Pathology 6
HC 4
The fundamental and shared characteristics of all cancers include:
- It is a genetic disorder caused by DNA mutations, which are induced by mutagens or
occur spontaneously. Moreover, also epigenetic changes occur, like altered DNA
methylation or histone modifications. Together, the expression and function of key
genes is dysregulated.
- Genetic alterations are heritable, as they are maintained upon cell divisions. So, cells
with the alterations experience Darwinian selection and ‘survival of the fittest’.
Those with mutations that favor growth and survival are more fit than regular,
normal cells and thus start to dominate the population. This allows, unfortunately,
for evolution of cancers as well, rendering cancers with more aggressive
characteristics.
- The (epi)genetic alterations that bring about morphological and characteristic
changes of cancers are known as hallmarks.
Nomenclature
Neoplasia means ‘new growth’, of cells that disregard regulatory mechanisms to limit
further growth. They are thus autonomic yet depend on the host for nutrition and blood
supply. Neoplasms are also referred to as tumors, with the study of tumors being called
oncology. Tumors can be benign or malignant:
- Benign tumors are relatively innocent, as they remain localized and are amenable for
surgical removal. They are furthermore non-invasive or metastatic, as does the
population exist of normally differentiated cells.
o The suffix -oma is added to the cell type from which the tumor arises, for
example from fibrous tissue is a fibroma. Epithelial tumors have a more
complex name, like glandular epithelium is adenoma and squamous
epithelium is papilloma.
- Malignant tumors are dangerous as they do invade and thereby damage adjacent
tissues, along with their ability to metastasize – spread to distant sites – and cause
death by invading key organs and influencing their functioning. Cells here are fast-
growing and poorly differentiated, with central cells lacking necessary nutrients and
blood supply (resulting in necrosis).
o The naming for malignant tumors follows that of benign tumors, only with
some additions:
If derived from solid mesenchymal tissues = sarcoma, with further
specifications about its origin, like liposarcoma.
If derived from mesenchymal cells of blood = leukemia
If derived from mesenchymal cells of lymph = lymphoma
If derived from epithelial cells = carcinoma, regardless of tissue of
origin.
If grown in glandular pattern = adenocarcinoma
If associated with squamous cells = squamous cell carcinoma
All tumors feature a parenchyma, transformed neoplastic cells, and the stroma, which is the
host derived, non-neoplastic, supporting connective tissue/blood vessels/inflammatory
, cells. The parenchyma lends the cancer its biological characteristics, along with its name, the
stroma is crucial for the survival of the parenchyma.
Both types of tumors can be seen to stem from one single transformed progenitor cell, as
they share a resemblance – in some cases, there are mixed tumors which stemmed from
also one progenitor cell, but which was not yet differentiated and could do so along multiple
lineages. These neoplasms are also referred to as pleomorphic, having multiple cell types
and nuclei. An even more special type of tumor is a teratoma, which derived from totipotent
germ cells and thus can harbor cells from any germ layer.
Histological Characteristics
There are three fundamental, common features for both benign and malign tumors,
discussed shortly. Malignant tumors also in general are fast-growing.
- Differentiation and anaplasia: the extent to which neoplasms resemble their
parenchymal cells of origin, morphologically and functionally. When there is a lack,
this is anaplasia. Benign tumors are well differentiated, whereby for example a
lipoma resembles a normal fat cell – further mitosis is rare. Malignant tumors exhibit
cell differentiation and morphological alterations that betray their malignancy;
especially anaplasia is an indicator of malignancy. Undifferentiated or anaplastic
tumors may arise from stem cells and then fail to differentiate. Specific anaplastic
characteristics include:
o Pleomorphism: variation in size and shape.
o Nuclear abnormalities: variation in size and shape, multiple nuclei or larger
ones.
o Tumor giant cells: considerably larger cells.
o Atypical mitosis: multiple spindles with tripolar or quadripolar mitotic figures.
o Loss of polarity: disoriented, disorganized cells with a loss of communal
structures. May be referred to as dysplasia, or disorderly architecture.
Differentiated tumors retain their functional capabilities, whereas anaplastic ones
less likely have special functionalized activities.
- Local Invasion: progressive infiltration, invasion and destruction of surrounding
tissue is especially characteristic to malignant tumors. Benign tumors grow and
expand slowly, growing as a cohesive expansile mass that remains localized and
mostly encapsulated. Malignant cancers do not have capsules and infiltrate adjacent
tissue, whereby a surrounding tissue must also be removed surgically to get rid of
the cancer.
- Metastasis: the spread of a tumor to distant sites of the body, which characterize a
neoplasm as malignant. The more anaplastic and larger the primary neoplasm, the
more likely the metastatic spread. Dissemination is via seeding within body cavities,
lymphatic spread or hematogenous spread. Lymphatic spread is more typical of
carcinomas, while hematogenous spread is favored by sarcomas. Yet, the lymph and
blood vessel system being connected, dissemination also often occurs via both
systems. Spread through lymph often follows the lymph node pattern, whereby the
sentinel lymph node is the first regional lymph node that receives lymph flow from a
primary tumor. Those lymph nodes may enlarge because of necrotic neoplastic
products or tumor antigens that spark an immunological response. What regards
hematogenous spread, the liver and lungs are the most frequent site of seeding, as
here the first major capillary beds are after venous drainage of a tumor tissue.
