Characteristics of Benign and Malignant Neoplasms 

The difference in characteristics of these neoplasms can be conveniently discussed under the following headings:

1.  Differentiation & anaplasia

2.  Rate of growth

3. Local invasion

4. Metastasis

1. Differentiation and anaplasia 

 -  Differentiation refers to the extent to which parenchymal cells resemble comparable normal cells both morphologically and functionally. Thus, well-differentiated tumours cells resemble mature normal cells of tissue of origin. Poorly differentiated or undifferentiated tumours have primitive appearing, unspecialized cells. In general, benign neoplasms are well differentiated. Malignant neoplasms in contrast, range from well differentiated, moderately differentiated to poorly differentiate types. Malignant neoplasm composed of undifferentiated cells are said to be anaplastic, literally anaplasia means to form backward.

-  Morphology of anaplastic cell includes large Pleomorphic; hyperchromatic nucleus with high nuclear cytoplasmic ratio 1:1(normally 1:4 to 1:6). The cell usually reveals large nucleoli with high and often abnormal mitoses. Tumour giant cells and frequent loss of polarity of epithelial arrangements are encountered. 

-  On functional differentiation, the well differentiated the neoplasm, the more completely it retains the functional capabilities found in its normal counterparts thus, endocrine tumours produce hormone (ex. Thyroid, adrenal) so also, well differentiated squamous cell carcinoma and well differentiated hepatocellular carcinomas produce keratine and bile respectively. 

-  However, highly anaplastic or undifferentiated cells of what cell tissue of origin come to resemble each other functionally and morphologically more than the normal cells which they have arisen this is called chemical convergence. 

2. Rate of growth 

 -  Most benign tumours grow slowly whereas; most malignant tumours grow rapidly sometimes, at erratic pace. Some benign tumours for example uterine leiomyoma increase in size during pregnancy due to probably steroidal effects (estrogen) and regress in menopause.  In general, the growth rate of neoplasms correlate with their level of differentiation and thus, most malignant neoplasms grow more rapidly than do benign neoplasms. On occasions, cancers have been observed to decrease in size and even spontaneously disappear. Examples include renal cell carcinoma, malignant melanoma, choriocarcinoma.      

3. Local invasion 

 -  Nearly all benign neoplasms grow as cohesive expansile masses that remains localized to their site of origin and do not have the capacity to invade or metastasize to distant sites, as do malignant neoplasms. 

-  Rims of fibrous capsules encapsulate most benign neoplasms. However, hemangiomas and neurofibromas are exceptions. Thus, such encapsulations tend to contain the benign neoplasms as a discrete, rapidly palpable and easily movable mass  that can easily surgically enucleated.  

-  The growth of malignant neoplasms is accompanied by progressive infiltration, invasion and destruction of the surrounding tissue. Generally, they are poorly demarcated from the surrounding normal tissue (and a well-defined cleavage plane is lacking). 

-  Next to the development of metastasis, invasiveness is the most reliable feature that differentiates malignant from benign neoplasms.

-  Even though, malignant neoplasms can invade all tissues in the body, connective tissues are the favoured invasive path for most malignant neoplasms, due to the elaboration of some enzymes such as type IV collagnases & plasmin, which is specific to collagen of basement membrane. Several matrix-degrading enzymes including glycosidase may be associated with tumour invasion.

-   Arteries are much more resistant to invasion than are veins and lymphatic channels due to its increased elastic fibers contents and its thickened wall. Densely compact collagens such as membranous tendons, and joint capsules. Cartilage is probably the most resistant of all tissues to invasions and this is may be due to the biologic stability and slow turnover of cartilage.

Sequential steps in mechanisms of tumor invasion & metastasis:

a. Carcinoma in-situ 

b.  Malignant cell surface receptors bind to basement membrane components (ex laminin).

c.  Malignant cell disrupt and invade basement membrane by releasing collagenase type IV and other protease. 

d.  Invasion of the extracellular matrix 

e. Detachment

f. Embolization

g.  Survival in the circulation

h. Arrest

i. Extravasation

j.  Evasion of host defense

k. Progressive growth

l. Metastasis

Most carcinomas begin as localized growth confined to the epithelium in which they arise. As long as this early cancers do not penetrate the basement membrane on which the epithelium rests such tumours are called carcinoma in-situ.  In those situations in which cancers arise from cell that are not confined by a basement membrane, such as connective tissue cells, lymphoid elements and hepatocytes, an in-situ stage is not defined. 

