GENERAL MORPHOLOGY OF TUMORS. MESENCHYMAL TUMORS.

TUMORS OF THE NERVOUS SYSTEM AND BRAIN MEMBRANES.

 

Tumors etiology.  Carcinogen agents and their interaction with cells.  It is ascertained fact that tumors can be caused by physical, chemical and biological agents which are called cancirogens

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.   

Chemical cancirogens are wide-spreaded in invironment and the majority of them are of antropogenous origin. Same time  we shouldn’t exaggerate their role in  human being pathology as only about 100 compounds and manufacturing processes are acknowledged as carcinogenous for human beings. 

By their chemical structure carcinogens are divided into several groups.  The most important of them are as follows:  a) polycyclic aromatic hydrocarbons; b) aromatic amine and amides; c) nitrosoamines and nitrosoamides. 

First group consists of over than  200 substances with three and more benzene rings.  Only one of them, namely 3,4-benzpyrene considered to be the one able to cause cancerous diseases of human being.  The others cause tumors only in experimental animals.  The biggest amount of this group of carcinogens is in tobacco fume, exhaust gases of automobiles,  blast furnaces smoke, asphalt,  waste of chemical plants,  dried and overdone food. 

Substance of polycyclic structure shows mostly local carcinogenous influence.  In case during experiment they are applied on skin cancer occurs, in case they are applied under skin – sarcoma occurs. Polycyclic aromatic hydrocarbons are excreted by various organs of organism, so tumors of these organs occur – kidneys, skin, mammary glands.

The second group of carcinogens are mostly  azo dyes, for which two or more azo groups presence is charactristic   (mono-azobenzene,  2- naphthylamine, benzidine). These substances are used to color  natural and synthetic fibers, in  printing industry, cosmetics, color photography,  to synthesize medicines, insecticides. Cancirogeneous action of amines and amides becomes apparent when they are introduced in digestive tract, subcutaneous or in case they are applied on skin. Tumors appears in organs far from the place of application, the most often in liver, urinal bladder, bowels, kidneys.  

Nitrocompounds  (nitrosoamines and nitrosoamides) are characterized with  alkyl radical presence.  They are utilized as  antioxidants,  pesticides,  paints solvents,  semi-products under paints, medicines and polymers synthesis. Their cancinogenity  for human being is nor proved but experimental data causes oncologic alertness. Possibility of nitrocompounds synthesis of nitrites, nitrates, nitric oxide in human being’s intestinal tract  is proved.  Nitrites are widely used as conserved agents for foodstuff. 

Practically all chemical substances are not carcinogenic as they are.  They acquire these features after coming into organism and are subject to metabolic transformations.  Here is the origing of idea of  final carcinogens which are able to interact with  cells macromolecules – DNA, RNA, proteins.  Taking into consideration role of DNA in heredity information transfer the most attention is  focused to carcinogens’ binding exactly with this acid.   A number of products were found which made possible to  decode fine mechanisms of final carcinogens interaction with DNA. They mostly methylate guanine and  affect purine bases complementary character – instead of  normal combination  guanine – cytosine  paramethylated guanine – hymine is created. So,  carcinogens cause   point mutations in certain DNA positions.  In case these mutations refer to transforming genes, i.e. oncogenes a chain of events starts causing malignization. 

Radiation carcinogenesis. Physical carcinogens  includes ionizing radiation and  to a lesser extend – ultraviolet rays. Ionizing radiation acts indirectly, through  highly active free radicals  distorting DNA structure.  Ultraviolet rays prevent its reparation. 

Viral carcinogenesis. There are various biologic agents able to cause malignant growth.  The biggest group consists of viruses.  Indisputable proofs were acquired regarding viral origin of many animal tumors  – hens’ Rous sarcoma,  rabbits’ Shope fibroma and papilloma,  mice mammary glands cancer  (virus is transferred through milk). The quantity of human beings’ tumors which are indoubtfully caused by viruses is not big  – Burkitt’s lymphoma, rhinopharyngitis cancer, carcinoma of uterine cervix.

Viruses causing tumors are called oncogeneous.  They are divided into two groups depending of  genome’s molecular structure –  RNA-containing and DNA-containing.  Major group consists of RNA oncogenous viruses,  forming the group of retroviruses.  Their mutual charactristics is the fact that their genom is of one chain RNA, and that they have ferment RNA-dependent DNA-polymerase  (invertible transcriptase, revertase). The essence of virus inducted carcinogenesis adds up to the fact that  oncogenous viruses introduce their own genome in infected cell, this genome contains transforming gene – viral oncogene. Its activity product (oncoprotein) starts cell transformation and keeps it in transformed condition. 

Retroviruses are the major cause of human’s malignant growths, however they point the way to understand basic mechanism underlies this diseases. They became model system by means of which the most modern data was received of fine molecular distortions occuring under cellular transformations.  

All above said allows to make major conclusion: tumor starts from DNA damage.  This mechanism is obligatory for all tumors irrespectively what carcinogens caused them   – chemical, physical or biological.  All of them are carcinogens exectly because of the fact that they are able to cause genetic apparatus failures.  Chemical agents cause mostly point mutations, ionizing radiation  – mostly chromosome mutations and retroviruses introduce to DNA molecule additional genes and oncogenes are among them. In such a way DNA damages could be treated as molecular grounds of all further processes tranforming normal cell into  transformed cell.  In the other words DNA damage is common  denominator to which the action of all known carcinogens is reduced. 

 

Pathogenesis of tumors. Molecular grounds of cancerogenesis.  The question arises: what kind of DNA damage is realized into tumor?  The answer to that is not at all simple.  Based on modern knowledge scientific theory was formulated which is known  as oncogene consept. It combines all forms of carcinogenesis    (chemical, physical and viral) into one universal mechanism. There are really many causes of cancer, but all of them similar to water through watering-can should pass through one critical  channel – DNA and leave trace in it, meaning damage. This damage is specific. It will lead to normal cell transformation into malignant cell (tranformation phenomenon) only in case it localizes not at any random DNA portion, but exactly in the portion where genes controlling cells growth and differentiation are situated.  These genes are called   cellular oncogenes   or proto-oncogenes.  They are usual components of cellular genome and are absolutely necessary for cell’s vital activity. Cellular proliferation would be impossible without proto-oncogenes. 

It is considered that under minor damages normal function of cellular oncogenes as auxesis could be keept in principle, but it stops to subordinate controlling influences of the cell itself.  Normal controlled process of growth and maturing is lost and is interchanged with an endless process of  cellular divisions under which cells do not have time to differentiate meaning  to mature to condition when they are able to fulfill approprite specialized physiologic functions.  It comes out that cell from its creation beginning hides the  sprouts of its own death in the form of cellular oncogenes. 

