1) Pleomorphism means variation in size and shape of the tumor cells. The extent of cellular pleomorphism generally correlates with the degree of anaplasia.
2) Nucleocytoplasmic changes. These are as under:
Generally, the nuclei of malignant tumor cells are enlarged, so that the nucleocytoplasmic ratio is increased.
The nuclei too, show variation in size (anisonucleosis) and shape in malignant tumor cells.
Characteristically, the nuclear chromatin of malignant cell is increased and coarsely clumped, referred to as hyperchromatism. Besides, a prominent nucleolus or nucleoli may be present in these nuclei reflecting increased nucleoprotein synthesis.
It is most important to identify abnormal and atypical mitotic figures such as tripolar, quadripolar and multipolar spindles in malignant tumour cells because increased number of normal mitoses may be present in non-neoplastic proliferations such as in hematopoietic cells of the bone marrow, intestinal epithelium, hepatocytes etc.
Multinucleate tumor giant cells or giant cells containing a single large and bizarre nucleus, possessing nuclear characters of the adjacent tumor cells, are another important feature of anaplasia.
The cytoplasm of tumor cells in better-differentiated cancers and in benign tumors may show the normal constituents from which the tumor is derived. But the more anaplastic tumor cells lose such features.
3) Genetic abnormalities. All tumor cells have abnormal genetic composition and on division they transmit the genetic abnormality to their progeny. Most malignant tumors show aneuploidy.
4) Functional changes. Structural anaplasia in tumors is accompanied with functional anaplasia. The functional abnormality in neoplasms may be quantitative, qualitative, or both.
Generally, benign tumors and better-differentiated malignant tumors continue to function well qualitatively, though there may be quantitativeabnormality in the product, e.g. large or small amount of collagen produced by benign tumors of fibrous tissue, keratin formation in well-differentiated squamous cell carcinoma. In more anaplastic tumors, there is usually quantitative fall in the product made by the tumor cells, e.g. absence of keratin in anaplastic squamous cell carcinoma.
Hormones or hormone-like substances may be produced by certain tumors quite unrelated to the endocrine glands, called ectopic hormone production, e.g. oat cell carcinoma of the lung can secrete ACTH and ADH.
3. Angiogenesis and Tumor Stroma.
The connective tissue along with its blood supply forms the supportive framework on which the parenchymal tumor cells grow and receive nourishment. In order to provide nourishment to growing tumor, new blood vessels are formed from pre-existing ones (angiogenesis) that is probably stimulated by secretion of tumor angiogenesis factors from the parenchymal tumor cells such as vascular endothelial growth factor (VEGF). However, if the tumor outgrows its blood supply as occurs in rapidly growing tumors, its core undergoes ischemic necrosis. If the tumor is almost entirely composed of parenchymal cells, it is called medullary, if there is excessive connective tissue stroma, it is referred to as desmoplasiaand the tumor is hard or scirrhous.
4. Inflammatory Reaction.
At times, prominent inflammatory reaction is present in and around the tumors. It could be the result of ulceration in the cancer when there is secondary infection. However, some tumors show chronic inflammatory reaction, chiefly of lymphocytes, plasma cells and macrophages, and in some instances, granulomatous reaction, due to cell-mediated immunologic response by the host in an attempt to destroy the tumor, e.g. seminoma testis, malignant melanoma of the skin, lymphoepithelioma of the throat, medullary carcinoma of the breast, Warthin’s tumor of salivary glands etc.
TABLE 6: Contrasting Features of Benign and Malignant Tumors.
