TUMOURS OF EPITHELIUM
TUMORS OF MELANIN-PRODUCING TISSUE
TERATOMAS AND TERATOBLASTOMAS
First, it is necessary to emphasize that epithelial tumors are the most frequent ones in the man, they involve chiefly people of middle and old age. Every 6th person over 40 dies from this tumor. In Europe, cancers are 4 times more frequent than in Asia. For instance, stomach cancer affects around 8000 people per year in the UK, although the incidence is declining. It affects more men than women. It is rare under the age of 40 and becomes more common with increasing age. The decline in the rate of stomach cancer is thought to be associated with improvements in diet.
Skin cancer is very rare in children but is more• common as people get older. At the age of 20 only about 1 person in 100 000 has non-mdanoma skin cancer, whereas at the age of 80 about 200 per 100 000 have it.
The incidence of kidney cancer is increasing and now accounts for approximately 6 000 new cases pen year.
Cancer of the ovary is more common in womenj who have never had children than in those who have. It may occur at any age but is most usual between th ages of 50 and 80. Before age 30, the incidence is les than
Benign epithelial tumors are subdivided according In their origin from different types of epithelium into lie tumors of integumentary epithelium (papillomas), lumors of glandular epithelium (adenomas).
Papilloma is a tumor originating from the skin and mucous membranes, it looks like a ledge or a bush of branching papillae. It is a good example of an exophytic tumor. The base of the tumor consists of connective tissue containing blood vessels. It is a continuation of subepithelial connective tissue covered with epithelium like with a glove.
Depending on the stage of the development and the character of stroma, papilloma may be either hard of soft.
Hard papillomas are benign, they grow slowly,. seldom become ulcerative and seldom bleed. They appear on the skin and mucous membranes covered i with multilayer squamous epithelium (mouth, larynx, pharynx).
Soft papillomas are tender, their stroma is loose, swollen, consists of thin fibers with thin-walled vessels. They are covered with cylindrical transition or ciliated epithelium. Their thin branching papillae can be easily injured and bleed. These papillomas more olien occur on the mucous membranes (nose, uterus, gastrointestinal tract, fallopian tubes) and are ussociated with chronic irritation of the mucous membrane. The most dangerous are papillomas of the urinary bladder. They grow quickly, relapse, may be the cause of bleeding resulting in general anemia, they often become malignant turning into cancer. These papillomas are mainly found in the neck of the urinary bladder and in the region of the triangle. It is necessary to admit that in papilloma both epithelium and stroma are subjected to tumor growth, they are characterized by anaplasia, therefore papillomas are considered fibroepithelial tumors.
Adenoma is a benign epithelial tumor from the epithelium of the glands and glandular organs. More often they can be found in the breast, thyroid gland, liver, ovaries, prostatic gland, gastrointestinal tract. According to the histological composition adenoma maybe tubular and alveolar. In tubular adenoma, there are glandular cavities resembling tubes in the connective tissue with vessels. In alveolar adenoma, numerous bubbles bedded with cylindrical or cubic epithelium are observed in the connective tissue with vessels. In this cases, the epithelium is separated from the surrounding tissue by its own membrane.
Adenomas from compact organs (liver, adrenal gland) can be made of groups of respective cells separated from each other by a thin layer of stroma..j Thus, the structure of adenomas is similar to that off the original organ which is the cause of their ffinctiona1 similarity (ability of adenoma cells to produce. respective secretes) e.g. — adenomas of mucous membranes — mucus, adenomas of eosinophilic cell of the anterior lobe of pituitary — somatotropic hormone, medullar layer of adrenal gland — iiorepinephrine, beta cells of pancreas — insulin, etc. 1 his peculiarity must be always taken into account by
physician as it may contribute timely diagnosis of h ese tumors and correct treatment tactics. But, alone with similarity, adenomas (being tumors) have atypical structure which manifests in absence of ducts, variety ol shape, size and location, parenchyma and stroma ratio (fibroadenoma, adenofibroma) in the glandular tubules and vesicles.
Sometimes papilloid growth of epithelium, bedding glandular cavities, is observed.
In some adenomas glandular cavities are widened and form large cavities, cysts filled with serous fluid 0I mucus. These cyst-like adenomas are called cystoadenomas.
Sometimes epithelial integument of glandular cavities begin to grow in a cyst-like manner. The papillae fill cyst-like cavities with masses resembling cauliflower.
Sometimes epithelial growth is so intensive that the papillae invade the walls of the cyst, involve the peritoneum, produce metastases, relapse, cause cachexia and may cause sever consequences. These adenomas are termed papillary adenocystomas. They develop in ovaries, thyroid gland. Adenocystomas may become malignant more frequently than the other adenomas. Immature, or malignant, tumors of epithelium are also called cancers. The term came to us from the time of Hippocrates and Galen.