Right now nobody denies that normal cellular oncogenes under specific conditions could activate and cause malignant growth.  Several ways of their activation are differentiated.  One of them is viral transduction, in other words cellular oncogenes passage through viral genome.  It is proved that retroviruses damage DNA by the way of introduction to it so called viral oncogenes.  It was found that they are of cellular origin.  They are proto-oncogenes which on the certain stage of evolution were deported from infected cell nucleus by viruses and included into self-genome.  Starting from that moment they became viral oncogenes.  Right now over 20 of them are known.  All of them have cellular counteracts in various chromosomes. 

Viral oncogens coming into cell for the second time behaves uncontrolled.  The point is that they structurally differs of their cellular ancestry. Retroviruses, as a rule, capture cellular gene incomplete, without  repressor genes, so similar viral oncogene keeps ability to stimulate cells growth and differentiation but loses  regulator (operator) genes and becomes uncontrolled.  It causes unlimited non-corresponding organism’s needs cells division.  Cellular oncogene itself also is subject to structural changes at its capture by retrovirus.  This makes difficult regulative influences on it by resprssor genes as well as by epigenome cellular regulators. Thus, viral transduction deprives cellular oncogenes their primary positive function of growth stimulators and simultaneously  releases their hidden transformation abilities. Growth and proliferation genes starts to function as  cancer genes. 

Cellular oncogenes activation can occur in the result of  chromosomal translocations.  It was noted that under certain forms of tumors  chromosome discontinuities take place exectly in those portions where cellular oncogenes are situated. 

It was clarified that certain tumors, for example, Burkitt’s lymphoma occurs when any foreign (viral) genetic material inserts into DNA molecule close to proto-oncogene, even if this material doesn’t include oncogene.  Viral DNA built-in close to cellular oncogene activates it up to cancer level of expression.  This mechanism is called insertion. 

As a rule,  cellular oncogenes are represented in DNA in one copy but it was proved that copies quantity can increase in the result of DNA replication abnormality.  This phenomenon is called  amplification  (augmenting). Cellular oncogenes copies amount increase causes enhanced division of cells. This mechanism acts in human neuroblastoma and carcinoma of large intestine creation. 

Anyway, point mutations independently of their cause are considered to be major mechanism of proto-oncogene transformation into active cancer oncogene. It is proved that that‘s enough to change in human urine bladder cancer only one  base – guanine for the other one –  thymine as inactive proto-oncogene becomes transfomating.  Totality of scientific ideas of mutations’ decisive force in tumor etiology forms the grounds of mutation consept of cancerogenesis. 

Epigenome concept  adds up to the fact that the grounds of normal cell transformation into malignant one are not genetic apparatus’ structures changes, but  persistent failures in genous activity regulation.  The genes which should be repressed  are disinhibited and those which should be active  are clocked.  Cell loses its specificity, becomes  insensitive to regulative influences of the whole organism. 

Stages of cancerogenesis. Tumors occurrence and progress is multistage process.  There are three main stages – trasnformation  (initiation), promotion and progression.  Proto-oncogene activation finishes first stage – stage of initiation.  Main feature acquired by the cell in the result of proto-oncogene transformation into oncogene is  immortalization, meaning its potential ability to endless division, to immortality. However active oncogene presence is only potential possibilitity for expression.  Cell with active oncogene could stay for years in latent  (delitescence) state, doesn’t expressing itself in any way. Immortalized cell needs additional influences taking it out of latent state and  give a stimulus to endless division. 

Tumor growth risk factors. These  provocative factors could be additional doses of chemical or physical cancerogenes,  retroviral superinfection as well as various agents which do not cause tumors as they are, but are able to  take immortalized cells out of latent state.   Here starts old idea of  super multicauses of tumor growth however in reality  absolute majority of the factors  attributed etiologic role should be considered among  promotional conditions causing expression of latent, potentially cancerous, cells.  Factors activating pre-cancerous cells are called promoters. Under their influence trasnformed cells go into new stage of development – promotion stage for which  cellular oncogenes expresssion is charactristic. 

Provided that the fact of oncogenes participation in oncogenesis is not under the doubt at the moment, mechanism of their action is still a mystery. It was ascertained that oncogenes code specific proteins  (oncoproteins), most of them having  tyrosinase activity.  Further on it was found that  oncoproteins which cause uncontrolled growth of malignant cells  are similar to usual  growth factors  – thrombocyte growth factor,  epidermal growth factor,   insulin-like growth factors. Under the normal conditions growth factors comes into cell from outside providing cell dependability from organism. Malignant cells differs with the fact that they produce growth factors by themselves.  A part of them is aimed to support their own proliferation  (autocrine secretion), and the other one – for other type cells  (paracrine secreation).

Progression is the final phase of tumor progress. Under this term persistent,    irreversible qualitative changes of tumor to malignization are understood. For example hormone-dependent neoplasms became hormone-dependent,  tumor reacted medicines stoped to react them.  Progression is the last and the most long lasting stage of tumor progress lasting up to organism death. 

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 b-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 as   heterologous. In case tumor is developed from the cells of organ in which it occurred – this is  homotopy tumor.  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 proliferatioot 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 cells life could be kept artificially.  There are two methods to provide that: transplantation – tumor inoculation from one animal to the other one of the same species and  explantation  – malignant cells cultivation outrient medium. Tumor kept for a long time with transplantation or explantation method is called  tumor strain. First transplantation strain was made in 1905 (Ehrlich’s carcinoma in mice), first explantation  – in 1950 (Hela’s cells – carcinoma of uterine cervix).

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 organisation simplification. 

Tumor occurs from single parent cell subject to genous mutation. Malignant cells differs in several parameters from their commoormal 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 anaplasia  comes 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 betweeucleus 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. 

 

Biochemical anaplasia is peculiar of malignant cells’ metabolism caused by theirs genetic apparatus change.  Carcinogens are able not only to distort mitosis process and start endless division mechanisms, but  also to supress or unbrake the other genes.  As the result of that  malignant cells enzymatic range changes.   Intracellular enzyme insufficiency occurs  – some enzymes are inhibited but the other ones activate or  start to synthesize absolutely new substances which didn’t exist iormal cells. 

It is found that all tumors, subject to progression start to look like each other by their enzymes set independently of what cells they come from. Unification of tumors izoenzymal range independently of their  histogenesis is very characteristic manifestation of malignization. 

It is known that every tissue synthesize  enzymes specific for it,  where every enzyme is  represented with strictly specific set of  isoenzymes. This specific feature is lost in tumors. So called monotonization or isoenzymic simplification is developed – amount of isoenzymes reduces and their set becomes approximately the same for tumor of any origin.  Isoenzyme reconstruction goes in the direction of those enzymes increase which are peculiar for  embrional tissues. 

The most peculiar biochemical features of malignant cells relate to proteins and  carbohydrates metabolism. Proteins synthesis prevails their  decomposition.  To build own proteins tumor  captures aminoacides of the other organs (“tumor –  trap for nitrogen”).