| FEATURES | BENIGN (DIFFERENTIATED) | MALIGNANT (UNDIFFERENTIATED) |
| MACROSCOPIC FEATURES | | |
| 1. Boundaries | Encapsulated or well-circumscribed | Poorly-circumscribed and irregular |
| 2. Surrounding tissue | Often compressed | Usually invaded |
| 3. Size | Usually small | Often larger |
| 4. Secondary changes | Occur less often | Occur more often |
| II. MICROSCOPIC FEATURES | | |
| 1. Pattern | Usually resembles the tissue of origin closely | Often poor resemblance to tissue of origin |
| 2. Basal polarity | Retained | Often lost |
| 3. Pleomorphism | Usually not present | Often present |
| 4. Nucleo-cyto-plasmic ratio | Normal | Increased |
| 5. Anisonucleosis | Absent | Generally present |
| 6. Hyperchromatism | Absent | Often present |
| 7. Mitoses | May be present but are always typical mitoses | Mitotic figures increased and are generally atypical and abnormal |
| 8. Tumor giant cells | May be present but without nuclear atypia | Present with nuclear atypia |
| 9. Cytoplasm | May show normal constituents | Normal cytopiasmic elements are reduced or lost |
| 10. Function | Usually well maintained | May be retained, lost or become abnormal |
| III. GROWTH RATE | Usually slow | Usually rapid |
| IV. LOCAL INVASION | Often compresses the surrounding tissues without invading or infiltrating them | Usually infiltrates and invades the adjacent tissues |
| V. METASTASIS | Absent | Frequently present |
III. Growth rate
The tumor cells generally proliferate more rapidly than the normal cells. In general, benign tumors grow slowly and malignant tumors rapidly. The rate at which the tumor enlarges depends upon 3 main factors:
1. Rate of division and destruction of tumor cells. The rate of division of tumor cells depends upon 2 factors - proportion of cells undergoing mitosis (milotic index), and the duration taken to complete the mitotic cell cycle.
2. Non-neoplastic elements within the tumors. These are the connective tissue stroma, abundant mucoid material, cartilaginous matrix etc all of which add to the bulk of the tumors.
3. Degree of differentiation. In general, rate of growth of malignant tumor is directly proportionate to the degree of differentiation. Rarely, a malignant tumor such as choriocarcinoma and malignant melanoma may disappear spontaneously from the primary site, possibly due to necrosis caused by good host immune attack, only to reappear as secondaries elsewhere in the body. The regulation of tumor growth is under the control of growth factors secreted by the tumor cells.
Depending on the degree of the tumor differentiation, there are different types of its growth: expansive, apposition, infiltrating (invasive).
At expansive growth the tumor grows from itself moving away the surrounding tissues. This type of growth is slow, and is characteristic benign tumors.
Apposition growth is due to transformation of normal cells to tumor ones.
In infiltrating growth the cells of the tumor invade normal tissues and destroy them (so called destructive growth).
In relation to the lumen of the hollow organ, the growth of the tumor may be endophytic or exophytic.
Endophytic growth is infiltrating growth of the tumor deep into the wall of the organ.
Exophytic growth is expansive growth of the tumor to the cavity of the organ.
According to the number of foci of tumor development, they can be unicenter (one focus) and multicenter (several foci).
IV. Local invasion (direct spread)
Most benign tumors form encapsulated or circumscribed masses that push aside the surrounding normal tissues without actually invading, infiltrating or metastasising. Malignant tumors also enlarge by expansion. But, they are distinguished from benign tumors by invasion, infiltration and destruction of the surrounding tissue, besides distant metastasis. Often, cancers extend through tissue spaces, permeate lymphatics, blood vessels, and perineural spaces and may penetrate a bone by growing through nutrient foramina. More commonly, the tumors invade thin-walled capillaries and veins than thick-walled arteries.
V. Metastasis (distant spread)
Metastasis is defined as spread of tumor by invasion in such a way that discontinuous secondary tumor mass/masses are formed at the site of lodgement. Metastasis is the most important feature to distinguish malignant from benign tumors. Benign tumors do not metastasize while all the malignant tumors with a few exceptions like gliomas of the central nervous system and basal cell carcinoma of the skin, can metastasize.
Routes of metastasis:
1. Lymphatic spread.
2. Hematogenous spread.
3. Other routes (spread along epithelium-lined surfaces, spread via cerebrospinal fluid, implantation).
1. Lymphatic spread. In general, carcinomas metastasize by lymphatic route while sarcomas favour hematogenous route.The walls of lymphatics are readily invaded by cancer cells and may form a continuous growth in the lymphatic channels called lymphatic permeation, or may detach to form tumour emboli. The tumor emboli enter the lymph node at its convex surface and are lodged in the subcapsular sinus. Later, of course, the whole lymph node may be replaced and enlarged by the metastatic tumor. Sometimes lymphatic metastases do not develop first in the lymph node nearest to the tumor because of venous-lymphatic anastomoses or due to obliteration of lymphatics by inflammation or radiation, so called stop metastasis. Other times, due to obstruction of the lymphatics by tumor cells, the lymph flow is disturbed and retrograde metastasesmay be seen at unusual sites, e.g. metastasis of carcinoma prostate or stomach to the supraclavicular lymph nodes, metastatic deposits in the adrenals from carcinoma lung etc.
