Over 75% of human beings’ cancirous diseseas are caused by environmental factors, and in first turn – by chemical compounds. First experimental proofs of chemical compounds’ carcinogenicity, were Yamagiva’s and Ishikava’s researches (1915). They induced rabbit’s ear skin cancer by applying there coal-tar pitch for the period of 15 months.
The most important clinicopathologic implications of tumor growth.Interrelations between tumor and organism. Tumor negative influence on organism depends on its type (non-malignant or malignant), localization, speed of growth and directions of metastasis. Tumor directly injures organ in which it progresses disturbing its structure and functions. Surrounding organs are subject to atrophy and deformation, lumens of cavity organs narrows. Due to chronic intoxication with decay products and insufficient feeding cachesia develops. Hematosis depression, excessive hemolysis and chronic hemorrhage cause anemia.
In case tumor consists of hormone-active cells deseases occur connected with corresponding hormone hyperproduction or paraneoplastic syndromes of endocrinopathy, neurological aspects (dementia, neuropathy), skin implications, hematologic implications (hyper coagulability of blood, anemia, thrombocytopenia, polycythemia). Pheocromacytoma (cancer of adrenal glands cerebral layer, producing adrenalin) causes arterial hypertention progress, insulinoma (tumor of islet of Langerhans -cells) causes hypoglycemia, gastrinoma (pancreatic tumor producing gastrin - gastric secretion stimulator) causes stomach ulcer.
Tumors structure.There are various tumors by their macro- and microscopic structure. Their appearance can remind mushroom, cauliflower, node or intumescence. In section tumors are mostly of white, grey and red color. The following is often found in them: hemorrhages, necrosis and cysts cavity of which is filled with mucus or bloody mass. Some tumors are of brown color, for example, melanoma.
Tumor size depends mostly of its origin, location and growth period. In some cases they can reach giant sizes (fibroid tumors) in the other cases they can be seen only through magnifying glass or microscope (microcarcinomas). Tumors localized close to vitally important centers as a rule are of rather small size.
Tumor consistency is defined first of all by the type of outgoing tissue and ratio between stroma and parenchyma. Tumors of bone (osseous) tissue, cartilage tissue and fiber conjunctive tissue are of dense consistence. Malignant growth of epithelium in which stroma is underdeveloped are flaccid and by their consistence they are similar to new-born child’s brain (cancer-brainer).
Stroma and parenchyma are seen microscopically in each tumor. Parenchyma is its specific part which is represented by malignant cells and determines tumor place in hystologic classification. Even in tumors originating from mesenchyma cells producing intercellular substances (collagen fibers, basic substance of cartilage or bone tissue) are also should be treated as parenchyma. Stroma is mechanical-trophic framework including conjunctive tissue, blood and lymph vessels and nerves.
Most of tumors look like organ by their structure, i.e. have parenchyma and completely represented stroma. Such tumors are called organoid. In undifferentiated tumors parenchyma prevails and stroma is underdeveloped. They are called histioid. Blood circulation insufficiency causing necrosis easily occurs in them. At the same time there are tumors poor with parenchymatous elements and rich with stromal, for example gastric fibrocarcinoma or sccirrhous. These tumors cause complications due to stroma’s corrugation. They deform organ or narrow its lumen.
Tumor corresponding structure of the organ it is localized in is called homologous, and the one which structure differs from this organ structure is defined asheterologous. In case tumor is developed from the cells of organ in which it occurred – this is homotopytumor. In cases it occurs from the cells of embryonal displacement (heterotopia), it is called heterotopic, for example tumor of bone marrow in uterus.
Tumor (new growth, neoplasm, blastoma) is typical pathologic process in the form of excrescence of tissue subject to genetic apparatus change, characterized with potential infinity of its uncontrolled growth as well as structural elements’ atypicity.
Biology of tumor growth. Universal and mandatory feature of all the tumors – both non-malignant and malignant – is their ability to endless growth. This is fundamental feature of any tumor. Uncontrolled excessive proliferation of malignant cells doesn’t mean at all that they divide faster than homologous cells of healthy tissue. Vice versa, certain healthy tissues grow much more faster than the most malignant growth, for example, embryonal cells, regenerating liver. In such a way, malignant cells proliferation differs from normal cells proliferation not with cells division and growth speed, but in the character of division and growth.
Infinity of malignant cells growth is based on the fact that they are unable to exhaust division resource. It is found that genetic program limiting its divisions quantity is integrated into each cell. As a result of genetic somatic mutation malignant cell losses this restrictive program and starts to divide “endless”, escaping aging up to the death of host organism. In case these cells are carried from living organism to the other one of the same species, they will settle down and again will divide up to the death of recipient organism. In case these cells are carried to nutrient medium, there they will also divide endless times, in the other words they become independent of Heiflic’s rule. This ability of malignant cells to endless division is dominantly propagated to further cells generation.
