Download III. LOCAL INVASION

III. LOCAL INVASION
Benign tumors differ from malignant ones by the following
1. Grow as cohesive expansile masses
2. Remain localized to site of origin (no invasion or metastasis)
+ slow rate of growth
Rim of compressed CT (fibrous capsule)
Malignant tumors characterized by
1. Progressive infiltration (invasion)/destruction of surrounding tissue
Makes surgical resection difficult
necessary to remove margin of apparently normal tissues adjacent
to cancer (margin of safety)
Fibroadenoma Breast
Sharply demarcated mass, about 3 cm in diameter. The cut surface is solid, grayish white.
Fibroadenoma Breast
Well-defined fibrotic capsule surrounding the tumor. The latter consists of compressed ducts set within
fibroblastic stroma.
Follicular adenoma thyroid
This is a benign tumor of the thyroid gland. It is surrounded by a thin white capsule.
Carcinoma lung invasion
Malignant neoplasms are characterized by the tendency to invade surrounding tissues. Here, a lung
cancer is seen to be spreading along the bronchi into the surrounding lung tissues & pleura.
Ca breast invasion
This carcinoma of the breast is definitely infiltrating the surrounding breast. The central white area is very
hard in consistency and gritty on section, because the neoplasm is producing a desmoplastic reaction with
lots of collagen. This is often called a "scirrhous" appearance. There is also focal dystrophic calcification
leading to the gritty areas.
Ca breast invasion
On micrscopic examination, the infiltrating ductal carcinoma of the breast has pleomorphic cells
infiltrating through the stroma.
Ca breast invasion
On micrscopic examination, the infiltrating ductal carcinoma of the breast has pleomorphic cells
infiltrating through the stroma.
IV. METASTASIS
• Metastases: “tumor implants discontinuous with primary tumor”
- The only definite criterion of malignancy
- The major exceptions are
1. Most malignant gliomas of CNS (derived from glial cells)
2. Basal cell carcinoma of the skin. (Rodent ulcer)
Cancers more likely to metastasize are
1. The more aggressive & more rapidly growing
3. The larger the size
• Metastatic spread strongly reduces the possibility of cure
Basal cell carcinoma lower lip
These rarely metastasize, but are slow-growing and progressive over time. Leaving them to get larger
just makes the plastic surgeon's job much harder, with more disability to the patient, so early detection
and excision is a must. Most basal cell carcinomas occur in the head and neck area of adults with
prolonged sun exposure.
• The invasiveness of cancers permits penetration into
1. Blood vessels
2. Lymphatic vessels
3. Body cavities
Pathways of Spread
• Dissemination of cancers may occur through one of three
pathways:
1. Direct seeding of body cavities or surfaces
2. Lymphatic spread
3. Hematogenous spread
Seeding of Body Cavities and Surfaces
• Occurs when cancer penetrates into a natural "open field."
Peritoneal cavity/pleural/ pericardial/ subarachnoid/joint space
• Peritoneal cavity
- Seeding is characteristic of ovarian carcinomas
- Mucus-secreting carcinomas of appendix
pseudomyxoma
peritonei
• pleural cavity involved by lung carcinoma, Br. Ca etc.
Pouring of exudates (malignant pleural effusion)
Pseudomyxoma peritonei
The entire peritoneal cavity is occupied by a multinodular mucinous mass
Pseudomyxoma peritonei
Clusters of well-differentiated mucin-producing glandular cells are seen floating in a sea of mucin.
Metastatic breast carcinoma-pleura
Neoplasms can spread by seeding along body cavities, and this pattern is more typical for carcinomas than
other neoplasms. Here is a focus of metastatic breast carcinoma seen along the pleura overlying the lung.
Lymphatic Spread
• Commonest pathway for initial spread of ca (some sarc.)
• LN involvement follows natural routes of lymphatic drainage
- Br. Ca usually in UOQ
- Br. Ca inner quadrants
axillary LNs.
LNs along internal mammary As
- Later
infra-clavicular & supra-clavicular nodes
- Ca lung
tracheo-bronchial
mediastinal nodes
• Axillary LNs involvement in Br. Ca very important for
1. Assessing future course
2. Selecting suitable therapy.
- Assessment of LN involvement by
a. Full axillary LN dissection
morbidity
b. Sentinel node Bx
- also used for spread of melanomas, colon cancers, and others
- SLN "first node in a regional lymphatic basin that receives
lymph flow from primary tumor."
• Drainage of tumor cell antigens (no cells)
Reactive lymph node hyperplasia
• Enlargement of the regional nodes may be due to caused by either
1. The spread of cancer cells (metastasis) or
2. Reactive hyperplasia to tumor antigens
NODAL ENLARGEMENT NEAR A CANCER DOES NOT
NECESSARILY MEAN DISSEMINATION
Lymph node: metastatic adenocarcinoma
Microscopically, metastatic adenocarcinoma is seen in a lymph node here. It is common for carcinomas
to metastasize to lymph nodes. The first nodes involved are those draining the site of the primary.