Carbohydrates metabolism and power of malignant cells significantly differ from the norm.  In aerobic conditions normal cell provides itself with energy  mostly at the expense of more advantageous glucose aplittance in Crabbs’ cycle,  and in anaerobic conditions – it is forced to change to  glycolysis. In case amount of oxygen is sufficient, glycolysis is opressed with breathing ( Paster’s effect).

Malignant cell also provides its demands in energy on account of glycolysis and breathing, but  correlative meaning of these processes is different.  Peculiarities of tumors power supply are as follows: a) activation of anaerobic glycolysis and enzymes providing it  – pyruvatekinase,  hexokinase, fructokinase; b) presence of aerobic glycolisis for which normal cells are not able (exceptions – leukocytes,  spermatozoon,  eye retina cells); c) breath opression with glycolisis (Crabtree effect), to say exact – with  powerfult system of  glycolytic enzymes, which  intercept substrates – inorganic phosphorus, coenzymes. 

Among physical-chemical features of malignant cells the following should be emphasized: acidosis in the result of  lactic acid accumulation,  intracellular aquation, potassium ions accumulation,  electroconductivity increase,  colloids density reduction,  membrane negative change increase, their surface tension decrease. 

Antitumor immunity. Under immune anaplasia changes of malignant cell’s antigene features is understood.  These changes is the result of  protein metabolism rebuilding.  It is known that each tissue synthesize a set of antigenes specific for it.  This set is changed in tumor.  Tumor antigenes.  Antigene simplification and antigene  complication are differentiated.  Antigene simplification is characterized with antigenes synthesized by malignant cell numerous times decrease. 

Antigene complication is manifested with antigene  divergence and antigene reversion.   Antigene divergence  means that malignant cells start to  synthesize antigenes which are not characteristic for healthy cells, but these antigenes are usually synthesized by the other cells.  For example  hepatic tumor can synthesize antigenes of  spleen or kidneys. Tumor’s synthesis of embrional antigenes is called antigene reversion.  Renal carcinoma of human being synthesizes a– fetoprotein, which serves as the test for its diagnosis. In the course of tumor’s malignization it strats to synthesize antigenes characteristic for moire and more earlier stages of  intrauterine evolution.   

Organism is not defenseless towards carcinogenes and  transformed (mutant) cells. It has strong defensive mechanisms providing prevention of tumors occurrence or slow down their progress. Here relates a system of  carcinogenic compounds neutralization and their evacuation through  kidneys,  digestive tract and skin. Organism clears of mutant cells due to immune surveillance function, peculiar to  Т-lymphocytes.  System of endonucleases exists providing damages oncogenes renewal and stopping synthesis of oncoproteins coded by them. Tumor growth is also influenced with hormones – insulin,  adrenalin, tropic hormones of  hypophysis, gormones of thyroid gland and sexual glands. This influence is  ambiguous and depends on its combination with the other mechanisms of  antineoplastic defense. 

Functional anaplasia  is manifested with loss or distortion of function fulfilled by cell.  In thyroid gland malignant cells’ thyroid hormones synthesis can reduce or increase up to  myxedema or thyrotoxicosis occurrence.  Bilirubin conjugation is stopped in hepatoma (liver cell carcinoma).  In some cases tumors start to synthesize the products not peculiar to them.  For exmpale pulmonary and bronchi tumors can synthesis  hormonoform substances. 

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-malignant  or 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 betweeon-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

 

 

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 expansively  increases 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 growth is 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 growth  is 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. 

Hematogenic metastases 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.

Lymphogenic  metastasis 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. 

Recurrent tumor 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:   pretumor conditions  (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. 

Pretumor processes shouldn’t be connected with etiology.  Pretumor changes presence do not mean at all that tumor will occur on their ground.  So by cancer threat level they are distributed into   optional (under which cancer develops rarely) and obligatory (under which cancer develops rather often).

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;

f) tumors of hematopoietic and lymphoid tissue;

        g) teratomas .

 

 

MESENCHYMAL TUMORS

 

In ontogenesis, mesenchyma gives the beginning lo: 1) connective tissue, 2) vessels, 3) muscles, 4) tissues of musculoskeletal system, 5) serous membranes, 6) hemopoietic system.

Mesenchymal tumors develop from: 1) connective

(Fibrous) tissue, 2) fat tissue, 3) muscular tissue,

4) blood and lymphatic vessels, 5) synovial tissue,

6) mesothelial tissue, 7) bone tissue.

They may be benign (name of the tissue + oma) and malignant (name of the tissue + sarcoma). There are also special terms (e.g. desmoid, granular-cell tumor).

Connective (fibrous) tissue tumors

Main benign connective (fibrous) tissue tumors are:

1. Fibroma — a node of differentiated connective (issue with different direction of the bands:

a) dense-fibrous structures prevail over the cellular elements; b) soft (loose connective tissue with great amount of stroma cells — fibroblasts and fibrocytes).

Localization of fibroma is various: skin, breast, on the skin it may have a limb, cranial base, spinal canal, orbit.

2. Desmoid fibroma is a kind of dense fibroma and characterized by infiltrating growth and relapses. More often it is located on the anterior abdominal wall.

3. Dermatofibroma (histiocytoma) — small fibrous node with yellow-brown colour. More often it is located in the skin of the legs. It consists of capillaries and connective tissue with fibrous structures and fibroblasts, fibrocytes, histiocytes, macrophages. There are giant polynuclear cells with lipids and hemosiderin between cells.

Malignant connective (fibrous) tissue tumors are characterized by atypical cells, including loss of the structure.

Macroscopically sarcoma looks like fish flesh. As a rule sarcoma metastases are disseminated hematogenically.

1. Fibrosarcoma looks like node or indistinct formation. There are 3 types of fibrosarcoma:

a) Differentiated fibrosarcoma, termed cellulofibrous, when fibrous component prevails cellular component;

b) Poorly differentiated fibrosarcoma, termed cellular sarcoma. It produces metastases more frequently; c) Round-cell tumors of unknown origin,, termed unclassified tumor.

2. Protruding dermatofibroma (malignant hystiouytoma) — numerous polymorphic fibroblast cells with metastases. It grows slowly, its growth is ii[iltrating, the relapses of metastases are very rare.

Tumors of fat tissue

Benign

1. Lipoma: anode, sometimes in a capsule, yellow, made of lobules of different size. It may develop in every site where there is fat tissue.

Intramuscular infiltrating lipoma is a tumor without distinct borders, it infiltrates to intermuscular connective tissue.

2. Hybernoma: a rare tumor of brown fat. This consists of large round cells with granular or foamy cytoplasm (fat vacuoles).

Malignant

1. Liposarcoma (lipoblastic myoma) — a rare, large tumor, which is built of lipocytes of different degree of maturity and lipoblasts.

There are several types of liposarcoma:

a) mainly highly differentiated;

b) mainly myxoid (embryonic);

c) mainly round-cell;

d) mainly polymorphocellular.

It grows slowly, the metastases develop late. 2. Malignant hybernoma is a very rare tumor with cellular polymorphism and a lot of giant cells.

