Cancer of definite organs

Gastric carcinoma• Gastric cancer, commonly referred to as stomach cancer, can develop in

any part of the stomach and may spread throughout the stomach and to other organs; particularly the esophagus, lungs, lymph nodes, and the liver. Stomach cancer causes about 800,000 deaths worldwide per year.

• Gastric carcinoma comprises more that 90% of all gastric malignant tumors. Men at the age of 40-60 suffer more often than women.

• Gastric carcinoma is most commonly located in the region of the gastric canal, less common localization are the body, cardiac and fundus.

Pre-cancer changes:

• Chronic atrophic gastritis

• Adenoma (adenomatous polyps) of the stomach

Classification:

According to the deepness of the lesion in the gastric wall:• Early gastric carcinoma: only mucous layer• Advanced gastric carcinoma: penetrates mucous layer and

beyond

According to location:1. Pyloric gastric carcinoma2. Lesser curvature3. Cardial gastric carcinoma4. Fundal carcinoma5. Total gastric carcinoma

Macroscopic (anatomical) forms:1.Carcinoma with exopthytic growth:a) Superficial spreading type b) Polypoid type c) Fungating (fungiform) typed) Ulcerative type 2.Carcinoma with endophytic growth:a)Ulcerative-invasiveb)Diffuse 3.Carcinoma with exophytic and endophytic growth (mixed)

Microscopic (histological) types:-Adenocarcinoma-Poorly-differentiated: signet ring carcinoma, scirrhous carcinoma, solid carcinoma-Squamous cell carcinoma-Adenosquamous carcinoma

Early gastric carcinoma

• Early gastric carcinoma is a term used to describe cancer limited to the musoca and submucosa.

• Macroscpically, the lesions of early gastric carcinoma may have 3 patterns: superficial,polypoid and ulcer associated. The superficial type may furthur be of flat, elevated to depressed types.

• Microscpically, early gastric carcinoma is atypical granula adenocarcinoma, usuaally well differentiated.

Advanced gastric carcinoma• When the carcinoma crosses the basement membrane

into the muscular propria or beyond.• Ulcerative carcinoma(common). Tumor appears to be flat,

infiltrating and ulcerative growth. Macroscopically ulcerative carcinomas are pooorly diferentiated adenocarcinomas, which invade deeply inot stomach wall

• Fungating(polypoid) carcinoma. Cauliflower growth projection into the lumen. Microscopically fungating or polypoid carcinomas are well-differentiated adenocarcinomas, coomonly papillary type.

• Scirrhous carcinoma. Stomach wall is thickened due to extensive desmoplasia giving the appearcance as leather bottle stomach or linitis plastica Microscopically it may be an adenocarcinoma or signet ring cell carcinoma.

• Colloid carcinoma. Commonly in fundus, tumor grows like masses having gelitinous appearnce due to secretion of large quantities of mucus.

• Ulcer-cancer. Majority of ulcer-cancers are malignant lesions from the beginning.

Metastasis can be:• Lymphogenic: 1. Orthograde(with the lymph flow): lymph.nodes

along lesser and greter curvature 2. Retrograde (against the lymph flow): - Krukenberg (in the ovari), - Virchows (in the left supraclavicular lymph.node), - Shnitslers (lymph.nodes of pararectal fat tissue)• Hematogenic metastases are carried with the blood

flow to the liver,lungs,brain,bones,kidneys and adrenal glands.

• Implantation, when the carcinoma disseminates throught the peritionieum or penetrate to the pancreatic glands.

Complications

• Mortality 1-2%• Anastamotic leak, bleeding, ileus, transit

failure, cholecystitis, pancreatitis, pulmonary infections, and thromboembolism.

• Late complications include dumping syndrome, vitamin B-12 deficiency, reflux esophagitis, osteoporosis.

Outcome

• 5-year survival for a curative resection is 30-50% for stage II disease, 10-25% for stage III disease.

• Adjuvant therapy because of high incidence of local and systemic failure.