The popularity of this term can be explained by the increase of the cancer incidence in the 20th century when compared with previous centuries.
This fact can be explained by the increase of the life expectancy by 20 years, that is the group of people of <<cancer age>> enlarged (due to increased possibility to be exposed to carcinogenic factors, accumulation of the total number of precarcinogenic processes and increased chance to develop latent cancer with long duration). Besides, increase of the number of tumors can be associated with improvements in diagnosis. But the above does not exclude objective causes of cancer development, especially in the population of the developed countries due to increase of the number of industrial tumors (cancer of lungs, skin, urinary bladder) associated with exposure to chemical carcinogens (at present there are about 300 of them, mainly polycyclic aromatic hydrocarbon, azo- or aminocompounds).
The morphological classification is based on differentiation of the tumor cells.
According to it all cancers can be divided into 3 groups:
1) poorly-differentiated: small-cell or basal cell, medullar, scii-rhus, solid;
2) well-differentiated: squamous-cell, with k eratinization, without keratinization, adenocarcinoma (Irabecular, alveOlar, papillary, mucous);
3) special kinds: chorionepithelioma, seminoma, ypernephroid cancer.
This classification is important because main cli nico-morphological peculiarities of different cancers a’e due to the degree of differentiation, or anaplasia of their cellular elements: intensity and character of Ihe primary tumor growth, secondary changes, sensitivity to radiotherapy which in higher in undifIbrentiated, character, rate and terms of metastases appearance. Squamous-cell cancer of skin, bronchi, i.e. highly differentiated cancers, do not produce metastases for a prolonged period of time. Vice verse undifferentiated cancers, e.g. medullar, small-cell cancer of bronchi, even small in size, gives early and abundant metastases. This may be accounted by the Jocation of the cellular complexes in medullar cancers [forming pure cultures of free cells easily penetrating lymphatic and blood vessels. It is necessary to crnember about the association of the type and ci racter of the metastases with the age of the patient. Thus, the size of the primary tumor does not influence metastases appearance, its histological structure and the degree of anaplasia are more important.
As to metastases, it is important to know that LiIVa5i0n of the tumor cells to the veins is difficult because they become narrowed in the rapidly growing tumor and due to increase of intravenous pressure. Blood vessels in the tumors look differently. Usually they have the structure of capillaries. As a rule, vessels in tumors are new structures but they are connected with general circulation. The tumors may be connected with the sources of nutrition in different ways. The more directly they contact, the more intensive is the growth of the tumor, the more rapidly it produces metastases (e.g., chorionepithelioma, seminoma, hypernephroid cancer).
If both stroma and parenchyma of the tumor are anaplastic, they characterize combination tumors, tenned sarcocarcinomas or carcinosarcomas.
Together with tissue and cellular atypism, malignant tumors are characterized by infiltrating tumor growth.
Clinico-anatomical practice suggests that tumor, as a rule, does not appear at once, its development is preceded by different processes characterized by:
1) prolonged chronic course, 2) association with cell, multiplying, 3) failure of conservative treatment.
These kind of processes or states are called precancerous. There are a large number of them9 defects of development, including lost embryoni germs, chronic inflammatory diseases, chronic ulcer9 disturbed tissue regeneration (abundant granulatior metaplasia), hormonal hyperplasias, polyposis o mucous membrane, leukoplakias of the mucou membrane. The problem of the terms of transition or pre-cancerous states into cancers is disputable. It is thought that the period of malignization (latent period) may last for 15—20 years (gastric cancer). Clinical observations show that some precancerous states turn into cancers more often than the other. The former are called obligatory precancers (polyposis of the mucous membrane of the stomach, intestine, uterus, chronic gastric ulcer, cystic mastopathy, erosion of the uterine cervix), the latter are optional.
CANCERS OF DEFINITE ORGANS
Gastric carcinoma
Gastric carcinoma comprises more than 90% of all gastric malignant tumors. The men at the age of 4O—6O suffer more often than women.
Pre-cancer changes in the gastric mucosa.
1. Atrophic gastritis. 2. Adenomatous polyps of the stomach. 3. Chronic gastric ulcet
Gastric carcinoma is most commonly located in the region of gastric canal (prepyloric region), less common localization are the body, cardia and flindus.
Classification
According to the deepness of the lesion in the gastric wall there are 2 types of carcinoma:
1. Early gastric carcinoma, when carcinoma confined only mucosal layers. growth:
2. Advanced gastric carcinoma, when it penetrates the muscular layer or beyond.
According to the location gastric carcinoma may be:
1. Pyloric (50%) gastric carcinoma. 2. Lesser curvature of the stomach (27%). 3. Cardial gastric carcinoma (15%). 4. Greater curvature of the stomach (3%). 5. Fundal gastric carcinoma (2%). 6. Total gastric carcinoma (3%).
