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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/