• A recent Intergroup 0116 randomized study offers evidence of a survival benefit associated with postoperative chemoradiotherapy

Lung Carcinoma• Lung cancer is a disease that consists of

uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is the invasion of adjacent tissue and infiltration beyond the lungs. The vast majority of primary lung cancers are carcinomas, derived from epithelial cells. Lung cancer, the most common cause of cancer-related death in men and women, is responsible for 1.3 million deaths worldwide annually, as of 2004. The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss.

Precanceromatous processes

• Chronic inflammatory diseases (chronic bronchitis, bronchoectasis, pneumosclerosis)

• Precancer changes of epithelium - hyperplasia, - metaplasia, - dysplasia

Location• Bronchogenic (central) or Peripheral

• Central type: (common), arises in the main bronchus or one of its segmented branches in the hilar parts of the lung, more often the right side. The tumor grows into a friable spherical mass 1-5cm in diameter, narrowing and occluding the lumen. The tumor spreads within the lungs by direct extention or by lymphatics.

• Peripheral type: Small proportion of the lung cancers, chiefly adenocarcinomas including bronchoalveolar carcinomas, originate from small peripheral bronchiole but the exact site of origin may not bediscernible. The tumore may be single nodule or multiple nodules in the periphery producing pneumonia like consolidation.

ClassificationAccording to pecularities of growth:-Exophytic (endobrochial type)-Endophytic (exobronchial type, and peribronchial type)According to macroscopical signs-Superficial-Polypoid-Endobronchial-Nodular-Branching type-Nodular-Branching type

Accoridng to the WHO-Squamous cell carcinoma-Adenocarcinoma- Poorly-differentiated (large-cell, smal-cell carcinomas)- Rare forms (adenosquamous, bronchoalveolar, carcinoma of bronchial glands)

Localization of the first metastases

• - peribronchial l.n.• - bifurcative l.n.

Causes of death

• 1. Generalisation of tumor.• 2. Pulmonary complications (bleeding,

suppuration, pneumothorax)• 3. Cachexia

Breast Cancer• Breast cancer (malignant breast

neoplasm) is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas. The size, stage, rate of growth, and other characteristics of the tumor determine the kinds of treatment. Treatment may include surgery, drugs (hormonal therapy and chemotherapy), radiation and/or immunotherapy

Risk Factor

• Primary – sex, age, lack childbearing/ breastfeeding, higher hormone level, race, economy, dietary iodine deficiency.

• Age- advanced age (50 and above more likely to be affected). risk for breast cancer is increased if she starts menstruating before age 12, has her first child after 30, stops menstruating after 55, or has a menstrual cycle shorter or longer than the average 26-29 days.

.

• Smoking, later age at first birth, not having children, family history, past hormone replacement therapy .

• Genetic, high fat diet, alcohol intake, obesity, tobacco use, radiation, endocrine distruptor.

• Personal (1 of the breast had cancer), family (at least 2 close relatives with breast or ovarian cancer ).

• Weight gain as the aged.

Prevention

• Exercise, prevent smoking• Avoiding alcohol and obesity • Prevention bilateral mastectomy in patient

with BRCA1 and BRCA2• Breastfeeding• Do monthly self breast exam• Have yearly exam by doctor after 40

years,may have mammogram.

• Diet control- eating five or more servings of vegetables and

fruits each day, choosing wholegrains over processed (refined) grains, and limiting consumption of processed and red meats.

- fat and red meat has to be taken in moderation. It is also recommended that to maintain a desirable body weight, eat more high-fibre foods such as whole grains, cereals, breads, vegetable and soya, and limit the consumption of salt-cured, smoked, and preserved foods.

• Beans are also recommended as they are a high-fibre, low-fat, vitamin-packed source of protein. Beans are full of antioxidants. Black beans offer the most benefit, followed by lentils, soya beans and red kidney beans.

Diagnosis

• Screening technique- to detect lump (whether it is cance or simple cyst in benign)-need futher test.

-for earlier diagnosis-self breast exam – feeling lumps or other

abnormalities.-mammography- xray (frequent use can cause

radiation)• Ultrasound, MR imaging, mammography.

• Fine Needle Aspiration and Cytology (FNAC)- extract fluid from lump.

• Biopsy- remove breast lump (section or entire).

