Differentiation
Definition
The extent to which tumor cells resemble the cell of origin.
Resemblance to parent cells or cells of origin
There are three degrees of differentiation:
- Well differentiated –completely resemble
- Moderately differentiated –some resemblance
- Poorly differentiated/undifferentiated
Anaplasia
Lack of differentiation.
Considered as hallmark of malignant tumors. Different morphological changes are seen in anaplasia:
a. Pleomorphism
Change in size and shape of cell or nucleus. E.g. smooth muscle spindle tumor.
b. Mitosis (abnormal)
Tumors may have large number of mitosis but these may be seen in benign tumors or even hyperplasia.
Presence of abnormal, bizzare mitosis is the feature of malignancy.
c. Abnormal nuclear morphology
- Pleomorphic nuclei.
- Abundant DNA –become hyperchromatic (chromatin condenseàbasophilic stain)
- Coarse clumped chromatin,
- Distributed along nuclear membrane
- Nucleoli become prominent
- Change in nucleus to cytoplasmic ratio i.e. 1:1 (normal 1:4 or 1:6)
d. Loss of polarity
It is disturbed orientation of anaplastic cells.
Sheets and large masses of tumor cells grow in disorganized fashion.
e. Tumor giant cells (not constant feature)
Presence of large tumor cells in some malignant neoplasms.
Giant cell may possess a single huge nucleus or multiple nuclei.
Ischemic Necrosis
Growing tumor cells require blood supply. In many tumors, vascular stroma is less, so the centre of tumor area undergoes necrosis.
Architecture of cell is retained.
Dysplasia –seen in epithelial type of tumors
Disordered growth.
Definition
Loss in uniformity of individual cells as well as a loss in architecture orientation.
Cellular changes
Dysplastic cells possess:
- some degree of pleomorphism
- Hyperchromatic nuclei
- Abnormal mitosis
Dysplasia does not necessarily progress to cancer.
Degrees of dysplasia
Normal glandular epithelium (mucin secreting gland)
Mild moderate dysplasia
Seen in few layers of epithelium
Severe dysplasia (carcinoma in situ)
When all dysplastic changes seen in whole epithelial thickness but remain confined above the basement membrane. Basement membrane is intact.
Growth rate of tumors
Most malignant tumors grow more rapidly than do the benign tumors.
Aggressive tumors containing large pool of dividing cells respond quickly to chemotherapy as most anti-cancer agents act on cells that are in cycle.
Slow growing tumors have a peripheral compressed form, thus a capsule is present in benign tumors
Malignant tumors are rapidly growing, they infiltrate masses thus there is no chance of capsule formation
Local invasion
Normally all benign tumors grow as cohesive masses and remain localized.
They grow and expand and develop a rim of compressed connective tissue known as capsule.
Growth of cancer is rapid with infiltration and damage to surrounding structure.
Carcinoma in situ remains localized.
Metastasis
Metastasis involves tumor implants discontinuous with primary tumor.
Benign tumors do not spread.
With few exceptions, all cancers have property of metastasis:
- Gliomas in CNS
- Basal cell carcinoma in skin
Pathway of spread
- Seeding of body cavities
- Lymphatic spread
- Hematogenous spread
Nomenclature
Nomenclature includes cell of origin + suffix
Suffix for benign tumors is “oma”.
While that for malignant is divided into:
- For epithelial origin “carcinoma”
- For mesenchymal origin “sarcoma”
Fibroma | Fibrosarcoma |
Osteoma | Osteosarcoma |
Adenoma | Adenocarcinoma |
Chondroma | chondrosarcoma |
Exceptions include:
- Leukemia
- Lymphoma
- Glioma
Comparison of Benign and Malignant Tumors
Benign |
Malignant |
|
Differentiation | Well-differentiated | Poorly differentiated |
Anaplasia | Not a feature | Feature |
Pleomorphism | Cells are normal | Pleomorphism present |
Hyperchromatic cells | Absent | Present |
Nuclear chromatin | Normal distribution | Coarse, arranged along nuclear membrane |
Nucleus cytoplasm ratio | 1:6 | 1:1 |
Nuclear shape | Normal | Variable |
Mitotic number | Normal | Greater |
Abnormal mitosis | Absent | Tripolar, tetrapolar or even multipolar mitotic figures seen |
Loss of polarity | Absent | Present |
Dysplasia | Absent | Present |
Tumor giant cells | Absent | Present |
Ischemic necrosis | Absent | May be present |
Nomenclature | “oma” | “osteoma” or “sarcoma” |
Rate of growth | Slow | Aggressive |
Local invasion | Absent | Present |
Metastasis | Absent | Present |
Capsule | Present | Absent |
Effect on host | Slight harm | Significant harm |
Grading and staging | Not required | Done for treatment option selection |
Treatment | Surgical removal is sufficient | Aggressive treatment with chemotherapy/radiotherapy or surgery |