Benign

(Left) Corpus uteri showing multiple benign fibroleiomyomas. (Middle) Atypical glands (arrow) invading mucosa of gastric antrum, indicating carcinomatous transformation. (Right) Extensive metastases in liver of testicular tumor (seminoma).

 

Tumors from the muscles

1. Leiomyoma consists of smooth muscle with chaotic location of the muscular tissue bands, the stroma with vessels and nerves. If stroma prevails this tumor is termed fibromyoma. Secondary changes:

necrosis, hemorrhages, cysts, hyalinosis, petrifaction are characterized for leiomyoma.

2. Rhabdomyoma consists of striated muscles. It resembles embryonic muscular fibres and myoblasts. It appears against a background of tissue shifts and is accompanied by other development defects (large masses of striated muscles).

3. Granular-cell tumor (Abrikosov’s tumor): this is small tumor in a capsule. It is located in the tongue, esophagus, skin. The cells are round, large with granular cytoplasm (no lipids).

Squamous cell carcinoma of bronchus

Malignant

1. Leiomyosarcoma (malignant leiomyoma) with cellular and tissue atypism, a large number of mitoses (high mitotic index) are characteristic.

2. Rhabdomyosarcoma (malignant rhabdomyo-1 ma) is characterized by extreme polymorphism, loss of tissue characteristic (it is necessary to use special immune antibodies to veri’ the tumor).

3. Malignant granular-cell tumor (malignant myoblastoma) resembles malignant rhabdomyoma but lie cytoplasm is granular.

Tumors from blood and lymph vessels

Benign tumors from blood vessels

– Hemangioma is a tumor from blood vessels. ‘[here are several types of hemangioma:

a) capillary which develops in the skin, mucous membranes, gastrointestinal tract, liver, more often in children. It looks like cyanotic node of capillaries, hranchrng with a narrow lumen;

b) venous: vascular bands with smooth muscles, resembles veins;

c) cavity hemangioma in the liver, skin, bones, muscles, gastrointestinal tract, brain;

d) benign hemangiopericytoma in the skin, intramuscular spaces of the extremities.

2. Glomus tumor (glomus angioma). More often develops in hands and feet (fingers and toes) There lace vessels with endothelium, surrounded by muffles oiepithelioid (glomus) cells, rich ierves it is usually painful.

Malignant tumors from blood vessels

Angiosarcoma which may be:

a) malignant hemangioendothelioma;

b) malignant hemangiopericytoma: highly malignant, early metastases (skin, liver, muscles). Benign tumors from lymph vessels

Adenocarcinoma of colon

Lymphangioma: growth of lymphatic vessels in different direction with formation of a node or enlargement of the organ. If lymphangioma develops in the tongue, it is termed macroglossia, if lymphangioma develops in the lip it is termed macrocheilia. Microscopically it looks like cavities filled with lymph.

Malignant tumors from lymph vessels

Lymphangiosarcoma. This appears as a result of chronic lymphatic stasis.

Tumors from synovial tissue

1. Benign synovioma develops in the tendons and tendon sheath. It contains a lot of stroma with hyalinosis, and a little number of vessels. There may• occur xanthomic cells and clefts.

2. Synovial sarcoma (malignant synovioma)I develops in the large joints. It has polymorphic structure. Some tumors have polymorphic cells ana. pseudoepithelial gland formations with cysts, the other1 have fibroblastoid atypical cells and collagen fibers structures resembling tendons.

ibmors of mesothelial tissue

1. Benign mesothelioma resembles a dense nodi in serous membrane (pleura), its structure is similar t fibroma (fibroid mesothelioma).

2. Malignant mesothelioma (peritoneum, pleura,

pericardium) microscopically looks like atypical large

cells with vacuolized cytoplasm. Malignant mesotheI oma may has tubular and papillary structures. MesoI lielioma with tubular and papillary structures is called

epithelial mesothelioma.

Bone tumors

Benign

1. Osteoma develops as a rule in spongy and tubular bones, skull. 2 types of osteoma are known:

a) spongy osteoma, b) compact osteoma.

This benign tumor almost exclusively involves the skull and facial bones; the frontal sinus is the most common location. Males are affected more often than Ibmales, the lesion can occur at any age. Although osteoma is predominantly a solitary lesion, multiple osteomas can occur in association with intestinal polyposis and soft tissue tumors. The tumor of normal dense and mature bone originates from the periosteum. lihere is little evidence of osteoblastic activity.

2. Osteoid osteoma is common in young persons, iostly males. Macroscopically, an osteoid osteoma

gppears as a small round or oval mass containing a entral red-brown, friable area. Microscopically, the tumor appears as a maze of irregular bone trabeculae, fibrous tissue, and vessels. The center of the tumor is icIi in osteohlasts, calcification, and multinucleate liant cells. 3. Benign osteoblastoma predominantly affects the vertebrae and long bones of young males in the first three decades of life. Macroscopically, the lesions vary in size from a few to several centimeters. Microscopically, osteoblasts proliferate and osteoid production increases. Osteoclasts and multinucleate giant cells maybe very numerous, especially in areas of blood extravasation.

Osteogenic sarcoma

Osteogenic sarcoma

 

Malignant

1. Osteosarcoma (osteogenic sarcoma) from osteogenic tissue rich in atypical cells of osteoblastic type with a lot of mitoses, the bone is primitive. 2 types of osteosarcoma are known: a) osteoblastic type (bone formation), b) osteolytic type (bone destruction).

Osteosarcoma is a highly malignant bone tumor characterized by the production of osteoid and bone. Most osteosarcomas arise in the metaphyseal end of long bones (predominantly the femur, humerus, and tibia), but they can involve any bone, including the small bones of the hands, feet and face. Osteosarcoma is the most common primary malignant tumor of bone (next to multiple myeloma), accounting for approximately 16% of all bone malignancies. The disease. predominantly affects young males between age 10 and 20.

Macroscopical appearance. The tumor appears as a large necrotic and hemorrhagic mass. The lesion usually ends in the epiphyseal cartilage and rarely extends into the nearby joint space. Microscopic appearance. Three types of osteosarcomas have been differentiated according to their predominant histologic patterns: osteoblastic, I ibroblastic and chondroblastic. The hallmark of the iimor is the presence of a malignant stroma that contains osteojd and bone. The stroma shows bizarre pleomorphic cells,with hyperchromatic, irregular nuclei and abundant mitoses. Multinucleate giant cells ire seen most ofteear zones of necrosis and calcification. Malignant cartilage may be present in small foci or as a large proportion of the tumor.

2. Giant cell tumor of bone (osteoclastoma) is an ii ncommon malignant tumor characterized by multinucleate giant cells. It occurs predominantly in women over age 19 and peaks in the third decade qf liFe. The lesion almost always is localized in the distal portion of the long bones (femur or humerus), and 50% of these tumors occur in the area of the knee. Occasionally, the tumor involves the skull, pelvis, or small bones of the hands and feet.