• Vacuum-assisted breast biopsy (VAB)

Treatment

• Surgery, chemotherapy, radiation.• Surgery- to remove as much cancer as possible. mastectomy – removal the whole breast lumpectomy – a part of breast reconstruction surgery- to create the

look of a normal breast• Hormone blocking (or hormone positive cancer)• Hormone therapy- medicine in pill form taken to

work against estrogen in the body. The most common side effect is signs of menopause.

• Stage 1- lumpectomy, radiation, HER2+- treated with trastuzumab regime.

• The treatment is depending on the stage of the disease.

• Stage 1- surgery- lumpectomy tumor removal with some surrounding tissues

• radiation- after lumpectomy, kill missed cancer cell, usually not necessary after mastectomy.

• HER2+- treated with trastuzumab regime.

• Stage 2- surgery (lumpectomy or mastectomy- with or without removal of lymph node), chemotherapy, radiation.

. Stage 4- metastasis- surgery, radiation, chemotherapy, targeted therapy.

• Medication- nolvadex (tablet)• - adjuvant therapy (addition to

surgery)- hormone blocking therapy(estrogen-block receptor(tamoxifen) or its production (aromatose inhibitor-suitable for menopause patient), chemotherapy monoclonal antibodies.

• Chemotherapy- medicine given in an IV (intravenous) tube in a vein or as a pill. The medicine kills cancer cells. - stage 2-4, cyclophosmide with adriamycin (AC), destroy fast growing/replicating cancer by damage DNA. Sometimes added with docetaxel to attack microtubule in cancer cell. Can use cyclophosphamide, methotrexate, and fluorouracil (CMF).

• Lower the risk of cancer of coming back.

• Common side effects include feeling tired, hair loss and nausea. These side effects are often temporary.

• Monoclonal antibodies- HER2+ cancer treatment (because stimulated by growth factor make it overexpressed)- trastuzumab. Aspirin may be used.

• Radiotherapy- after surgery to destroy microscopic tumor that escaped surgery., external beam radiotherapy or brachytherapy (internal).can used intraoperatively. Can reduce recurrence, essential if the surgery only remove lump. Can be done 4 to 6 weeks after surgery.

Prognosis

• Important for treatment decision • Less invasive for a good prognosis one

( lumpectomy, radiation, hormone therapy)• Poor prognosis (extensive mastectomy,

chemotherapy drugs)• Prognosis factor – staging ( tumor size (invasive),

grade, metastasis, local involvement, lymph node status), recurrence of disease, age. Stage raised by invasiveness and aggressiveness, lowered by cancer-free zone and close to normal cell behaviour (grading).

• Good prognosis- 1• Poor prognosis – 3@4• Grading criteria- tubule formation (1 point-in

>75% of tumor, 2 points- in 10- 75% of tumor, 3 points- in , 10% of tumor), nuclear pleomorphism (1 point-minimal variation, 2- moderate, 3- marked variation)and mitotic count (1,2,3. count only at the periphery of tumor and begin at the most mitotic active area).

• Younger patient have poorer prognosis than menopausal one (firm lumpy tissue can hide a small lump and make it hard to feel)

• Patient without positive hormone R not be able to response to hormonal therapy.

• Presence of cell surface protein can effect the treatment and prognosis (HER2-more aggressive and have to be treated with targeted therapy)

Precancer processes

• 1. Fibroadenomatosis (mastopathy)• 2. Ductal papilloma

• Sclerosing Adenosis of Breast

Comments: Some cases of sclerosing adenosis don't have lobulocentric

architecture and may have infiltrative edges. This may lead to the mistaken diagnosis of well-differentiated ductal carcinoma, especially in limited needle

core biopsy specimens.

• Blunt Duct Adenosis (Columnar Cell Change)

Comments: The luminal columnar epithelial cells have basally-oriented

oval nuclei and prominent apical snouts. When the lining epithelium is more than 2 layers thick, the term columnar cell hyperplasia is applied.

• Intraductal Papilloma of Breast : Solid type

Comments: Another case of a solid intraductal papilloma. Fusion of papillary fronds creates secondary lumens. Myoepithelial cells are clearly seen at the periphery of the lumens.