Malignant cell has one more feature – uncontrolled growth. On the level of the whole organism tumor growth is controlled with nervous and endocrine systems, and on the local level – with mitogens and keylones. Malignant cell gets out of this hand, that is shows autonomy, independence of growth. It’s clear that this autonomy is not absolute but in this or that way is characteristic for all tumors. In case tumor partially keeps ability to come under control influence of hormones, it is called hormone-dependent tumor and in case it completely loses this ability - hormone-independent tumor. Autonomy doesn’t mean that tumor lost any connection with organism. This connection changed. They can be characterized as relations between host organism and parasite tissue.
Third peculiar feature of malignant cells is anaplasia, which means their persistent dedifferentiation, loss of ability to form specific tissue structures or produce specific substances characteristic for normal cells. In the other words its return to embrional state, structural-chemical organization simplification.
Tumor occurs from single parent cell subject to genous mutation. Malignant cells differs in several parameters from their common normal ancestor. This difference relates to cell’s and its organoids’ structure, metabolism, specific features and functions. Therefore morphologic, biochemical, physical-chemical, immunologic and functional anaplasia is differentiated.
The essence of morphological anaplasiacomes to tissue, cellular and subcellular atypicity occurrence. Polymorphism is inherent to malignant cells – they acquire smaller as well as bigger size and shape which is not peculiar for normal cells. Interrelation between nucleus and cytoplasm is shifted in favor of nucleus due to its enlargement. Multinuclear cells, nucleus hyperchromatosis are observed caused by nucleic acids accumulation in them, nucleolus amount increase and their migration into cytoplasm, of subcellular structures mitochondrions are subject to most prominent changes. Their quantity and size are decreased, membranes became thinner, cristas also become thinner and disappear. At tissue level structures’ created by malignant cells size and shape changes are observed. This referes for example to glandular follicles in adenocarcinomas and focuses of ossification in osteosarcomas. Sometimes tumor completely losses morphologic features indicating its origin from the certain differentiated tissue.
Secondary changes in tumor.Secondary metabolism disorders can develop in tumors, like sliming, hyalinosis, adiposity, calcification. Blood circulation functional insufficiency is characteristic for malignant growth as parenchyma always grows faster than stroma. Besides that, blood vessels are often thrombosed causing progress of necrosis on background of which ulcers, hemorrages, perforations occur.
Non-malignant growth and malignant growth. Tumors are not equivalent from the clinical point of view. Depending on the stage of differentiation, speed and character of growth, inclination to metastasis and recurrence, secondary changes in tumors, their influence on organism, they are distributed into non-malignant, malignant and the ones with local destructive growth.
Non-malignantor mature tumors are built of cells from structure of which it is always could be determined from what tissue they grow. In case they do not locate near vital important centers they are manifested with local changes and their influence on organism is minor. But these tumors can transform into malignant ones – malignizate.
Malignant(immature) tumors are built of low-differentiated or nondifferentiated cells which lose structural similarity to cells they originate from. Apart from non-malignant tumors they give metastasis, recur, manifest themselves with local changes and influence on the whole organism non-transforming into differentiated forms.
Tumors with local destructive growth occupy intermediate position between non-malignant and malignant. They have the features of infiltrating growth, but do not metastasis. These are hemangioma, desmoid tumor.
Basic differential features of non-malignant and malignant growth
Characteristic of non-malignant and malignant growth
Have minor deviations from parent tissue
Expressed atypism: tissue and cellular
Reach big size
Rear rich big size
Rare are subject to ulceration
Often are subject to ulceration
Do not give metastasis
Recurrence is not characteristic
Minor influence on patient’s general condition
Have major influence on the whole organism subject to ulceration
Tumors’ growth and spread in organism.Depending on differentiation level the following forms of tumor growth are differentiated: expansive, opposition and infiltrative (invasive). First form is peculiar for non-malignant growth, and second and third – for malignant ones.
Tumor which grows expansivelyincreases as a node, moving aside surrounding tissues. Cells surrounding it atrophy and stroma is subject to collapse causing pseudocapsule formation and sharpness of tumor boarder.
Opposition growthis intermediate between expansive and infiltrative. Tumor grows from multiple spots of growth – focal proliferates forming “tumor field”. Tumor transformation (malignization) is done consequentially from the center to peripheria and is finished with malignization focuses fusion into single node.
Infiltrative growthis characterized with tumor elements spreading into the least resistance directions and ingrown surrounding tissues destructing them. Tumor boarder in this case is indistinct, worn down.
In respect to organ’s cavity endophytic and exophytic growth are differentiated. Pre-invasive or intraepithelial neoplasia is observed as specific form. Hystologically epithelium displasia of epithelium, atypism are found, its normal distribution into layers disappears, but basal membrane is not injured.
Tumors which grow expansively do not spread out of organ’s boarder. In case infiltrative growth tumor spreads not only inside the organ but also out of it. Continuous contact tumor spread and metastasis are differentiated.