Hematogenous Spread
• Typical of sarcomas/ but seen with ca
• With venous invasion, spread follow venous flow draining site
• Liver & lungs most frequently involved by metastases
• Cancers close to vertebral column
Paravertebral plexus of veins
Vertebral (bone) metastases (ca thyroid/prostate)
• Certain cancers show remarkable tendency to invade veins
Renal cell ca
Renal vein
branches of the renal vein
IVC (snakelike fashion)
Rt. side of the heart
Hepatocellular carcinomas
portal and hepatic veins
main venous channels
• Histologic evidence of penetration of small vessels at site of
primary neoplasm is ominous feature
Liver metastases
Liver metastasis by adenocarcinoma
Pulmonary metastases
Metastatic adenocarcinoma lung
PRECANCEROUS CONDITIONS
• Conditions having ↑ risk of association with cancer
• Divided into two groups
A. Non-neoplastic conditions; e.g.
1. Chronic atrophic gastritis
2. Actinic keratosis of skin
3. Chronic ulcerative colitis
4. Leukoplakia of oral cavity, vulva, and penis
5. Chronic viral B & C hepatitis
B. Benign neoplasms; e.g.
1. Villous adenoma of colon*
2. Familial adenomatous polyposis (FAP) of colon
Local and Hormonal Effects
• GIT tumors
Obstruction
Intussusception*
• Tumors with critical locations e.g. Pituitary adenoma:
enlargement/expansion
destruction remaining gland
panhypopituitarism
• Tumors of endocrine glands may be functional
- A benign β-cell adenoma of pancreatic islets
↑↑insulin
fatal hypoglycemia
- Nonendocrine tumors may produce hormone-like substances
Paraneoplastic syndromes
•
Destructive growth of cancers/expansile pressure of
tumor on skin/mucosa of bronchi/ GIT/bladder
1. Ulcerations/secondary infections
2. Bleeding: hemoptysis/melena/hematuria
benign
Cancer Cachexia
• Loss of weight + weakness + anorexia + anemia
• ? Origin
- ↓intake of food + tumor parasitism + Action of TNF** + ↑BMR*
• Cancer cachexia
equal loss of fat and muscle (protein)*
GRADING AND STAGING OF CANCERS
To assess prognosis & effectiveness of various forms of treatment
Separation of cancers into groups
each with members of high degree of similarity.
Systems of
grading & staging
Reflecting seriousness of various cancers
Expresses degree of differentiation
+
Other micro. Features
- no. of mitoses
- Necrosis
Expresses extent of cancer spread
Grades 1 to 4
• Staging is of great importance in selection of best therapy & has
proved to be of greater clinical value than grading.
• Staging of cancers is based on
1. Size of primary tumor
2. Extent of spread to regional LNs
3. Presence/absence of blood-borne metastases
• Two major staging systems in use
1. TNM (ICC)
2. AJC on Cancer Staging.
• The TNM varies for each specific form of cancer
General principles
T - T1 to T4 with ↑size
- TIS (in situ)
N
- N0: no nodal involvement
- N1 to N3: involvement of an ↑number and range of nodes
M
- M0: no distant metastases,
- M1 or M2: presence of blood-borne metastases.
•The AJC: divides all cancers into stages 0 to IV,
depending on
- Size of the primary tumor
- Nodal spread
- Distant metastases.
TNM staging for ca breast
LABORATORY DIAGNOSIS OF CANCER
• Becomes more complex & specialized
• Several approaches to correct Dx
- Sometimes > than one approach employed
A. Histologic and Cytologic Methods
• Separating benign from malignant not usually difficult
- Difficulty is Dx of borderline tumors
- Clinical data and surgical findings very useful
• Specimen delivered to lab must be
1. Adequate
2. Representative
3. Properly preserved
•
Several sampling approaches are available
1. Incisional or Excisional biopsy specimen for
a. conventional histopathological diagnosis
b. frozen section diagnosis
2. Needle Biopsies
a. Fine needle aspiration material (cytology)
b. Needle-core biopsy material (histopathology)
3. Endoscopic biopsy material
4. Laparoscopic, or thoracoscopic biopsies
5. Cytologic smears from the tumor in question
• In Excisional biopsies,
the entire lesion is removed, usually with a rim of normal
tissue, and therefore the procedure serves both a diagnostic
and a therapeutic function.
• Incisional biopsy
means that only a portion of the lesion is sampled, and therefore the
procedure is strictly of a diagnostic nature.