• Intraductal Papilloma of Breast : Solid type

Comments: Florid epithelial hyperplasia has filled up virtually all the space

between fibrovascular stalks imparting a solid appearance.

Macroscopic forms

• 1. Nodular• 2. Diffused• 3. Cancer of nipple and nipples area (rare)

• Infiltrating Ductal Carcinoma

Comments: In more advanced cases of infiltrating ductal carcinoma, the

overlying skin may be invaded (as seen here). Fortunately, such cases are rarely seen these days.

• Infiltrating Ductal Carcinoma

Comments: In a typical invasive ductal carcinoma, NOS, the tumor is firm

and poorly circumscribed with a yellowish gray cut surface. It cuts with a gritty sensation. It may show strands radiating into the surrounding fat.

• Mucinous Carcinoma of Breast

Comments: Another example of mucinous carcinoma of breast. The tumor has ill-defined margins as compared to the previous case. This is seen

more often in tumors with mixed mucinous and ductal differentiation.

• Mucinous Carcinoma of Breast

Comments: Mucinous carcinoma is more common in post-menopausal women. Pure mucinous carcinomas comprise up to 2% of all breast cancers. Focal mucinous differentiation is seen in additional 2% of breast cancers. For prognostic reasons, the term mucinous carcinoma should be applied to pure mucinous tumors. Grossly, the tumor is generally well-

circumscribed and has a gelatinous or jelly-like cut surface.

• Medullary Carcinoma of Breast

Comments: Medullary carcinoma is usually seen in patients under age 50.

It is common in Japanese women and in carriers of BRCA1 mutations. The tumor is well-circumscribed and may be partially cystic (as seen here). The cut surface is solid and uniform and may have areas of hemorrhage or necrosis.

• Phyllodes Tumor : High-grade

Comments: This specimen of high-grade phyllodes tumor shows a circumscribed tumor with areas of hemorrhage and necrosis. The sections showed infiltrative borders, stromal overgrowth with considerable cytologic atypia and frequent mitoses. The histologic features were those of sarcoma, NOS. Clear-cut distinction between benign and malignant phyllodes tumor may not always be possible.

• Phyllodes Tumor : High-grade

Comments: High-grade (malignant) phyllodes tumor of the breast in a 35

y/o female. The specimen weighed 1166 grams and measured 18 x 14 x 10 cm.

According to WHO, breast carcinomas are divided into Non-Invasive and Invasive ones.

Non-Invasive carcinomas. Characterized by histologically by the prescence of tumor cells within the ducts or lobules without evidence of invasion. Two types are describes: Intraductal carcinoma or lobular carcinoma in situ.

Intraducatal carcinoma (in situ): confined within the larger mammary ducts. Tumor initially begins with atypical hyperplasia of the ductile epithelium followed by filling of the duct with tumor cells. Macroscopically the tumor may vary from a small poorly defined focus to 2.5-5.5cm diameter in mass. Microscopically the proliferating tumor cells within the ductile Lumina may have 4 types of patterns in different combinations: solid, comedo, papillary and cribriform.

Intralobular carcinoma (in situ): identified only microscopically. Characterized by filling up of terminal ducts and ductile or acini by rather uniform cells which are loosely cohesive and have small, rounded nuclei with indistinct cytoplasm margins.

Invasive carcinomas:Infiltrating ductal carcinoma is the classic breast cancer.

Macroscopically, the tunor is irregular, 1-5cm in diameter, hard cartillage like mass that cuts with grating sounds.

Infiltrating lobular carcinoma: invasive cancers in being more frequently bilateral and within the same breast, may have multicentric origin.Macroscopically, appearance is scirroius.

Rare (speshial) forms:Medulary carcinoma has a singificantly better prognosisi that

the usual infiltrating duct carcinoma probably due to good host immune response.

Colloid carcinoma contains large amount of extracellular epithelial mucin and acini filled with mucin. Cuboidal to tal columnar cells, some showing mucus vacuolation, are see floating in large takes of mucin.