2. Hematogenous spread. Metastasis through blood vessels is the common route for sarcomas but certain carcinomas also frequently metastasize by this mode, especially those of the lung, breast, thyroid, kidney and prostate. The common sites for blood-borne metastasis are the liver, lungs, kidneys, brain and bones, all of which provide “good soil” for the growth of “good seeds” (seed-soil theory)than are the unfavourable sites like the spleen and muscles. The cancer cells readily invade the walls of capillaries, venules and veins than the arteries which are thick-walled and contain elastic tissue resistant to invasion.
Cancers of the organs draining into portal veins frequently establish metastasis in the liver, while cancers of organs draining into caval veins metastasize to the lungs.
Etiology and pathogenesis of neoplasia
The etiology of tumors is various, 4 theories are recognized.
1. Virogenetic theory. It states integration of the genomes of the virus and the normal cell that is combination of nucleic acid of the virus with genetic apparatus of the cell, which turns into tumor ceil. Oncogenic viruses are those containing DNA and RNA (Epstein-barr virus, herpes virus, hepatitis B- Virus, etc.).
2. Physicochemical theory suggests that tumor appears under the influence of different physical and chemical substances, so called carcinogens.
3. Dysontogenetic theory was created by J. Cohnheim; According to his theory, tumors appear from embryonic tissue and abnormally developed tissues under the influence of different causative agents.
4. Polyetiological theory emphasizes the importance of different factors, i.e. chemical, physical, viral, parasite, dyshormonal.
Based on the current state of knowledge, these factors are broadly described under 2 main headings:
I. Predisposing epidemiologic factors, which include a number of endogenous host factors and exogenous environmental factors.
II. Carcinogenesis, that encompasses exogenous agents like chemical, physical, hormonal and biological substances.
Carcinogenesis
Carcinogenesis means inductions of tumors; agents, which can induce tumors, are called carcinogens. Carcinogens are a variety of extrinsic agents, which are broadly divided into 4 groups:
1. Chemical carcinogens.
2. Physical carcinogens (mainly radiation).
3. Hormonal carcinogens.
4. Biologic carcinogens (chiefly viruses).
Clinical aspects of neoplasia
Two major aspects of clinical significance in assessing the course and management of neoplasia are tumor-host inter-relationship and laboratory diagnosis of cancer.
Effect of tumor on host
Malignant tumors produce more ill effects than the benign tumors.
1. Local effects. Both benign and malignant tumors cause local effects on the host due to their size or location. Some of the local effects of tumors are as under
Compression.
Mechanical obstruction.
Tissue destruction.
Infarction, ulceration, hemorrhage.
2. Cancer cachexia. Patients with advanced and disseminated cancers terminally have asthenia (emaciation), and anorexia, together referred to as cancer cachexia.
3. Fever. Fever of unexplained origin may be presenting feature in some malignancies such as in Hodgkin’s disease, adenocarcinoma kidney, osteogenic sarcoma and many other tumors. The exact mechanism of tumor-associated fever is not known but probably the tumor cells themselves elaborate pyrogens.
4. Paraneoplastic syndromes. Paraneoplastic syndromes (PNS) are a group of conditions developing in patients with advanced cancer, which are not explained by direct and distant spread of the tumor (endocrine, neuromuscular, hematologic, gastrointestinal, renal syndromes, amyloidosis).
5. Secondary changes in the tumor result from disturbances of blood circulation, from chemo*-or radiotherapy. They manifest by foci of necrosis, hemorrhages, inflammation, formation of mucus, calcification.
Diagnosis of cancer. The most certain and reliable method which has stood the test of time is the histological examination of biopsy, cytological methods, histochemistry and cytochemistry, immunohistochemistry.