The tumor is believed to originate from the rnesenchymal cells of connective tissue.

Macroscopicafly, the tumor characteristically uppears as multiple hemorrhagic cystic cavities that destroy the adjacent bone and are enclosed by a thin shell of new bone formation.

Microscopically, a vascularized stroma composed ol spindle cells that contain multinucleate giant cells [intermixes with areas of hemorrhage, inflammation, and hemosiderin deposits. Mitoses are present. Cartilage tumors

Benign

1. Chondroma derives from hyaline cartilage in the feet, spine, breastbone, pelvis. If tumor is located in the peripheral area of the bone it is termed exchondroma, if in the center area of the bone, enchondroma.

Ollier’s disease (enchondromatosis) is a rare, nonhereditai-y disorder in which multiple chondromas are present in the metaphysis and diaphysis of various bones.

Maffucci’s syndrome is a congenital disease characterized by dyschondroplasia and multiple hemangiomas in the skin and viscera.

This neoplasm is thought to originate from heterotropic cartilaginous cell; nests in the medullary cavities of bones. Macroscopically, the lesion appears as a confluent mass of bluish hyaline cartilage with a lobular configuration. Microscopically, the cartilage appears moderately cellular, with occasional binucleate cells. Mitoses are absent.

2. Osteochondroma is the most common benign tumor of bone affecting patients under age 21. The lesions may be single or multiple and predominantly involve the metaphysis of long bones. Macroscopi-:

cally, the tumor may range in size from 1 to several. centimeters and appears as a stalked protuberance, with a lobulated surface jutting from the affected bone. The periosteum of the adjacent bone covers the lesion. Microscopically, the cartilaginous cells appear lined up, mimicking the orientation of cartilaginous cells in a normal epiphysis. No mitoses are present.

3. Benign chondroblastoma consists of chondroblasts, interstitial substance, marked osteoclast reaction. Chondroblastoma is a rare cartilaginous [umor that almost always involves the epiphyseal portion of the long bones. The tumor predominantly affects males in the second decade of life. Macroscopically, the tumor is round or oval in shape, with areas of cystic degeneration and hemorrhage. Microscopically, proliferation ofchondroblasts is intermixed with varying amounts of fibrous stroma and chondroid material. Multinucleate giant cells and calcifications are present. Mitoses are virtually absent.

4. Chondromyxoid fibroma is most commonly located in the metaphysis of long bones but occasionally can involve the epiphysis. It primarily affects males in the first and second decades of life. Macroscopically, the tumor is a well-circumscribed, solid mass with a cartilaginous appearance. The cortex of the bone is expanded by the tumor, which is limited by the periosteum. Microscopically, a variety of fibrous, myxomatous, and chondroid elements are seen together with multinucleate giant cells and inacrophages that contain hemosiderin. When the tumor forms lobules, a condensation of nuclei occurs beneath the rim of the compressed adjacent tissue. Malignant

Chondrosarcoma is a malignant cartilaginous tumor. The most common locations are the spine, pelvic bones, and upper ends of the femur and humerus. The tumor may arise de novo (primary chondrosarcoma) or originate from a preexisting benign cartilaginous lesion (secondary chondrosarcoma). Chondrosarcomas comprise between 7% and 15% of all bone neoplasms. The tumor occurs in patients between age 30 and 60 and in men three times more often than in women.

Macroscopically, a chondrosarcoma appears as a lobulated white or gray mass that contains mucoid material and foci of calcification.

Microscopically, there are islands of immature or poorly developed cartilage in which anaplastic cells with two or more nuclei are present within the lacunar space.

The neoplasm is slow growing and can remain locally aggressive for years, with a high tendency to recur and implant in soft tissues. Hematogenous dissemination to the lungs, liver, and kidneys takes place over the years, with eventual death of the patient. The 10-year survival rate ranges from 50% to 60%.

Stages of individual work in class

Study and describe macrospecimens

Fibroma of the skin. Characterize the appearance of the tumour, its connection with the skin, name the most frequent ocahzations, enumerate the types of fibroma according to the density.

Fibromyoma of the uterus. Describe the appearance of

lie tumour, its colour, presence of a capsule, enumerate the

Ivpes of fibromyoma of the uterus according to the layer of the last one, possible complications, malignant analogue.

Lipoma. Describe the appearance of the tumour, its colour, consistency, localization, name the malignant analogue of lipoma.

Cavernous hemangioma of the liver. Describe the appearance of the tumour, its color, borders, the content of the cavities, type of the tumour.

Sarcoma of the femur forearm, foot. Name the organ, describe the tumour, its attitude to the surrounding tissue, the ways of dissemination.

Terminology

Blastoma, oncology, unicentric and multicentric growth, tissue and cellular atypism, sex chromatin, anaplasia, invasive, expansive, endophytic and exophytic growth, metastasis, relapse, choristia, chamartia, progonoma, teratoma, fibroma, lipoma, hibemoma, leiomyoma, rhabdomyoma, haemangioma, haemangiopericytoma, glomus-angioma, lymphangioma, synoviorna, osteoma, osteoblastoma, chondroma, chondroblastoma, haemangioendothelioma, sarcoma.

 

TUMORS OF NERVOUS SYSTEM,

BRAIN MEMBRANES AND MELANIN-PRODUCING TISSUE

TUMORS OF THE NERVOUS SYSTEM AND BRAIN MEMBRANES

 

Tumors of nervous system are various. They develop from different elements of the nervous system:

1) central; 2) vegetative; 3) peripheral; 4) mesenchymal elements, which are also a part of this system.

The etiology and prognosis of brain tumors are poorly studied.

According to many authors, there are six etiological groups of tumor and tumor-like diseases of human and animal nervous system: 1) genetically dependent (hereditary); 2) con-genital; 3) radiation; 4) chemically-induced; 5) meta-bolic (including dyshormonal); 6) viral.

Recklinghausen’s neurofibromatosis is an example of a human hereditary tumot Some authors believe that neurodermal melanosis belongs to this group. Congenital tumors and tumor-like diseases are medulloblastoma and astrocytoma in children. Radiation tumors of brain were described in experimental animals as well as in the people who were administered iitensive radiotherapy or exposed to high-dose ionizing radiation due to accidents (Hiroshima and Nagasaki). Brain tumors caused by exogenic admiiiistration of pure carcinogenic substances were observed in experimental animals. It is believed that ome brain tumors occur as a result of disturbed iiictabolism, so-called hormone-depending tumors. I lormone-depending tumors are observed both in

people and animals, e.g. arachnoidendothelioma. Ihese tumors become active during pregnancy. In some cases, they disappear after delivery of a child. Virus-induced tumors are known only in animals. Thus, polyoma virus may cause hemorrhagic sarcomatosis of pia mater. Some adenoviruses may cause ependymoblastoma in hamsters. Some authors (I .I. Smirnov, AR Avtsin, B.S. Khominsky, A.N. Age- eva) introduced the idea about preblastoma (in particular focal proliferation with them).