Continuous spread is tumor ingrowth into neighbour tissues. Under infiltrative growth malignant cells can reach serous tunic where reactive inflammation occurs and excudate organization is ended with commissure formation with neighbour organs. Through commissures tumor ingrow these organs (for example gastric carcinoma grows into liver or pancreas). In case cavity organs coalescence, fistulas formation is possible due to continuous spread and necrosis. Coloenteric fistula, for example, is observed in case gallbladder carcinoma.
Metastasis (dissimination) is malignant cells transfer from primary focus into distant parts with their further settle down and secondary focuses creation. Several ways of tumor dissemination exists: hematogenic, lymphogenic, perineural, implant, mixed.
Hematogenicmetastases occur when malignant growth’s cells come into blood circulation system and moves by venous or arterial blood stream. Spreading through veins is the most often way of metastasis. In this case two possible directions exist: first is through vena cava system when malignant cells from primary focus (uterum, kidney, skeleton bones) are transferred into lungs, and the second one - through portal vein, when gastric, intestine carcinoma, tumor of pancreas metastasis in liver. Sometimes paradoxical and retrograde metastases are possible. Arterial way of metastasis relates, in the first turn, primary focus localized in lungs. At it metastasis into cerebrum, bone marrow, liver and other organs are possible. Hematogenic way of metastasis is most peculiar to sarcomas.
Lymphogenicmetastasis is malignant cells transfer into regional, and further on – into distant lymph nodes. Later on malignant cells come into blood circulation system through thoracal lymphatic vessel.
Perineural metastases could be better characterized as an example of endless spread. Cells are disseminated through perineurium fissures.
Implantation metastasis is called tumor extension through serous cavities or natural channels. When serous tunic is invaded with malignant cells, they can come off and disseminate in serous cavity. In case conditions are favorable, they settle down and new focuses occur – implantation metastases. Macroscopically these metastases look like white plaques or humps. At that hemorrhagic inflammation occurs. Implantation metastases should be differentiated from lymphogenous metastases (carcinoma of pleura, peritoneum) when similar humps are formed downstream lymphatic vessels. Quite rare intracanalicular extension occurs. For example, malignant cells of bronchi, esophagus, pharynx oimplant into mucus tunic of little bronchi, ventricle, bowels and cause new tumors occurrence. Implantation metastases also include subinoculated metastasis (malignant cells transfer with surgeon’s hands and surgical tools) and contact metastasis (transfer from one organ to the other one, for example from labrum to labium).
Metastase cells have parent tumor structure and function. Intensity of metastasis depends on the stage of tumor differentiation and immunologic reactivity of organism. There is no correlation between tumor size and metastasis intensity. Malignant growth is able to metastasis from the moment of its occurrence. Metastases size often exceed parent tumor’s size. Most of cells die when transferred to the other place, so metastases could stay latent for a long time.
Recurrenttumor is repeated occurrence of the same tumor by its features in the place of removed or treated tumor. Both non-malignant and malignant tumors recur, the latter - more often.
In clinical picture the following is differentiated: pretumorconditions (diseases at which the risk of tumor progress is increased) and precursors of cancer (histologic ‘;abnormalities” of tissues). They are classified in the following types: a) pathologic regeneration an example of which can be chronic bronchitis with epithelium metaplasia, mucus tunics’ leukoplakia, chronic atrophic gastritis, chronic stomach ulcer, subacute skin ulcer; b) chronic proliferative inflammation, first of all polyps of ventricle and large intestine; c) dishormonal diseases – proliferative mastopathy, glandular hyperplasia of endometrium, endocervicitis, prostatic hypertrophy; d) tissues development abnormalities – teratomas, nevus pigmentosis and birthmarks.
At practical work it is necessary to know from what tissue tumor originates, in other words to make clear its histogenesis. In case tumor is built of differentiated cells keeping similarity to the parent one, its relatively easy to be done. In case undifferentiated cells prevail, histogenesis understanding faces with difficulties, sometimes it even becomes impossible.
Tumors classification. Terminology.Modern classification is built by histogenetic principle taking into consideration morphologic structure, localization, structure features in certain organs (organo-specificity), non-malignancy or malignancy. Tumor name ends with ‘oma” (mioma, fibroma). Malignant epithelium growth are called “cancer”, mesenchymal – “sarcoma”, tumors of embrional tissues – “blastoma”, of several embryonic leafs - “teratomas”. Some tumors are called with the name of the author described them – Kaposi's sarcoma (angiosarcoma), Wilms' tumor (nephroblastoma). International TNM system is used in respect to tumor process extention, where Т(tumor) – tumor characteristic, N(nodus) – presence of metastases in lymph nodes, M(metastasis) – presence of distant hematogenous metastases. Seven groups of tumors were differentiated combining over 200 names:
a) epithelial tumors without specific localization (organo-nonspecific);
b) organospecific epithelial tumors;
c) mesenchymal tumors;
d) tumors of melanin creating tissue;
e) tumors of nervous system and cerebral membranes;