EPITHELIAL TUMORS
Benign epithelial tumors
Benign epithelial tumors are subdivided according to their origin from different types of epithelium into the tumors of integumentary epithelium (papillomas), tumors of glandular epithelium (adenomas).
Papilloma has following features
Bening tumor.
Origin from the skin and mucous membranes.
It looks like a ledge or a bush of branching papillae.
Exophytic tumor.
Slow growth.
The base of the tumor consists of connective tissue containing blood vessels.
It is a continuation of subepithelial connective tissue covered with epithelium like.
May be hard of soft.
Hard papillomas locate on the skin and mucous membranes covered with multilayer squamous epithelium (mouth, larynx, pharynx).
Soft papillomas consist 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. They grow quickly. 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.
Adenoma
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 may be 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.
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.
Thus, the structure of adenomas is similar to that of the original organ, which is the cause of their functional 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 - noradrenaline, beta cells of pancreas - insulin, etc.
Adenomas have atypical structure, which manifests in absence of ducts, variety of shape, size and location, parenchyma and stroma ratio (fibroadenoma, adenofibroma) in the glandular tubules and vesicles.
In some adenomas glandular cavities are widened and form large cavities, cysts filled with serous fluid or mucus. These cyst-like adenomas are called cystoadenomas.
Sometimes epithelial growth is so intensive that the papillae invade the walls of flie 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.
Malignant epithelial tumors
Immature, or malignant, tumors of epithelium are also called carcinoma. The term came to us from the time of Hippocrates and Galen.
Precancerous states: defects of development, including lost embryonic germs, chronic inflammatory diseases, chronic ulcers, disturbed tissue regeneration (abundant granulation, metaplasia, displasia), hormonal hyperplasias, polyposis of mucous membrane, and leukoplakias of the mucous membrane.
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 large-cell, medullar, scirrhus, solid.
2) Well-differentiated: squamous-cell, with keratinization, without keratinization, adenocarcinoma (trabecular, alveolar, papillary, mucous.
3) Special kinds: chorionepithelioma, seminoma, hypernephroid cancer.
As to metastases, it is important to know that invasion of the tumor cells in the veins is difficult because they become narrowed. 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, termed sarcocarcinomas or carcinosarcomas.
Together with tissue and cellular atypism, malignant tumors are characterized by infiltrating tumor growth.
Clinical-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.
THE MOST OFTEN TUMORS
Gastric carcinoma
Gastric carcinoma comprises more than 90% of all gastric malignant tumors. The men at the age of 40-60 suffer more often than women;
Pre-cancer changes in the gastric mucosa: 1. Atrophic gastritis, 2. Adenomatous polyps, 3. Chronic gastric ulcer.
Gastric carcinoma is most commonly located in the region of gastric canal (prepyloric region), less common localization are the body, cardia and fundus.
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 mucosa layers. 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).
2. Advanced gastric carcinoma, when it penetrates the muscular layer or beyond. 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 fundus. The tumor undergoes necrosis and infection commonly. Microscopically, fungating 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 may be an adenocarcinoma or signel-nng cell carcinoma, extensively infiltrating the stomach wall, but due to marked desmoplasia cancer ceils may 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 secretion of large quantities of mucus. Microscopically, mucoid carcinoma contains abundant pools of mucin in which are 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, the 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.
According to the location gastric carcinoma may be:
Pyloric (50%) gastric carcinoma.
Lesser curvature of the stomach (27%).
Cardial gastric carcinoma (15%).
Greater curvature of the stomach (3%).
Fundal gastric carcinoma (2%).
Total gastric carcinoma (3%).
According to the histoiogical signs there are the following types of gastric carcinoma:
Adenocarcinoma: papillary, mucoid, trabecular (well- differentiated).
Signet-ring cell carcinoma, scirrhous carcinoma, solid carcinoma (poorly-differentiated).
Squamous-cell carcinoma.
Adenosquamous carcinoma.
Metastases can be:
1. Lymphogenic. There are 2 types of them: orthograde (with the lymph flow) and retrograde (against the lymph flow).
In orthograde 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 lymphnode (Virchow’s gland), ovaries (Krukenberg tumor), pararectal tissue (Shnitsler’s 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 lungs
According to the types of growth pulmonary carcinoma may be:
Exophytic (endobronchial) type.