According to the peculiarities of growth there are the following types of gastric carcinoma:
1. Carcinoma with exophytic and expensive
a) Fungating (resembling a mushroom) type;
b) Superficial spreading type;
c) Polypoid type;
d) Ulcerative type:
— primary-ulcerative,
like source (Cancer-ulcer),
— cancer from chronic ulcer ( Ulcer-cancer).
2. Carcinoma with endophytic — infiltrating
a) Ulcerative-invasive (infiltrating) type;
b) Diffhsely spreading type (Linitis plastica).
3. Carcinoma with exophytic and endophytic growth. (Mixed types of carcinoma).
According to the histological signs there are thel following types of gastric carcinoma:
1. Adenocarcinoma: papillary, mucoid, trabecular (well-differentiated).
2. Signet-ring cell carcinoma, scirrhous carcinona, solid carcinoma (poorly-differentiated).
3. Squamous-cell carcinoma.
4. Adenosquamous carcinoma.
Early gastric carcinoma is the term used to describe cancer limited to the mucosa and submucosa. [‘he diagnosis of this condition has been made possible by extensive work on histogenesis of gastric cancer by Japanese pathologists by the use of fiberoptic endoscope and gastrocamera.
Macroscopically, the lesions of early gastric carcinoma may have 3 patterns — superficial, polypoid and ulcer-associated. The superficial type may further he of flat, elevated to depressed subtypes. Microscopically, early gastric carcinoma is a typical glandular adenocarcinoma, usually well-differentiated.
Early gastric carcinoma must be distinguished from certain related terms: epithelial dysplasia (cellular atypia seen in intestinal metaplasia such as in atrophic gastritis and pernicious anemia); carcinoma in situ in the stomach (a state of severe cellular atypia or dysplasia, without invasion across the basement membrane of the glands).
Advanced gastric carcinoma. When the carcinoma crosses the basement membrane into the muscular propria or beyond, it is referred to as advanced gastric carcinoma. Advanced gastric carcinoma has following patterns:
1. Ulcerative carcinoma. This is the most common pattern. The tumour appears as a flat, infiltrating and ulcerative growth with irregular necrotic base and raised margin. It is seen more commonly in the region of gastric canal. Macroscopically, ulcerative carcinomas are poorly-differentiated adenocarcinomas, which invade deeply into the stomach wall. Tubular and acinar patterns are seen more commonly.
2. Fungating (polypoid) carcinoma. The second common pattern is a cauliflower growth projecting into:
the lumen, similar to what is commonly seen in the large intestine. It is seen more often in the frmndus. The tumor undergoes necrosis and infection commonly. Microscopically, fiingating or polypoid carcinomas are well-differentiated adenocarcinomas, commonly papillary type.
3. Scirrhous carcinoma. In this pattern, the stomach wall is thickened due to extensive desmoplasia giving the appearance as <<leather bottle stomach>> or <<linitis plastica>>. The involvement may be localized to pyloric antrum, or diffuse affecting whole of the stomach from• the cardia to pylorus. The lumen of the stomach is:
reduced. There are no ulcers but rugae are prominent.. Microscopically, it maybe an adenocarcinoma or signet- ring cell carcinoma, extensively infiltrating the
stomachS wall, but due to marked desmoplasia cancer cells mayO be difficult to find.
4. Colloid (mucoid) carcinoma. This pattern is usually seen in the fundus. The tumour grows like masses having gelatinous appearance due to secreti of large quantities of mucus. Microscopically, muco: carcinoma contains abundant pools of mucin in which Ire seen a small number of tumor cells, sometimes having signet-ring appearance.
5. Ulcer-cancer. Majority of ulcer-cancers are malignant lesions from the beginning. For confirmation of cancer in a pre-existing gastric ulcer, he characteristic microscopic appearance of peptic ulcer should be demonstrable with one portion of the base or the margin of the ulcer showing carcinomatous changes. Microscopically, ulcer-cancers are adenocarcinomas without any specific features.
Metastases can be:
1. Lymphogenic. There are 2 types of them:
orthograde (with the lymph flow) and retrograde (against the lymph flow). In ortbograde metastases, they are carried through the lymphatic vessels to regional lymphatic nodes — along the lesser and greater curvature, around the cardial and suprapancreatic lymphnodes.
In retrograde metastases they are carried through the lymphatic vessels to the left supraclavicular Iymphnode (Virchow’s gland), ovaries (Krukenberg tumor), pararectal tissue (Shnitsler metastases).
2. Hematogenic metastases are carried with the blood flow to the liver, lungs, brain, bones, kidneys and adrenal glands.
3. Implantation (contact), when the carcinoma disseminates through the peritoneum or penetrates to the pancreatic glands. Carcinoma of lung
95% of all primary lung tumors is bronchogenic carcinoma.
