14 5-13 ipmr approach to cancer diagnosis

Approach to Cancer Diagnosis

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Clinical Suspicion

• Cause of symptoms where the diagnosis is not obvious.

• Thorough clinical history • Family history• Social history (eg, smoking),• Occupational history (eg, shipyard worker,

miner),• Diet and geographic origin • Sexual and childbearing history

• Physical examination is directed toward finding localizing symptoms or signs

• Mass lesion that may be sampled by biopsy or aspiration

Early Diagnosis

• Routine (screening) examinations of asymptomatic individuals • Routine cytologic screening in the form of annual cervical

smears (papanicolaou smears)• Dysplastic epithelium can be detected • Unfortunately, screening methods do not exist for most other

types of cancer.• Public education campaigns • To examine their breasts monthly to detect small lumps and to

undergo mammography after age 40 years every 2 or 3 • 50 and older are encouraged to undergo sigmoidoscopy every 3–

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Cytologic Diagnosis

• Samples obtained by a variety of techniques.• (1) Exfoliated cells can be identified in samples of

sputum, urine, cerebrospinal fluid, and body fluids.

Recognition of malignant cells in blood (as in the leukemias) or bone marrow smears (leukemias, myeloma, metastatic carcinoma

• (2) Brushing or scraping of epithelium or of a lesion that has been visualized by endoscopy

• (3) A fine (22-gauge) needle can be passed into virtually any location to aspirate material directly from a mass lesion (fine-needle aspiration (FNA)

• Remarkably accurate performed by a trained pathologist.

• Immunoperoxidase techniques improved the reliability of cell and tumor identification.

• Cytologic diagnosis must be confirmed by histologic diagnosis

• In many centers, radical surgery is undertaken on the basis of positive results on fine-needle aspiration for carcinomas such as those of the breast, pancreas, and thyroid.

Histologic Diagnosis

• Definitive method of establishing the diagnosis • A trained pathologist with an adequate specimen • Immunohistology, special stains, and electron

microscopy

• Excisional biopsy • Incisional biopsy or • With a large-bore cutting needle.

TechniquesFrozen Section Method

• Providing information while the patient is still on the operating table (often within 15 minutes).

• Cytologic details in the preparation are poor, and the diagnosis is less accurate than when processed tissue (paraffin sections) is used.

Paraffin Section Method

• Provide the best material for microscopic diagnosis. • Small blocks of formalin-fixed tissue are dehydrated • Embedded in paraffin • 24 hours. • Hematoxylin and eosin (H&E) the standard stain• Nuclei blue, • Eosin stains cytoplasm and extracellular material

pink.

Immunoperoxidase Techniques

• Immunohistochemical stains use specific labeled antibodies—identify marker antigens in cells and tissues

• When the peroxidase label reacts with a substrate, it produces a colored product that identifies the location of the antigen in the tissues.

• This method is analogous to the use of fluorescent labeled antibody method but gives better results on paraffin sections

Immunohistochemistry.

• Specific monoclonal antibodies • The identification of cell products or surface markers.

Some examples of the

Utility of immunohistochemistry in the diagnosis or management of malignant neoplasms

• Categorization of undifferentiated malignant tumors

• Categorization of leukemias and lymphomas• Determination of site of origin of metastatic

tumors• Detection of molecules that have prognostic or

therapeutic significance

Anticytokeratin immunoperoxidase stain of a tumor of epithelial origin (carcinoma)

Electron Microscopy

• Special fixation (in glutaraldehyde) and processing

• Ultrastructural features visible

• Useful in recognizing many types of neoplasms, eg, anaplastic squamous carcinoma, melanoma, endocrine tumors, and muscle cell tumors.

Flow Cytometry

Rapidly and quantitatively measure several individual cell characteristics

• Membrane antigens (classification of leukemias and lymphomas)

• DNA content of tumor cells

They say that life is a school, but nobody mentioned the tuition fee!

• Information provided by pathologic diagnosis

Type of Neoplasm

• The name of the neoplasm will be given in the pathology report.

Biologic Behavior• The pathology report will state whether the

neoplasm is benign or malignant

Histologic Grade

• Describes the degree of differentiation of the neoplasm

• Either in words (eg, well), moderately, or poorly differentiated adenocarcinoma) or

• In numbers (eg, grade I, II, or III transitional cell carcinoma of the bladder—grade I being the least and III the most malignant)

Degree of Invasion

• Planning treatment of some neoplasms; • In malignant melanoma of the skin, • The treatment is based on the depth of infiltration • In bladder neoplasms, it is imperative to state whether

or not muscle invasion has occurred in the biopsy specimen

Pathologic Stage

• Extent of spread of a neoplasm. • Extent of infiltration and metastasis (eg, depth of

invasion of the wall of a viscus; lymph node, bone marrow, or organ involvement).

• Determines further treatment

• Valuable guide to prognosis.

Serologic Diagnosis

• Theoretically, it may be possible to diagnose cancer by detecting cancer cell products in the serum,

• Molecules secreted by malignant cells or antigens released by periodic death of such cells.

• No general serologic screening methods exist for cancer, but several tests are of value for certain tumors

Serologic Assays for Cancer Diagnosis or Follow-Up.

Substance in Serum Cancer Type

Carcinoembryonic antigen (CEA) Gastrointestinal tract cancer (especially colon),.

–Fetoprotein (AFP) Hepatoma, yolk sac tumors.

Human chorionic gonadotropin (hCG) Greatly elevated in choriocarcinoma

Prostatic acid phosphatase; prostate–specific epithelial antigen

Two separate molecules; levels of both are elevated in metastatic prostatic cancer.

Monoclonal immunoglobulin Myeloma, some B cell lymphomas.

Specific hormones Endocrine neoplasms and ectopic hormone–producing tumors.

CA 125 Ovarian carcinoma;

Radiologic Diagnosis

• CT and magnetic resonance imaging (MRI) scans, are invaluable for localizing masses as part of the primary diagnosis or for staging tumors.

• As a general rule, radiologic findings suggestive of cancer must be confirmed by either cytologic or histologic examination of biopsy material before treatment can be started.

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