Endophytic (exobronchial and peribronchial) type.
According to the macroscopical signs pulmonory carcinoma may be:
Superficial spreading type.
Polypoid type.
Endobronchial diffusely spreading type.
Nodular type.
Branching type.
Nodular-branching type.
According to the histological types the bronchogenic carcinoma may be:
1. Squamous-cell carcinoma.
2. Adenocarcinoma:
Acinar carcinoma.
Papillary carcinoma.
Bronchiole-alveolar carcinoma.
Solid carcinoma.
3. Small cell carcinoma:
Oat cell carcinoma.
Small cell carcinoma, intermediate cell type.
Combined oat-cell carcinoma.
4. Large cell carcinoma.
5. Adenosquamous carcinoma.
According to its location bronchogenic carcinoma may be hilar and peripheral.
Hilar type has following features:
Etiopathogenesis: smoking, atmospheric pollution, occupational causes, dietary factors, genetic factors, chronic scarring.
The lung cancer arises in the main bronchus or one of its segmental branches in the hilar parts of the lung.
More often on the right side.
The tumor begins as a small roughened area on the bronchial mucosa at the bifurcation.
As the tumor enlarges, it thickens the bronchial mucosa producing nodular or ulcerated surface.
Nodular carcinoma grows into a friable spherical mass, 1 to 5 cm in diameter, narrowing and occluding the lumen.
The cut surface of the tumour is yellowish-white with foci of necrosis and hemorrhages which may produce cavitary lesions.
It is common to find secondary changes in the lungs such as bronchopneumonia, abscess formation and bronchiectasis as a result of obstruction and accompanying infections.
The tumor soon spreads within the lungs by direct extension or by lymphatics, and to distant sites by lymphatic or hematogenous routes.
Peripheral type:
A small proportion of lung cancers, chiefly adenocarcinomas including bronchioloalveolar carcinomas.
It originates from a small peripheral bronchiole but the exact site of origin may not be discernible.
The tumor may be a single nodule or multiple nodules in the periphery of the lung producing pneumonia-like consolidation of a large part of the lung.
The cut surface of the tumor is grayish and mucoid.
Squamous cell (epidermoid) carcinoma
These tumors usually arise in a large bronchus and are prone to massive necrosis and cavitation.
The tumor 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 situ.
Adenocarcinoma of lungs.
Adenocarcinoma is the most common bronchogenic 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 frequently peripherally located in the lungs and is found in relation to pulmonary scars (scar carcinoma).
3. Bronchiole-alveolar carcinoma is characterized by cuboidal to tall columnar and mucus-secreting epithelial cells growing along the existing alveoli and forming numerous papillary structures.
4. Solid carcinoma is a poorly-differentiated adenocarcinoma lacking acini, tubules or papillae but having mucus-containing vacuoles in many tumor cells.
Small cell carcinomas.
Small cell carcinomas are frequently hilar or central in location, have strong relationship to cigarette smoking and are highly malignant tumors. They are most often associated with ectopic hormone production because of the presence of neurosecretory granules in majority of tumour cells which are similar to those found in argentaffm or Kulchitsky cells normally found in bronchial epithelium. Small cell carcinomas may be:
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 cytbplasm. These cells are organized into cords, aggregates and ribbons or around small blood vessels forming pseudorosettes.
Small cell carcinoma, intermediate cell type is composed of cells slightly larger than those of oat cell carcinoma and have similar nuclear characteristics but have more abundant cytoplasm. These cells are organized into lobules.
Combined oat-cell carcinoma is a tumour in which there is a definite component of oat cell carcinoma with squamous cell and/or adenocarcinoma.
Large cell carcinoma.
These are undifferentiated carcinomas, which lack the specific features by which they could be assigned into squamous cell carcinoma or adenocarcinoma.
Large cell carcinomas are more common in men, have strong association with cigarette smoking and are highly malignant tumors.
The tumor cells have large nuclei, prominent nucleoli, abundant cytbplasm 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.
Secondary complications: hemorrhages, necrosis of the tumor as well as cachexia.
Breast cancer
There are cancer of ducts, parenchyma, nipple and areola.