When excision of the whole lesion is not possible, incisional biopsy is
performed, however, selection of an appropriate site for a biopsy of a
large mass by the surgeon requires awareness that the margins of the
lesion may not be representative and its center may be largely necrotic.
Frozen section Biopsy:
Requesting an intra-operative "quick-frozen section"
diagnosis is sometimes desirable, for example, in
determining the nature of a mass lesion or in
evaluating the margins of an excised cancer to
ascertain that the entire neoplasm has been
removed.
This method permits histologic evaluation within
minutes, while the patient is still under anesthesia.
The results in such cases will modify the course of
the surgical operation.
•
Core needle biopsy
A wide-bore needle with a cutting tip is used to draw a thin core of
tissue (the size of a match stick) out of a suspicious area.
Image-guided biopsy combines an imaging procedure, such as X-ray,
computerized tomography (CT) or ultrasound, with a needle biopsy.
Image-guided biopsy allows access to suspicious areas that cannot
be felt through the skin, such as a suspicious lesion of the liver or
prostate.
3. Endoscopic biopsies
• During endoscopy, a thin, flexible tube with a light on the end (endoscope) is
used to see structures inside the body.
• Special tools are passed through the tube to take small samples of tissue for
pathological analysis.
4. Laparoscopy,
Laparoscopy is similar to endoscopy but is used to look inside the
abdominal cavity and remove tissue samples.
A small incision is made in the abdomen then the laparoscope is
passed through this opening to see the inside.
Similar procedures to look inside the chest are called thoracoscopy
and mediastinoscopy
Histochemistry
The basis of surgical pathology is the examination of the
specimens following fixation in formalin, processing in graded
alcohols and xylene, embedding in paraffin, cutting of sections
with a microtome, and staining with hematoxylin-eosin (H&E).
•Immunohistochemistry (IHC)
This is the application of immunologic principles & techniques to the study
of cells & tissues.
The availability of specific monoclonal antibodies has greatly facilitated
the identification of cell products or cell surface markers.
In several situations, the differentiation between neoplasms may be very
difficult.
Differentiation between these is of prognostic & therapeutic implications.
Examples of the utility of immunohistochemistry in
the diagnosis or management of malignant
neoplasms include
1. Categorization of undifferentiated malignant
tumors
2. Categorization of leukemias and lymphomas
3. Determination the site of origin of metastatic
tumors
4. Detection of molecules that have prognostic or
therapeutic significance
Serum Tumor Markers
Tumor markers are either substances released by cancer cells into the
blood (or urine) or substances created by the body in response to
cancer cells.
They include cell-surface antigens, cytoplasmic proteins, enzymes,
and hormones.
. Their main utility is a laboratory test to
1.
support the diagnosis of cancer
2.
to determine the response to therapy
3-
to indicate recurrence during the follow-up period.
Carcinoembryonic antigen (CEA)
is a complex glycoprotein that is elaborated by many
different neoplasms.
Its serum levels are reported to be positive in colorectal,
pancreatic, gastric and breast carcinomas.
In patients with CEA-positive colon carcinomas, the
persistence of elevated CEA levels 6 weeks after surgical
removal indicates a residual (left behind) tumor tissues,
whereas a rising CEA levels indicates recurrence.
Prostate-specific antigen (PSA)
An elevated PSA level in the blood may indicate prostate
cancer, but other conditions such as benign prostatic
hyperplasia (BPH) and even prostatitis can also raise PSA
levels.
PSA levels are used also to evaluate how a patient has
responded to treatment and to check for tumor
recurrence.
The development of tests to detect cancer markers in
blood and body fluids is an active area of research.
D. Electron microscopy:
The main use of diagnostic electron microscopy is involved not
with the question of whether a tumor is malignant or not, but
with the issue of tumor classification.
Cytoplasmic organelles such as melanosomes are indicative of
melanocytic lesions such as malignant melanoma,
the presence of desmosomes points to an epithelial tumor
(carcinoma),
and structures such as myosin and actin filaments arranged in
"Z" bands are indicative of skeletal muscle differentiation and
hence if found in a tumor would suggest a rhabdomyosarcoma.
Neurosecretory dense core granules are found in tumors with
neuroendocrine differentiation.
•Flow Cytometry
is a technique used to measure individual cell characteristics such as
membrane antigens and DNA content of tumor cells.
The classification of leukemias and lymphomas is based on cell surface
antigens which can be easily identified by flow cytometry.
DNA ploidy appears to correlate with prognosis in a variety of tumors.
In general, aneuploidy seems to be associated with a poorer prognosis in
early-stage breast cancer, bladder, lung, colorectal and prostate cancer.
•Molecular techniques such as polymerase chain reaction (PCR), the Southern
blot analysis of DNA and the Northern blot analysis of RNA are used in tumor
diagnosis.
•DNA microarray analysis
•Tissue microarrays analysis