Tamara Datsko associate Professor of Pathology, sectional course and forensic medicine. The EPITHELIAL tumors.
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The appearance of tumors may be associated with various exogenous and endogenous factors, physical and chemical factors, carcinogens, and viruses, and inherited genetic disorders.
This means disordered development, as observed in histological sections.
The changes consist of increased mitosis, the production of abnormal cells in varying numbers and a tendency to disorder in their arrangement (cellular atypia). Some cases of dysplasia progress to malignancy.
The diagram illustrates changes which are common in the uterine cervix
Tumours may be classified in two ways: (1) clinical and (2) histological origin.
The tumour is classified according to its morbid anatomy and behaviour. Two main groups are recognised — benign (simple) and malignant.
Although tumours may arise from any tissue in the body, they can be conveniently accommodated in six groups.
Mesodermic connective tissues including muscle, bone and cartilage
Blood and lymph vessels
Cells originating from developmental abnormalities
In practice, tumours most often take origin from tissues which normally have a rapid turnover of cells and are active in repair — epithelia of skin and mucous membranes, breast and female reproductive organs, connective tissue, bone and haemopoietic cellsHISTOLOGICAL ORIGIN
(1) Differentiatedand (2) Undifferentiated.
The degree of differentiation roughly corresponds to the character of the neoplasm. Cells of simple tumours arc well differentiated; those of malignant tumours tend to remain undifferentiated, and the more primitive the cells the greater the malignancy
Lack of differentiation is often termed anaplasia, and anaplastic tumours are highly malignant. There is a spectrum of change in neoplasms from the very slowly growing, highly differentiated simple types to the rapidly growing, undifferentiated malignant examples
Again the proliferation of epithelium of a gland causes the formation of tubules which ramify and become increasingly compound. The original communication with the parent gland duct or acinus tends to become lost
In the case of a hollow viscus, such as the intestine or gall bladder, the adenomatous proliferation, instead of growing down into the subjacent connective tissue, is usually pushed upwards into the lumen of the viscus. — The growth therefore combines the features of a papilloma and an adenoma. The term adenomatous polyp is often applied in such a case.Simple epithelial tumours
In the type which grows into the subjacent connective tissue, the constant budding of the epithelium results in new acini which become nipped off from the parent acini.
In cases in which retention of secretion is marked, a cyst forms and the tumour is then called a cystadenoma which may reach an enormous size, e.g. some cystadenomas of the ovary may be 30-40 cm in diameter,Simple epithelial tumours
This represents an intermediate stage in the production of a cancer. All the cytological features of malignancy are present, but the cells have not invaded the surrounding tissues. It is frequently found in the cervix uteri at the junction of ecto and endocervix.
These premalignant conditions may revert to normal, but most commonly they become truly malignant and invade the surrounding tissues. The determining factors are unknown.
The concept of progressive premalignant proliferation applies equally in other organs (e.g. stomach, bowel, bronchus, etc.).
An important principle is that these permeating tumour cells take the line of least physical resistance
The following diagram illustrates the basic mechanisms of cancer cell invasion
Theemboliappearfirstinthecorticalsinus, andthenprogressivelyinvadethetissuesofthenode. Eventuallytheyreachthemedullaandgrowintotheefferentchannelandproducemetastasesinothernodes. Invadednodesareenlarged, firmandwhite.
Growthofcarcinomacellsin a noderesultsinocclusionofafferentandefferentchannels. Lymphflowisthusdivertedandthishastwoeffects:
Although lymphatic embolism is of major practical importance , tumour cell may also grow along lymphatic channels in continuous in continuous solid columns lymphatic permeation
Asinlymphatics, growthoftumourwithin a veinmaycausereversalofbloodflow. Inaddition, reversalofflowisapttohappenincertainareasofthebodywhereveinsform a richplexusandaredeficientinvalves, e.g. inthepelvisandaroundvertebrae. Changesinintraabdominalandintrathoracicpressureseasilyinducechangesinbloodflowinthesechannels. Itisforthisreasonthatsecondarytumoursarerelativelycommoninvertebralbodies.
SEED and SOIL ANALOGY
Thedistributionofcarcinomatousemboliisdeterminedinpartbyanatomy, butmanycomplexfactorsbothinthe'seed' (thecancercell) andthe'soil' (thepotentialmetastaticsite) areatplayintheestablishmentofmetastasesatparticularsites. Theyincludesurfacepropertiesandsecretoryproductsofthecancercellsandreceptorspresentinthecellsandmatrixatthemetastaticsite. Variationinthehost IMMUNE RESPONSE isalsoimportant.
Actively moving tissues: muscle, tendon.Cancercellsmayremainlatentatremotesites (e.g. breastcancercellsinvertebralbonemarrow) andcommenceaggressivegrowthaftermonthsoryears.
Because this assessment is subjective, it is usual to assign no more than 3 histological grades: well (Grade I), moderately (Grade II) and poorly differentiated (Grade III).
This is well exemplified in Hodgkin's disease where numerical staging has proved very useful.
TNM staging is widely used: T 0-3 indicates local tumour spread, N 0-1 indicates lymph node metastases and M 0-1 distant metastases.
As malignant cells sink in peritoneal cavity, they will settle in various sites. They cause an inflammatory reaction with fibrin formation. This anchors the cells and also causes adhesions between organs, providing routes for further spread.
Histologically, it is composed of irregular strands and columns of invading epithelium which infiltrate the subjacent connective tissue. If well differentiated, the central cells of the invading masses show conversion into eosinophilic keratinised squames, while the outer layer consists of young basophilic cells. In cross-section, the appearance is typical.
The usual features of malignancy — variation in size and shape of cell accompanied by frequent mitotic activity — are present.
Itstartsas a flattenedpapillomawhichslowlyenlargesovermonthsorperhaps a yearortwo.
Thesurfacebreaksdownand a shallow, raggedulcerwithpearlyedgesisformed.
Usuallythemalignanttissuespreadsslowlybutprogressively, mainlyin a lateraldirection. Itiscomposedofcellsresemblingthoseofthebasallayeroftheskinfromwhichittakesoriginandhas a characteristichistologicalappearance.
Occasionaly a carcinoma will produce large quantities of mucus and merit the term mucoid carcinoma. The alveoli may be filled with mucus in which only a few carcinoma cell persist, the cell appearing to dissolve in the mucus. They are commonest in organs normally containing large numbers of mucus-secreting cell, e.g. large intestine, stomach, etc.
These tumours are grouped under the the descriptive term sarcoma, from the Greek sarcoma meaning “Fresh”
Sarcomas are less common that carcinomas/ Next to leukaemia, they are the most common malignant tumours in children and young adults. In older age groups, 90% of malignant tumours are carcinomas.
Unlike the sinuous infiltrating carcinoma, sarcomas are large fleshy tumours. Arising from and within connective tissues means that infiltration between normal cells advance on a broad front destroing and replacing normal cell.
On naked eye assessment these appearances give a false impression and surgical 'shelling out' procedures are almost inevitably followed by local recurrence due to microscopic aggregates of malignant cells remaining in the tumour bed