According to the WHO, carcinoma of the breast is subdivided on 2 main types non-invasive carcinoma and invasive one.
Non-invasive (in situ) carcinoma
The 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.
1. Lobular carcinoma in situis identified only microscopically. In situ lobular carcinoma is characterized by filling up of terminal ducts and ductules or acini by rather uniform cells, which are loosely cohesive and have small, rounded nuclei with indistinct cytoplasmic margins.
2. Carcinoma-in situ confined within the larger mammary ducts is called intraductal carcinoma. Morphological features are:
The tumor initially begins with atypical hyperplasia of ductal epithelium followed by filling of the duct with tumour cells.
Macroscopically, the tumor 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 papilloma (papillary pattern).
Micrpscopically, the proliferating tumour cells within the ductal lumina may have 4 types of patterns in different combinations: solid, comedo, papillary and cribriform. They may occur:
a) Solid type is characterized by filling and plugging of the ductal lumina with tumorous cells.
b) Comedo type is centrally placed necrotic debris surrounded by neoplastic cells in the duct.
c) Papillary type has formation of intraductal papillary projection of tumor cells, which lack a fibrovascular stalk so as to distinguish it from intraductal papilloma.
d) Cribriform type is recognized by neat punched out fenestrations in the intraductal tumor.
Invasive carcinoma
1. Infiltrating ductal(not otherwise specified) is the classic breast cancer.
Macroscopically, the tumor is irregular, 1-5 cm in diameter, hard cartilage-like mass that cuts with grating sound.
The sectioned surface of the tumor is gray-white to yellowish with chalky streaks and often extends irregularly into the surrounding fat.
Microscopically, as the name NOS suggests, the tumor is different from other special types in lacking a regular and uniform pattern throughout the lesion. There are 3 histological types of this carcinoma:
Anaplastic tumor cells forming solid nests, cords, poorly-formed glandular structures and some intraductal foci.
Infiltration by these patterns of tumor cells into diffuse fibrous stroma and fat.
Invasion into perivascular and perineural spaces as well as lymphatic and vascular invasion.
2. Infiltrating (invasive) tubular 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:
Pattern - a characteristic single file (Indian file) linear-arrangement of stromal infiltration by the tumor cells with very little tendency to gland formation is seen. Infiltrating ceils may be arranged concentrically around ducts in a target-like pattern.
Tumor cytology - individual tumor cells resemble cells of in situ lobula of carcinoma. They are round and regular with very little pleomorphism and infrequent mitoses. Some tumors may show signet-ring cells distended with cytoplasmic mucus.
3. Medullary carcinomahas a significantly better prognosis than the usual infiltrating duct carcinoma, probably due to good host immune response in the form of lymphoid infiltrate in the tumour stroma.
Macroscopically, the tumour is characterized by a large, well-circumscribed, rounded mass that is typically soft and fleshy brain-like and hence the alternative name of “encephaloid carcinoma.”
Cut section shows areas of hemorrhages and necrosis.
There arc 2 histological characteristics of this tumor:
Pleomorphic tumor cells with abundant cytoplasm, large vesicular nuclei and many bizarre and atypical mitoses are diffusely spread in the scanty stroma.
The loose connective tissue stroma is scanty and usually has a prominent lymphoid infiltrate.
4. Colloid (mucinous) carcinomacontains large amount of extracellular epithelial mucin and acini filled with mucin. Cuboidal to tall columnar tumour cellsi some showing mucus vacuolation, are seen floating iti large lakes of mucin.
Paget’s disease of the nipple
The nipple bears a crusted, scaly eczematoid lesion with a palpable subareolar mass in about half the cases.
Macroscopically, the skin of the nipple and areola is crusted, fissured and ulcerated.
Microscopically, the skin lesion is characterized the presence of Paget’s cells singly or in small clusters in the epidermis. These cells are larger than the epidermal cells, spherical, having hyperchromatic nuclei with eytoplasmic 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, which shows no obvious direct invasion of the skin of nipple.
The metastases are either local or distant, the former to the lymphatic nodes of the breast base, axilla, subclavicutar, parasternal nodes. Distant metastases are hematogenic ones, 40 - 50% to the bones, lungs, and liver. Late metastases and relapses occur 5 - 20 years after the operation.