According to the peculiarities of their growth there are following types of pulmonory carcinoma:
1. Exophytic (endobronchial) type.
2. Endophytic (exobronchial and peribronchial) type.
According to the macroscopical signs there are following types of pulmonory carcinoma:
1. Superficial spreading type.
2. Polypoid type.
3. Endobronchial diffusely spreading type.
4. Nodular type.
5. Branching type.
6. Nodular-branching type.
According to the WHO, there are following histological types of bronchogenic carcinoma:
1. Squamous-cell carcinoma.
2. Adenocarcinoma:
a) acinar carcinoma;
b) papillary carcinoma:
c) bronchiolo-alveolar carcinoma;
d) solid carcinoma with mucos formation.
3. Small cell carcinoma:
a) oat cell carcinoma;
b) small cell carcinoma, intermediate cell
c) combined oat-cell carcinoma.
4. Large cell carcinoma.
5. Adenosquamous carcinoma.
According to its location, bronchogenic carcinol ila may be hilar and peripheral.
Hilar type. Most commonly, the lung cancer arises in the main bronchus or one of its segmental branchesthe hilar parts of the lung, more often on the right side. The tumour begins as a small roughened area on the bronchial mucosa at the biftrcation. As the tumour enlarges, it thickens the bronchial mucosa producing nodular or ulcerated surface. As the nodules coalesce, the carcinoma grows into a friable spherical mass, 1 to
Peripheral type. A small proportion of lung cancers, cii icily adenocarcinomas including bronchioloalveolar carcinomas, originate from a small peripheral bronchiole ‘but the exact site of origin may not be discernible. The ‘tumour may be a single nodule or multiple nodules in tim periphery of the lung producing pneumonia-like ‘consolidation of a large part of the lung. The cut surface of the tumour is grayish and mucoid. Squamous cell (epidermoid) carcinoma. This is the most common type of bronchogenic carcinoma found more commonly in men, particularly with the history of tobacco smoking. These tumors usually arise in a
large bronchus and are prone to massive necrosis and cavitation. The tumour is diagnosed microscopically by identification of either intercellular bridges or keratinization. Usually the spread of squamous cell carcinoma is more rapid than the other histologic types. Frequently, the edge of the growth and the adjoining uninvolved bronchi show squamous• metaplasia, epithelial dysplasia and carcinoma in situH
Adenocarcinoma is the most common bronchogenie carcinoma in women and is slow-growing. Adenocarcinoma is further subclassified into 4 types;
1. Acinar adenocarcinoma which has predominance of glandular structure and often occurs in the larger bronchi.
2. Papillary adenocarcinoma which has a pronounced papillary configuration and is frequentl3 peripherally located in the lungs and is found in relation to pulmonary scars (scar carcinoma).
3. Bronchioloalveolar carcinoma is characterized by cuboidal to tall columnar and mucus-secretin epithelial cells growing along the existing alveoli an forming numerous papillary structures.
4. Solid carcinoma is a poorly-differentiate adenocarcinoma lacking acini, tubules or papillae bi having mucus-containing vacuoles in many tumour Small cell carcinomas are frequently hilar or central
I location, have strong relationship to cigarette smoking
mid are highly malignant tumors. They are most often
I ssociated with ectopic hormone production because
(1 the presence of neurosecretory granules in majority
ui tumour cells which are similar to those found in
iigentaffin or Kulchitsky cells normally found in
bronchial epithelium. Small cell carcinomas may be:
1. Oat-cell carcinoma is composed of uniform, small cells, larger than lymphocytes with dense, round or oval nuclei having diffuse chromatin, inconspicuous nucleoli and very sparse cytoplasm. These cells are organized into cords, aggregates and ribbons or around small blood vessels forming pseudorosettes.
2. Small cell carcinoma, intermediate cell type is c(inposed of cells slightly larger than those of oat cell carcinoma and have similar nuclear characteristics but
Ihive more abundant cytoplasm. These cells are ‘lorganized into lobules.
3. Combined oat-cell carcinoma is a tumour in which there is a definite component of oat cell
[‘rcinomawith squamous cell and/or adenocarcinoma. Large cell carcinoma. These are undifferentiated carcinomas which lack the specific features by which tlicy could be assigned into squamous cell carcinoma
adenocarcinoma. Large cell carcinomas are more common in men, have strong association with cigarette smoking and are highly malignant tumors. The tumour cells have large nuclei, prominent nucleoli, abundant cytoplasm and well-defined cell borders. Adenosquamous carcinoma. These are a small proportion of peripheral scar carcinomas having clear evidence of both keratinisation and glandular differentiation.
Metastases can be:
1. Lymphogenic — through the lymphatic vessels to regional lymphatic nodes — hilar, mediastinal, cervical, supraclavicular and paraaortic lymphnodes.
