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) is
important, if left, such lesions might progress to
become invasive, whereas early detection and
treatment is often curative.


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 squamous
cell carcinoma
Villous adenomas of the colon colorectal carcinoma
Dysplasia
Any disordered growth and maturation of an epithelium,
which is still reversible if the factors driving it are
eliminated.
Disorderly but non-neoplastic proliferation.
Pre-malignant lesion
Graded as mild, moderate, severe
Severe dysplasias represent a more advanced progression
towards malignant transformation, and the risk of
transforming into cancer is high.
Carcinoma in situ is thought by some to be a
premalignancy but others regard it as evidence of actual
malignant change but without invasion.
Microscopic Features of Dysplasia
Loss in uniformity
Nuclear & cellular pleomorphism marked variation in
size & shape
Nuclear abnormalities
Increased nuclear-to-cytoplasmic ratio (approach 1:1)
Prominent or multiple nucleoli
Hyperchromatic nuclei
Increased rate of cell proliferation
Increased number of mitotic figures appear in abnormal
locations
Architectural Changes
The precursor lesions of squamous cell carcinomas may antedate the
appearance of invasive tumor by years. Some of the earliest (and "mild")
changes in smoking-damaged respiratory epithelium include goblet cell
hyperplasia (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 of
nuclear polarity, nuclear hyperchromasia, 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 invasive
squamous 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.
Dysplasia may progress to a pattern of carcinoma-in-
situ (cytologic features are fully developed cancer do
not infiltrate below the basement membrane)
Normal epithelium
process of genomic instability
goes through an initial stage of hyperplasia
several stages of preinvasive neoplasia (mild, moderate
and severe dysplasias)
Carcinoma
Dysplasia vs. Neoplasia
Neoplasm - abnormal mass of tissue, the growth
of which exceeds and is uncoordinated with that
of the surrounding normal tissues and persists in
the same excessive manner after cessation of the
stimuli that evoked the change.

Molecular
Basis of
Cancer
Mutation in no single
gene is sufficient to
cause cancer.
Cancer develops when
multiple mutations
involving multiple
genes accumulate.
Genes that are important in making a cell cancerous:
Oncogenes - encourage the cell to multiply
Tumour Suppressor Genes - stop the cell from
multiplying
DNA Repair Genes - repair other damaged genes
Genes that regulate apoptosis


Mutation
Mutations can happen by chance when a cell is
reproducing.
Cells often destroy themselves if they have a mutation
or the immune system might recognise them as
abnormal and kill them. Most precancerous cells die
before causing cancer.
Hereditary predisposition to a type of cancer - higher
risk of cancer
Inherited Predisposition to Cancer
Chemical Carcinogens
Carcinogenic Agents
Radiation
Viral and Microbial:
Human Papillomavirus
Epstein-Barr Virus
Hepatitis B & Hepatitis C Viruses
Helicobacter pylori
Multistep pancreatic carcinogenesis. The progression of
pancreatic neoplasia from pre-malignant pancreatic
lesions (PanIN, left) to carcinoma (right)
Preneoplastic Lesion
Cervix: precursors of invasive cervical
cancer
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)

Lung:
precursors of Squamous cell
carcinoma
Squamous dysplasia
Atypical adenomatous
hyperplasia
Diffuse idiopathic pulmonary
neuroendocrine cell hyperplasia

Oral:
Leukoplakia
Erythroplakia
Oral Submucous Fibrosis

Breast, Uterine endometrium
Atypical hyperplasia
Dysplasia
Carcinoma-in-situ


Carcinoma in Situ (CIS) of Cervix
- Some of the cervix cells have cancerous changes but the
abnormal cells are all contained within the surface layer of
the cervix.
- In molecular terms it is probable that the genetic
abnormalities allowing metastasis have not yet developed.

Dysplasia --- CIS --- Cervical cancer

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

CIS might develop into a cancer after some years.
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 need
careful 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)

Ideal conditions that trigger the conversion of
premalignant conditions to cancer are not always
present and sometimes these conditions do not
develop into full-blown cancer. But the threat is always
present and needless to say better safe than sorry.

--- Paul M Speight,
PhD, FDSRCPS, FRCPath
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
Preventionedited by Eduardo L. Franco, Thomas E. Rohan
Medline Plus http://www.nlm.nih.gov/medlineplus/
WHOs cervical cancer screening programmes: managerial
guidelines Naila Baig Ansari, The Aga Khan University,
Pakistan
Pre-Cancerous Lesions - Condition Medindia
http://www.medindia.net/