According to the degree of maturity, brain tumors nay be more or less mature (benign) or immature (malignant).

Special attention should be paid to the characleristic features of brain tumors.

1. The term <<benign>> is not suitable in this case as they are located in the brain and indeed are always malignant. Even slow growth affects vitally important centers and causes their dysfunction.

L2. Neuroectodermal (neuroepithelial) tumors of brain originating from neuroectoderm derivatives are dysontogenetic, i.e. develop from the cells which are known as precursors of mature CNS elements. Therefore, it may be difficult to determine their histological type. More often their cellular composition corresponds to definite stages of development of neuronal and glial elements.

3. Brain tumors produce metastases within the skull, that is with the help of liquor.

4. Their microscopic appearance is characterized by prolonged fascicular structures, lying either in wave-like or curl-like manner.

Neurodermal tumors are subdivided into astrocyte, oligodendroglial, ependymal tumors and those of choroid epithelium, neuronal, poorly differentiated and embryonic.

Astrocyte tumors or gliomas are the most frequent brain tumors. They develop from astrocytes and can be found in all brain portions. The highest incidence is observed between the age 25—45. The diameter of the tumor is about 5—10 cm. They do not always have distinct boundaries with the surrounding tissue. It is homogeneous on incision. As a rule, considerable enlargement of the brain portions is observed. Astrocytoma is characterized by cyst formation (one or several). They contain colloid substance or yellowish fluid with large amount of protein. There are three histological types of astrocytoma: 1) fibrillar, 2) protoplasmatic, 3) fibrillar-protoplasmatic. Fibriflar tumor is rich in glial fibers looking like parallel bands,it contains small amount of astrocytes. Protoplasmatic istroma consists of different in size cells with processes which resemble astrocytes, their processes lorm thick interlacing. A fibrillar-protoplasmatic tumor is characterized by even location of astrocytes [lid glial cells. Cerebellar astrocytoma and subependynal astrocytoma are separate subtypes. A malignant type is astroblastoma characterized by rapid growth, polymorphism and necroses in the tumor. This tumor is rare, it disseminates through the liquor routs.

Oligodendroglial tumors. In the majority of cases these are benign. The highest incidence is observed at Ihe age of 30—40. In rare cases, they occur in children. they are mainly localized in the large hemispheres of (lie brain, more seldom in the region of visual tuber and in the trunk. Very seldom, they develop in the area of cerebellum and spinal cord. Primary multiple oligodendrogliomas of meninges and visual nerves were also described.

Macroscopically, the tumor is pinkish-gray, resembles brain substance and is diagnosed by the enargement of the brain portion. Its consistency may he paste-like, when calcifications are present it may he dense.

Microscopically it consists of homogeneous small cells with round nuclei and narrow outline of cytoplasm which is poorly colored. Sometimes it is characterized by the structure resembling honeycombs. [he tumor is usually poor in vessels. Flyalinosis and calcification may also be observed.

The types of oligodendrogliomas are: 1) flisiform cell, 2) polymorphocellular.

A malignant type of the tumor is oligodendroglioblastoma characterized by special cell location, marked polymorphism with giant cells. It is also characterized by numerous mitoses and necrosis foci. The metastases spread through the liquor routs, more often along the walls of the ventricles. Symmetrical location of the tumor nodes in the walls of the ventricles is typical.

Ependymal tumors and tumors of choroid epithelium. According to LI. Smimov, three types of ependymal tumors are distinguished.

Ependymoma (glioma connected with ventricular ependymoma) looks like intra- or extraventricular node. The foci of necrosis and cysts can be found in I it. Clasters of uni- and bipolar cells around the vessels (so-called pseudorosettes) and cavities covered with epithelium (true rosettes) are typical. Most frequently they are located in caudal portions of rhomboid fossa. Ependymoma may go down the spinal canal (craniospinal tumors). Ependymoma is usually localized in the bed of the 4th ventricle and in the 3tl ventricle. In the area of the spinal cord, they first grow intramedullary, then become extramedullar Macroscopically they look like nodes of different siz with tuberous (4th ventricle) or villous (latera ventricle) surface. The color is pinkish-gray, th consistency is soft. Microscopic study reveals pen vascular structures of radially located cells. Their processes form a fibrous ring between the body of the tell and the wall of the vessel and over the body of the tell. In the rest of the tumor tissue, the cells are located mosaic manner. Single and multiple clefts and tubes

bedded with cylindrical epithelium are common.

Ependymoblastoma is a malignant type of ependymoma. This is characterized by marked cellular polymorphism. It grows quickly, metastases spread through the liquor system.

Dedifferentiated ependymoma is a transitory form between the two types.

Choroid papilloma is a tumor from the epithelium of vascular plexus, looking like a villous node in the cavity of the brain ventricle. It consists of numerous villous structures of cubic or prismatic epithelial cells. It is mainly observed in young people. It is located within the brain ventricles. Heterotopic types are rare (horse’s tail).

Macroscopic study demonstrates well-outlined I nodes of various size. The surface of the tumor is small or large-villous, has cauliflower- or mulberry-like appearance. Its consistency is either dense or soft, the color is pinkish-gray.

Microscopically it consists of villi, their connective tissue stroma is covered with cubic or cylindrical cpthelium. Hyalinosis can be frequently observed.

Choroid carcinoma is a malignant type of clloroidpapilloma. It is made of anaplastic cells covering he vascular plexus. Papillary cancer is a rare tumor Neuronal tumors

Ganglioneuroma is a rare mature tumor. Most frequently it is localized in the bed of the 3th ventricle, rarer in the hemispheres of the brain. It usually occurs in children and juveniles. The tumor consists of mature ganglionic cells divided with the bands of glial stroma. Macroscopically ganglioneuroma looks like a limited node. In the medulla oblongata it is diffuse, in the cerebellum it looks like hyperplastic folds.

Cerebellum ganglioma is characterized by proliferation of large nervous elements ofPurkinjer’s cell type.

Ganglioneuroblastoma is a malignant analogue of ganglioneuroma (malignant gangliocytoma). This is an extremely rare tumor of CNS. It is characterized by cellular polymorphism and similar to malignant glioma

Neuroblastoma is a rare highly malignant brain tumor. It occurs mainly in children. The tumor is formed from large cells with bubble-like nucleus. Mitoses are numerous. The cells grow like sincitium. There are a lot of vessels.

Poorly differentiated and embryonic tumors

Medulloblastoma and glioblastoma belong to this group. The latter occurs in children. Medulloblastoma is a tumot made by immature cells, medulloblasts, therefore it is highly malignant. The most frequent localization is vermis celebelli. Macroscopically, it is pinkish-gray. Microscopically medulloblastoma conists of homogeneous small cells with dark round or uval nucleus and poorly seen rim of cytoplasm. The cells are located close to each other. Rosette, so-called collonar, structures are typical. Mitoses are numerous. Vessels are not numerous. Metastases spread through the liquor routs.