2. Hematogenic metastases are carried with the blood flow to the liver, pancreas, brain, bones, kidneys, adrenal and thyroid glands.
3. Implantation (contact) when the carcinoma disseminates through the pleura or penetrates to the peribronchial lung tissue.
In carcinoma, irrespective of its location patients die from metastases and secondary complications, i.e. hemorrhages, necrosis of the tumor as well as cachexia.
Esophageal cancer
Esophageal cancer occupies special place as i the majority of cases the death of the patients is cause by hunger long before the disease become incompatible with the life. Even gastrostomy cannd save the patient, it only slows down the rate cachexia. This cancer is on the 2nd—3rd place ii occurrence. Men suffer more often than women (70k 30). The tumor is localized mainly in the middle an lower part of the esophagus. Carcinoma of the oesophagus is mainly of .‘ types — squamous cell (epidermoid) and adenoc;ircinOma.
Squamous cell (epidermoid) carcinoma. Iuamous cell or epidermoid carcinoma comprises R)% of primary esophageal cancers. The sites of predilection are the three areas of esophageal constrictions. Half of the squamous cell carcinomas ol esophagus occur in the middle third, then in the lower third, and then in the upper third part of esophagus. Macroscopically, 3 types are recognized:
I) Polypoid hingating type is the most common form. IL appears as a cauliflower-like friable mass protruding into the lumen; 2) Ulcerating type is the next common fbrrn. It looks grossly like a necrotic ulcer with everted edges; 3) Diffuse infiltrating type appears as an annular, stenosing narrowing of the lumen due to infiltration into the wall of esophagus.
Microscopically, the majority of squamous cell carcinomas of the esophagus are well- or moderatelydifferentiated. Prickle cells, keratin formation and epithelial pearls are commonly seen. However, nonkeratinising and anaplastic growth patterns can also 1occur.
Adenocarcinoma. The common locations of adenocarcinomas are lower and middle third of the esophagus.
Macroscopically, esophageal adenocarcinoma appears as nodular, elevated mass in the lower esophagus. Microscopically, adenocarcinoma of the esophagus may be: 1) Intestinal type (adenocarcinoma with a pattern similar to that seen in adenocarcinoma of intestine or stomach); 2) Adenosquamous type (the pattern in which there is an irregular admixture of adenocarcinoma and squamous cell carcinoma); 3) Adenoid cystic type (an uncommon variety and is akin to similar growth in saliVaIY gland i.e. a cribriform appearance in an epithelial tumour).
Besides the two histological types of esophageal cancer, a few other varieties are occasionally encountered. These are as under:
1. Mucoepidermoid carcinoma is a tumour having characteristics of squamous cell as well as mucus- secreting carcinomas.
2. Malignant melanoma is derived from melanoblasts in the epitheliUm of the esophagus.
3. Oat-cell carcinoma arises from argyrophil edit in the basal layer of the epithelium.
4. Undifferentiated carcinoma is an anaplastic carcinoma which cannot be classified into any recognizable type of carcinoma.
5. Carcinosarcoma consists of malignant epithelial as well as sarcornatous components.
6. Secondai-y tumors rarely occur in the esophagus from carcinomas of the breast, kidney and adrenals.
Metastases are lyniphogenic. Hematogenic metastases are rare, chiefly to the liver, lungs, adrenal glands. Complications: involvement of trachea, stomach, spiration pneumonia, lung gangrene, etc.
Breast cancer
Breast cancer is a frequent disease but as it is diagnostically and surgically accessible, it appears in surgical material more frequently than in autopsy. In women with malignant tumors, breast cancer occurs in 18% (S.A. Kholdin). In unmarried and nuliparous women it occurs 3 times more often. In men this cancer is rare (100 times rarer than in women). It is frequent in gynecomastias which is believed to be a precanceious state in women.
There are cancer of ducts, parenchyma, nipple and areola. In 95% of cases it develops •from ductal epithelium near the base of the nipple, which frequently causes its pulling in (e.g. cancer of large and medium ducts). Cancer from the parenchyma as well as from small and medium ducts develops deep in the organ Breast cancer may at first develop in the axillary legion. These aberrant cancers occur in 10% of cases. [he most frequent location of the tumor is upper external quadrant of the breast.
Intestinal glandular hyperplasia
According to the W}IO, carcinoma of the breast are subdivided on 2 main types non-invasive carcinoma and invasive one. Non-invasive carcinoma may be intraductal carcinoma and lobular carcinoma. There are several types of invasive carcinoma. They are infiltrating ductal carcinoma-NOS, invasive lobular carcinoma, medullary carcinoma, colloid carcinoma, papillary carcinoma, tubular carcinoma, adenoid cyst carcinoma, secretory carcinoma, inflammatory carcinoma and carcinoma with metaplasia.
