keratosis – commonly associated with cutanate cancers – baldness, skin lesions, superficial brown hyperkeratotic plaques. A particular form is the cutaneous horn, located on the lower lip.
Scleroatrophic lichen or vulvar kraurozis affects women over 50 years, consists of vulvar itching, burning on urination, dyspareunia (pain during intercourse), discoloration of the vulva that has a white or yellowish color. Can develop vulvar malignancies requiring supervision of the lesion, and in case of spotting, biopsy is required.
2. Precursor or precancerous lesions: appear as a result of known external or internal risk factors . The primary lesions are diffuse, multifocal and involve altering the genetic material of cells.
From a histological point of view, precursor lesions are classified into different degrees of severity: metaplasia → dysplasia → hyperplasia → carcinoma in situ.
Hyperplasia is characterized by the excessive production of a certain type of tissue histologically normal. It may be typical or atypical.
Metaplasia is the transformation of morphological and functional differentiated tissue into another differentiated tissue: epithelial squamous metaplasia in the urothelium with the development of squamous-type tumors in the bladder; cylindrical epithelium metaplasia in squamous epithelium, apocrine metaplasia of the mammary gland epithelium.
Dysplasia consists of both architectural and cytological abnormalities that occur in adult tissues.
Dysplastic lesions may remain a long time in the state of reversibility, but at that time they may most easily become malignant.
There are three degrees of dysplasia described: mild, moderate and severe (carcinoma in situ).
Carcinoma in situ is considered by some authors a precursor lesion, while others consider it an early cancer that has 100% chance of healing if properly treated, corresponding to stage 0.
The following are some of the precancerous lesions exemplified:
The presence of certain benign proliferation in the mammary gland is associated with an increased risk of developing invasive carcinomas. These lesions are often multifocal, presenting a risk of progression to invasive carcinoma of 10-30%.
This proliferation is:
Moderate and severe hyperplasia, ductal or lobular
Sclerosing adenomatosis (increases the risk of breast cancer 1.5- 2 times)
Carcinoma in situ
Carcinogenesis in breast cancer:
Normal epithelium -> atypical hyperplasia ->cancer in situ -> invasive breast cancer.
Atypical ductal or lobular hyperplasia increases the risk of breast cancer 4-5 times than the normal population.
Ductal carcinoma in situ is regarded as a real precancerous lesion preceding invasive cancer as opposed to lobular carcinoma in situ, which is more a measure of the risk of breast cancer.
Patients with a family history of breast cancer associated with personal history of atypical hyperplasia, present an increased risk of breast cancer 8 times only to those with a family history and 11 times more than the population without risk factors.
The presence of Barrett’s esophagus (adenomatosis metaplasia, severe dysplasia in the distal esophagus caused by esophageal reflux) is associated with an increased risk of esophageal cancer.
Gastric intestinal metaplasia is a common premalignant lesion and appears in 80% of the parts of gastrectomy in Japan.
Pancreatic premalignant lesions are: atypical ductal hyperplasia and ductal hyperplasia papillary and non-papillary, whose potential for malignant transformation is determined by identifying the mutated K-ras genes, using PCR. This method could be used in screening using secretions such as bile and pancreatic juice.
Leukoplakia or erythroplasia of Queyrat are precursor lesions to cancers of the upper aero-digestive tract.
Dysplastic adenomatous polyp is the main precancerous lesion in the colon.
Colorectal carcinogenesis follows this path: normal epithelium → hyperplasia → early adenoma → intermediate adenoma→ late adenoma → cancer in situ → invasive cancer.
For preinvasive lesions of the cervix the Bethesda classification is used in the USA, which divides dysplastic epithelial abnormalities into:
Atypical changes with uncertain significance
Low-grade squamous intraepithelial lesions
Intraepithelial lesions with increased risk, comprising CIN II (moderate dysplasia), CIN III (severe dysplasia), carcinoma in situ
Endometrial hyperplasia with atypic cytology is considered severe cytologic precancerous lesion for endometrial cancer.
Precancerous skin lesions are
Bowen’s disease (intraepithelial epidermoid carcinoma of the skin and mucous membranes) which is a rare condition represented by papiliforme skin lesions with umbilical center, bluish brown, translucent, polycyclic. They have malignant transformation potential within 5-10 years.
Paget’s nipple disease, which is manifested through erythematous plaques and which may correspond to an underlying intracanalicular breast cancer or invasive cancer.
Dysplastic nerves, which can be congenital or acquired, are precursors of malignant melanoma.
Solar keratosis – skin lesions appear on the areas exposed to the sun, which are irregular, variable in color, covered with scaly keratotic skin and have a high risk of malignancy.
The precancerous lesions should be properly diagnosed and treated as they are considered a major risk factor for cancer. The development of precancerous conditions varies from several years to several decades. This range is important because of the possibility to identify and treat the lesions.