Glioblastoma is the second (after astrocytoma) in the incidence. It occurs at the age of 40—60. It is situated in the white substance of the brain. This tumor is mainly located in the large hemispheres of the brain, sometimes in the trunk. It is characterized by rapid infiltrative growth without distinct boundaries. (Ilioblastoma usually produces regional metastases, Ihose to the inner organs are rare (lungs). Macroscopically it is motley-colored due to necroses and hemorrhages. Microscopically the tumor is characterized by marked polymorphism. The cells are located disorderly (cellular chaos), their size and shape are various, from small lymphocyte-like to giant polynuclear. Necroses, hemorrhages and vascular growths are typical. Mitoses and centers of atypical division are frequent. (Synonyms: multiform glioblastoma, gl i oblastoma, spongioblastoma).

Meningovascular tumors

These tumors appear from the meninges. The most frequent is meningioma and its malignant variant iieningeal sarcoma. Arachnoidendothelioma (meningioma) is the most frequent type of meningovascular tumors. They mainly occur in adults over 30, while in children, they are rare. They are characterized by slow expansive growth. Arachnoendothelioma is usually localized in:

1) longitudinal sinus and Paccionian bodies, 2) convex,

3) falciform process, 4) olfactory region, 5) wings and body of main bone, 6) tubercle of the saddle, 7) the region of semilunar node of trigeminal nerve, 8) tentorium cerebelli, 9) vascular plexi, 10) meninges of spinal cord.

Macroscopically, arachnoidendothelioma looks like well-limited solitary (in rare cases, multiple) nodes, their consistency is dense, elastic. The tumor is on incision they are grayish-pink with light bands. Microscopically it is characterized by large endothehum-like cells. The cells usually form groups (platelike, curl-like, band-like), so-called endotheliomatous structures. In these tumors, there are secondary changes (calcifications, psalmoma bodies, paste). It is also termed psalmoma. Types of arachnoidendotheliomas:

1) endotheliomatous; 2) fibrous arachnoidendothelioma with plenty of connective tissue fibers; 3) meningotheliomatous characterized by microcircular structures; 4) alveolar; 5) xantomatous.

Malignant type of the tumor is meningeal sarcoma. Histologically it resembles fibrosarcoma, polymorphocellular sarcoma, diffuse sarcomatosis of the meninges. Thus, morphogenetic variety of CNS tumors, difficult diagnosis and differential diagnosis as well s their localization allow to include them into a separate group. Special attention should be paid to development of secondary signs which appear due to lie influence on the craniobasal and distal regions of Ilie brain. Secondary syndromes are dislocation syndromes which are dangerous for the life of the

patient; entrance of the temporal lobe to the tentorial t)ramen with strangulation of the midbrain; vasomotor vascular crises, heart failure; wedging of cerebellum tonsil to the great foramen; regional foci of circulation disturbance (insults and hemorrhages); epileptiform attacks. Only correct diagnosis helps to determine the tactics of treatment for such patients.

Tumors of vegetative nervous system

Tumors of vegetative nervous system originate horn ganglionic cells of different degree of maturity (sympathogonias, sympathoblasts, ganghioneurocytes)

‘ sympathetic ganglia as well as from the cells of nonchromophinic paraganglia (glomes) genetically

jconnected with sympathetic nervous system. Such [bcnin tumors as ganghioneuroma, paraganglioma Jglome tumor, chemodentoma) belong to this group.

I Ganglioneuromas are localized in the medullar lubstance of the adrenal gland, sympathetic trunks, perebrospinal nerves. It usually develops in young patients. The tumor differs from normal ganglia as it has the signs of atypism (polynuclear cells, tigrolysis, nuclear decentralization.

Schwann’s glia is represented by satellite cells. The tumor does not produce metastases.

Malignant ganglioneuroblastoma is a combination of neuroblastoma and ganglioneuroma. The tumor develops intrauterinely or during the first years of life.. It may be localized in any region of vegetative nervous system, small intramural ganglia of the inner organs,1 medullar layer of adrenal glands and sympathetic trunks. Sometimes it matures and turns into ganglioneuroma.

Nonchromophilic paraganglioma is a benign variant. It resembles the tumors of APUD systemi (APUDomas). It can produce ACTH and serotonin. The tumor is localized in the middle ear, retroperitoneally. It may be large, its histological structure ir alveolar and trabecular with large number of sinusoi4 vessels.

Malignant variant is paraganglioma. This i characterized by cellular polymorphism, infiltratin growth, lymphogenic metastases. Thus, the tumors peripheral ganglias correspond to different stages ci their embryonic structure. The lest mature i neuroblastoma, the most mature is ganglioneurom Ganglioneuroblastoma occupies an intermediate placi Tumors of peripheral nervous system

Tumors of peripheral nervous system originate rum the nerve membranes. Neurilemma (Schwannoma), neurofibroma, neurofibromatosis (Recklinghausen’s disease) are benign ones.

Schwamioma is formed of spinder-like cells with i-oil-shaped nuclei. The cells and fibers form rhythmical sirLictures. Neurofibroma is a tumor connected with the nerve membrane. It consists of connective tissue with nervous cells, bodies and fibers.

Neurofibromatosis is a systemic disorder characterized by development of multipleneurofibromas associated with different development defects. This ay be peripheral and central.

Malignant neurilemma is neurogenic sarcoma. Dilymorphocellular atypism, polynuclear symplasts, arden-like structure are characteristic.

 

TUMORS OF MELANIN-PRODUCING TISSUE

Melanin-producing cells (melaninocytes) are of peurogeneous origin. They may become the origin of umor-like formations (nevi) and melanomas. Nevi are cnign tumors of skin consisting of melanocytes of piclermis and derma. Neurogeneous origin of helanocytes is generally recognized. Nevi are defects p1 development ofneuroectodermal pigment elements. Fhcy look like brown spots of different size, and may be either flat or elevated over the surface or be wart- like. Sometimes their size is enormous (giant pigmented nevus).

According to the WHO classification (1974), there are the following types of nevi: 1) junctioevus, 2) compound nevus, 3) intradermal, 4) epithelioid nevus (intracellular), 5) balloon-cell nevus, 6) halonevus, 7) giant pigmented nevus, 8) involutioevus:

(fibrous papule of the nose), 9) blue nevus, 10) cellular• blue nevus.

Junctioevus. Nests of nevus cells are found on the border of epidermis and dermis. The nests are round or oval. Their cytop’asm is homogeneous,. slightly granular. The nevus cells are localized in the. area of reticular layer apices.

Compound nevus. Together with the nevus cells located on the border of dermis and epidermis, there are nests of nevus cells in derma itself.

Intradermal nevus. Nevus cells are located only:

in derma. Some of them can be found on the borde between derma and epidermis. They resemble nests The nevus cells look like compact mass. The cells i mature nevi may be polynuclear. Macroscopically the have papillomatous appearance and may contain hairs!