Non-invasive a situ) carcinoma. In general, non- invasive or in situ carcinoma is characterized histologically by presence of tumour cells within the ducts or lobules without evidence of invasion. Two types of carcinoma in situ are described: intraductal carcinoma and lobular carcinoma in situ. Intraductal carcinoma. Carcinoma in situ confined within the larger mammary ducts is called intraductal carcinoma. The tumour initially begins with atypical hyperplasia of ductal epithelium followed by filling of the duct with tumour cells. Macroscopically, the tumour may vary from a small poorly-defined focus to 2.5—5.5 cm diameter mass. On cut section, tumor shows cystically dilated ducts containing cheesy necrotic material (comedo pattern), or the intraductal tumour may be polypoid and friable resembling intraductal papillomal (papillary pattern). Microscopically, the proliferating tumour cells within the ductal lumina may have 4 types of patterns in different combinations: solid, comedo, papillary and cribriform. Solid type is characterize by filling and plugging of the ductal lumina with tumour cells. Comedo type is centrally placed necrotiø debris surrounded by neoplastic cells in the duct1 Papillary type has formation of intraductal papillaryl projection of tumour cells which lack a fibrovascular si ilk so as to distinguish it from intraductal papilloma. (ribriform type is recognized by neat punched out cnestrations in the intraductal tumour.
Lobular carcinoma in situ is identified only microscopically. In situ lobular carcinoma is characterized by filling up of terminal ducts and (luctules or acini by rather uniform cells which are loosely cohesive and have small, rounded nuclei with indistinct cytoplasmic margins.
Invasive carcinoma. Infiltrating ductal cardnuma-NOS (not otherwise specified) is the classic breast cancer. Macroscopically, the tumor is irregular, I —5 cm in diameter, hard cartilage-like mass that cuts with grating sound. The sectioned
(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).
surface of the tumour is gray-white to yellowish with chalky streaks and often extends irregularly into the surrounding fat. Microscopically, as the name NOS suggests, the tumour is different from other special types in lacking a regular and uniform pattern throughout the lesion. Thеre are 3 histological types of this carcinoma:
• anaplastic tumour cells forming solid nests, cords, poorly-formed glandular structures and some inraductal foci;
• infiltration by these patterns of tumour cells into di [fuse fibrous stroma and fat;
• invasion into perivascular and perineural spaces as well as lymphatic and vascular invasion. Infiltrating (invasive) lobular carcinoma. Invasive cancers in being more frequently bilateral; and within the same breast, it may have multicentric origin. Macroscopically, the appearance varies from a well-defined scirrhous mass to a poorly-defined area of induration that may remain undetected by inspection as well as palpation. Microscopically, there are 2 characteristics: 1) Pattern — a characteristic single file (Indian file) linear arrangement of stromal infiltration by the tumour cells with very little tendency I to gland formation is seen. Infiltrating cells may be arranged concentrically around ducts in a target-likej pattern ; 2) Tumour cytology — individual tumour cells resemble cells of in situ lobular carcinoma. They are round and regular with very little plemorphism and infrequent mitoses. Some tumors may show signet1 ring cells distended with cytoplasmic mucus.
Medullary carcinoma has a significantly bette; prognosis than the usual infiltrating duct carcinomaj probably due to good host immune response in th4 form of lymphoid infiltrate in the tumour stromal Macroscopically, the tumour is characterized by
large, well-circumscribed, rounded mass that i typically soft and fleshy brain-like and hence th alternative name of <<encephaloid carcinoma>>. Cul section shows areas of hemorrhages and necrosiç There are 2 histological characteristics of this tumoti The first — pleomorphic tumour cells with abundani cytoplasm, large vesicular nuclei and many bizarre an ypical mitoses are diffusely spread in the scanty
suoma. The second — the loose connective tissue oma is scanty and usually has a prominent lymphoid
iiililtrate.
Colloid (mucinous) carcinoma contains large iinount of extracellular epithelial mucin and acini filled with mucin. Cuboidal to tall columnar tumour cells, some showing mucus vacuolation, are seen floating iii large lakes of mucin.
Paget’s disease of the nipple. The nipple bears a crusted, scaly eczematoid lesion with a palpable sibareolar mass in about half the cases.
Macroscopically, the skin of the nipple and areola is crusted, fissured and ulcerated with oozing of serosanguineous fluid from the erosions. Microscopically, the skin lesion is characterized the presence ni Paget’s cells singly or in small clusters in the epidermis. These cells are larger than the epidermal cells, spherical, having hyperchromatic nuclei with kytoplasmic halo that stains positively with mucicarmine. In these respects, Paget’s cells are adenocarcinoma-type cells. In addition, the underlying breast contains invasive or non-invasive duct carcinoma twluch shows no obvious direct invasion of the skin of ,nipple.
