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Neoplasia
Definition:
A neoplasm is an abnormal mass of tissue, the growth of which is virtually autonomous and exceeds that of normal tissues. Unlike non-neoplastic proliferations (like hyperplasia, regeneration, and repair), the growth of neoplasms persist even after the cessation of the stimuli that have initiated the change.
Neoplasms (tumors) are generally classified into two broad categories, benign and malignant.
Nomenclature:
All neoplasms have two basic components:
1- The "transformed" neoplastic cells (the parenchyma).
2- The supportive stroma (non-neoplastic like connective tissues & blood vessels).
Classifications of neoplasms are based on their parenchymal components.
Benign tumors, in general, their names end with the suffix "oma".
Benign mesenchymal tumors are named after their tissue of origin +"oma".
Examples:
Leiomyoma (smooth muscle)
Lipoma (fatty tissue)
Chondroma (cartilage)
Benign epithelial tumors are named after their tissue of origin, sometimes combined with "oma".
E.g. adenomas are tumors arising from or differentiating to glandular tissues, Cystadenomas as adenomas but with cystic components.
Papillomas characterized by the production of finger like projections.
Malignant tumors are generally called cancers. Their nomenclature is based on their appearance (the morphology of their parenchymal cells) and the presumed tissue of origin.
They are broadly divided into two categories:
1- Carcinomas arising from epithelial cells e.g.
Squamous cell carcinomas, adenocarcinomas…etc
2- Sarcomas arising from or differentiating towards mesenchymal tissues e.g.
Osteosarcoma (bone)
Leiomyosarcoma (smooth muscle)….etc
Some tumors have more than one parenchymal cell type, these include:
1- Teratomas, which are tumors of germ cell origin; they show differentiation along all the three germ layers (ectoderm; like skin and its adnexae such as hair, endoderm; like gut epithelia and mesoderm; like bone, cartilage and muscle…etc), thus a variety of parenchymal cell types (and tissues) may be seen in these neoplasms.
e.g. teratoma of the ovary.
2- Mixed tumors; these differ from teratomas in that they are derived from one germ cell layer, and differentiate into more than one parenchymal cell type.
e.g. pleomorphic adenoma of salivary glands.
Exception to the above rules include tumors that are always malignant such as
Lymphomas, melanomas, and seminomas….etc.
Non-neoplastic masses:
Choristoma is a non-neoplastic ectopic rests of tissue e.g. ectopic pancreatic tissue in gastric wall. (it is histologically similar to the original tissue but is present in an abnormal site.
Hamartoma is a malformation that presents as a mass of disorganized tissue indigenous to the particular site from which it has originated i.e. the constituent tissues are normally present at the site but their relative proportions are different from normal.
e.g. melanocytic nevi.
& Lung hamartoma.
Comparison between benign and malignant tumors
Benign tumors Malignant tumors
Mode of growth - Expansion,
- Remain localized. - Infiltrates locally& metastasizes.
Rate of growth slower faster
Histological features - Similar to tissue of origin.
- Nuclei are normal,
- Cells uniform in size and shape. - Many differ from tissue of origin.
- Enlarged pleomorphic, hyperchromatic, prominent nucleoli, increased mitotic activity & abnormal mitosis.
Clinical effects - Local pressure effects.
- Hormone secretion.
- Cured by adequate excision. - Local pressure and tissue destructive effects.
- Inappropriate hormone secretion / paraneoplastic syndromes.
- Not cured by local excision because of metastasis.
Differentiation and anaplasia:
Differentiation is the extent to which tumor cells resemble comparable normal cells of the tissue of origin. In most benign tumors constituent cells closely mimic normal cells. Malignant tumors display a range of differentiations (well differentiated, moderately differentiated, & poorly differentiated carcinomas). This range of differentiation forms the basis of tumor grading.
Lack of differentiation is referred to anaplasia and the tumor is called anaplastic tumor.
Histopathological features of anaplasia:
1- Cellular & nuclear pleomorphism.(variation in size and shape of cell and nuclei).
2- Hyperchromatism.(dark stain nuclei due to abnormal increased chromatin).
3- Increased nuclear-cytoplasmic ratio(N/C).(may reach 1:1 instead of normal 1:4 or1:6).
4- Abundant mitoses.(increased proliferation).
5- Abnormal mitoses.(tripolar instead of normal bipolar mitosis).
6- Tumor giant cells.
7- Prominent nucleoli.
8- Cytoplasmic basophilia.(due to active protein synthesis).
9- Loss of orientation & disarray of tissue architecture (loss of polarity).
Rate of growth:
Most cancers grow faster than benign tumors.
Some cancers are hormone sensitive & their rate of growth may be affected by variation in hormone levels associated with pregnancy & menopause (e.g. breast cancer).
Local invasion:
Most benign tumors grow as cohesive expansile masses that develop a rim of condensed connective tissue (capsule) at the periphery which facilitates its surgical removal.
Malignant tumors are invasive, they invade, destroy normal surrounding tissues & lack a well defined capsule, and thus their enucleation is impossible so their surgical removal requires removal of a safety margin of healthy uninvolved tissue.
Metastasis:
This process involves invasion of blood vessels, lymphatics and body cavities by the malignant tumor cells, followed by their transport & eventually growth of deposits of tumor cells within the new site. These masses are discontinuous with the primary tumor. these new masses are called secondaries or metastatic foci.
Metastasis is the absolute criterion of malignancy.
Pre-invasive malignancy:
Recently, cancer screening programs have emphasized the prevalence of lesions, which appear to represent the early stages of cancer development. E.g. dysplasia and intraepithelial neoplasia.
PARANEOPLASTIC SYNDROMES:
Definition
Symptoms not directly related to the primary tumor or its metastasis or elaboration of hormones indigenous to the tissue from which the tumor arose.
Paraneoplastic syndromes may be the earliest manifestation of a tumor and may mimic distant spread.
Grading and staging of tumors:
Grading is the degree of tumor differentiation. Thus grade 1 is "well differentiated" while grade 3 is "poorly differentiated" and grade 2 lies in-between grade 1 & 3.
Staging is the extent of tumor spread.
The commonest staging system presently in use is the TNM (Tumor, Node, and Metastasis) staging system.
Both grading and staging of tumors are valuable for the:
1- Determination of prognosis.
2- Planning of therapy.
Laboratory diagnosis of cancer:
I. Histological and cytological methods;
A. Histological methods. Are the most important in diagnosis, including the quick frozen section used intraoperatively.
B. Cytological methods. E.g fine needle aspiration (with or without ultrasound or CT scan guided), exfoliative cytology and brush cytology.
II. Immunohistochemistry; which involves the detection of cell products or surface markers of malignant cells by monoclonal antibodies.
III. Molecular diagnosis- DNA probe analysis.
IV. Flowcytometry; which measure the DNA content of tumor cells.
V. Tumor markers; these are tumor derived or associated antigens, enzymes, proteins and hormones that can be detected in blood or other body fluids. They are not primary methods of diagnosis but are useful adjuncts. They are also important in monitoring therapy & in early detection of relapse.
e.g. prostatic specific antigen PSA in prostatic cancer, CA-125 in ovarian cancer, and carcinoembryonic antigen CEA in colon & stomach cancers.
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