DIAGNOSIS OF CANCER
Histologic diagnosis of cancer.Microscopic examination of tissue or cells is requiredto make the diagnosis of cancer. Material suitable for diagnosis of a tumor may be obtained by complete excision, biopsy, fine needle aspiration, or cytologic smears (Pap test).
Immunohistochemistry may be helpful in confirming the tissue of origin ofmetastatic or poorly differentiated tumors. The technique uses monoclonal antibodies that are specific for a cellular component. Among the many anti-bodies that are clinically useful are:
· All of the serum tumor markers
· Thyroglobulin (thyroid cancers)
· S100 (melanoma and neural tumors)
· Actin (smooth and skeletal muscle)
· CD markers (lymphomas/leukemias)
· Estrogen receptors (breast cancer)
· Intermediate filaments
Ancillary tests for the diagnosis of cancer include electron microscopy, flowcytometry, cytogenetics, and PCR/DNA probes.
Serum tumor markers.Tumor markers are usually normal cellular components thatare increased in neoplasms but may also be elevated in nonneoplastic conditions. Serum tumor markers are used for screening (e.g., prostate specific antigen [PSA]) for cancer, monitoring treatment efficacy, and detecting recurrence of cancers.
· Clinically useful tumor markers include alpha-fetoprotein (AFP, used forhepatoma, nonseminomatous testicular germ cell tumors); beta human cho-rionic gonadotropin (hCG, used for trophoblastic tumors, choriocarcinoma); calcitonin (used for medullary carcinoma of the thyroid); carcinoembryonic antigen (CEA, used for carcinomas of the lung, pancreas, stomach, breast, and colon); CA-125 (used for malignant ovarian epithelial tumors); CA19-9 (used for malignant pancreatic adenocarcinoma); placental alkaline phosphatase (used for seminoma); and prostate specific antigen (PSA, used for prostate cancer).
Grading and staging. Tumor grade is a histologic estimate of the malignancy ofa tumor, and typically uses criteria such as the degree of differentiation from low grade (well-differentiated) to high grade (poorly differentiated/anaplastic) and the number of mitoses.
Tumor stage is a clinical estimate of the extent of tumor spread. TNM staging system criteria is used for most tumor types:
· T indicates the size of the primary tumor.
· N indicates extent of regional lymph node spread.
· M indicates the presence or absence of metastatic disease.
In general, staging is a better predictor of prognosis than tumor grade.
Tumor progression refers to the tendency of a tumor to become more malignantover time. This progression can be related to both natural selection (evolution of a more malignant clone over time due to a selective growth advantage) and genetic instability (malignant cells are more prone to mutate and accumulate additional genetic defects).
Metastasis.Lymphatic spread is the most common initial route of spread for epi-thelial carcinomas. Early hematogenous spread is typically seen with most sarcomas (e.g., osteogenic sarcoma), renal cell carcinoma (because of the proximity of the large renal vein), hepatocellular carcinoma (because of the presence of the hepatic sinusoids), follicular carcinoma of the thyroid, and choriocarcinoma (because of its propensity to seek vessels). Seeding of body cavities and surfaces occurs in ovarian carcinoma. Transplantation via mechanical manipulation (e.g., surgical incision, needle tracts) may occur but is relatively rare.