Neoplasia

NEOPLASIA

Dr Mustafa Salah Fadhil MSc, FIBMS path

Premalignant conditions:

Conditions having ↑ risk of association with cancer

A- malignant change in benign tumors : e.g.

1- Colonic adenoma (esp. Villous adenoma & Familial adenomatous polyposis (FAP) of colon)
2- Neurofibroma

B-Intraepithelial neoplasia “dysplasia” :

-The epithelial cells show the cytological features of malignancy but have not yet developed the ability to invade adjacent normal tissues.
It can affect epithelia of all types.
squamous, transitional (e.g. bladder) and glandular (e.g. stomach).
e.g. cervical intraepithelial neoplasia (CIN).

C- malignancy developing in chronic inflammation :

Chronic damage & repair during chronic inflammation may lead to cancer ,e.g.

1- Long standing ulcerative colitis → colonic cancer

2- Hashimotos’ thyroiditis → lymphoma
3- Ch. Hepatitis→ Liver Cirrhosis → hepatocellular carcinoma.
4- Reflux esophagitis (Barrett esophagus) → esophageal carcinoma.

Laboratory Diagnosis of Cancer

Although clinical, radiological and biochemical findings all contribute towards the diagnosis of a tumor, the final diagnosis is made in almost all cases by microscopic examination.
Histologic and Cytologic Methods
(1)Histopathology:
• Excisional or incisional biopsy
• Core needle biopsy (deep-seated ones under radiological control, can be sampled by needle biopsy in which a thin core of tissue is removed).
(2) Cytology
- Fine needle aspiration cytology(FNAC)
- Cytological smears (screen for carcinoma of the cervix)

Additional techniques :

Some of tumors are undifferentiated and very difficult to reach the diagnosis by H&E stain.
So we need additional techniques to reach final diagnosis and give the proper treatment, so may need:
Electron microscope
Immunohistochemistry: special technique which is depended on antigen –antibody reaction (using antibodies to cell constituents)

Molecular and Cytogenetic Diagnostics.

- Polymerase chain reaction (PCR)
- In-situ hybridization (e.g. FISH): used to detect gene expression as a way of determining tumor type

Tumor Markers

These are substances produced by tumor cells
They are detectable in the blood
Are of value in:
Diagnosis of tumor
Monitoring progress following treatment or detect recurrence

Tumor

Marker
Carcinomas of the colon, pancreas, stomach, and breast
Carcinoembryonic antigen (CEA)
Hepatocellular carcinomas, yolk sac tumor
Alpha-fetoprotein (AFP)
Ovarian tumors,
CA-125
Prostate cancer
Prostate-specific antigen (PSA)
Choriocarcinoma and some testicular tumors
Human chorionic gonadotropin (hCG)
Medullary carcinoma of thyroid
Calcitonin
Carcinoid
5- HIAA
Pheochromopcytoma
vanillyl mandilic acid (VMA)


Causes of Neoplasia:

Cancer is not a single disease, it is most common in adults older than 60 years of age, but can occur in adults at all ages, in children and infants.

The origin for many neoplasm is obscure

However, both genetic and environmental factors contribute to the development of cancer.

I) Environmental Factors

Account for over 80% of human tumors
1- Chemical Carcinogens:
- Alkylating agent (Chemotherapy) → Leukemia
- Aniline dyes → bladder cancer
- Cigarette smoke → lung cancer
- Aflatoxine → hepatocellular carcinoma.
- Benzene→Acute myeloid leukemia
- Asbestos→ Mesothelioma.

2- Oncogenic viruses:

RNA viruses:
Human T-cell leukemia virus type 1 (HTLV-1) → adult T-cell leukemia/lymphoma
HCV→ hepatocellular carcioma


DNA viruses:
Human papilloma virus (HPV)
high-risk HPV(types 16 & 18)→Squamous cell carcinoma of cervix
hepatitis B virus (HBV)→ hepatocellular carcinoma.
Epestein Barr virus (EBV) → Burkitt’s lymphoma and Nasopharyngeal carcinoma
Herpes virus 8 → Kaposi sarcoma

3- Radiation

- UV light→ skin cancer
- Ionizing radiation →thyroid, lung , colon and Breast cancer.
4- Geographical Variations
-American women have breast cancer more often than Japanese women while Japanese and chinese men have stomach cancer far more often than American men.
5- Diet
6- Others as obesity, alcohol consumption

II) Genetic Factors:

E.g.
-Familial adenomatous polyposis coli: (APC) gene (autosomal dominant) characterized by the growth of numerous adenomas in the colon and the almost inevitable development of colonic carcinoma by middle age.


-Familial retinoblastoma: retinoblastoma gene (Rb) lies on the long arm of chromosome 13.

-Familial breast carcinoma: BRCA1 and BRCA2 genes .

Familial Polyposis coli, with numerous small polyps covering the colonic mucosa. there is a 100% risk over time for development of adenocarcinoma

Carcinogenesis

is a multistep process:
I-Initiator: (carcinogenic agent) lead to irreversible DNA damage however, is not sufficient for tumor formation.

-Direct-acting carcinogens: require no metabolic conversion to become carcinogenic e.g. Alkylating agent like cyclophosphamide .

-Indirect-acting carcinogens: require metabolic conversion to become active carcinogens. e.g. aflatoxin


II-Promotors: Lead to proliferation of mutagenic cells (initiated cells), they are nontumorigenic by themselves but they there appears to be a "dose-threshold" concentration of promoter below which neoplasia will not occur. eg: hormone therapy estrogen.

Molecular basis of cancer

• Nonlethal genetic damage, the initial damage (or mutation) may be :
A) Acquired by environmental factors such as:
- Radiation
- Chemical substances
- Viruses
B) Inherited in the germ line cells , e.g. Familial adenomatous polyps (APC gene) autosomal dominant disorder.

• A tumor is formed by the clonal expansion of a single precursor (progenitor) cell that has incurred genetic damage (i.e., tumors are clonal).



• Involvement of normal regulatory genes. Four classes of normal regulatory genes are involved in carcinogenesis:
• Proto-oncogenes.
• Tumor Suppressor Genes.
• Programmed cell death genes.
• DNA repair genes.

Thanks