Tumors cervix and body uterus
Cervix is both a sentinel for potentially serious upper genital tract infections and a target for viral or chemical cancerogens, which may lead to invasive carcinoma.
Squamous cell carcinoma may occur in any age from the second decade of life to senility.
Invasive cervical carcinoma manifests in three somewhat distinctive patterns: fungating (or exophytic), ulcerating, and infiltrative cancer.
Histologically, about 95% of squamous cell carcinomas are composed of relatively large cells either keratinizing (well-differentiated) or non-keratinizing (moderately differentiated) patterns.
Cervical cancer is staged as follows:
1. Carcinoma in situ.
2. Carcinoma confined to the cervix: preclinical carcinoma diagnosed only microscopically but showing;
3. Carcinoma extends beyond the cervix but not onto the pelvic wall. Carcinoma involves the vagina, but not to the lower third.
4. Carcinoma has extended onto the pelvic wall. The tumor involves the lower third of the vagina.
5. Carcinoma has extended beyond the true pelvis or has involved the mucosa of the bladder or rectum. This stage obviously includes those with metastatic dissemination.
Ten to twenty-five per cent of cervical carcinoma constitutes adenocarcinoma, adenosquamous arcinoma and undifferentiated carcinoma.
With current methods of treatment, there is % year survival rate about 80 to 90% with stage 1, 75% with stage 2, 35% with stage 3 and 10 to 15% with stage 4 disease.
Carcinoma of endometrium
The uterine corpus including its endometrium and myometrium is affected by a great variety of neoplastic growth.
These can be benign or malignant and can arise from
The endometrium glands (endometrial polyps and endometrial carcinomas).
The endometrial stroma (stromal nodule and stromal sarcoma).
Mixed mesodermal tumors.
The smooth muscle of the myometrium (leiomyoma, leiomyosarcoma).
The most common of these tumors are the endometrial polyps, leiomyomas, and endometrial carcinomas.
Endomterial polyps are bening tumors.
There are sessile masses of variable size that project into the endometrial cavity. They may be single or multiple, asymptomatic or may cause abnormal bleeding if the ulcerate or undergo necrosis.
Histologically, they are generally of two types, made up of
Functional endometrium.
More commonly hyperplastic endometrium, mostly of the cystic variety.
Rarely, adenocarcinomas may arise within endometrial polyps.
Carcinoma of endometrium
Carcinoma of endometrium is the most common invasive cancer of the female genital tract.
It is uncommon in women younger than 40 years of age. The peak incidence is in the 55 to 65-year-old women.
In terms of potential pathogenesis, two general groups of endometrium cancer can be identified. The first and the most well-studied develops on a background of prolonged estrogen stimulation and endometrial hyperplasia.
Grossly, endometrial carcinoma presents as a localized polypoid tumor or as a diffuse tumor involving the entire endometrial surface.
Eventually dissemination to the regional lymph nodes occurs, and in the late stages, the tumor may be hematogenously borne to the lungs, bones and other organs.
Histologically, most endometrial carcinoma is adenocarcinomas characterized by more or less well-differentiated gland patterns lined by malignant stratified columnar epithelial cells.
The more well-differentiated tumors tend to be those of endometrial differentiation.
Squamous elements most commonly are histologically benign in appearance (called adenocarcinoma with squamous metaplasia or more traditionally, adenoacantoma) when associated with well-differentiated adenocarcinomas.
Although classification as a poorly differentiated adenocarcinoma typically requires a less of glandular differentiation and the presence of solid growth, two histologic patterns behave as poorly differentiated regardless of their degree of differentiation and include papillary serous carcinoma.
Carcinoma of prostate gland
Cancer of the prostate is the second most common form of cancer in males, followed in frequency by lung cancer. It is a disease of men above the age of 50 years and its prevalence increases with increasing age so that 60% or more of men 80 years old have asymptomatic carcinoma of the prostate.
Precursor for prostatic cancer:
Androgens level is high.
Administration of estrogens.
In patients with Klinefelter’s syndrome.
Racial and geographic influences (in Americans).
Nodular hyperplasia.
There are following 4 types carcinoma of the prostate:
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