The metastases are either local or distant, the fbrmer to the lymphatic nodes of the breast base, axilla, siihclavicular, parasternal nodes. Distant metastases are hematogenic ones, 40—50% to the bones, lungs, liver. Late metastases and relapses occur 5—20 years
after the operation.
Stages of individual work in class Study and describe macrospecimens
Papilloma of the skin. Describe the appearance of the tumour, its connection with the skin, the mast frequent localization, outcomes of papilloma, name the malignant type.
Polyposis of the stomach and colon. Describe the appearance of the tumour: size, colour, surface, quantity ofi tumours, malignant variant.
Papilloma of the urinary bladder Types of the tumour at the side of the mucous membrane, possible complications, malignant variant.
Cystoadenoma of the ovary. Describe the surface of the tumour, the thickness of the wall, the character of the content, possible complications.
Cancer of the mammary gland. Describe the appearance:
size, colour, localization; name microscopic type of the tumour; name pre-cancer states.
Cancer of the stomach. Describe the appearance of thd tumour, name the macroscopic form of it, its localisation, ways of dissemination. What pre-cancer conditions do you know
Cancer of the uterine body. Localisation of the tumour its colour, size; the character of growth, possible complications enumerate the most frequent metastases. Name pre-cancers uterine cervix and body. Pay aft ention to: cancer of the live (primary and metastatic), cancer of the kidneys and thyroid glands the most difficult for diagnosis.
(cKrukenberg cancer of ovaries. Describe the tumour] Characterize the tumour invasion (multiple lesion of the bot aries, size, tumour nodes). At what primary localization of Nisic focus may the tumour occur, what are the ways of metastasis?
Central cancer of the lung. Define general microscopic changes in the bronchial wall in cancer of the lung (localization md dissemination of the tumour, bronchi involvement, growth). \V hat changes developed in the adjacent lung tissue and pleura? I lie relation of the tumour to the organs of the mediastinum, possible histological variants.
Peripheral cancer of the lung. What is the difference hetween this tuinourand central cancer of the lung (localization, size, shape, attitude to the pleura, state of the surrounding lung tissue).
Fibroadenoma and nodular breast cancer. Give the d Ilerential diagnosis of benign and malignant tumour of the breast (localization, dissemination, consistency, the boundary between it and gland tissue, flexibility of the tumour and its attitude to the skin).
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 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
|
Non-malignant growth |
Malignant growth |
|
Have minor deviations from parent tissue |
Expressed atypism: tissue and cellular |
|
Expansive growth |
Infiltrative growth |
|
Grow slowly |
Grow fast |
|
Reach big size |
Rear rich big size |
|
Rare are subject to ulceration |
Often are subject to ulceration |
|
Do not give metastasis |
Metastasis |
|
Recurrence is not characteristic |
Recur often |
|
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 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 .
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.
Teratomas and teratoblastomas: organismoid and organoid teratomas – tumors derivated from three germ layers are found in testis, ovaries, mediastinal, extraperitoneal, base of brain. In girls’ ovaries malignant teratoblastomas develop more often and benign teratomas – in testis, throat teratomas grow as polyps, are of benign course, intracranial teratomas more often are of malignant course, they often are hormonally active.
Tumors of cambial embryonal tissues: medulloblastoma is malignant tumor in tentorium, retinoblastoma is malignant tumor from embryonal poorly differentiated cells of retina, neuroblastoma is malignant tumor in sympathetic ganglia, adrenal meddula, fast metastasizes, discharge catecholamine.
Tumors developing like adults’ tumors are tumors of nervous system: astrocytomas, hematopoietic system: leucosis, malignant lymphomas; bones’ tumors: osteomas, chondromas, osteosarcomas, Ewing’s sarcomas.
Cancer begins in cells, the building blocks that make up tissues. Tissues make up the organs of the body.
Normally, cells grow and divide to form new cells as the body needs them. When cells grow old, they die, and new cells take their place.
Sometimes, this process goes wrong. New cells form when the body does not need them, and old or damaged cells do not die as they should. The buildup of extra cells often forms a mass of tissue called a growth, polyp, or tumor.
Tumors in the stomach can be benign (not cancer) or malignant (cancer). Benign tumors are not as harmful as malignant tumors:
ü Benign tumors:are rarely a threat to life
ü can be removed and usually don’t grow back
ü don’t invade the tissues around them
ü don’t spread to other parts of the body
ü Malignant tumors:
ü may be a threat to life
ü often can be removed but sometimes grow back
ü can invade and damage nearby organs and tissues
ü can spread to other parts of the body
Stomach cancer usually begins in cells in the inner layer of the stomach. Over time, the cancer may invade more deeply into the stomach wall. A stomach tumor can grow through the stomach’s outer layer into nearby organs, such as the liver, pancreas, esophagus, or intestine.
