CANCERS OF DEFINITE ORGANS

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 of the stomach. 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 mucosal layers.

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 growth:

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 growth:

a) Ulcerative-invasive (infiltrating) type;

b) Diffusely spreading type (Linitis plastica).

3. Carcinoma with exophytic and endophytic growth. (Mixed types of carcinoma).

According to the histological signs there are the following types of gastric carcinoma:

1. Adenocarcinoma: papillary, mucoid, trabecular (well-differentiated).

2. Signet-ring cell carcinoma, scirrhous carcinoma, 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. The 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 be 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 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 signet-ring cell carcinoma, extensively infiltrating the stomach wall, but due to marked desmoplasia cancer cells 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.

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 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 type;

c) combined oat-cell carcinoma.

4. Large cell carcinoma.

5. Adenosquamous carcinoma.

According to its location, bronchogenic carcinoma may be hilar and peripheral.

Hilar type. Most commonly, 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 tumour begins as a small roughened area on the bronchial mucosa at the bifurcation. 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 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 tumour soon spreads within the lungs by direct extension or by lymphatics, and to distant sites by lymphatic or hematogenous routes, as described later.

Peripheral type. A small proportion of lung cancers, chiefly 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 the 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 situ.

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. Bronchioloalveolar 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 tumour cells.

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 argentaffin 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 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.

3. 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 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 in the majority of cases the death of the patients is caused by hunger long before the disease becomes incompatible with the life. Even gastrostomy cannot save the patient, it only slows down the rate of cachexia. This cancer is on the 2nd—3rd place in occurrence. Men suffer more often than women (70 to 30). The tumor is localized mainly in the middle and lower part of the esophagus.

Carcinoma of the oesophagus is mainly of 2 types — squamous cell (epidermoid) and adenocarcinoma.

Squamous cell (epidermoid) carcinoma. Squamous cell or epidermoid carcinoma comprises 90% of primary esophageal cancers. The sites of predilection are the three areas of esophageal constrictions. Half of the squamous cell carcinomas of 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: 1) Polypoid fungating type is the most common form. It appears as a cauliflower-like friable mass protruding into the lumen; 2) Ulcerating type is the next common form. 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 moderately-differentiated. Prickle cells, keratin formation and epithelial pearls are commonly seen. However, non-keratinising and anaplastic growth patterns can also occur.

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 salivary gland i.e. a cribriform appearance in an epithelial tumour).

Besides the two main 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 sarcomatous components.

6. Secondary tumors rarely occur in the esophagus from carcinomas of the breast, kidney and adrenals.

Metastases are lymphogenic. Hematogenic metastases are rare, chiefly to the liver, lungs, adrenal glands.

Complications: involvement of trachea, stomach, aspiration 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 precancerous 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 region. These aberrant cancers occur in 10% of cases. The most frequent location of the tumor is upper external quadrant of the breast.

According to the WHO, 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 (in situ) carcinoma. In general, noninvasive 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 papilloma (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 characterized by filling and plugging of the ductal lumina with tumour cells. Comedo type is centrally placed necrotic debris surrounded by neoplastic cells in the duct. Papillary type has formation of intraductal papillary

projection of tumour cells which lack a fibrovascular stalk so as to distinguish it from intraductal papilloma. Cribriform type is recognized by neat punched out fenestrations 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 ductules or acini by rather uniform cells which are loosely cohesive and have small, rounded nuclei with indistinct cytoplasmic margins.

Invasive carcinoma. Infiltrating ductal carci-noma-NOS (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 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. There are 3 histological types of this carcinoma:

• anaplastic tumour cells forming solid nests, cords, poorly-formed glandular structures and some intraductal foci;

• infiltration by these patterns of tumour cells into diffuse 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 to gland formation is seen. Infiltrating cells may be arranged concentrically around ducts in a target-like 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 signet-ring cells distended with cytoplasmic mucus.

Medullary carcinoma has 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 are 2 histological characteristics of this tumor. The first — pleomorphic tumour cells with abundant cytoplasm, large vesicular nuclei and many bizarre and

atypical mitoses are diffusely spread in the scanty stroma. The second — the loose connective tissue stroma is scanty and usually has a prominent lymphoid infiltrate.

Colloid (mucinous) carcinoma contains large amount of extracellular epithelial mucin and acini filled with mucin. Cuboidal to tall columnar tumour cells, some showing mucus vacuolation, are seen floating in 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 with oozing of serosanguineous fluid from the erosions. 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 cytoplasmic halo that stains positively with muci-carmine. In these respects, Paget's cells are adeno-carcinoma-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, subclavicular, 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.