• Ductal Carcinoma-in-situ : Micropapillary

• Comments: The papillae in this case of micropapillary DCIS range from small bumps or mounds of tumor cells to slender papillary structures. The nuclear grade is high. Some of the papillary fronds projecting into the lumen may be cut transversely resulting in appearance of small detached irregular clusters of tumor cells in the lumen (as seen here). Cellular debris, usually a feature of cases with high nuclear grade, is also present in the lumen.

• Ductal Carcinoma-in-situ

Comments: The tumor cells with high nuclear grade nearly fill the lumen

in this example of DCIS. The cytoplasmic borders are sharply demarcated.

• Lobular Carcinoma-In-Situ

Comments: Following the diagnosis of LCIS, approximately 20% to 30% of

patients will develop invasive carcinoma in the absence of therapy. The increased risk applies to both breasts, although it is greater on the side of the diagnostic biopsy. The invasive carcinoma could be either lobular or ductal type.

• Infiltrating Lobular Carcinoma : Signet Ring Type

Comments: High power view of the previous image shows the signet ring morphology in this infiltrating lobular carcinoma. Elsewhere in the case, classical Indian filing pattern was seen.

• Invasive Papillary Carcinoma of Breast

Comments: The diagnosis of invasion in a papillary carcinoma of the

breast can be quite difficult. Many cases have areas of fibrosis, recent or remote hemorrhage, inflammation or reaction to previous needle biopsy procedures. Extension of carcinoma beyond the tumor borders and desmoplastic stromal reaction generally support the presence of invasion (as seen in this image).

• Intracystic Papillary Carcinoma of Breast

Comments: Higher power view of the previous case shows several

papillary structures with fibrovascular cores. Features favoring carcinoma are uniformity in the size and shape of epithelial cells, lack of myoepithelial cells, nuclear hyperchromasia, nuclear enlargement, and high mitotic activity. Lack of benign proliferative changes in the adjacent breast also favor carcinoma.

• Carcinoma arising in a Fibroadenoma

Comments: Higher power view from the previous case shows clusters of

tumor cells in pools of mucin. In rare cases of malignancy arising in a fibroadenoma, sarcomatous transformation may be seen.

• Medullary Carcinoma of Breast

Comments: The tumor cells grow in clusters or sheets with no evidence of

glandular differentiation. A prominent lymphoplasmacytic infiltrate within and around the tumor is always present.

• Mucinous Carcinoma of Breast

Comments: The nuclei are plump and vesicular with prominent nucleoli. Mitotic figures are easily found.

Medullary Carcinoma of Breast

Comments: Higher magnification view of the previous slide shows the highly anaplastic tumor cells in a background of lymphoplasmacytic infiltrate.

• Metaplastic Carcinoma of Breast

Comments: Another example of densely cellular metaplastic carcinoma of

breast. The tumor was largely composed of plump spindle cells with vague storiform pattern. The nuclei showed immunoreactivity for p63.

Localization of the first lymphogenic metastases

• 1. subaxillary l.n.• 2. anterior pectoral l.n.• 3. subclavian l.n.• 4. juxta-pectoral l.n.• 5. supraclavian l.n.

Localization of the first hematogenic metastases

• 1. bone (spine)• 2. lung• 3. liver• 4. kidney

Paget’s nipple disease• Paget's disease of the breast is a malignant

condition that outwardly may have the appearance of eczema, with skin changes involving the nipple of the breast.

• The condition occurs when Paget's cells, which are large and irregular, form in the skin of the nipple. Although Paget believed the cells were not cancerous, it was later proved that the cells were themselves malignant, in addition to indicating underlying breast cancer. Since the condition is often innocuous and limited to a surface appearance, it is sometimes dismissed, despite the fact that it is indicative of a condition (breast cancer) that may prove fatal if left untreated.

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 areaok is crusted , fissured and ulcerated with oozing of serosanguineous fluid from erisions.

Microscopically the skin lesion is charaterized the presnce of pagents cells singly or in small clusters in the epidermis.

The meatastases are either local or distant, the former to the lymphatic nodes of the breast base, axilla, subclavicular, parasternal nodes. Distant metastases are hematogenic ones. Late metastases and relapses occur 5-20 years after the operation.

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