Stomach cancer cells can spread by breaking away from the original tumor. They enter blood vessels or lymph vessels, which branch into all the tissues of the body. The cancer cells may be found in lymph nodes near the stomach. The cancer cells may attach to other tissues and grow to form new tumors that may damage those tissues.
The spread of cancer is called metastasis. See the Staging section for information about stomach cancer that has spread.
The ovaries are two small organs located on either side of the uterus in a woman’s body. They make hormones, including estrogen, which trigger menstruation. Every month, the ovaries release a tiny egg. The egg makes its way down the fallopian tube to potentially be fertilized. This cycle of egg release is called ovulation.
What causes ovarian cysts?
Cysts are fluid-filled sacs that can form in the ovaries. They are very common. They are particularly common during the childbearing years.
There are several different types of ovarian cysts. The most common is a functional cyst. It forms during ovulation. That formation happens when either the egg is not released or the sac — follicle — in which the egg forms does not dissolve after the egg is released.
Other types of cysts include:
Polycystic ovaries. In polycystic ovary syndrome (PCOS), the follicles in which the eggs normally mature fail to open and cysts form.
Endometriomas. In women with endometriosis, tissue from the lining of the uterus grows in other areas of the body. This includes the ovaries. It can be very painful and can affect fertility.
Cystadenomas. These cysts form out of cells on the surface of the ovary. They are often fluid-filled.
Dermoid cysts. This type of cyst contains tissue similar to that in other parts of the body. That includes skin, hair, and teeth.
What causes ovarian tumors?
Tumors can form in the ovaries, just as they form in other parts of the body. If tumors are non-cancerous, they are said to be benign. If they are cancerous, they are called malignant. The three types of ovarian tumors are:
Epithelial cell tumors start from the cells on the surface of the ovaries. These are the most common type of ovarian tumors.
Germ cell tumors start in the cells that produce the eggs. They can either be benign or cancerous. Most are benign.
Stromal tumors originate in the cells that produce female hormones.
Doctors aren’t sure what causes ovarian cancer. They have identified, though, several risk factors, including:
Age — specifically women who have gone through menopause
Smoking
Obesity
Not having children or not breastfeeding (however, using birth control pills seems to lower the risk)
Taking fertility drugs (such as Clomid)
Hormone replacement therapy
Family or personal history of ovarian, breast, or colorectal cancer (having the BRCA gene can increase the risk)
What are the symptoms of ovarian cysts and tumors?
Often, ovarian cysts don’t cause any symptoms. You may not realize you have one until you visit your health care provider for a routine pelvic exam. Ovarian cysts can, however, cause problems if they twist, bleed, or rupture.
If you have any of the symptoms below, it’s important to have them checked out. That’s because they can also be symptoms of ovarian tumors. Ovarian cancer often spreads before it is detected.
Symptoms of ovarian cysts and tumors include:Pain or bloating in the abdomen
ü Difficulty urinating, or frequent need to urinate
ü Dull ache in the lower back
ü Pain during sexual intercourse
ü Painful menstruation and abnormal bleeding
ü Weight gain
ü Nausea or vomiting
ü Loss of appetite, feeling full quickly
he term “ovarian cancer” includes several different types of cancer that all arise from cells of the ovary. Most commonly, tumors arise from the epithelium, or lining cells, of the ovary. These include epithelial ovarian (from the cells on the surface of the ovary), fallopian tube, and primary peritoneal (the lining inside the abdomen that coats many abdominal structures) cancer. These are all considered to be one disease process. There is also an entity called borderline ovarian tumors that have the microscopic appearance of a cancer, but tend not to spread much.
However, there are also less common forms of ovarian cancer that come from within the ovary itself, including germ cell tumors and sex cord-stromal tumors. All of these diseases will be discussed, as well as their treatment.
Epithelial ovarian cancer
Epithelial ovarian cancer (EOC) accounts for about 70% of all ovarian cancers. It is generally thought of as one of three types of cancer that include ovarian, fallopian tube, and primary peritoneal cancer that all behave, and are treated the same way, depending on the type of cell that causes the cancer. The four most common cell types of epithelial ovarian cancer are serous, mucinous, clear cell, and endometrioid. These cancers arise due to DNA changes in cells that lead to the development of cancer. Serous cell type is the most common variety. It is now thought that many of these cancers actually come from the lining in the fallopian tube, and fewer of them from the lining on the surface of the ovary, or the peritoneum. However, it is often hard to identify the sources of these cancers when they present at advanced stages, which is very common.
Borderline ovarian tumors
Borderline ovarian tumors account for a small percentage (approximately 10%) of epithelial ovarian cancers. They are most often serous or mucinous cell types. They often have presentations of large masses, but uncommonly metastasize. Often, thorough surgical staging is curative, even at more advanced stages.
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).