Epithelioid nevus can often appear on the face especially in children. It looks like flat or bal1-lik node. The surface of the skin is smooth, sometime papillomatous changes are observed. Microscopical1 it looks like compound nevils with borderline change

S( unetimes marked acanthosis is present. The amount ui melanin is small, it may also be absent. The cells have light basophilic cytoplasm and hyperchromic iticlei. Epithelioid cells with large foamy light cytoplasm may be present. Mitoses are not numerous. I ni- or polynuclear cells resemble Touton’s cells. There are a lot of vessels.

Blue nevus. Macroscopically this looks like bluish or bluish-brown or bluish-gray sport, its shape is round or oval, it does not elevate over the surface of the skin. Microscopic examination reveals stretched melanocytes.

Melanoma. In the case of malignant melanoma, at the age of 20, only one person per 300 000 (0.3 per 100 000) has the cancer, and at the age of 80 about 30 per 300 000(10 per 100 000) have it. The numbers of skin cancers rise with age because the main cause of all types of skin cancers is sunlight exposure. Sunlight contains ultraviolet light (UV), and this is what does the harm, particularly to the skin of babies and young children. The numbers of skin cancers vary from country to country. In tropical countries with large wli ftc populations, the numbers are proportional to the amount of sunlight. Australia, South Africa and the Southern American states all have a very high incidence of skin cancer in their white populations. JUack people are better protected by their skin colouring. Melanoma is one of the most malignant tumors, it spreads through the lymphatic and hematogenic routs. 70% of melanomas develop on the skin of the face, body and extremities.

Two kinds of melanoma are known.

1. Melanoma against a background of pigmented Hutchinson’s sport (freckles) or malignant lentigo.

2. Superficially disseminated melanoma (invasive melanoma, nodular melanoma). Melanomas may not contain pigments. In the tumor, there are a lot of mitoses, hemorrhages and necroses. At the tumor decomposition, a great amount of melanin and chromelanin enter the bloodstream, which is accompanied by melaninemia and melaninuria. The tumors are localized on the skin, pigment membrane of the eye, meninges, medullar layer of adrenal glands, in rare cases mucous membranes.

 

 

Glioblastoma. Pay attention to the presence of tumout tissue in the cerebral one, the outlines of its margins, its colour Explain its varied appearance.

Ependymotna. Describe the tumour localization, chai racterise its growth to the surrounding tissues, the colour o the tumour on dissection, its consistency. The significance a the tumour for the organism. Name of the tuniour in the casi

of malignancy. Medulloblastoma. Determine the localization of the Ilinour, describe the growth to the surrounding tissues, the ci ief of its margins, its colour on dissection, consistency. Name I Lie ways of intracranial metastases.

NeuroIbromatosis. Describe the size, shape and localization of the tumour nodes, the consistency, the ippearance of the tumour, the degree of skin pigmentation. (Nyc the surname of the scientist who described neuroI ihi-omatosis.

Arachnoidendothelioma. Describe its localization, ippearance, consistency, changes in the surrounding cerebral (issues, the margins of tumour node.

Skin melanoma and its metastases (into the liver and lanes). Describe the colour, surface, type of growth to the surrounding tissues. Pay attention to the uneven colouring of the tumour nodes in the liver and vertebrae. What are the possible non-skin localizations of primaiy melanoma nodes?

 

 Fibroma. Hematoxylin-eosin stain.

 

Lipoma. Hematoxylin-eosin stain.

 

 

 

Uterine Leiomyoma. Hematoxylin-eosin stain.

 

 

Cavernous hemangioma. Hematoxylin-eosin stain.

 

 

 

 

 

Chondroma. Hematoxylin-eosin stain.

 

 

Osteoid osteoma. Hematoxylin-eosin stain.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Fibrosarcoma. Hematoxylin-eosin stain.

 

 

 

Liposarcoma. Hematoxylin-eosin stain.

 

 

 

 

 

 

 

Osteosarcoma. Hematoxylin-eosin stain.

 

 

Melanoma skin.

 

Melanoma of the eye.

 

Fibroma. Hematoxylin-eosin stain.

 

 

 

 

 

 

 

 

 

Fibroids uterine.

 

Chondroma lungs.

Astrocytoma. Hematoxylin-eosin stain.

 

Glioblastoma.  Hematoxylin-eosin stain.

 

 

 

 

 

 

 

Neuromas.  Hematoxylin-eosin stain.

 

Medulloblastoma. Hematoxylin-eosin stain.

 

 

 

 

 

Liposarcoma. Hematoxylin-eosin stain.

 

Lipoma. Hematoxylin-eosin stain.

 

 

 

 

 

 

 

 

Meningioma.

 

Meningioma. Hematoxylin-eosin stain.

 

 

 

Carcinoma of the lung is the most frequent cause of cancer death worldwide (32% of cancer deaths in males, 25% in females). Bron­chogenic carcinoma is classified into small-cell lung carcinoma (ISCLCl oat cell) and non-small-cell lung carcinoma (NSCLC), which includes squamous cell carcinoma (SCO, large-cell

anaplastic carcinoma (LC), and adenocarcinoma (AC). Lung carci­nomas vary in their primary location, spread, and overall biok>gi< behavior. They frequently metastasize to regional lymph nodes (hilar, mediastinal) and to extralymphatic sites such as adrenal glands, brain, bone, and liver.

 

 

 

 

Small-cell lung cancer accounts tor 207» of all lung cancers, with a male predominance and relation to cigarette smoking. It presents as a rapidly growing and metastasizing central lung mass occasion­ally accompanied by a paraneoplastic syndrome (myasthenia of Eaton-Lambert syndrome, ectopic corticotropin production, diabetes insipidus). The tumor consists histologic ally of sheets of small round or spindle cells with high mitotic index and scattered necroses. SCLC is essentially more sensitive to chemotherapy and therefore separated from all other lung cancers. However, it has the poorest 5-year survival rate (approximately 5%).

 

 

There are several nonmetastatic extrapulmonary manifestations ol primar\ lung carcinoma, which are summarized as paraneoplastic syndromes. In addition to those pictured, these include skin changes, such as acanthosis nigricans, dermatomyositis/polymyosi-tiv and myasthenia. Progressive multifocal leukoencephalopathy, occasionally also described as paraneoplastic syndrome, results

from reactivation of latent polyomavirus infection (JC virus), and progressive focal demyelination in the central nervous system as can also be seen in other cases of immune deficiency (e.g., in HIV/acquired immunodeficiency virus AIDS and in certain cases of chronic lymphocytic leukemia).

 

 

Pancoast tumor characterizes a special growth pattern of bron­chogenic carcinoma with early invasion of homolateral soft tissues of the lower neck. The tumor subsequently grows into regional nerves (arm plexus, sympathicus, parasympathicus) and vessels causing the clinical Horner syndrome: enophthalmos, ptosis, mio­sis, and anhydrosis (sunken-in eyeball, lowering of upper eyelid, narrowing of pupil, and loss of sweating).