Precursors of Cancer

8/10/2019 Precursors of Cancer

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Preneoplastic Disorders Conditions that are well recognized predispositions to

the development of malignant neoplasia (cancer).

In most instances cancer does not develop

The diagnosis of precancerous stage (precursor) isimportant, if left, such lesions might progress to

become invasive, whereas early detection andtreatment is often curative.


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Example of Preneoplastic

Conditions Persistent regenerative cell replication hepatocellular

carcinoma in cirrhosis of the liver

Hyperplastic and dysplastic proliferations Chronic atrophic gastritis gastric carcinoma in

pernicious anaemia or H. pylori infection

Chronic ulcerative colitis colorectal carcinoma

Leukoplakia of oral cavity, vulva or penis squamouscell carcinoma

Villous adenomas of the colon colorectal carcinoma


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The precursor lesions of squamous cell carcinomas may antedate theappearance of invasive tumor by years. Some of the earliest (and "mild")changes in smoking-damaged respiratory epithelium include goblet cellhyperplasia (A),basal cell hyperplasia (B),and squamous metaplasia (C).

More ominous changes include the appearance of squamous dysplasia (D),characterized by the presence of disordered squamous epithelium, with loss ofnuclear polarity, nuclearhyperchromasia, pleomorphism, and mitotic figures.Squamous dysplasia may, in turn, progress through the stages of mild,moderate, and severe dysplasia.

Carcinoma-in-situ (CIS) (E)is the stage that immediately precedes invasivesquamous carcinoma (F),and apart from the lack of basement membrane

disruption in CIS, the cytologic features are similar to those in frank carcinoma.Unless treated, CIS will eventually progress to invasive cancer.


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Dysplasia may progress to a pattern of carcinoma-in-situ (cytologic features are fully developed cancer donot infiltrate below the basement membrane)

Normal epithelium

process of genomic instability

goes through an initial stage of hyperplasia

several stages of preinvasive neoplasia (mild, moderateand severe dysplasias)

Carcinoma


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Dysplasia vs. Neoplasia

Neoplasm - abnormal mass of tissue, the growthof which exceedsand is uncoordinatedwith thatof the surrounding normal tissues and persists inthe same excessive manner after cessation of

thestimulithat evoked the change.


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Molecular

Basis ofCancer

Mutation in no singlegene is sufficient tocause cancer.Cancer develops when

multiple mutationsinvolving multiplegenes accumulate.


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Genes that are important in making a cell cancerous:

Oncogenes - encourage the cell to multiply

Tumour Suppressor Genes - stop the cell frommultiplying

DNA Repair Genes - repair other damaged genes

Genes that regulate apoptosis


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Mutation Mutations can happen by chance when a cell is

reproducing.

Cells often destroy themselves if they have a mutationor the immune system might recognise them asabnormal and kill them. Most precancerous cells diebefore causing cancer.

Hereditary predisposition to a type of cancer - higherrisk of cancer


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Inherited Predisposition to Cancer


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Chemical Carcinogens


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Preneoplastic Lesion

Cervix: precursors of invasive cervicalcancer

Cervical intraepithelial neoplasia grade 1 (CIN I)- mild dysplasia,

CIN II moderate dysplasia,

CIN III severe dysplasia & carcinoma in situ

Prostate:

Prostate intraepithelial neoplasia (PIN),

Atypia adenomatous hyperplasia (AAH)

Skin:

Dysplasia nevi (DN) precursor of melanoma

Colorectum:

Adenomatous polyps precursor of colorectal cancer

(dysplastic epithelial glands)


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Lung:precursors of Squamous cellcarcinoma

Squamous dysplasia

Atypical adenomatoushyperplasia

Diffuse idiopathic pulmonaryneuroendocrine cell hyperplasia

Oral: Leukoplakia

Erythroplakia

Oral Submucous Fibrosis

Breast, Uterine endometrium Atypical hyperplasia

Dysplasia

Carcinoma-in-situ


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Carcinoma in Situ (CIS) of Cervix

- Some of the cervix cells have cancerous changes but theabnormal cells are all contained within the surface layer ofthe cervix.

- In molecular terms it is probable that the geneticabnormalities allowing metastasis have not yet developed.

Dysplasia --- CIS --- Cervical cancer

Human papillomavirus (HPV DNA is present 93% ofcervical cancer and its precursor lesions)

CIS might develop into a cancer after some years.


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CIS of Cervix

Carcinoma in situ can be found during cervical screening tests. Treatment depends on the degree of dysplasia.

Mild dysplasia (CIN I) may go away without treatment but needcareful observation with repeat Pap smears every 3 - 6 months. If the changes do not go away or get worse, treatment is

necessary:

Cryosurgery to freeze abnormal cells Laser therapy, which uses light to burn away abnormal tissue LEEP (loop electrosurgical excision procedure), which uses

electricity to remove abnormal tissue Surgery to remove the abnormal tissue (cone biopsy)


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Ideal conditions that trigger the conversion ofpremalignant conditions to cancer are not alwayspresent and sometimes these conditions do not

develop into full-blown cancer. But the threat is alwayspresent and needless to say better safe than sorry.

--- Paul M Speight,PhD, FDSRCPS, FRCPath


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Resources Robins Basic Pathology, Kumar, Abbas & others

Core Pathology, Stevens, Lowe, Scott

Cancer Research UK http://www.cancerresearchuk.org/

Current Health Sciences Journal http://www.chsjournal.org/

An overview of the classification and predictive value of oral

epithelial dysplasia Paul M Speight, University of Sheffield, UK Cancer Precursors: Epidemiology, Detection, and

Preventioneditedby Eduardo L. Franco, Thomas E. Rohan

Medline Plus http://www.nlm.nih.gov/medlineplus/

WHOs cervical cancer screening programmes: managerialguidelines Naila Baig Ansari, The Aga Khan University,Pakistan

Pre-Cancerous Lesions - Condition Medindiahttp://www.medindia.net/

Documents

Precursors of Cancer