4. Metastasis

-  It is defined as a transfer of malignant cells from one site to another not directly connected with it (as it is described in the above steps). 

-  Metastasis is the most reliable sign of malignancy. The invasiveness of cancers permits them to penetrate in to the blood vessel, lymphatic and body cavities providing the opportunity for spread. 

-  Most malignant neoplasm metastasies except few such as gliomas in the central nervous system, basal cell carcinoma (Rodent ulcer) in the skin and dermatofibrosarcoma in soft tissues. 

-  Organs least favoured for metastatic spread include striated muscles and spleen.

-  Since the pattern of metastasis is unpredictable, no judgment can be made about the possibility of metastasis from pathologic examination of the primary tumour. 

-  Approximately 30% of newly diagnosed patients with solid tumours (excluding skin cancers other than melanoma) present with metastasis in the studied populations.

Pathways of spread:

Dissemination of malignant neoplasm may occur through one of the following pathways. 

1. Seeding of body cavities and surfaces (transcoelomic spread)

-  This seeding may occur wherever a malignant neoplasm penetrates into a natural “open field”. Most often involved is the peritoneal cavity, but any other cavities such as pleural, pericardial, sub-arachnoid and joint spaces-may be affected.

-   Particular examples are krukenberg tumour that is a classical example of mucin producing signet ring adenocarcinomas arising from gastrointestinal tract, pancreas, breast, and gall bladder may spread to one or both ovaries and the peritoneal cavities.

-  The other example is pseudomyxoma peritoni which are mucus secreting adrocarcinoma arising either from ovary or appendix. These carcinomas fill the peritoneal cavity with a gelatinous soft, translucent neoplastic mass. It can also be associated with primaries in the gallbladder and pancreas. 

2. Lymphatic spread

-  Lymphatic route is the most common pathway for the initial dissemination of carcinomas

 -  The pattern of lymph node involvement follows the natural routes of drainage. Lymph nodes involvement in cancers is in direct proportion to the number of tumour cell reaching the nodes.

-   Due to numerous inter connections between vascular and lymphatic channels the emphasis that used to be given, lymphatic spread for carcinomas and vascular spread for sarcomas is misreading.   

-   Metastasis to lymph nodes first lodge in the marginal sinus and then extends throughout the node. The cut surface of this enlarged lymph node usually resembles that of the primary tumour in colour and consistency. The best examples of lymphatic spread of malignant neoplasm can be exemplified by breast carcinoma.  

  -Skip metastasis may occur when local lymph nodes may be by- passed and occasionally found in lymph node distant from the site of the primary malignant neoplasm. Skip metastasis happen to occur because of venous lymphatic anastomoses or because inflammation or radiation has obliterated the lymphatic channels for example abdominal cancer (gastric cancer) may be initially signaled by supra clavicular (sentinel node). 

-  A clinical presence of enlarged lymph node  is not necessarily synonymous with a metastasis. Conversely, the absence of tumour cells in reseated lymph nodes does not guarantee that there is no underlying cancer.

3. Hematogenous spread 

-  Typical for all sarcomas and certain carcinomas- the spread appears to be selective with seed and soil phenomenon. Lung & liver are common sites of metastasis because they receive the systemic and venous out flow respectively. Other major sites of hematogenous spread include brain and bones. 

-  In the circulation, tumour cells form emboli by aggregation and by adhering to circulating leukocytes particularly platelets. The site where tumour cell emboli lodge and produce secondary growth is influenced by

•  Vascular (and lymphatic) drainage from the site of the primary   tumour 

•  Interaction of tumour cells with organ specific receptors 

•  The microenvironment of the organ or site, example a tissue rich in protease inhibitors might be resistant to penetration by tumour cells.

References

Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. and Bedane,A.; Desta, A.(2004). General Pathology. Jimma University, Gondar University Haramaya University, Dedub University.